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We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions. The evidence from RCTs for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs. | We identified only one randomised controlled trial (RCT), which compared plasma exchange with sham exchange, in 18 participants with either IgA or IgG paraproteinaemic neuropathy. The results were reported after three weeks of treatment. The trial did not report our primary outcome measure, which was improvement in disability measured by a validated scale six months after randomisation, or our other specified outcomes at six months. The trial demonstrated a modest benefit in improvement of weakness and overall disability as measured by the neuropathy disability score (NDS) over a period of three weeks. There was no improvement in this timescale in measures of sensory disturbance or electrical studies of the nerves. Adverse events were not reported. Further RCTs of this and other treatments with larger numbers of participants are needed. This is an update of a review first published in 2007. We found no additional trials for inclusion. The evidence is current to January 2014. |
The review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline. Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when regular formoterol was compared with placebo (Peto odds ratio (OR) 1.57; 95% CI 1.06 to 2.31). One extra serious adverse event occurred over 16 weeks for every 149 people treated with regular formoterol (95% CI 66 to 1407 people). The increase was larger in children than in adults, but the impact of age was not statistically significant. Data submitted to the FDA indicate that the increase in asthma-related serious adverse events remained significant in patients taking regular formoterol who were also on inhaled corticosteroids. No significant increase in fatal or non-fatal serious adverse events was found when regular formoterol was compared with regular salbutamol or terbutaline. In comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant. Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related. | There was no statistically significant difference in the number of people who died during treatment with formoterol compared with placebo or salbutamol. Because so few people die of asthma, huge trials or observational studies are normally required to detect a difference in death rates from asthma. There were more non-fatal serious adverse events in people taking formoterol compared to those on placebo; for every 149 people treated with formoterol for 16 weeks, one extra non-fatal event occurred in comparison with placebo. There was no significant difference in serious adverse events in people on formoterol compared to regular salbutamol. We conclude that regular formoterol should not be taken by people who are not taking regular inhaled steroids due to the increased risk of serious adverse events. Formoterol should not be used as a substitute for inhaled corticosteroids, and adherence with inhaled steroids should be kept under review if separate inhalers are used when formoterol is added to inhaled corticosteroids. |
We inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n=512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early ( n=1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n=1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.32 to 10.43). The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients. | An update search was carried out in 2012 and the review now includes 55 studies that assess the effects of chlorpromazine in treating schizophrenia compared with no active treatment (‘dummy’ treatment or placebo). Evidence was, in the main, rated by the review authors as low quality. There is some evidence to suggest that chlorpromazine reduces relapse and improves people’s mental health, symptoms and functioning. However, the side effects of chlorpromazine are severe and debilitating. Chlorpromazine causes sleepiness and sedation. It also causes movement disorders (such as tremors and uncontrollable shaking), considerable weight gain and lowering of blood pressure with accompanying dizziness. Chlorpromazine is low-cost and widely available. Despite its many side effects, chlorpromazine is likely to remain a benchmark drug and one of the most widely used treatments for schizophrenia worldwide. It should be noted that the quality of evidence from the 55 included studies was low and in addition to this, 315 studies were excluded because of flaws in the reporting of information or data and in research design and methods. Larger, better conducted and reported trials should focus on important outcomes such as quality of life, levels of satisfaction, relapse, hospital discharge or admission and number of violent incidents. |
Cognitive training was not associated with positive or negative effects in relation to any reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to a number of participant and caregiver outcomes, and was generally of high quality. Available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefit derived from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardised outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further, well-designed studies of cognitive training and cognitive rehabilitation are required to obtain more definitive evidence. Researchers should describe and classify their interventions appropriately using available terminology. | This review included 11 trials of cognitive training and a single trial of cognitive rehabilitation. We found no evidence for the efficacy of cognitive training in improving cognitive functioning, mood or activities of daily living in people with mild to moderate Alzheimer's disease or vascular dementia; however the quality of the studies was generally not high. The single trial of cognitive rehabilitation provided preliminary indications of the potential benefits of individual cognitive rehabilitation in improving activities of daily living in people with mild Alzheimer's disease. More high-quality trials of both cognitive training and cognitive rehabilitation are needed to establish their efficacy for people with early-stage dementia. |
One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6/14 patients versus 2/7 patients in the propofol and thiopental sodium groups, respectively (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.40 to 5.61, low quality evidence). Mortality was seen in 3/14 patients versus 1/7 patients in the propofol and thiopental sodium groups, respectively (RR 1.50, 95% CI 0.19 to 11.93, low quality evidence). Our third primary outcome of length of ICU stay was not reported. For our secondary outcomes of adverse events, infection was seen in 7/14 patients versus 5/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.70; 95% CI 0.35 to 1.41). Hypotension during administration of study drugs and requiring use of vasopressors was seen in 7/14 patients versus 4/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.87; 95% CI 0.38 to 2.00). The other severe complication noted was non-fatal propofol infusion syndrome in one patient. Patients receiving thiopental sodium required more days of mechanical ventilation when compared with patients receiving propofol: (median (range) 17 days (5 to 70 days) with thiopental sodium versus four days (2 to 28 days) with propofol). At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Since the last version of this review we have found no new studies. There is a lack of robust, randomised, controlled evidence to clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large RCTs for this serious condition. | The evidence is current to August 2016. We could only identify one trial, which was terminated early due to recruitment problems. This study enrolled only 24 participants of the required 150. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. There was no difference between the two drugs in their ability to control seizure activity. The only difference noted was the requirement for prolonged mechanical ventilation for patients in the thiopental sodium group. This could be due to the prolonged presence of the drug in the body due to its slow removal. We judged the quality of the evidence for our primary outcomes of total control of seizures and in-hospital mortality to be low. There is a clear need for a large randomised controlled trial to study the efficacy of anaesthetic agents in the treatment of RSE. |
A total of four studies were included that involved 823 participants, 412 in the exercise group and 411 in the control group. Follow-up of participants ranged from 16 weeks to 6 months. Overall, the included studies had a high risk of selection, detection, and attrition bias. Meta-analysis was not possible because the interventions (setting, type and intensity of exercise) and outcome measurements were not comparable, and the risk of bias in the identified studies was high. No study assessed cardiovascular or all‑cause mortality or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life but the available evidence was not sufficient to determine the effectiveness of exercise. Adverse events and smoking cessation were not assessed in the included studies. Evidence to date is entirely limited to small studies with regard to sample size, short-term follow-up, and high risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of aerobic or resistance exercise on groups with increased cardiovascular risk or in individuals with two or more coexisting risk factors. Further randomized clinical trials assessing controlled exercise programmes on total cardiovascular risk in individuals are warranted. | We included four studies, with 823 participants in total, comparing exercise for increased-risk individuals against control or no treatment. Follow-up of patients ranged from 16 weeks to six months. No study assessed cardiovascular or all-cause mortality, or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life, but the results did not provide conclusive evidence of the effects of exercise in this population. The included studies did not assess smoking cessation or any adverse effects of the exercise intervention. We conclude that the evidence to date is entirely limited to small studies in terms of sample size, short-term follow-up, and high-risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of the exercise carried out in the included trials on total cardiovascular risk, mortality, or cardiovascular events. It is necessary to conduct high-quality clinical trials that evaluate the effect of exercise on people with increased cardiovascular risk. |
We included 19 studies (2256 participants). Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients. Epinephrine versus salbutamol showed no differences among outpatients for admissions at Day 1 or 7. Inpatients receiving epinephrine had a significantly shorter LOS compared to salbutamol (mean difference -0.28; 95% CI -0.46 to -0.09). One large RCT showed a significantly shorter admission rate at Day 7 for epinephrine and steroid combined versus placebo (RR 0.65; 95% CI 0.44 to 0.95). There were no important differences in adverse events. This review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care. Exploratory evidence from a single study suggests benefits of epinephrine and steroid combined for later time points. More research is required to confirm the benefits of combined epinephrine and steroids among outpatients. There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients. | Our systematic review found 19 studies involving 2256 children that use epinephrine for the treatment of bronchiolitis in acute care settings. When comparing epinephrine with placebo, no differences were found for length of hospital stay but there is some indication that epinephrine is effective for reducing hospital admissions. Exploratory results from one large, high-quality trial suggest that combined treatment with systemic glucocorticoids (dexamethasone) and epinephrine may significantly reduce admissions. There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among children admitted to the hospital. The evidence shows no important differences in adverse effects with epinephrine over the short-term with long-term safety not being assessed. Some limitations of this review include the quality of the included studies and inconsistent timing of measurement across studies which limited the number of children included in some meta-analyses. Further research is needed to confirm the efficacy, applicability and long-term safety of epinephrine as a treatment for bronchiolitis. In summary, our systematic review provides evidence that epinephrine is more effective than placebo for bronchiolitis in outpatients. Recent research suggests combined epinephrine and steroids may be effective for outpatients. There is no evidence to support the use of epinephrine for inpatients. |
We did not identify any new trials for inclusion in this fifth update. Seven trials involving a total of 10,157 participants were included. Four of the included trials had three comparison groups. The antiseptic used in all trials was 4% chlorhexidine gluconate (Hibiscrub/Riohex). Three trials involving 7791 participants compared chlorhexidine with a placebo. Bathing with chlorhexidine compared with placebo did not result in a statistically significant reduction in SSIs; the relative risk of SSI (RR) was 0.91 (95% confidence interval (CI) 0.80 to 1.04). When only trials of high quality were included in this comparison, the RR of SSI was 0.95 (95%CI 0.82 to 1.10). Three trials of 1443 participants compared bar soap with chlorhexidine; when combined there was no difference in the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Three trials of 1192 patients compared bathing with chlorhexidine with no washing, one large study found a statistically significant difference in favour of bathing with chlorhexidine (RR 0.36, 95%CI 0.17 to 0.79). The smaller studies found no difference between patients who washed with chlorhexidine and those who did not wash preoperatively. This review provides no clear evidence of benefit for preoperative showering or bathing with chlorhexidine over other wash products, to reduce surgical site infection. Efforts to reduce the incidence of nosocomial surgical site infection should focus on interventions where effect has been demonstrated. | This review identified seven trials, with over 10,000 patients, that tested skin antiseptics (chlorhexidine solution) against normal soap or no presurgical washing. The review of these trials did not show clear evidence that the use of chlorhexidine solution before surgery was better than other wash products at preventing surgical site infections from developing after surgery. |
We included eight randomised controlled trials with a total of 391 participants. Six trials focused on children and two on adults. Trials compared tube thoracostomy drainage (non-surgical), with or without intrapleural fibrinolytics, to either VATS or thoracotomy (surgical) for the management of pleural empyema. Assessment of risk of bias for the included studies was generally unclear for selection and blinding but low for attrition and reporting bias. Data analyses compared thoracotomy versus tube thoracostomy and VATS versus tube thoracostomy. We pooled data for meta-analysis where appropriate. We performed a subgroup analysis for children along with a sensitivity analysis for studies that used fibrinolysis in non-surgical treatment arms. The comparison of open thoracotomy versus thoracostomy drainage included only one study in children, which reported no deaths in either treatment arm. However, the trial showed a statistically significant reduction in mean hospital stay of 5.90 days for those treated with primary thoracotomy. It also showed a statistically significant reduction in procedural complications for those treated with thoracotomy compared to thoracostomy drainage. We downgraded the quality of the evidence for length of hospital stay and procedural complications outcomes to moderate due to the small sample size. The comparison of VATS versus thoracostomy drainage included seven studies, which we pooled in a meta-analysis. There was no statistically significant difference in mortality or procedural complications between groups. This was true for both adults and children with or without fibrinolysis. However, mortality data were limited: one study reported one death in each treatment arm, and seven studies reported no deaths. There was a statistically significant reduction in mean length of hospital stay for those treated with VATS. The subgroup analysis showed the same result in adults, but there was insufficient evidence to estimate an effect for children. We could not perform a separate analysis for fibrinolysis for this outcome because all included studies used fibrinolysis in the non-surgical arms. We downgraded the quality of the evidence to low for mortality (due to wide confidence intervals and indirectness), and moderate for other outcomes in this comparison due to either high heterogeneity or wide confidence intervals. Our findings suggest there is no statistically significant difference in mortality between primary surgical and non-surgical management of pleural empyema for all age groups. Video-assisted thoracoscopic surgery may reduce length of hospital stay compared to thoracostomy drainage alone. There was insufficient evidence to assess the impact of fibrinolytic therapy. A number of common outcomes were reported in the included studies that were not directly examined in our primary and secondary outcomes. These included duration of chest tube drainage, duration of fever, analgesia requirement, and total cost of treatment. Future studies focusing on patient-centred outcomes, such as patient functional scores, and other clinically relevant outcomes, such as radiographic improvement, treatment failure rates, and amount of fluid drainage, are needed to inform clinical decisions. | We included eight trials with a total of 391 participants. Six trials focused on children and two on adults. The trials compared chest tube drainage (non-surgical), with or without fibrinolysis, to either VATS or thoracotomy (surgical). Two studies declared no financial conflicts of interest; the remaining six studies did not report funding source. There was no difference in the proportion of patients of all ages who survived empyema in relation to surgical or non-surgical treatment. However, this finding was based on limited data: one study reported one death with each treatment option, and seven studies reported no deaths. There was no difference in rates of complications between patients treated with surgical or non-surgical options. There was limited evidence to suggest that VATS reduced length of stay in hospital compared to non-surgical treatments. The quality of the evidence was moderate overall. The main limitations were few included studies for each analysis and inconsistencies among studies. |
One randomized controlled trial comparing high target serum concentration and low target serum concentration tacrolimus versus placebo was identified and included in the review. Clinical remission was observed in 19% (4/21) of patients in the high target serum concentration group, in 9% (2/22) in the low target serum concentration group and in 5% (1/20) in the placebo group (OR 2.27; 95% CI 0.35 to 14.75). A statistically significant benefit for clinical improvement at two weeks was observed. Clinical improvement was observed in 62% (13/21) of patients in the high target serum concentration group, in 36% (8/22) in the low target serum concentration group and in 10% (2/20) in the placebo group (OR 8.66; 95% CI 1.79 to 42.00; RD 0.39; 95% CI 0.20 to 0.59; NNT = 3). Patients in the high serum target concentration group were significantly more likely than placebo patients to experience adverse events related to treatment (P = 0.043). Finger tremor (n = 6) was the most common adverse event in the tacrolimus group. Other adverse events included: gastroenteritis, sepsis, sleepiness, hot flush, headache, queasiness and stomach discomfort. Tacrolimus may be effective for short-term clinical improvement in patients with refractory ulcerative colitis. However, these results should be interpreted with caution due to the small number of patients enrolled in the trial and other study limitations. Insufficient treatment and follow-up intervals prevent any conclusions with regard to long term safety and efficacy. The use of tacrolimus in the clinical setting requires careful consideration of risks versus benefits as well as close monitoring for adverse events. More data from well designed and controlled studies are needed to determine the long-term efficacy and safety of tacrolimus. | One study that tested the effectiveness of tacrolimus as therapy for treatment resistant ulcerative colitis was reviewed. Ulcerative colitis is a relapsing inflammatory disease restricted to the colon. Symptoms include bloody diarrhea, passage of pus and/or mucus and abdominal cramping during bowel movements. Tacrolimus is an immunosuppressant that may inhibit transcription of the interleukin 2 gene required for T cell activation thereby suppressing the inflammation associated with ulcerative colitis. The study compared two dosing regimens of tacrolimus (high serum concentration and low serum concentration) with placebo (inactive pill) and found that tacrolimus was effective for improving the symptoms of ulcerative colitis at two weeks. No benefit for induction of remission was noted. Patients in the high serum concentration group were significantly more likely than placebo patients to experience side effects related to treatment. Most of the side effects that occurred during the study were mild and included finger tremor, sleepiness, hot flush, headache, queasiness, stomach discomfort, hypomagnesemia and kidney problems. Two patients developed serious side effects during the study. One patient in the high serum concentration group developed serious viral gastroenteritis. A patient in the low serum concentration group developed Acinetobacter sepsis. Tacrolimus treatment was withdrawn in these patients and both patients recovered after medical therapy. Other side effects that have been associated with tacrolimus in other studies included liver problems, seizures, hypertension, diabetes mellitus, hyperkalemia, itching, insomnia, confusion, loss of appetite, hyperglycemia, weakness, depression, cramps, neuropathy, and infections. Tacrolimus may be effective for short-term improvement in symptoms in patients with treatment resistant colitis. There are no data from controlled trials to allow conclusions with regard to long term safety and effectiveness. The use of tacrolimus needs to be weighed against the potential risk of serious side effects. More data from well designed and controlled studies are needed to determine the long-term safety and effectiveness of tacrolimus. |
We identified 85 studies involving 9765 participants. Seventy-five trials included 8520 adults and 10 trials included 1245 children. Most studies had risk of bias issues, with attrition bias being the largest source across studies due to incomplete outcome data. In adults, pain intensity on day one was reduced by 0.75 cm on a 10 cm VAS after LA (MD -0.75, 95% CI -1.04 to -0.45; 20 RCTs; 2421 participants; low-quality evidence). Wound infections were less likely after LA (Peto OR 0.42, 95% CI 0.35 to 0.51; 63 RCTs; 7612 participants; moderate-quality evidence), but the incidence of intra-abdominal abscesses was increased following LA (Peto OR 1.65, 95% CI 1.12 to 2.43; 53 RCTs; 6677 participants; moderate-quality evidence). The length of hospital stay was shortened by one day after LA (MD -0.96, 95% CI -1.23 to -0.70; 46 RCTs; 5127 participant; low-quality evidence). The time until return to normal activity occurred five days earlier after LA than after OA (MD -4.97, 95% CI -6.77 to -3.16; 17 RCTs; 1653 participants; low-quality evidence). Two studies showed better quality of life scores following LA, but used different scales, and therefore no pooled estimates were presented. One used the SF-36 questionnaire two weeks after surgery and the other used the Gastro-intestinal Quality of Life Index six weeks and six months after surgery (both low-quality evidence). In children, we found no differences in pain intensity on day one (MD -0.80, 95% CI -1.65 to 0.05; 1 RCT; 61 participants; low-quality evidence), intra-abdominal abscesses after LA (Peto OR 0.54, 95% CI 0.24 to 1.22; 9 RCTs; 1185 participants; low-quality evidence) or time until return to normal activity (MD -0.50, 95% CI -1.30 to 0.30; 1 RCT; 383 participants; moderate-quality evidence). However, wound infections were less likely after LA (Peto OR 0.25, 95% CI 0.15 to 0.42; 10 RCTs; 1245 participants; moderate-quality evidence) and the length of hospital stay was shortened by 0.8 days after LA (MD -0.81, 95% CI -1.01 to -0.62; 6 RCTs; 316 participants; low-quality evidence). Quality of life was not reported in any of the included studies. Except for a higher rate of intra-abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, wound infections, length of hospital stay and time until return to normal activity in adults. In contrast, LA showed advantages over OA in wound infections and length of hospital stay in children. Two studies reported better quality of life scores in adults. No study reported this outcome in children. However, the quality of evidence ranged from very low to moderate and some of the clinical effects of LA were small and of limited clinical relevance. Future studies with low risk of bias should investigate, in particular, the quality of life in children. | We included 85 studies involving 9765 participants, of which 75 trials compared laparoscopic appendectomy versus open appendectomy in adults. The remaining 10 studies included only children. The evidence is current to February 2018. The main advantages of laparoscopic compared to open appendectomy were reduced postsurgical pain, reduced risk of wound infection, shorter hospital stay, and more rapid return to normal activities in adults. In contrast, laparoscopic appendectomy showed advantages over open appendectomy in wound infections and shorter hospital stay in children. Two studies reported that adults who received laparoscopic appendectomy had better quality of life two weeks, six weeks, and six months after surgery. Data from children were not available. As for disadvantages of laparoscopic appendectomy, a higher rate of intra-abdominal abscesses were identified in adults but not in children. Except for a trend towards decreased intra-abdominal abscesses after LA, the results for children were similar to those seen in adults. The quality of the evidence varied from moderate to low because of poorly conducted studies. |
Five trial reports were retrieved using the search strategies. Four trials were excluded. We did not identify any randomised controlled trials for inclusion but we included one quasi-randomised study (involving 210 women) that evaluated the effect of extra fluid for breastfeeding mothers on breastfeeding outcomes. The study was considered to be at a high risk of bias. Only one of this review's primary outcomes was reported (breast milk production (as defined by the trialist)) but data were not in a suitable format for analysis (no standard deviations or standard errors were reported). The trialist reported that advising women to drink extra fluids did not improve breast milk production. No data were reported for the review's other primary outcomes: satisfactory weight gain in the infant (as defined by the trialists) and duration of exclusive breastfeeding (months). Similarly, no data were reported for any of this review's secondary outcomes: duration of any breastfeeding; mother's satisfaction with breastfeeding; hydration in mother; dehydration in the infant; or episodes of gastrointestinal illness. This review only identified one small quasi-randomised controlled trial of low quality and high risk of bias. The study provided limited data on only one of this review's primary outcomes, breast milk production, but the data were not reported in a format that permitted further analysis. The trialist reported that extra fluids did not improve breast milk production. However, this outcome was measured by using test feeds (also known as test weighing). In the 1950s, when the study was conducted, it was common for babies in developed countries to be weighed before and after a feed, known as test weighing or test feeding. However, this practice is not now routinely practiced for term infants due to concerns about lack of precision as a measure of breast milk production. The included study did not report on this review's other primary outcomes (satisfactory weight gain in the infant or duration of exclusive breastfeeding) nor any of the review's secondary outcomes. The effect of additional fluids for breastfeeding mothers remains unknown, due to a lack of well-conducted trials. However, because the physiological basis for any such improvement remains unclear, the conduct of further clinical trials may not be a priority. There is not enough evidence to support an increased fluid intake beyond what breastfeeding mothers are likely to require to meet their physiological needs. | This review aimed to assess whether increasing fluid intake of breastfeeding mothers has a beneficial effect on breast milk production and infant growth. However, the review only identified one small quasi-randomised controlled trial (involving 210 women). The trial was of low quality and did not report on two of this review's important outcomes (satisfactory weight gain in the infant or duration of exclusive breastfeeding). The study did report on breast milk production (this review's other main outcome), but the data were not in a format that would permit further analysis in this review. The trial reported that advising women to consume extra fluids did not result in increased breast milk production, as measured by test feeds (also known as test weighing). In the 1950s, when the study was conducted, it was common for babies in developed countries to be weighed before and after a feed, known as test weighing or test feeding. However, this practice is not now routinely practiced for term infants due to concerns about lack of precision as a measure of breast milk production. The included study did not report any of this review's secondary outcomes: duration of any breastfeeding; mother's satisfaction with breastfeeding; hydration in mother; dehydration in the infant; or episodes of gastrointestinal illness. The effect of additional fluids for breastfeeding mothers remains unknown, due to a lack of well-conducted trials. However, because the physiological basis for any such improvement remains unclear, the conduct of further clinical trials may not be a priority. There is not enough evidence to support an increased fluid intake beyond what breastfeeding mothers are likely to require to meet their physiological needs. |
We included 27 RCTs based on data from 1251 participants. Three trials compared early treatment with a functional appliance versus late treatment for overjet, ANB and incisal trauma. After phase one of early treatment (i.e. before the other group had received any intervention), there was a reduction in overjet and ANB reduction favouring treatment with a functional appliance; however, when both groups had completed treatment, there was no difference between groups in final overjet (MD 0.21, 95% CI −0.10 to 0.51, P = 0.18; 343 participants) (low-quality evidence) or ANB (MD −0.02, 95% CI −0.47 to 0.43; 347 participants) (moderate-quality evidence). Early treatment with functional appliances reduced the incidence of incisal trauma compared to late treatment (OR 0.56, 95% CI 0.33 to 0.95; 332 participants) (moderate-quality evidence). The difference in the incidence of incisal trauma was clinically important with 30% (51/171) of participants reporting new trauma in the late treatment group compared to only 19% (31/161) of participants who had received early treatment. Two trials compared early treatment using headgear versus late treatment. After phase one of early treatment, headgear had reduced overjet and ANB; however, when both groups had completed treatment, there was no evidence of a difference between groups in overjet (MD −0.22, 95% CI −0.56 to 0.12; 238 participants) (low-quality evidence) or ANB (MD −0.27, 95% CI −0.80 to 0.26; 231 participants) (low-quality evidence). Early (two-phase) treatment with headgear reduced the incidence of incisal trauma (OR 0.45, 95% CI 0.25 to 0.80; 237 participants) (low-quality evidence), with almost half the incidence of new incisal trauma (24/117) compared to the late treatment group (44/120). Seven trials compared late treatment with functional appliances versus no treatment. There was a reduction in final overjet with both fixed functional appliances (MD −5.46 mm, 95% CI −6.63 to −4.28; 2 trials, 61 participants) and removable functional appliances (MD −4.62, 95% CI -5.33 to -3.92; 3 trials, 122 participants) (low-quality evidence). There was no evidence of a difference in final ANB between fixed functional appliances and no treatment (MD −0.53°, 95% CI −1.27 to −0.22; 3 trials, 89 participants) (low-quality evidence), but removable functional appliances seemed to reduce ANB compared to no treatment (MD −2.37°, 95% CI -3.01 to -1.74; 2 trials, 99 participants) (low-quality evidence). Six trials compared orthodontic treatment for adolescents with Twin Block versus other appliances and found no difference in overjet (0.08 mm, 95% CI −0.60 to 0.76; 4 trials, 259 participants) (low-quality evidence). The reduction in ANB favoured treatment with a Twin Block (−0.56°, 95% CI −0.96 to −0.16; 6 trials, 320 participants) (low-quality evidence). Three trials compared orthodontic treatment for adolescents with removable functional appliances versus fixed functional appliances and found a reduction in overjet in favour of fixed appliances (0.74, 95% CI 0.15 to 1.33; two trials, 154 participants) (low-quality evidence), and a reduction in ANB in favour of removable appliances (−1.04°, 95% CI −1.60 to −0.49; 3 trials, 185 participants) (low-quality evidence). Evidence of low to moderate quality suggests that providing early orthodontic treatment for children with prominent upper front teeth is more effective for reducing the incidence of incisal trauma than providing one course of orthodontic treatment in adolescence. There appear to be no other advantages of providing early treatment when compared to late treatment. Low-quality evidence suggests that, compared to no treatment, late treatment in adolescence with functional appliances, is effective for reducing the prominence of upper front teeth. | This review is based on 27 studies including 1251 participants. Participants were children and adolescents aged under 16 years who had prominent upper front teeth (Class II Division 1 malocclusion). The evidence in this review is up to date as of 27 September 2017. The evidence suggests that providing orthodontic early treatment to children with prominent upper front teeth reduces the incidence of damage to upper incisor teeth significantly (middle four teeth at the top) as compared to treatment that is provided in one phase in adolescence. There are no other advantages of providing a two-phase treatment (i.e. between age seven to 11 years and again in adolescence) compared to treatment in one phase in adolescence. The evidence also suggests that providing treatment with functional appliances for adolescents with prominent upper front teeth, significantly reduces their prominence when compared to adolescents who did not receive any treatment. The studies did not suggest that any particular appliance was better than any other for reducing teeth prominence. The overall quality of the evidence is low for most comparisons and outcomes, therefore further research is needed and may change the findings. |
We included two trials that randomised 4523 women and their infants. Both trials were conducted in Ireland. One trial (which quasi-randomised 3742 women, and analysed 3152 women) compared universal screening versus risk factor-based screening, and one trial (which randomised 781 women, and analysed 690 women) compared primary care screening versus secondary care screening. We were not able to perform meta-analyses due to the different interventions and comparisons assessed. Overall, there was moderate to high risk of bias due to one trial being quasi-randomised, inadequate blinding, and incomplete outcome data in both trials. We used GRADEpro GDT software to assess the quality of the evidence for selected outcomes for the mother and her child. Evidence was downgraded for study design limitations and imprecision of effect estimates. Universal screening versus risk-factor screening (one trial) Mother More women were diagnosed with GDM in the universal screening group than in the risk-factor screening group (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.12 to 3.04; participants = 3152; low-quality evidence). There were no data reported under this comparison for other maternal outcomes including hypertensive disorders of pregnancy, caesarean birth, perineal trauma, gestational weight gain, postnatal depression, and type 2 diabetes. Child Neonatal outcomes: large-for-gestational age, perinatal mortality, mortality or morbidity composite, hypoglycaemia; and childhood/adulthood outcomes: adiposity, type 2 diabetes, and neurosensory disability, were not reported under this comparison. Primary care screening versus secondary care screening (one trial) Mother There was no clear difference between the primary care and secondary care screening groups for GDM (RR 0.91, 95% CI 0.50 to 1.66; participants = 690; low-quality evidence), hypertension (RR 1.41, 95% CI 0.77 to 2.59; participants = 690; low-quality evidence), pre-eclampsia (RR 0.80, 95% CI 0.36 to 1.78; participants = 690;low-quality evidence), or caesarean section birth (RR 1.00, 95% CI 0.80 to 1.27; participants = 690; low-quality evidence). There were no data reported for perineal trauma, gestational weight gain, postnatal depression, or type 2 diabetes. Child There was no clear difference between the primary care and secondary care screening groups for large-for-gestational age (RR 1.37, 95% CI 0.96 to 1.96; participants = 690; low-quality evidence), neonatal complications: composite outcome, including: hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, shoulder dystocia, five minute Apgar less than seven at one or five minutes, prematurity (RR 0.99, 95% CI 0.57 to 1.71; participants = 690; low-quality evidence), or neonatal hypoglycaemia (RR 1.10, 95% CI 0.28 to 4.38; participants = 690; very low-quality evidence). There was one perinatal death in the primary care screening group and two in the secondary care screening group (RR 1.10, 95% CI 0.10 to 12.12; participants = 690; very low-quality evidence). There were no data for neurosensory disability, or childhood/adulthood adiposity or type 2 diabetes. There are insufficient randomised controlled trial data evaluating the effects of screening for GDM based on different risk profiles and settings on maternal and infant outcomes. Low-quality evidence suggests universal screening compared with risk factor-based screening leads to more women being diagnosed with GDM. Low to very low-quality evidence suggests no clear differences between primary care and secondary care screening, for outcomes: GDM, hypertension, pre-eclampsia, caesarean birth, large-for-gestational age, neonatal complications composite, and hypoglycaemia. Further, high-quality randomised controlled trials are needed to assess the value of screening for GDM, which may compare different protocols, guidelines or programmes for screening (based on different risk profiles and settings), with the absence of screening, or with other protocols, guidelines or programmes. There is a need for future trials to be sufficiently powered to detect important differences in short- and long-term maternal and infant outcomes, such as those important outcomes pre-specified in this review. As only a proportion of women will be diagnosed with GDM in these trials, large sample sizes may be required. | We searched for evidence (January 2017) and included two trials involving 4523 women and their babies. Both trials were conducted in Ireland and were at a moderate to high risk of bias. We could not combine the data from these trials because they looked at different interventions and comparisons. One compared ‘universal’ screening with ‘risk factor’-based screening for GDM. The other compared screening women at their general practitioners' clinic (primary care) versus at the hospital (secondary care). In one trial (with information available for 3152 women), more women were diagnosed with GDM in the group of women who received ‘universal’ screening, compared with the group of women with ‘risk factor’-based screening (low-quality evidence). The trial did not report on outcomes relating to the mothers, including high blood pressure disorders of pregnancy, caesarean birth, perineal trauma, weight gain in pregnancy, postnatal depression, and type 2 diabetes. The trial did not report outcomes relating to the babies including being born large-for-gestational age, death (before or shortly after birth), death or a serious complication, hypoglycaemia, or adiposity, type 2 diabetes, and disability in childhood or adulthood. In the second trial (with information available for 690 women), screening at the general practitioner's clinic versus the hospital did not make a clear difference to the number of women diagnosed with GDM (low-quality evidence), high blood pressure (low-quality evidence), pre-eclampsia (low-quality evidence), or the number who had a caesarean birth (low-quality evidence). This trial did not report perineal trauma, weight gain in pregnancy, postnatal depression, or type 2 diabetes. Screening at the general practitioner's clinic versus at the hospital did not make a clear difference to the number of babies born large-for-gestational age (low-quality evidence), death (before or shortly after birth), death or a serious complication (low-quality evidence), or hypoglycaemia (very low-quality evidence). Childhood or adulthood adiposity, type 2 diabetes, and disability were not reported in the trial. There is not enough evidence to guide us on effects of screening for GDM based on different risk profiles or settings on outcomes for women and their babies. Further large, well-designed, randomised controlled trials are required to assess important short- and long-term outcomes for mothers and their babies. |
The search identified nine trials of cognitive behavioural and psychodynamic therapy approaches, together with a small group of 'active control' interventions. No trials relating to other psychotherapeutic approaches and techniques were found. A total of seven trials provided sufficient data for inclusion in the comparison between CBT and controls. No trials compared psychodynamic psychotherapy with controls. Based on five trials (153 participants), cognitive behavioural therapy was more effective than waiting list controls (WMD -9.85, 95% CI -11.97 to -7.73). Only three small trials compared psychodynamic therapy with CBT, with no significant difference in treatment effect indicated between the two types of psychotherapeutic treatment. Based on three trials with usable data, CBT was superior to active control interventions when using the Hamilton Depression Rating Scale (WMD -5.69, 95% CI -11.04 to -0.35), but equivalent when using the Geriatric Depression Scale (WMD -2.00, 95% CI -5.31 to 1.32). Only a small number of studies and patients were included in the meta-analysis. If taken on their own merit, the findings do not provide strong support for psychotherapeutic treatments in the management of depression in older people. However, the findings do reflect those of a larger meta-analysis that included patients with broader age ranges, suggesting that CBT may be of potential benefit. | In this review we included seven small trials, involving a total of 153 participants, that examined psychotherapeutic treatments for depression in older people. Five trials compared a form of cognitive behavioural therapy (CBT) against control conditions, and the findings showed that CBT was more effective than control. Two individual trials compared CBT against psychodynamic therapy, with no significant difference in effectiveness indicated between the two approaches. Our review shows that there is relatively little research in this field and care must be taken in generalising what evidence there is to clinical populations. |
We included 13 studies randomizing 417 participants with 7184 teeth/brackets. We assessed two studies (15%) as being at low risk of bias, 10 studies (77%) as being at high risk of bias and one study (8%) as being at unclear risk of bias. Self etching primers (SEPs) versus conventional etchants Eleven studies compared the effects of SEPs with conventional etchants. Only five of these studies (three of split-mouth design and two of parallel design) reported data at the participant level, with the remaining studies reporting at the tooth level, thus ignoring clustering/the paired nature of the data. A meta-analysis of these five studies, with follow-up ranging from 5 to 37 months, provided low-quality evidence that was insufficient to determine whether or not there is a difference in bond failure rate between SEPs and convention etchants (risk ratio 1.14; 95% confidence interval (CI) 0.75 to 1.73; 221 participants). The uncertainty in the CI includes both no effect and appreciable benefit and harm. Subgroup analysis did not show a difference between split-mouth and parallel studies. There were no data available to allow assessment of the outcomes: decalcification, participant satisfaction and cost-effectiveness. One study reported decalcification, but only at the tooth level. SEPs versus SEPs Two studies compared two different SEPs. Both studies reported bond failure rate, with one of the studies also reporting decalcification. However, as both studies reported outcomes only at the tooth level, there were no data available to evaluate the superiority of any of the SEPs over the others investigated with regards to any of the outcomes of this review. We did not find any eligible studies evaluating different etching materials (e.g. phosphoric acid, polyacrylic acid, maleic acid), concentrations or etching times. We found low-quality evidence that was insufficient to conclude whether or not there is a difference in bond failure rate between SEPs and conventional etching systems when bonding fixed orthodontic appliances over a 5- to 37-month follow-up. Insufficient data were also available to allow any conclusions to be formed regarding the superiority of SEPs or conventional etching for the outcomes: decalcification, participant satisfaction and cost-effectiveness, or regarding the superiority of different etching materials, concentrations or etching times, or of any one SEP over another. Further well-designed RCTs on this topic are needed to provide more evidence in order to answer these clinical questions. | Cochrane Oral Health carried out this review of existing studies, which includes evidence current up to 8 March 2013. This review includes 13 published studies in which a total of 417 children and adults randomly received different tooth preparations before fixed orthodontic braces were bonded to their teeth. Eleven of these studies compared SEPs with conventional etching, and two compared two different SEPs. Only five of the studies provided usable evidence for this review and the combined results did not enable a conclusion to be made about whether or not there is a difference in bond failure (when the orthodontic fixings come away from the tooth) between SEPs and conventional etching. There was also no usable evidence to suggest whether SEPs or conventional etchants lead to less decay around the etching site, or are associated with fewer costs or better participant satisfaction. There was also no usable evidence to enable conclusions to be drawn about which was the best SEP, acid, concentration or etching time. The evidence presented is of low quality due to issues with the way in which some of the studies were conducted. |
We included six RCTs and were able to extract data from five studies. The total number of included participants was 206. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres, n = 165, 5 RCTs, low-quality evidence; minimal important difference was 30 metres), the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min, n = 145, 4 RCTs, low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher, n = 145, 4 RCTs, low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points, n = 33, 2 RCTs, low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs, low-quality evidence). One study reported a single adverse event, where a participant stopped exercise training due to lightheadedness. In people with PH, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL, these may not be clinically important. Overall, we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH. | The review included six studies on 206 people with pulmonary hypertension and we could combine data from five of these studies. We could only use data for 165 participants, however not all of these data could be included in the analysis for all outcome measures. The majority of studies implemented an inpatient exercise rehabilitation programme with only a small number of studies examining an outpatient programme. The methods used to conduct these trials were of low quality. Given this low-quality evidence, it was not possible to generalise the results of this review across the spectrum of people with pulmonary hypertension. |
From a total of 502 references, we retrieved 47 papers for more detailed evaluation. We selected 20 papers, reporting data from seven studies, which included 1137 participants, of which 559 were randomized to TMLR. Participants and professionals were not blinded, which suggests high risk of performance bias. Overall, 43.8% of participants in the treatment group decreased two angina classes, as compared with 14.8% in the control group: odds ratio (OR) 4.63, 95% confidence interval (CI) 3.43 to 6.25), and heterogeneity was present. Mortality by intention-to-treat analysis was similar in both groups at 30 days (4.0% in the TMLR group and 3.5% in the control group), and one year (12.2% in the TMLR group and 11.9% in the control group). However, the 30-day mortality as-treated was 6.8% in the TMLR group and 0.8% in the control group (pooled OR was 3.76, 95% CI 1.63 to 8.66), mainly due to a higher mortality in participants crossing from standard treatment to TMLR. The assessment of subjective outcomes, such as improvement in angina, was affected by a high risk of bias and this may explain the differences found. Other adverse events such as myocardial infarction, arrhythmias or heart failure, were not considered in this review, as they were not predefined outcomes in trials design and they show a high inconsistency across studies. No new trials on transmyocardial laser revascularization have been published in the last ten years and it is very unlikely that new research will be undertaken in this field. This review shows that risks associated with TMLR outweigh the potential clinical benefits. Subjective outcomes are subject to high risk of bias and no differences were found in survival, but a significant increase in postoperative mortality and other safety outcomes suggests that the procedure may pose unacceptable risks. | Several studies have been carried out to determine the efficacy and safety of this intervention, but most had important methodological limitations and high risk of performance bias in relation to subjective outcomes such as angina pain. Overall, 43.8% of patients in the group treated with laser had their chest pain improved significantly, compared with 14.8% in the medication group. However, the evaluation of chest pain was performed without blinding (patients and doctors were aware of the intervention) and this may have biased the results. On the other hand, the risk of dying at one year was similar between the groups, but there is an excess risk of early mortality following the intervention in the laser group. This updated review concludes that there is no evidence of clinical benefits after TMLR, but data on safety suggests that the procedure may pose unacceptable risks. The intervention is becoming obsolete and it is not expected that new research in this field would change this conclusion. |
Eighteen studies (20 reports) involving a total of 933 participants with COPD, chronic respiratory disease, chronic heart failure, and/or thoracic cancer met the inclusion criteria for this update, an additional seven studies since the previous version of this review. All but one study that compared NMES to resistance training compared a programme of NMES to no treatment or placebo NMES. Most studies were conducted in a single centre and had a risk of bias arising from a lack of participant or assessor blinding and small study size. The quality of the evidence using GRADE comparing NMES to control was low for quadriceps muscle strength, moderate for occurrence of adverse events, and very low to low for all other secondary outcomes. We downgraded the quality of evidence ratings predominantly due to inconsistency among study findings and imprecision regarding estimates of effect. The included studies reported no serious adverse events and a low incidence of muscle soreness following NMES. NMES led to a statistically significant improvement in quadriceps muscle strength as compared to the control (12 studies; 781 participants; SMD 0.53, 95% confidence interval (CI) 0.19 to 0.87), equating to a difference of approximately 1.1 kg. An increase in muscle mass was also observed following NMES, though the observable effect appeared dependent on the assessment modality used (eight studies, 314 participants). Across tests of exercise performance, mean differences compared to control were statistically significant for the 6-minute walk test (seven studies; 317 participants; 35 m, 95% CI 14 to 56), but not for the incremental shuttle walk test (three studies; 434 participants; 9 m, 95% CI -35 to 52), endurance shuttle walk test (four studies; 452 participants; 64 m, 95% CI -18 to 146), or for cardiopulmonary exercise testing with cycle ergometry (six studies; 141 participants; 45 mL/minute, 95% CI -7 to 97). Limited data were available for other secondary outcomes, and we could not determine the most beneficial type of NMES programme. The overall conclusions have not changed from the last publication of this review, although we have included more data, new analyses, and an assessment of the quality of the evidence using the GRADE approach. NMES may be an effective treatment for muscle weakness in adults with advanced progressive disease, and could be considered as an exercise treatment for use within rehabilitation programmes. Further research is very likely to have an important impact on our confidence in the estimate of effect and may change the estimate. We recommend further research to understand the role of NMES as a component of, and in relation to, existing rehabilitation approaches. For example, studies may consider examining NMES as an adjuvant treatment to enhance the strengthening effect of programmes, or support patients with muscle weakness who have difficulty engaging with existing services. | 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. Overall, the quality of the evidence was low for the effect on thigh muscle strength and very low to moderate for the effects on other outcomes. There were problems with the design of some studies; often people taking part or assessors knew if they were receiving or testing NMES. In addition, the results for many outcomes were inconsistent or imprecise. This review suggests that NMES is a potentially effective treatment for muscle weakness in people with progressive diseases such as cancer, advanced chronic respiratory disease, and chronic heart failure, though the quality of the evidence is low. NMES might be considered for use within rehabilitation programmes. It was not possible to compare the effects of NMES to other forms of exercise, for example weight training, because the majority of studies compared NMES to a control group that received no treatment or a sham treatment. Further research is needed to understand the effect of NMES on the ability to exercise and quality of life. |
Our search strategies led to 149 potentially relevant references, but only a single small study met our inclusion criteria. The included study was published as a full text article and investigated the feasibility and effect of Tibetan Yoga additional to standard care (N = 20; 1 person dropped out before attending any classes and no data were collected) compared to standard care only (N = 19). The study included people with all stages of Hodgkin and non-Hodgkin's lymphoma, with and without current cancer treatment. The mean age was 51 years. We judged the overall risk of bias as high as we found a high risk for performance, detection and attrition bias. Additionally, potential outcome reporting bias could not be completely ruled out. Following the recommendations of GRADE, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the methodical limitations and the very small sample size. The influence of yoga on HRQoL and OS was not reported. There is no evidence that yoga in addition to standard care compared with standard care only can improve distress in people with haematological malignancies (mean difference (MD) -0.30, 95% confidence interval (CI) -5.55 to 4.95; P = 0.91). Similarly, there is no evidence of a difference between either group for fatigue (MD 0.00, 95% CI -0.94 to 0.94; P = 1.00), anxiety (MD 0.30, 95% CI -5.01 to 5.61; P = 0.91) or depression (MD -0.70, 95% CI -3.21 to 1.81; P = 0.58). There is very low quality evidence that yoga improves the overall quality of sleep (MD -2.30, 95% CI -3.78 to -0.82; P = 0.002). The yoga groups' total score for the Pittsburgh Sleep Quality Index (PSQI) was 5.8 (± 2.3 SD) and better than the total score (8.1 (± 2.4 SD)) of the control group. A PSQI total score of 0 to 5 indicates good sleep whereas PSQI total score 6 to 21 points towards significant sleep disturbances. The occurrence of AEs was not reported. The currently available data provide little information about the effectiveness of yoga interventions for people suffering from haematological malignancies. The finding that yoga may be beneficial for the patients' quality of sleep is based on a very small body of evidence. Therefore, the role of yoga as an additional therapy for haematological malignancies remains unclear. Further high-quality randomised controlled trials with larger numbers of participants are needed to make a definitive statement. | We included a single trial with 39 participants in the review (20 in the yoga group and 19 in the control group). The trial looked at a seven-week Tibetan Yoga program in a group of people with Hodgkin and non-Hodgkin's lymphoma. The average age was 51 years. The trial involved patients who were currently receiving anti-cancer therapy as well as patients who were not receiving active therapy. The trial found insufficient data to make a judgement about the efficacy of yoga on distress, fatigue, depression and anxiety compared with patients not practicing yoga. Yoga can improve the patients' quality of sleep. The trial gave no information about health-related quality of life, overall survival or adverse events. On the basis of the GRADE criteria, we judged the overall quality of evidence for yoga concerning the outcomes distress, fatigue, anxiety, depression and quality of sleep as 'very low'. There are not enough data to say how effective yoga is in the management of haematological malignancies. Therefore, the role of yoga for haematological malignancies remains unclear. Further large, high-quality randomised controlled trials are needed. The evidence is up-to-date as of 4 February 2014. |
Seven randomised controlled trials, involving 582 women undergoing caesarean section were included in this review. The risk of bias of included trials was variable, with some trials not adequately describing allocation or randomisation. Three comparisons were included. 1. Tocolysis versus no tocolysis A single randomised trial involving 97 women was identified and included in the review. Birth trauma was not reported. There were no cases of any maternal side-effect reported in either the nitroglycerin or the placebo group. No other maternal and infant health outcomes were reported. 2. Reverse breech extraction versus head push for the deeply impacted head at full dilation at caesarean section Four randomised trials involving 357 women were identified and included in the review. The primary outcome of birth trauma was reported by three trials and there was no difference between reverse breech extraction and head push for this rare outcome (three studies, 239 women, risk ratio (RR) 1.55, 95% confidence interval (CI) 0.42 to 5.73). Secondary outcomes including endometritis rate (three studies, 285 women, average RR 0.52, 95% CI 0.26 to 1.05, Tau I² = 0.22, I² = 56%), extension of uterine incision (four studies, 357 women, average RR 0.23, 95% CI 0.13 to 0.40), mean blood loss (three studies, 298 women, mean difference (MD) -294.92, 95% CI -493.25 to -96.59; I² = 98%) and neonatal intensive care unit (NICU)/special care nursery (SCN) admission (two studies, 226 babies, average RR 0.53, 95% CI 0.23 to 1.22, Tau I² = 0.27, I² = 74%) were decreased with reverse breech extraction. No differences were observed between groups for many of the other secondary outcomes reported (blood loss > 500 mL; blood transfusion; wound infection; mean hospital stay; average Apgar score). There was significant heterogeneity between the trials for the outcomes mean blood loss, operative time and mean hospital stay, making comparison difficult. However the operation duration was significantly shorter for reverse breech extraction, which may correspond with ease of delivery and therefore, the amount of tissue trauma and therefore, significantly less blood loss. Given the heterogeneity, we cannot define the amount of difference in blood loss, operative time or hospital stay however. 3. Instrument (vacuum or forceps) versus manual extraction at elective caesarean section Two randomised trials involving 128 women were identified and included in the review. Only one trial reported maternal and infant health outcomes as prespecified in this review. This trial reported birth trauma as an outcome but there were no instances of birth trauma in either comparison group. There were no differences found in mean fall in haemoglobin (Hb) between groups (one study, 44 women, MD 0.03, 95% CI -0.53 to 0.59), or in uterine incision extension (one study, 44 women, RR 0.70, 95% CI 0.13 to 3.73). There is currently insufficient information available from randomised trials to support or refute the routine or selective use of tocolytic agents or instrument to facilitate infant birth at the time of difficult caesarean section. There is limited evidence that reverse breech extraction may improve maternal and fetal outcomes, though there was no difference in primary outcome of infant birth trauma. Further randomised controlled trials are needed to answer these questions. | This review includes a total of seven studies, involving 582 women and examines which techniques are safest for mother and baby. The risk of bias in trials was variable, with some trials not adequately describing the methods of randomisation. At an emergency caesarean after a long labour, there is evidence from the developing world that delivery of the buttocks or feet of the baby first (reverse breech extraction) is safer than delivery of the head by pushing from the vagina back into the uterus. In four trials involving 357 women, delivery of the buttocks or feet first was associated with fewer adverse outcomes for the mother, including less bleeding, infection and a shorter operation duration. There was no significant difference in trauma to the baby but admission to special care or neonatal intensive care was decreased with delivery of the buttocks or feet first than when the head was pushed up from the vagina. At a planned, non-labouring caesarean section there is limited evidence to support techniques (forceps or vacuum extractor on the baby's head) other than the use of the surgeon's hands to deliver the head of the baby through the uterine incision. Two trials involving 128 women compared forceps/vacuum with manual delivery without any significance difference in outcomes. There is also insufficient evidence to support the use of medication to relax the uterus (tocolysis) at the time of a caesarean to assist with safe delivery of the baby, with only one trial involving 97 women addressing this question. |
Thirteen studies involving 741 participants with alcoholic or diabetic neuropathy were included. In the comparison of vitamin B with placebo, two small trials showed no significant short-term benefit in pain intensity while one of the trials showed a small significant benefit in vibration detection from oral benfotiamine, a derivative of thiamine. In the larger of two trials comparing different doses of vitamin B complex, there was some evidence that higher doses resulted in a significant short-term reduction in pain and improvement in paraesthesiae, in a composite outcome combining pain, temperature and vibration, and in a composite outcome combining pain, numbness and paraesthesiae. There was some evidence that vitamin B is less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in the short-term improvement of clinical and nerve conduction study outcomes but the trials were small. There were few minor adverse effects reported. There are only limited data in randomised trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful. One small trial in alcoholic peripheral neuropathy reported slightly greater improvement in vibration perception threshold with oral benfotiamine for eight weeks than placebo. In another small study, a higher dose of oral vitamin B complex for four weeks was more efficacious than a lower dose in reducing symptoms and signs. Vitamin B administered by various routes for two to eight weeks was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve conduction study outcomes. Vitamin B is generally well-tolerated. | This review of 13 trials on diabetic and alcoholic peripheral neuropathy with a total of 741 participants showed only one study that suggested possible short-term benefit from eight-week treatment with benfotiamine (a derivative of vitamin B1) with slightly greater improvement in vibration perception threshold compared to placebo. Vitamin B complex when given in a higher dose administered for four weeks was more efficacious than a lower dose in reducing pain and other clinical problems based on another study. Two to eight weeks of treatment with vitamin B was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve test findings. All these findings require confirmation in larger studies before they can be accepted as definite. Vitamin B is generally well-tolerated with only a few reports of mild side effects. |
We only found one study eligible for this review (22 participants). We assessed the risk of bias for most domains as unclear. We graded the overall quality of evidence as very low. Compared to placebo, patients treated with pregabalin showed no significant improvement of motor tasks on the 36-point subscale of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (MD −2.15 points; 95% CI −9.16 to 4.86) or on the 32-point functional abilities subscale of the TRS (MD −0.66 points; 95% CI −2.90 to 1.58).The limited evidence showed no difference in study withdrawal (Mantel-Haenszel RD −0.09; 95% CI −0.48 to 0.30) and presentation of adverse events between pregabalin and placebo (Mantel-Haenszel RD 0.18; 95% CI −0.13 to 0.50). The effects of pregabalin for treating essential tremor are uncertain because the quality of the evidence is very low. One small study did not highlight any effect of this treatment; however, the high risk of bias and the lack of other studies on this topic limit further conclusion. | We found one study comparing pregabalin versus placebo, involving 22 randomised participants with essential tremor. The impact of pregabalin on functional abilities and adverse effects is uncertain because the quality of the evidence is very low. The lack of studies and the significant limitations in the one included trial preclude firm conclusions about the risk-benefit profile of this treatment. |
Only one small trial of the seven included studies truly evaluated TCM for schizophrenia. The other trials evaluated Chinese herbs for schizophrenia. We found one study comparing Chinese herbal medicine with antipsychotic drugs. Data for the global state outcome 'no change/worse' favoured people allocated to antipsychotic medication (n=90, RR 1.88 CI 1.2 to 2.9, NNH 4 CI 2 to 12). Six trials compared Chinese herbal medicine in combination with antipsychotic with antipsychotic drugs alone. One trial found global state 'not improved/worse' favoured the herbal medicine/antipsychotic combination (n=123, RR 0.19 CI 0.1 to 0.6, NNT 6 CI 5 to 11). Two studies (n=103) also found short-term data from the Clinical Global Impression scale favoured the herbal medicine plus antipsychotic group (WMD -0.46 CI -0.9 to -0.1) compared with those given only antipsychotics. Significantly fewer people in the experimental group left the study early compared with those given antipsychotics alone (n=1004, 6 RCTs, RR 0.30 CI 0.16 to 0.58, NNT 21 CI 18 to 35). Reports of constipation were significantly lower in the treatment group compared to those receiving antipsychotics (n=67, 1 RCT, RR 0.03 CI 0.0 to 0.5, NNH 2 CI 2 to 4). Chinese herbal medicines, given in a Western biomedical context, may be beneficial for people with schizophrenia when combined with antipsychotics. Traditional Chinese medicine is also under-evaluated, but results from one pioneering study that attempted to evaluate TCM should encourage further trials. Note: the 45 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed. | The use of Chinese herbs in a Western medicine context, without incorporating TCM methodology, has been evaluated in six trials, although again these are limited by their sample size and study length. The results of these six trials suggest that using Chinese herbs alone for psychotic symptoms may not be indicated, but if used in conjunction with Western antipsychotic drugs, they may be beneficial in terms of mental state, global functioning and decrease of adverse effects. However, further trials are needed before the effects of TCM for people with schizophrenia can be evaluated with any real confidence. |
We included 42 trials with a total of 9606 couples. Comparing rFSH to all other gonadotrophins combined, irrespective of the down-regulation protocol used, did not result in any evidence of a statistically significant difference in live birth rate (28 trials, 7339 couples, odds ratio (OR) 0.97, 95% CI 0.87 to 1.08). This suggests that for a group with a 25% live birth rate using urinary gonadotrophins the rate would be between 22.5% and 26.5% using rFSH. There was also no evidence of a difference in the OHSS rate (32 trials, 7740 couples, OR 1.18, 95% CI 0.86 to 1.61). This means that for a group with 2% risk of OHSS using urinary gonadotrophins, the risk would be between 1.7% and 3.2% using rFSH. When different urinary gonadotrophins were considered separately, there were significantly fewer live births after rFSH than HMG (11 trials, N=3197, OR 0.84, 95% CI 0.72 to 0.99). This means that for a live birth rate of 25% using HMG, use of rFSH instead would be expected to result in a rate between 19% and 25%. There was no evidence of a difference in live births when rFSH was compared with FSH-P (5 trials, N=1430, OR 1.26, 95% CI 0.96 to 1.64) or when rFSH was compared with FSH-HP (13 trials, N=2712; OR 1.03, 95% CI 0.86 to 1.22). Clinical choice of gonadotrophin should depend on availability, convenience and costs. Differences between urinary gonadotrophins were considered unlikely to be clinically significant. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety. | Several systematic reviews compared recombinant FSH with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. We included 42 trials with in total 9606 couples. Comparing rFSH with urinary gonadotrophins overall did not result in any difference in live birth rate, OHSS or any of the other outcomes. Comparing rFSH with HMG/HP-HMG resulted in a significantly lower live birth rate in the rFSH group though differences were small. There was no proof of a difference in live birth when comparing rFSH with FSH-P or with FSH-HP. We may conclude that all these gonadotrophins are equally effective and safe, and that further trials are unwarranted. |
Seven trials are included but few reported the outcomes selected for this review. A meta-analysis of ciclosporin versus placebo from two trials (59 participants) - one as monotherapy (20 participants) and the other with corticosteroids (39 participants) - showed that it resulted in improvement of participants in the ciclosporin group compared with those in the placebo group, with a relative rate of improvement of 2.44 (95% confidence interval (CI) 1.13 to 5.27). In addition the weighted mean difference in QMG score between the ciclosporin and placebo groups was -0.34 (95% CI -0.52 to -0.17). Azathioprine (plus prednisolone for first month) had no significant benefit over prednisolone alone (41 participants). The effects of azathioprine plus prednisolone versus prednisolone plus placebo were similar (34 participants). Cyclophosphamide was reported to be statistically more efficacious than placebo at 12 months in corticosteroid-dependent participants (23 participants), but no raw data were available. Trials of mycophenolate mofetil and tacrolimus did not provide relevant endpoint data for this review. All trials had low numbers of participants. Adverse event reporting was variable. Trial protocol heterogeneity prevented comparison of the different immunosuppressants. In generalised MG, limited evidence from small RCTs suggests that ciclosporin, as monotherapy or with corticosteroids, or cyclophosphamide with corticosteroids, significantly improve MG. Limited evidence from RCTs shows no significant benefit from azathioprine (as monotherapy or with steroids), mycophenolate mofetil (as monotherapy or with either corticosteroids or ciclosporin) or tacrolimus (with corticosteroids or plasma exchange). Bigger, better-designed, longer trials are needed. | There were seven randomised controlled trials to include in this review. Each trial compared different interventions in generalised MG: (1) azathioprine plus initial prednisolone versus prednisolone - 41 participants; (2) azathioprine plus prednisolone versus prednisolone plus placebo (dummy treatment) - 34 participants; (3) ciclosporin monotherapy versus placebo - 20 participants; (4) ciclosporin plus prednisolone versus prednisolone plus placebo - 39 participants; (5) cyclophosphamide plus prednisolone versus prednisolone plus placebo - 23 participants; (6) mycophenolate mofetil plus either ciclosporin or prednisolone or no immunosuppressants versus placebo plus either ciclosporin or prednisolone or no immunosuppressants trial - 14 participants; (7) tacrolimus plus corticosteroids with or without plasma exchange versus no tacrolimus plus corticosteroids with or without plasma exchange trial - 34 participants. It is difficult to draw useful clinical conclusions from this small number of often short-term, randomised controlled trials. Each trial had relatively few participants and different trials used different study designs. The limited evidence available found that MG improved significantly with either ciclosporin (alone or in combination with corticosteroids) or cyclophosphamide (in combination with corticosteroids) compared with placebo. There is no clear evidence from randomised controlled trials of benefit for any of the immunosuppressant drugs used more commonly in MG - azathioprine (alone or in combination with corticosteroids), mycophenolate mofetil (as monotherapy or in combination with either corticosteroids or ciclosporin) or tacrolimus (in combination with corticosteroids or plasma exchange or both). There is no randomised controlled trial of methotrexate in MG. Long-term studies of the potentially formidable toxic effects of all of these drugs are lacking in MG. |
We identified 10,488 unique records, with 323 screened as full text. Five studies were included for the main analysis: one RCT with a low risk, two CBAs with a moderate risk and two CBAs with a high risk of bias. Three CBAs evaluated multicomponent slum upgrading strategies. Road paving only was evaluated in one RCT and water supply in one CBA. A total of 3453 households or observations were included within the four studies reporting sample sizes. Most health outcomes in the main studies related to communicable diseases, for which the body of evidence was judged to be low quality. One CBA with a moderate risk of bias found that diarrhoeal incidence was reduced in households which received water connections from a private water company (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.27 to 1.04) and the severity of diarrhoeal episodes (RR 0.48; 95% CI 0.19 to 1.22). There was no effect for duration of diarrhoea. Road paving did not result in changes in parasitic infections or sickness in one RCT. After multicomponent slum upgrading, claims for a waterborne disease as opposed to a non-waterborne disease reduced (RR 0.64; 95% CI 0.27 to 0.98) in one CBA with a high risk of bias but there was no change in sanitation-related mortality in a CBA with a moderate risk of bias. The majority of socio-economic outcomes reported within the main studies related to financial poverty, for which the body of evidence was of very low quality. Results were mixed amongst the main studies; one RCT and two CBAs reported no effect on the income of slum dwellers following slum upgrading. One further CBA found significant reduction in monthly water expenditure (mean difference (MD) -17.11 pesos; 95% CI -32.6 to -1.62). One RCT also showed mixed results for employment variables, finding no effect on unemployment levels but increased weekly worked hours (MD 4.68; 95% CI -0.46 to 9.82) and lower risk of residents intending to migrate for work (RR 0.78; 95% CI 0.60 to 1.01). There was no evidence available to assess the impact of slum upgrading on non-communicable diseases or social capital. Maternal and perinatal conditions, infant mortality, nutritional deficiencies, injuries, self-reported quality of life, education and crime were evaluated in one study each. Nine supporting studies were included that measured varying outcomes (6794 households or observations within eight studies reporting sample sizes). One CPI evaluated cement flooring only while three UBAs and five CPIs evaluated multicomponent slum upgrading strategies. All studies but one had a high risk of bias. The studies reinforced main study findings for diarrhoea incidence and water-related expenditure. Findings for parasitic infections and financial poverty were inconsistent with the main studies. In addition, supporting studies reported a number of disparate outcomes that were not evaluated in the main studies. Five supporting studies included some limited information on slum dweller perspectives. They indicated the importance of appropriate siting of facilities, preference for private facilities, delivering synergistic interventions together, and ensuring that infrastructure was fit for purpose and systems were provided for cleaning, maintenance and repair. A high risk of bias within the included studies, heterogeneity and evidence gaps prevent firm conclusions on the effect of slum upgrading strategies on health and socio-economic wellbeing. The most common health and socio-economic outcomes reported were communicable diseases and indicators of financial poverty. There was a limited but consistent body of evidence to suggest that slum upgrading may reduce the incidence of diarrhoeal diseases and water-related expenditure. The information available on slum dwellers’ perspectives provided some insight to barriers and facilitators for successful implementation and maintenance of interventions. The availability and use of reliable, comparable outcome measures to determine the effect of slum upgrading on health, quality of life and socio-economic wellbeing would make a useful contribution to new research in this important area. Given the complexity in delivering slum upgrading, evaluations should look to incorporate process and qualitative information alongside quantitative effectiveness data to determine which particular interventions work (or don’t work) and for whom. | We found five main studies with suitable methods for examining the effect of slum upgrading on health, quality of life and social wellbeing (for example poverty). Nine supporting studies were also included, which used methods that could indicate associations between interventions and outcomes but could not assess whether interventions caused the effect. Only one main study had a low risk of bias, with the rest having a mixed or high risk of bias. The majority of supporting studies had a high risk of bias, meaning their methods had several limitations that made the study results unreliable. In addition, the studies measured different interventions and outcomes, making it difficult to compare results. Overall, there was limited but consistent evidence to suggest that slum upgrading may reduce diarrhoea in slum dwellers and their water-related expenses. There were mixed results for whether slum upgrading reduced parasitic infections, general measures of communicable diseases, financial poverty and unemployment outcomes. There was very little information on other health or social outcomes, or which types of interventions were most beneficial. Some of the studies asked slum dwellers for their views and their experiences of slum upgrading interventions. They suggested a number of reasons why facilities were not used as intended and which may have reduced the benefits. Future research, with improved study designs and common outcome measures, is needed to determine how best to improve the conditions of existing slums and to offer the most benefit to the health, quality of life and social wellbeing of slum dwellers. |
We identified six trials that met our inclusion criteria. The trials compared 3, 24 and 96 hour infusions and one trial examined different schedules (1 versus 3 day). From the included RCTs we found no evidence of a difference between short and long infusions in terms of overall and progression-free survival and tumour non-response. In most cases a greater proportion of adverse events and severe toxicity occurred in the 24 hour infusion group compared to the 3 hour group with many of the analyses being highly statistically significant (RR = 0.32, 95% CI 0.22, 0.47, RR = 0.06, 95% CI 0.02, 0.17, RR = 0.59, 95% CI 0.40, 0.88, RR = 0.52, 95% CI 0.28, 0.97 for severe hypersensitivity, febrile neutropenia, sore mouth and diarrhoea outcomes respectively). Although a meta analysis of three trials found that 3 hour infusions were associated with a statistically significant increase in the risk of neurosensory changes compared with 24 hour infusions (RR = 1.26, 95% CI 1.09 to 1.46). Adverses events were not comprehensively reported for any of the other comparisons. Outcomes were incompletely documented and QoL outcomes were not reported in any of the trials. The strength of the evidence is weak in this review as it is based on meta analyses of very few trials or single trial analyses and all trials were at moderate risk of bias and two were published in abstract form only. Ideally, large, multi-centre supporting trials are needed as outcomes were incompletely reported in included trials in this review. It may be beneficial to design a multi-arm trial comparing 3, 24 and 96 hour infusions or maybe looking at different schedules. In the absence of such trials, the decision to offer short or long infusions in advanced adenocarcinoma may need to be individualised, although it certainly appears that women have less toxicity, apart from sensory nerve damage, with a shorter infusion. Efficacy appearing similar regardless of infusion duration. | Six randomised trials were included in this review, which found that short (three hour) infusions are more convenient and caused significantly fewer adverse (side) effects (i.e. decreased white blood cell counts, fever, infection or sore mouth). With short-infusion paclitaxel there is no obvious loss of effectiveness when compared with longer infusions, although further clinical trials are needed to be sure of this. |
Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. | One study (22 adult participants) was included in the review. The participants with sickle cell disease had proteinuria or microalbuminuria and were selected randomly to be treated for six months with either captopril (an angiotensin-converting enzyme inhibitor) or placebo (dummy drug with no active medication). The results from this small study were not convincing, with minor analysis changes leading to very different study conclusions. This study did not show that angiotensin-converting enzyme (ACE) inhibitors could reduce the level of protein or albumin in the urine. The level of creatinine and potassium in the blood were reported constant throughout the study. No serious adverse events were noted, although the potential for causing low blood pressure should be highlighted. More long-term studies involving multiple centers and larger numbers of participants are needed. Overall, the study appeared to be well run, although the actual method used to assign participants to treatment groups was not reported, nor whether it was concealed which group they were assigned to. |
We included 15 trials (1376 participants) in this review. We downgraded the quality of evidence for many of our outcomes on the basis of high risk of bias. Low-quality evidence suggests that immunonutrition decreases all-cause mortality (RR 0.49, 95% CI 0.29 to 0.80). The effect of immunonutrition on other outcomes from a subset of the included trials was uncertain. Subgrouping trials by type of enteral nutrition did not explain any variation in effect. We found mainly very low-quality evidence for the effects of probiotics on the main outcomes. One eligible trial in this comparison reported a higher rate of serious adverse events leading to increased organ failure and mortality due to low numbers of events and low risk of bias. When we excluded this study as a post hoc sensitivity analysis, risks of mortality (RR 0.30, 95% CI 0.10 to 0.84), organ failure (RR 0.74, 95% CI 0.59 to 0.92) and local septic complications (RR 0.40, 95% CI 0.22 to 0.72) were lower with probiotics. In one trial assessing immunonutrition with probiotics and fibres, no deaths occurred, but hospital stay was shorter with immunonutrition (MD -5.20 days, 95% CI -8.73 to -1.67). No deaths were reported following semi-elemental enteral nutrition (EN), and the effect on length of hospital stay was small (MD 0.30 days, 95% CI -0.82 to 1.42). Fibre-enriched formulations reduced the number of other local complications (RR 0.52, 95% CI 0.32 to 0.87) and length of hospital stay (MD -9.28 days, 95% CI -13.21 to -5.35) but did not significantly affect all-cause mortality (RR 0.23, 95% CI 0.03 to 1.84) and other outcomes. Very low-quality evidence from the subgroup of trials comparing EN versus no intervention showed a decrease in all-cause mortality with EN (RR 0.50, 95% CI 0.29 to 0.86). We found evidence of low or very low quality for the effects of immunonutrition on efficacy and safety outcomes. The role of supplementation of enteral nutrition with potential immunomodulatory agents remains in question, and further research is required in this area. Studies assessing probiotics yielded inconsistent and almost contrary results, especially regarding safety and adverse events, and their findings do not support the routine use of EN enriched with probiotics in routine clinical practice. However, further research should be carried out to try to determine the potential efficacy or harms of probiotics. Lack of trials reporting on other types of EN assessed and lack of firm evidence regarding their effects suggest that additional randomised clinical trials are needed. The quality of evidence for the effects of any kind of EN on mortality was low, and further studies are likely to have an impact on the finding of improved survival with EN versus no nutritional support. Evidence remains insufficient to support the use of a specific EN formulation. | We included 15 trials with 1376 participants. Two trials included more than two study groups comparing different EN formulations. Six trials compared immunonutrition (EN supplemented with substances potentially able to change the immune response) versus control (other EN, sham treatment (placebo) or no treatment), and six trials investigated EN enriched with probiotics (live bacteria or yeasts that replace or add to helpful bacteria in the gastrointestinal tract). Two trials researched the use of semi-elemental formulations, which are types of EN in which nutrients are broken down to smaller particles. Two trials studied fibre-enriched EN, which may stimulate the growth of intestinal micro-organisms. Only one trial compared immunonutrition enriched with probiotics and fibres versus control. Immunonutrition compared with control showed reduction in all-cause mortality. However, when only specific types of EN were compared, this could not be confirmed. Available evidence does not support the effectiveness of probiotics in AP. One trial that made this comparison reported a higher rate of serious adverse events, and consequently more occurrences of organ failure and higher mortality rate. When this trial was excluded, results showed a decrease in mortality, organ dysfunction and pancreatic infectious complications, but with evidence of low to very low quality. Fibre-enriched formulations had a beneficial effect on decreasing local non-infectious complications and shortening hospitalisation. No effects were confirmed for semi-elemental formulations and immunonutrition enriched with probiotics and fibres. These results are inconclusive because of the paucity of data. Comparison of any kind of EN versus no intervention revealed a beneficial effect on all-cause mortality. Overall, EN was associated with a rather small number of mild adverse events (most often nausea, vomiting, bloating, diarrhoea, pain relapse and higher serological concentrations of sodium) not requiring cessation of tube feeding. We cannot be certain that EN is safe in this population because the quality of evidence for adverse event outcomes is low. All included trials have been assessed as having high risk of bias, most often because they did not provide enough information for adequate assessment of certain study design characteristics, but also because some clear flaws were noted in the way they were designed and carried out. The quality of the evidence throughout this review is considered to be low to very low primarily because of the relatively small numbers of study participants and events included. Study results may reflect systematic and random errors. |
We included seven trials involving 800 women. The comparisons revealed a very high clinical heterogeneity. As a result of the heterogeneity in the randomisation unit, we did not combine trials but reported the individual trial results in the ‘Data and analysis’ section and in the text. Half of trials have unclear or high risk of bias in several domains. We did not find any trial reporting data about maternal mortality. In terms of postoperative pain, PCB does not improve the control of postoperative pain when it is compared against sedation/analgesia or versus no anaesthesia/no analgesia. In the comparison of PCB with lidocaine versus PCB with saline solution, significant differences favouring the group with lidocaine were found in one trial (moderate or severe postoperative pain) (risk ratio (RR) 0.32; 95% confidence interval (CI) 0.18 to 0.59). When opioids were used, postoperative nausea and vomiting was more frequent in two trials comparing those versus PCB. In terms of requirement of blood transfusion, two trials showed conflicting results. Particular considerations that influence the choice of anaesthesia for this procedure such as availability, effectiveness, safety, side effects, practitioner's choice, costs and woman's preferences of each technique should continue to be used until more evidence supporting the use of one technique or another. | We included seven trials involving 800 women. None of the included studies reported any maternal mortality. We did not combine the results of the trials because the trials were very different in the clinical interventions used and how the outcomes were assessed. One study reported higher maternal satisfaction with the use of general anaesthesia than sedation and analgesia. Paracervical block did not improve the control of postoperative pain when compared against sedation and analgesia. More nausea and vomiting were reported when opioid drugs were used. Currently, the levels of postoperative pain experienced by women undergoing surgical evacuation of incomplete miscarriage are not completely relieved. Further studies in this context should be conducted to address this question. Key factors that influence the choice of anaesthesia include availability, effectiveness, safety, side effects, and costs. Other factors include patient preference, practitioner choice, facility resources and medical indications. |
We included 55 trials (3121 patients). Thirty-seven trials assessed physical methods, including 26 trials employing mattress encasings. Ten trials involved chemical methods and eight trials involved a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1665 patients), the standardised mean difference (SMD) was 0.01 (95% confidence interval (CI) -0.08 to 0.11). There were no statistically significant differences either in number of patients improved (risk ratio 1.01, 95% CI 0.80 to 1.27), asthma symptom scores (SMD -0.06, 95% CI -0.16 to 0.05), or in medication usage (SMD -0.05, 95% CI -0.17 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended. It is doubtful whether further studies, similar to the ones in our review, are worthwhile. If other types of studies are considered, they should be methodologically rigorous and use other methods than those used so far, with careful monitoring of mite exposure and relevant clinical outcomes. | We included 55 randomised trials on 3121 people with asthma. There are both chemical (10 trials) and physical methods such as mattress encasings (37 trials) of reducing mite allergen levels and we included both types in this review. There were also eight trials that used both physical and chemical methods. Many trials were of poor quality and would therefore be expected to exaggerate the reported effect, but we did not find an effect of the interventions. There was no difference in peak flow (a measure of lung function), asthma symptoms and medication scores, or the number of patients reporting an improvement in their asthma symptoms. While reducing exposure to house dust mites is recommended in guidelines, we did not find an effect of control measures to reduce the exposure to mites or their products. . |
We included seven RCTs comprising 577 participants. There was no significant heterogeneity among trials for the outcome of PEP (P = 0.32; I2 = 15%). The PGW technique significantly increased PEP compared to other endoscopic techniques (RR 1.98, 95% CI 1.14 to 3.42; low-quality evidence). The number needed to treat for an additional harmful outcome was 13 (95% CI 5 to 89). Among the three studies that compared the PGW technique with persistent CC, the incidence of PEP was 13.5% for the PGW technique and 8.7% for persistent CC (RR 1.58, 95% CI 0.83 to 3.01; low-quality evidence). Among the two studies that compared the PGW technique with precut sphincterotomy, the incidence of PEP was 29.8% in the PGW group versus 10.3% in the precut group (RR 2.92, 95% CI 1.24 to 6.88; low-quality evidence). Among the two studies that compared the PGW technique with PD stent placement, the incidence of PEP was 11.7% for the PGW technique and 5.0% for PD stent placement (RR 1.75, 95% CI 0.08 to 37.50; very low-quality evidence). There was no significant difference in common bile duct (CBD) cannulation success with the randomised technique (RR 1.04, 95% CI 0.87 to 1.24; low-quality evidence) or overall CBD cannulation success (RR 1.04, 95% CI 0.91 to 1.18; low-quality evidence) between the PGW technique and other endoscopic techniques. There was also no statistically significant difference in the risk of other ERCP-related complications (bleeding, perforation, cholangitis, and mortality). The results were robust in sensitivity analyses. The overall quality of evidence for the outcome of PEP was low or very low because of study limitations and imprecision. In people with difficult CBD cannulation, sole use of the PGW technique appears to be associated with an increased risk of PEP. Prophylactic PD stenting after use of the PGW technique may reduce the risk of PEP. However, the PGW technique is not superior to persistent attempts with CC, precut sphincterotomy, or PD stent in achieving CBD cannulation. The influence of co-intervention in the form of rectal peri-procedural nonsteroidal anti-inflammatory drug administration is unclear. | We conducted a search of the literature on 15 April 2016. We identified seven randomised controlled trials conducted in China, Japan, South Korea, Spain, Thailand, and the United States including a total of 577 participants. These trials compared the PGW technique versus persistent use of traditional techniques or other advanced techniques in people undergoing ERCP in whom access to the bile duct using traditional techniques was considered by the endoscopists to be difficult. As in clinical practice, the criteria used to define difficult access to the bile duct were highly variable among studies. We assessed outcomes of post-ERCP pancreatitis (PEP), success rates in accessing the bile duct, and other post-ERCP complications (bleeding, infection, hole in the bowel wall, death). Contrary to popular belief, the PGW technique appears to increase the risk of PEP and does not improve the success rate of gaining access to the bile duct compared to other endoscopic techniques. The technique may increase the risk of mild PEP, but not moderate or severe PEP. There was no significant difference in success rates for accessing the bile duct. The risks for other complications such as bleeding, hole in the bowel wall, inflammation of the bile duct, and death appear to be low. Overall, we considered the quality of evidence for the outcome of PEP to be low. We considered none of the included studies to be at low risk of bias for all criteria. In most of the studies, both the participants and the medical staff were aware of which method was being used, therefore their judgments may not have been objective and the results should be interpreted cautiously. |
We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine. Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults. These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed. | randomised clinical trials (studies where people are randomly put into one of two or more treatment groups) where participants had come to medical attention because they had taken a paracetamol overdose, intentionally or by accident, regardless of the amount of paracetamol taken or the age, sex, or other medical conditions of the person involved. There are many different interventions that can be used to try to treat people with paracetamol poisoning. These interventions include decreasing the absorption of the paracetamol ingested and hence decreasing the amount absorbed into the bloodstream. The agents include activated charcoal (that binds paracetamol together in the stomach), gastric lavage (stomach washout to remove as much paracetamol as possible), or ipecacuanha (a syrup that is swallowed and causes vomiting (being sick)). Paracetamol once absorbed into the bloodstream goes to the liver where the majority is broken down to harmless products. However, a small amount of the medicine is converted into a toxic product that the liver can normally handle but, when large amounts of paracetamol are taken, the liver is overwhelmed. As a consequence, the toxic product can damage the liver leading to liver failure, kidney failure, and in some cases death. Other interventions to treat paracetamol poisoning include medicines (antidotes) that may decrease the amount of the toxic products (such as a medicine called cimetidine) or breakdown the toxic products (including medicines called methionine, cysteamine, dimercaprol, or acetylcysteine). Finally, attempts can be made to remove paracetamol and its toxic products from the bloodstream using special blood cleansing equipment. All these treatments were examined. We found 11 randomised clinical trials with 700 participants. Most of these trials looked at different treatments. activated charcoal, gastric lavage, and ipecacuanha may reduce absorption of paracetamol if started within one to two hours of paracetamol ingestion, but the clinical benefit was unclear. Activated charcoal seems to be the best choice if the person is able to take it. People may not be able to take charcoal if they are drowsy and some may dislike its taste or texture (or both). Of the treatments that remove the toxic products of paracetamol, acetylcysteine seems to reduce the rate of liver injury from paracetamol poisoning. Furthermore, it has fewer side effects than some other antidotes such as dimercaprol and cysteamine; its superiority to methionine was unclear. Acetylcysteine should be given to people with paracetamol poisoning at risk of liver damage, risk is determined by the dose ingested, time of ingestion, and investigations. More recent clinical trials have looked at ways to decrease side effects of intravenous (into a vein) acetylcysteine treatment, by altering the way it is given. These trials have shown that by using a slower infusion and lower initial dose of acetylcysteine, the proportion of side effects such as nausea (feeling sick) and vomiting, and allergy (the body's bad reaction to the medicine such as a rash) may be lowered. this review of interventions for paracetamol poisoning found surprisingly few published randomised clinical trials for this very common condition. Furthermore, the majority of trials had few participants and all were at high risk of bias. Accordingly, the quality of the evidence should be considered as low or very low. |
We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia. Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13). Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported. We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia. | This review of the evidence found one randomised controlled trial (RCT) of the LNG-IUS versus oral progestin therapy in women with any type of endometrial hyperplasia. It was conducted in Norway and included 153 women, but only 19 of the women had a confirmed histological diagnosis of atypical endometrial hyperplasia; the other women had other types of endometrial hyperplasia. The evidence is current to July 2018. The included RCT compared LNG-IUS versus oral continuous or cyclic medroxyprogesterone (MPA) for treating endometrial hyperplasia. After six months of treatment, there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the MPA group. The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the MPA group (n = 10/13). Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea, but vaginal bleeding was more common in the LNG-IUS group. The quality of the evidence was low or very low for all outcomes. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. |
We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment. | We identified 25 randomised clinical trials involving 2505 people undergoing laparoscopic cholecystectomy. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. The choice of whether the participants received the different painkillers (or not) was determined by a method similar to the toss of coin so that the treatments compared were conducted in people who were as similar as possible. The treatments in all the included trials were aimed at decreasing the pain after laparoscopic cholecystectomy before the participants reported pain. Participants were allowed to take additional painkillers as required in most of the trials. There were no deaths in either group in three trials (183 participants) that reported deaths. The differences in the serious complications between the groups was imprecise in all the comparisons. None of the trials reported quality of life or the time taken to return to normal activity. The differences in length of hospital stay and the time taken to return to work was imprecise in all the comparisons that reported these. Pain was lower in the participants who received painkillers compared with those who received controls at 4 to 8 hours and at 9 to 24 hours as measured by the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10). This is a modest reduction and is comparable to other methods of pain reduction such as administering local anaesthetics (drugs that numb part of the body, similar to the ones used by the dentist to prevent the people from feeling pain) during the operation. In summary, different painkillers reduce pain scores in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. The overall quality of evidence was very low. Further trials are necessary. Such trials should include outcomes such as quality of life, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing laparoscopic cholecystectomy and the people who provide funds for the treatment. |
Four RCTs involving 3925 women were identified and included in this review. All were high quality with minimal risk of bias. Three trials compared the addition of RT to BCS. One trial was a two by two factorial design comparing the use of RT and tamoxifen, each separately or together, in which participants were randomised in at least one arm. Analysis confirmed a statistically significant benefit from the addition of radiotherapy on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI 0.41 to 0.58, P < 0.00001), ipsilateral invasive recurrence (HR 0.50; 95% CI 0.32 to 0.76, p=0.001) and ipsilateral DCIS recurrence (HR 0.61; 95% CI 0.39 to 0.95, P = 0.03). All the subgroups analysed benefited from addition of radiotherapy. No significant long-term toxicity from radiotherapy was found. No information about short-term toxicity from radiotherapy or quality of life data were reported. This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS. No long-term toxicity from use of radiotherapy was identified. | The review identified four large randomised controlled trials (3925 women) that compared treatment with breast conserving surgery alone and breast conserving surgery with the addition of RT. The addition of RT reduced the risk of a recurrence of either DCIS or invasive cancer in the treated breast by 51%. Older trials of breast conserving surgery followed by RT for invasive breast cancer have shown long-term toxicity from the addition of RT. We found no evidence of increased toxicity from the use of RT although some trials did not report on the causes of non-breast cancer deaths (deaths which potentially could be related to side effects). The number of non-breast cancer deaths reported were similar in both radiotherapy and control groups. Changes in delivery of RT between older and more recent trials and a subsequent decrease in exposure of normal tissue may account for this finding. Longer follow up of trial participants is required before a definite conclusion can be drawn, however radiotherapy techniques are continuing to improve and future patients are likely to experience a further decrease in exposure of nearby normal tissues. Overall survival was high and similar between each group whether radiotherapy was used or not. There were no reports of short-term toxicity from use of radiotherapy, or quality of life data. |
Four trials, involving a total of 149 participants, compared the effectiveness of oral corticosteroids against placebo. All the trials were small and of low methodological quality. Although there was an overall significant effect of corticosteroids compared with placebo medication on complete caloric recovery at one month (risk ratio (RR) of 2.81; 95% confidence interval (CI) 1.32 to 6.00, P = 0.007), no significant effect was seen on complete caloric recovery at 12 months (RR 1.58; 95% CI 0.45 to 5.62, P = 0.48), or on the extent of caloric recovery at either one month (mean difference (MD) 9.60%; 95% CI -20.66 to 39.86, P = 0.53) or at 12 months (MD 6.83%; 95% CI -27.69 to 41.36, P = 0.70). In addition, there was no significant difference between corticosteroids and placebo medication in the symptomatic recovery of vestibular function following idiopathic acute vestibular dysfunction with respect to vertigo at 24 hours (RR 0.39; 95% CI 0.04 to 3.57, P = 0.40) and use of the Dizziness Handicap Inventory score at one, three, six and 12 months. Overall, there is currently insufficient evidence from these trials to support the administration of corticosteroids to patients with idiopathic acute vestibular dysfunction. We found no trials with a low risk of methodological bias that used the highest level of diagnostic criteria and outcome measures. We recommend that future studies should include health-related quality of life and symptom-based outcome measures, in addition to objective measures of vestibular improvement, such as caloric testing and electronystagmography. | This review identified four randomised controlled trials including 149 adult patients with idiopathic acute vestibular dysfunction (vestibular neuritis) treated with either corticosteroids or placebo. The studies were varied in that they used different drugs and different treatment regimens. On the basis of these studies, there is currently insufficient evidence in favour of corticosteroids over placebo medication in the symptomatic recovery and objective testing of vestibular function, both in the short-term and long-term. Further studies of higher quality are needed to test the effectiveness of corticosteroids in patients with the condition. |
A total of 10 studies recruiting 6292 apparently healthy adults met the inclusion criteria. All of the studies took place in high-income countries. The effect of interventions on self-reported PA at one year (eight studies; 6725 participants) was positive and moderate with significant heterogeneity (I² = 74%) (SMD 0.19; 95% CI 0.06 to 0.31; moderate quality evidence) but not sustained in three studies at 24 months (4235 participants) (SMD 0.18; 95% CI -0.10 to 0.46). The effect of interventions on cardiovascular fitness at one year (two studies; 349 participants) was positive and moderate with no significant heterogeneity in the observed effects (SMD 0.50; 95% CI 0.28 to 0.71; moderate quality evidence). Three studies (3277 participants) reported a positive effect on increasing PA levels when assessed as a dichotomous measure at 12 months, but this was not statistically significant (OR 1.52; 95% CI 0.88 to 2.61; high quality evidence). Although there were limited data, there was no evidence of an increased risk of adverse events (one study; 149 participants). Risk of bias was assessed as low (four studies; 4822 participants) or moderate (six studies; 1543 participants). Any conclusions drawn from this review require some caution given the significant heterogeneity in the observed effects. Despite this, there was some indication that the most effective interventions were those that offered both individual and group support for changing PA levels using a tailored approach. The long term impact, cost effectiveness and rates of adverse events for these interventions was not established because the majority of studies stopped after 12 months. Although we found evidence to support the effectiveness of face-to-face interventions for promoting PA, at least at 12 months, the effectiveness of these interventions was not supported by high quality studies. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions, and assess impact on quality of life, adverse events and economic data. | We included a total of 10 studies recruiting 6292 apparently healthy adults in this review. The findings of the review indicate that interventions can successfully support adults' attempts to become active and fitter, for example with personal counselling and advice, feedback and offering choices of exercise, and supervision. Outcomes are improved if the intervention comprises a specified type of physical activity and is supervised by a non-health professional using a combination of group and individual approaches. New physical activity can be maintained for up to at least one year and does not increase the risk of falls or exercise related injuries. More research is needed to establish which methods of exercise promotion work best in the long term to encourage specific groups of people to be more physically active. |
The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo. One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence). Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence). Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence). In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate. | This review looks at the effectiveness of depot flupenthixol decanoate in comparison with no active treatment (placebo), oral antipsychotics and other depot preparations for people with schizophrenia and other severe mental illnesses. An electronic search for relevant trials was carried out in 2013. Fifteen trials with 626 participants could be included. All evidence from these trials was rated by the authors to be low or very low quality. Currently, from the data reported, there is nothing to choose between depot flupenthixol decanoate and other depot or oral antipsychotics. There was some evidence that it would be understandable to offer a standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. Overall, this review highlights the lack of evidence based information available for the review question and the need for large, well-designed and reported randomised clinical trials to address the medical, social, personal and economic effects of flupenthixol decanoate. This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert: Rethink Mental Illness. |
Only one study met our inclusion criteria, involving 1106 adult patients with relapsing-remitting MS (RRMS) and an entry Expanded Disability Status Scale (EDSS) score of ≤ 5.5 and an entry disease duration of ≥ 6 months. Five hundred and fifty patients treated with laquinimod at a dose of 0.6 mg orally administered once daily in a capsule were compared with 556 patients treated with a matching placebo capsule. The study had a high risk for attrition bias (21.9%). Laquinimod had potential benefits in reducing relapse rates and was safe for most patients with RRMS in the short term. The most common adverse events included headache, back pain, arthralgia, diarrhoea, cough, urinary tract infection, elevated alanine aminotransferase, insomnia, nausea, abdominal pain and sinusitis. One ongoing trial was identified. We found low-level evidence for the use of laquinimod as a disease-modifying therapy for MS because only one study with limited quality (high risk of attrition bias) was included. The published study suggests that laquinimod at a dose of 0.6 mg orally administered once daily may be safe and have potential benefits for most patients with RRMS in the short term. We are waiting for the publication of ongoing trials. | The authors of this review assessed the efficacy and safety of laquinimod in patients with MS. Concerning the outcomes, they considered relapse, disability progression, inflammatory lesion, and brain atrophy. Among the pertinent literature only one study met the inclusion criteria. The study involved a total of 1106 patients with relapsing-remitting MS and evaluated the efficacy and safety of laquinimod as unique therapy versus placebo. As far as safety was concerned, common adverse events included headache, back pain, arthralgia, diarrhoea, cough, urinary tract infection, elevated alanine aminotransferase, insomnia, nausea, abdominal pain and sinusitis. The authors were unable to give any clear recommendations for the use of laquinimod as a DMD for MS because the study was poor quality and was funded by a pharmaceutical company. Future studies with higher methodological quality are needed to assess the potential benefits and the safety in a longer period of administration. |
A total of 13 trials with 8,698 participants were included. Primary outcomes (HIV and STI prevalence and incidence) were reported in seven trials. Of these, HIV incidence was reported in only three trials. After a 6-month follow-up assessment, there was no evidence that social cognitive behavioral intervention was effective in reducing HIV incidence (RR 0.12, 95% CI 0.01 to 2.22). However, there was a reduction in HIV incidence at 3-month follow-up assessment of promotion of female and male condom (RR 0.07, 95% CI 0.00 to 1.38). Social cognitive interventions and promotion of female and male condom use were significantly reduced STIs incidence (RR 0.57, 95% CI 0.34 to 0.96) and (RR 0.63, 95% CI 0.45 to 0.88), respectively. Secondary outcomes were identified in 13 trials. Meta-analyses showed evidence that interventions to promote the use of female and male condoms do reduce non-condom use (RR 0.83, 95% CI 0.65 to 1.05) compared to promotion of male condoms alone, and that social cognitive interventions reduced drug use among sex workers (RR 0.65, 95% CI 0.36 to 1.16) compared to standard care. Available evidence nevertheless suggests that compared with standard care or no intervention, behavioral interventions are effective in reducing HIV and the incidence of STIs amongst female sex workers (FSWs). Given the benefits of social cognitive theory and the promotion of condom use in reducing HIV/STI and the public health need to control transmission amongst FSWs, there is a clear finding in favour of behavioral interventions. However, it should be recognized that there is a lack of information about most other outcomes and target populations, and that all of the trials were conducted in low- and middle-income countries. | The review found seven individual randomised controlled trials (RCTs), two cluster-RCTs and four quasi-RCTs involving 8,698 participants examining a variety of behavioral interventions to evaluate whether they reduced HIV/STIs rates or resulted in changed behavior among sex workers and their clients. Results showed that the interventions were effective in HIV/STI prevention, including reducing the incidence and prevalence of HIV and STIs. Furthermore, there were some differences in self-reported behavior including increased condom use and a reduction in the risk of drug use. However, these trials were small and generally had few participants. As a result, evidence for the effectiveness of social cognitive theory and promoting condom use in reducing HIV/STI incidence compared to other behavioral interventions was limited, because no RCTs examined the effects of these interventions on HIV prevalence or on sex workers other than FSWs. In future research and program agendas therefore it is important to assess other potentially more potent behavioral change strategies. |
We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients. | The evidence is current to June 2017. Ten trials met our inclusion criteria, and included 1815 people. Three trials compared phenytoin (an AED) with a placebo or no treatment. One trial compared the AEDs phenytoin or carbamazepine with no treatment. One trial compared the AEDs phenytoin or phenobarbital with no treatment. Five other trials were head-to-head trials (where one drug is directly compared against another drug) of AEDs (phenytoin versus valproate; zonisamide versus phenobarbital and levetiracetam versus phenytoin). We did not find any consistent evidence to suggest that preventative AED treatments are effective in reducing the number of seizures that occurred postsurgery, deaths or adverse effects. Taking all the trials together, we considered that the quality of the evidence was low due to potential problems with the designs of the trials. Also the differences in the designs of the trials relating to the treatments examined and the results reported meant that it was difficult to compare results across trials. Further good-quality studies are needed to validate the findings mentioned above. |
We identified three prophylactic trials which recorded 37 cases of community-acquired pneumonia in 2335 people. Only one was satisfactorily randomised, double-blind and placebo-controlled. Two trials examined military recruits and the third studied boys from "lower wage-earning classes" attending a boarding school in the UK during World War II. Each of these three trials found a statistically significant (80% or greater) reduction in pneumonia incidence in the vitamin C group. We identified two therapeutic trials involving 197 community-acquired pneumonia patients. Only one was satisfactorily randomised, double-blind and placebo-controlled. That trial studied elderly patients in the UK and found lower mortality and reduced severity in the vitamin C group; however, the benefit was restricted to the most ill patients. The other therapeutic trial studied adults with a wide age range in the former Soviet Union and found a dose-dependent reduction in the duration of pneumonia with two vitamin C doses. We identified one prophylactic trial recording 13 cases of hospital-acquired pneumonia in 37 severely burned patients; one-day administration of vitamin C had no effect on pneumonia incidence. The identified studies are clinically heterogeneous which limits their comparability. The included studies did not find adverse effects of vitamin C. The prophylactic use of vitamin C to prevent pneumonia should be further investigated in populations who have a high incidence of pneumonia, especially if dietary vitamin C intake is low. Similarly, the therapeutic effects of vitamin C should be studied, especially in patients with low plasma vitamin C levels. The current evidence is too weak to advocate prophylactic use of vitamin C to prevent pneumonia in the general population. Nevertheless, therapeutic vitamin C supplementation may be reasonable for pneumonia patients who have low vitamin C plasma levels because its cost and risks are low. | Vitamin C was identified in the early 1900s and suggestions that one of its biological roles may be to resist infections are supported by numerous animal studies. We looked for studies in humans and found three trials with a total of 2335 participants that looked at whether vitamin C prevents pneumonia in the community. Two of these preventive trials studied soldiers while the third studied boys in a UK boarding school in the 1940s. Two therapeutic trials with a total of 197 pneumonia patients looked at whether vitamin C might be beneficial for pneumonia patients. One studied patients aged 66 to 94 years in the UK with pneumonia. The other therapeutic trial was conducted in the former Soviet Union but the social and nutritional backgrounds of the patients were not described. One study with 37 burns patients examined the effect of vitamin C on hospital-acquired pneumonia. Our searches were up-date-as of April 2013. Five of the identified trials found preventive or therapeutic benefits of vitamin C against pneumonia but the study on hospital-acquired pneumonia found no effect. The overall quality of the studies was good. However, the five trials with positive findings were carried out in such extraordinary conditions that the results should not be extrapolated to the general population. Therefore, more research is needed. In the meantime, supplementing pneumonia patients who have low plasma vitamin C levels may be reasonable because of its safety and low cost. None of the five trials reported noteworthy adverse effects of vitamin C. |
One-hundred-and-two quasi-experimental studies, with 666,615 children are included in this review. The 'Risk of bias' analysis indicates that the evidence base contains studies with unclear risk for selection bias, performance bias, detection bias, reporting bias, and attrition bias, with the highest risk associated with selection bias and the lowest associated with reporting bias. The outcome data suggest that children in kinship foster care experience fewer behavioural problems (standardised mean difference effect size -0.33, 95% confidence interval (CI) -0.49 to -0.17), fewer mental health disorders (odds ratio (OR) 0.51, 95% CI 0.42 to 0.62), better well-being (OR 0.50, 95% CI 0.38 to 0.64), and less placement disruption (OR 0.52, 95% CI 0.40 to 0.69) than do children in non-kinship foster care. For permanency, there was no difference on reunification rates, although children in non-kinship foster care were more likely to be adopted (OR 2.52, 95% CI 1.42 to 4.49), while children in kinship foster care were more likely to be in guardianship (OR 0.26, 95% CI 0.17 to 0.40). Lastly, children in non-kinship foster care were more likely to utilise mental health services (OR 1.79, 95% CI 1.35 to 2.37). This review supports the practice of treating kinship care as a viable out-of-home placement option for children removed from the home for maltreatment. However, this conclusion is tempered by the pronounced methodological and design weaknesses of the included studies. | This review was designed to help find out if research studies could tell us which kind of placement is best. We found 102 studies with 666,615 children that met the methodological standards we considered acceptable. Wherever possible we combined the data from studies looking at the same outcome for children, in order to be more confident about what the research was telling us. Current best evidence suggests that children in kinship foster care may do better than children in traditional foster care in terms of their behavioural development, mental health functioning, and placement stability. Children in traditional foster care placements may do better with regard to achieving adoption and accessing services they may need. There were no negative effects experienced by children who were placed in kinship care. The major limitation of this systematic review is that the quality of research on kinship care is weakened by the poor methods of the included studies. Implications for practice and future research are discussed. |
Five RCTs involving 604 people were included. The pooled results revealed that the addition of corticosteroids reduces statistically significant the risk for acute GvHD grade I to IV (HR 0.58; 95% CI 0.45 to 0.76) and II to IV (HR 0.69; 95% CI 0.51 to 0.92). No evidence was found that it has any clinical relevance on overall survival (HR 0.99; 95% CI 0.79 to 1.25) or disease-free survival (HR 0.95; 95% CI 0.74 to 1.23). As well, no statistically significant influence was found for acute GvHD grade III to IV (HR 0.78; 95% CI 0.52 to 1.15), chronic GvHD (HR 1.21;95% CI 0.89 to 1.65]), relapse incidence (HR 0.82; 95% CI 0.57 to 1.18) or non-relapse mortality (HR 0.88;95% CI 0.61 to 1.26). No clear evidence was found that the rate of infectious complications (under the concomitant use of antiviral or antibacterial medication or both) increases with the addition of corticosteroids. With respect to the other outcomes no significant differences could be detected. The addition of corticosteroids reduces the incidences of acute GvHD grade I to IV and II to IV. This reduction, however, did not show any effect on overall survival and disease-free survival. Further randomised controlled studies are needed to evaluate if the timing of steroid administration has a significant influence on the outcome; data on quality of life should be assessed systematically. | Five RCTs involving 604 people were included in this review. Analyses of these studies showed that the incidence of moderate forms of GvHD can be reduced by prophylactic corticosteroid regimens. However, there is no evidence that the incidence of life-threatening forms or patient mortality can be reduced. Effects on quality of life could not be estimated because this information was not systematically collected during these studies. Further studies are needed to determine if the timing of steroid administration influences the outcomes of GvHD. |
Eleven randomised clinical trials involving 716 patients with primary biliary cirrhosis fulfilled the inclusion criteria. No significant differences were detected between colchicine and placebo/no intervention on the number of deaths (RR 1.21, 95% CI 0.71 to 2.06), the number of deaths and/or patients who underwent liver transplantation (RR 1.00, 95% CI 0.67 to 1.49), liver complications, liver biochemical variables, liver histological measurements, and adverse events. Trial methodology was generally low and some trials had high drop-out rate. A best-worst-case-scenario analysis showed no significant effect of colchicine on mortality (RR 0.59, 95%CI 0.30 to 1.15), while a worst-best-case-scenario analysis showed a significant detrimental effect of colchicine on mortality (RR 2.28, 95% CI 1.17 to 4.44). Colchicine significantly decreased the number of patients without improvement of pruritus (RR 0.75, 95% CI 0.65 to 0.87). However, this estimate was based on only 156 patients from three trials. The effect of the combined treatment with ursodeoxycholic acid was not significantly different from that of colchicine alone. We did not find evidence either to support or refute the use of colchicine for patients with primary biliary cirrhosis. As we are not able to exclude a detrimental effect of colchicine, we suggest that it is only used in randomised clinical trials. | Colchicine, a plant alkaloid, has been used to treat patients with primary biliary cirrhosis and was tested in randomised clinical trials. When all identified trials were combined, colchicine appeared to be not significantly different from placebo/no intervention in respect to mortality, mortality and/or patients who underwent liver transplantation, liver complications, liver biochemistry, liver histology, and the occurrences of adverse events. Colchicine may reduce pruritus, but this finding may be due to bias. The addition of ursodeoxycholic acid did not significantly influence the effect of colchicine. |
The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias. The NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine. Pair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence). We were unable to perform any of our planned subgroup analyses due to the low number of TNS events. Results from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia. Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia. Due to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed. | We included all randomized trials and quasi-randomized trials comparing the frequency of TNS and neurological complications after spinal anaesthesia with lidocaine compared to other local anaesthetic agents. Randomized trials compare two or more treatments where the treatments are allocated to participants in a random manner that cannot be predicted by the study organizers. Quasi-randomized studies are similar but are not truly random, but carry a greater likelihood that the study organizer can predict which treatment the participants receive (e.g. based on date of birth or the order in which people were recruited). The evidence is current to 25 November 2018. We included 24 trials reporting on 2226 participants, 239 of whom developed TNS. There was no evidence TNS was associated with any specific neurological disease and symptoms disappeared spontaneously by the fifth postoperative day. The risk of developing TNS with lidocaine for spinal anaesthesia was increased compared to bupivacaine, prilocaine, or procaine; and similar compared to 2-chloroprocaine and mepivacaine. Specifically, when alternative local anaesthetics were compared directly to lidocaine, the risk of developing TNS was reduced by between 82% and 90% when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine were used rather than lidocaine. There were no clear differences in TNS between lidocaine and 2-chloroprocaine or mepivacaine. In the case of 2-chloroprocaine, TNS occurred in only one study and the results varied greatly for the small number of participants. Painful symptoms stopped by the fifth postoperative day in all participants. Among pregnant women undergoing surgery, only 3/310 women developed TNS; no conclusions could be drawn on whether symptoms were more likely with lidocaine. The authors also used the statistical method of network meta-analysis to compare the various local anaesthetics. This analysis similarly showed that the risk of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine, while 2-chloroprocaine and mepivacaine did not differ in risk of TNS compared to lidocaine. Due to the very low- to moderate-quality of evidence among currently available studies, future research efforts in this field are needed to assess alternatives to lidocaine that can provide high-quality anaesthesia without TNS development. Lidocaine has been the drug of choice for inducing spinal anaesthesia in ambulatory surgery (or day surgery) because of its rapid onset of action, intense nerve blockade, and short duration of action. The present review shows that lidocaine is more likely to cause TNS than bupivacaine, prilocaine, and procaine. However, these drugs produce longer local anaesthetic effects and therefore are not desirable for ambulatory patients. Our results suggest that 2-chloroprocaine might be a viable alternative to lidocaine for day surgery of short duration and obstetric procedures since this local anaesthetic has a rapid onset of action, is quickly metabolized, and has low toxicity. However, this conclusion is based on only two studies and low-quality evidence. |
We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants) There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants) One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants) Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants) Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants) Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence). We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures. | The evidence is up-to-date to January 2016. We included 30 trials involving 2319 participants. We looked at trials that compared midazolam with no active treatment ('dummy' treatment/placebo) or a different medication for sedation before a procedure. The trials involved children and adults having procedures to diagnose medical problems rather than procedures for treatment of a disease. We disregarded trials where people received a general anaesthetic or other medications for sedation or pain relief in addition to midazolam during their procedure. Midazolam administered into the bloodstream compared with other medications did not seem to make the participants more drowsy, reduce anxiety or pain, or make the procedure easier to perform. This is based on the low-quality evidence currently available. A potential benefit is that children and adults who received midazolam compared with no active treatment did not remember as much about the procedures. Midazolam made them drowsy, reduced anxiety and made it easier to perform a procedure. There is moderate-quality evidence that a solution of midazolam given to children to drink before a procedure was not as effective as a different medication called chloral hydrate. A nasal spray of midazolam before a procedure made the participants drowsy and reduced their anxiety, but this did not make it easier to perform procedures on them. This review cannot be used to assess the harms of midazolam for sedation before a procedure. We rated the evidence, in the main, as being of low quality. Particularly concerning was that many trials did not explain how participants were randomized to either midazolam or to a different treatment, and that the results did not give us a very clearly defined answer. |
We included two studies with 1711 participants in the analyses. Both studies were conducted in UK general dental practices and involved adults without severe periodontitis who were regular attenders at dental appointments. One study measured outcomes at 24 months and the other at 36 months. Neither study measured adverse effects, changes in attachment level, tooth loss or halitosis. Comparison 1: routine scaling and polishing versus no scheduled scaling and polishing Two studies compared planned, regular interval (six- and 12-monthly) scale and polish treatments versus no scheduled treatment. We found little or no difference between groups over a two- to three-year period for gingivitis, probing depths, oral health-related quality of life (all high-certainty evidence) and plaque (low-certainty evidence). The SMD for gingivitis when comparing six-monthly scale and polish treatment versus no scheduled treatment was –0.01 (95% CI –0.13 to 0.11; two trials, 1087 participants), and for 12-monthly scale and polish versus no scheduled treatment was –0.04 (95% CI –0.16 to 0.08; two trials, 1091 participants). Regular planned scale and polish treatments produced a small reduction in calculus levels over two to three years when compared with no scheduled scale and polish treatments (high-certainty evidence). The SMD for six-monthly scale and polish versus no scheduled treatment was –0.32 (95% CI –0.44 to –0.20; two trials, 1088 participants) and for 12-monthly scale and polish versus no scheduled treatment was –0.19 (95% CI –0.31 to –0.07; two trials, 1088 participants). The clinical importance of these small reductions is unclear. Participants' self-reported levels of oral cleanliness were higher when receiving six- and 12-monthly scale and polish treatments compared to no scheduled treatment, but the certainty of the evidence is low. Comparison 2: routine scaling and polishing at different recall intervals Two studies compared routine six-monthly scale and polish treatments versus 12-monthly treatments. We found little or no difference between groups over two to three years for the outcomes of gingivitis, probing depths, oral health-related quality of life (all high-certainty evidence) and plaque (low-certainty evidence). The SMD for gingivitis was 0.03 (95% CI -0.09 to 0.15; two trials, 1090 participants; I2 = 0%). Six- monthly scale and polish treatments produced a small reduction in calculus levels over a two- to three-year period when compared with 12-monthly treatments (SMD –0.13 (95% CI –0.25 to –0.01; 2 trials, 1086 participants; high-certainty evidence). The clinical importance of this small reduction is unclear. The comparative effects of six- and 12-monthly scale and polish treatments on patients' self-reported levels of oral cleanliness were uncertain (very low-certainty evidence). Comparison 3: routine scaling and polishing provided by dentists compared with dental care professionals (dental therapists or hygienists) No studies evaluated this comparison. The review findings in relation to costs were uncertain (very low-certainty evidence). For adults without severe periodontitis who regularly access routine dental care, routine scale and polish treatment makes little or no difference to gingivitis, probing depths and oral health-related quality of life over two to three years follow-up when compared with no scheduled scale and polish treatments (high-certainty evidence). There may also be little or no difference in plaque levels over two years (low-certainty evidence). Routine scaling and polishing reduces calculus levels compared with no routine scaling and polishing, with six-monthly treatments reducing calculus more than 12-monthly treatments over two to three years follow-up (high-certainty evidence), although the clinical importance of these small reductions is uncertain. Available evidence on the costs of the treatments is uncertain. The studies did not assess adverse effects. | We included two studies with a total of 1711 participants in our review. Both studies involved adults without severe periodontitis who were regular attenders at dental appointments in the UK. The studies were conducted in general dental practices, which is the most appropriate setting to evaluate 'routine scale and polish' treatments. One study measured outcomes at 24 months and one study at 36 months. The studies found little or no difference between regular planned scale and polish treatments compared with no scheduled scale and polish for the early signs of gum disease (gingivitis or bleeding gums; plaque deposits; and probing depths or gum pockets). There was a small reduction in calculus (tartar) levels, but it was uncertain if this is important for patients or their dentists. Participants receiving six-monthly and 12-monthly scale and polish treatments reported feeling that their teeth were cleaner than those who were scheduled to receive no treatment. However, there did not seem to be a difference between groups in terms of quality of life. Available evidence on the costs of the treatments was uncertain. Neither of the studies measured side effects (such as damage to tooth surfaces and tooth sensitivity), changes in attachment level, tooth loss or halitosis (bad breath). Neither study compared scale and polish treatments provided by different professionals, e.g. dentists, dental therapists and hygienists. We judged the certainty of the evidence to be high for gingivitis, probing depths, calculus and quality of life, but low for plaque, and low to very low for patient perception of oral cleanliness. The certainty of evidence for costs was very low. The high-certainty evidence for gingivitis means that we can be confident that routine scale and polish does not significantly reduce the signs of mild gum disease when measured up to three years. |
We identified five studies including 318 participants (180 participants with and 138 participants without common bile duct stones) that reported the diagnostic accuracy of ERCP and five studies including 654 participants (125 participants with and 529 participants without common bile duct stones) that reported the diagnostic accuracy of IOC. Most studies included people with symptoms (participants with jaundice or pancreatitis) suspected of having common bile duct stones based on blood tests, ultrasound, or both, prior to the performance of ERCP or IOC. Most studies included participants who had not previously undergone removal of the gallbladder (cholecystectomy). None of the included studies was of high methodological quality as evaluated by the QUADAS-2 tool (quality assessment tool for diagnostic accuracy studies). The sensitivities of ERCP ranged between 0.67 and 0.94 and the specificities ranged between 0.92 and 1.00. For ERCP, the summary sensitivity was 0.83 (95% confidence interval (CI) 0.72 to 0.90) and specificity was 0.99 (95% CI 0.94 to 1.00). The sensitivities of IOC ranged between 0.75 and 1.00 and the specificities ranged between 0.96 and 1.00. For IOC, the summary sensitivity was 0.99 (95% CI 0.83 to 1.00) and specificity was 0.99 (95% CI 0.95 to 1.00). For ERCP, at the median pre-test probability of common bile duct stones of 0.35 estimated from the included studies (i.e., 35% of people suspected of having common bile duct stones were confirmed to have gallstones by the reference standard), the post-test probabilities associated with positive test results was 0.97 (95% CI 0.88 to 0.99) and negative test results was 0.09 (95% CI 0.05 to 0.14). For IOC, at the median pre-test probability of common bile duct stones of 0.35, the post-test probabilities associated with positive test results was 0.98 (95% CI 0.85 to 1.00) and negative test results was 0.01 (95% CI 0.00 to 0.10). There was weak evidence of a difference in sensitivity (P value = 0.05) with IOC showing higher sensitivity than ERCP. There was no evidence of a difference in specificity (P value = 0.7) with both tests having similar specificity. Although the sensitivity of IOC appeared to be better than that of ERCP, this finding may be unreliable because none of the studies compared both tests in the same study populations and most of the studies were methodologically flawed. It appears that both tests were fairly accurate in guiding further invasive treatment as most people diagnosed with common bile duct stones by these tests had common bile duct stones. Some people may have common bile duct stones in spite of having a negative ERCP or IOC result. Such people may have to be re-tested if the clinical suspicion of common bile duct stones is very high because of their symptoms or persistently abnormal liver function tests. However, the results should be interpreted with caution given the limited quantity and quality of the evidence. | We identified five studies including 318 participants that reported the diagnostic test accuracy of ERCP and five studies including 654 participants that reported the diagnostic test accuracy of IOC. Most studies included people with symptoms (participants with jaundice or pancreatitis) who were suspected of having CBD stones based on blood tests, ultrasound (use of sound waves higher than audible range to differentiate tissues based on how they reflect the sound waves), or both, prior to the having ERCP or IOC. Most studies included participants who had not previously undergone cholecystectomy. Given an average sensitivity of 83% for ERCP, we would expect that on average 83 out of 100 people (this may vary between 72 and 90 out of 100 people) with CBD stones would be detected while the remaining 17 people would be missed and would not receive appropriate treatment. Based on an average specificity of 99% for ERCP, we would expect that on average 99 out of 100 people without CBD stones would be identified as not having CBD stones; 1 out of 100 (this could vary between 0 and 17 out of 100 people) would be false positive and would not receive appropriate treatment. For IOC, an average sensitivity of 99% means that on average 99 out of 100 people (this may vary between 83 and 100 out of 100 people) with CBD stones would be detected while only one person would be missed and would not receive appropriate treatment. In terms of specificity, an average of 99% for IOC means that 99 out of 100 people without CBD stones would be identified as not having CBD stones with only one false positive (this could vary between 0 and 5 out of 100 people) who would not receive appropriate treatment. It appears that both tests are fairly accurate in guiding further invasive treatment as most people diagnosed with CBD stones by these tests have CBD stones. However, some people may have CBD stones in spite of having a negative ERCP or IOC test result. Such people may have to be re-tested if the clinical suspicion of CBD stones is very high because of their symptoms. All the studies were of low methodological quality, which may question the validity of our findings. Further studies of high methodological quality are necessary. |
We included 20 studies with 13,102 cases of acute GABHS pharyngitis. The updated search did not identify any new eligible studies; the majority of studies were at high risk of bias. However, the majority of the results were consistent. Compared to standard duration treatment, the short duration treatment studies had shorter periods of fever (mean difference (MD) -0.30 days, 95% confidence interval (CI) -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to -0.22); lower risk of early clinical treatment failure (odds ratio (OR) 0.80, 95% CI 0.67 to 0.94); no significant difference in early bacteriological treatment failure (OR 1.08, 95% CI 0.97 to 1.20) or late clinical recurrence (OR 0.95, 95% CI 0.83 to 1.08). However, the overall risk of late bacteriological recurrence was worse in the short duration treatment studies (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10 mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications. Out of 8135 cases of acute GABHS pharyngitis, only six cases in the short duration treatment versus eight in the standard duration treatment developed long-term complications in the form of glomerulonephritis and acute rheumatic fever, with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64). Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis. . In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution. | We summarized medical literature regarding the effect of two to six days of oral antibiotics (short duration) in treating children with streptococcal throat infection, compared with 10 days of oral penicillin (standard duration). We included 20 studies with 13,102 cases of acute group A beta hemolytic streptococcus (GABHS) pharyngitis. The short duration treatment resulted in better compliance but more side effects. All side effects were self-limiting: mostly mild to moderate diarrhea, vomiting and abdominal pain. Three studies reported the rate of long duration complications with no statistically significant difference. Our study has several limitations. Firstly, only 3 out of the 20 included studies followed the participants for a sufficient duration to be able to study the prevalence of complications of GABHS pharyngitis. Although these three studies had a total of 8135 participants, results were too under-powered to draw any conclusions on differences in complication rates. This means our conclusion is not applicable in low-income countries where the prevalence of rheumatic heart disease is high. Another limitation is that the primary studies evaluated different antibiotics for variable durations (three to six days). Also, studies were of limited quality. Finally, although the shorter antibiotic duration appeared to be effective and more convenient, it is more expensive than the standard duration 10 days of penicillin. However, one must take into account the reality of patient behavior and the price of unsuccessful or incomplete therapy. Three to six days of oral antibiotics for children with streptococcal throat infection is a safe treatment with a comparable effect to the standard duration of 10 days of penicillin. However, our results must be interpreted with caution in low-income countries where acute rheumatic fever is still a problem. |
Our search identified 604 potentially relevant studies. Of these, 14 studies (15 interventions) were RCTs and met our inclusion criteria. The numbers of participants were 352, 138 and 1745 for aspirin, steroid and NSAIDs groups, respectively. One selected study comprised two separate interventions. Interventions assessed in these studies were grouped into four categories: aspirin (three interventions), steroids (one intervention), traditional NSAIDs (six interventions), and selective cyclooxygenase-2 (COX-2) inhibitors (five interventions). All studies were evaluated for internal validity using a risk of bias assessment tool. The risk of bias was low for five studies, high for seven studies, and unclear for two studies.There was no significant improvement in cognitive decline for aspirin, steroid, traditional NSAIDs and selective COX-2 inhibitors. Compared to controls, patients receiving aspirin experienced more bleeding while patients receiving steroid experienced more hyperglycaemia, abnormal lab results and face edema. Patients receiving NSAIDs experienced nausea, vomiting, elevated creatinine, elevated LFT and hypertension. A trend towards higher death rates was observed among patients treated with NSAIDS compared with placebo and this was somewhat higher for selective COX-2 inhibitors than for traditional NSAIDs. Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD. | Fourteen studies met our inclusion criteria for this review and none of the exclusion criteria. Aspirin, steroid and non-steroidal anti-inflammatory drugs (NSAIDs) (traditional and the selective cyclooxygenase-2 (COX-2) inhibitors) showed no significant benefit in the treatment of Alzheimer's disease. Therefore, the use of these drugs cannot be recommended for the treatment of Alzheimer's disease. |
One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment periods. Compared with people taking a double dose of ICS, fewer people taking a LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence intervals for both outcomes did not exclude the possibility that double dose ICS was more effective. Serious adverse events and exacerbations requiring hospitalisation occurred in similarly low numbers of people taking each treatment, but confidence intervals were too wide to suggest that the two treatment options were equivalent. Asthma-related quality of life was similar in both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI − 0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale measuring asthma control than those increasing their ICS dose (MD in change from baseline − 0.18, 95% CI − 0.34 to − 0.02), although the difference was clinically small. Evidence was deemed low quality for both quality of life and asthma control. There was moderate-quality evidence that participants' trough forced expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to 0.17). Only one randomised trial was found, comparing tiotropium add-on to increased dose beclomethasone. Differences between the treatments were too small or imprecise to understand whether adding a LAMA to ICS is safer or more effective than increasing the dose of ICS, and there is a possibility of carry-over effects due to the study's cross-over design. LAMA add-on may lead to more improvement in lung function (FEV1) than an increased dose of ICS. The results of this review, alongside pending results from related reviews assessing the use of LAMA against other treatments, will help to define the role of these drugs in asthma management, and this review should be updated as results from future trials emerge. Studies assessing the role of LAMA add-on should be longer and include a double-ICS treatment arm so that the results can be interpreted in the context of the guideline-recommended treatment options that are available to physicians. | Two people looked for published and unpublished research in several databases and websites to find relevant studies comparing LAMA plus ICS with increased doses of ICS for asthma in adults. We analysed the results available up to April 2015 in this systematic review. What did we find? We found one study involving 210 patients with asthma. The trial compared adding tiotropium (a LAMA) to doubling the dose of beclomethasone (a steroid). In the trial, people taking a combination of the LAMA and ICS were slightly less likely to have an asthma attack needing treatment with oral steroids. Our results suggest that for every 1000 people, 18 fewer in the LAMA group would need these treatments compared to patients treated with an increased dose of ICS. However, there is a relatively wide margin of error in this estimate, and the actual number of patients on LAMA who might need steroids because of an asthma attack could range from 52 fewer to 26 more people per 1000. Similarly, neither option was more clearly beneficial on any of the following measures: asthma attacks resulting in hospitalisation or admission to the emergency department, serious adverse events, control of asthma or quality of life related to asthma. On the other hand, LAMA plus ICS might improve lung function a bit more than increasing ICS dose. We didn't have much confidence in the findings because the one included study only looked at one type of LAMA (tiotropium) for a short period of time (14 weeks). |
We included two RCTs involving 72 participants. Sixty-nine participants were included in one meta-analysis (balance). Both trials assessed QoL, along with secondary outcomes measures relating to movement and psychological outcomes; one also measured disability. In one study the Stroke Impact Scale was used to measure QoL across six domains, at baseline and post-intervention. The effect of yoga on five domains (physical, emotion, communication, social participation, stroke recovery) was not significant; however, the effect of yoga on the memory domain was significant (mean difference (MD) 15.30, 95% confidence interval (CI) 1.29 to 29.31, P = 0.03), the evidence for this finding was very low grade. In the second study, QoL was assessed using the Stroke-Specifc QoL Scale; no significant effect was found. Secondary outcomes included movement, strength and endurance, and psychological variables, pain, and disability. Balance was measured in both studies using the Berg Balance Scale; the effect of intervention was not significant (MD 2.38, 95% CI -1.41 to 6.17, P = 0.22). Sensititivy analysis did not alter the direction of effect. One study measured balance self-efficacy, using the Activities-specific Balance Confidence Scale (MD 10.60, 95% CI -7.08,= to 28.28, P = 0.24); the effect of intervention was not significant; the evidence for this finding was very low grade. One study measured gait using the Comfortable Speed Gait Test (MD 1.32, 95% CI -1.35 to 3.99, P = 0.33), and motor function using the Motor Assessment Scale (MD -4.00, 95% CI -12.42 to 4.42, P = 0.35); no significant effect was found based on very low-grade evidence. One study measured disability using the modified Rankin Scale (mRS) but reported only whether participants were independent or dependent. No significant effect was found: (odds ratio (OR) 2.08, 95% CI 0.50 to 8.60, P = 0.31); the evidence for this finding was very low grade. Anxiety and depression were measured in one study. Three measures were used: the Geriatric Depression Scale-Short Form (GCDS15), and two forms of State Trait Anxiety Inventory (STAI, Form Y) to measure state anxiety (i.e. anxiety experienced in response to stressful situations) and trait anxiety (i.e. anxiety associated with chronic psychological disorders). No significant effect was found for depression (GDS15, MD -2.10, 95% CI -4.70 to 0.50, P = 0.11) or for trait anxiety (STAI-Y2, MD -6.70, 95% CI -15.35 to 1.95, P = 0.13), based on very low-grade evidence. However, a significant effect was found for state anxiety: STAI-Y1 (MD -8.40, 95% CI -16.74 to -0.06, P = 0.05); the evidence for this finding was very low grade. No adverse events were reported. Quality of the evidence We assessed the quality of the evidence using GRADE. Overall, the quality of the evidence was very low, due to the small number of trials included in the review both of which were judged to be at high risk of bias, particularly in relation to incompleteness of data and selective reporting, and especially regarding the representative nature of the sample in one study. Yoga has the potential for being included as part of patient-centred stroke rehabilitation. However, this review has identified insufficient information to confirm or refute the effectiveness or safety of yoga as a stroke rehabilitation treatment. Further large-scale methodologically robust trials are required to establish the effectiveness of yoga as a stroke rehabilitation treatment. | We found two research studies that had assessed yoga for stroke survivors. Seventy-two people took part in the two studies. One study was in the USA and one was in Australia. On average, the stroke survivors were between 60 and 63 years old and it had been between four years three months and nine years since they had had a stroke. In the American study, yoga classes were held twice a week for eight weeks. In the Australian study, yoga classes were held once a week for 10 weeks. Both studies encouraged people to practice yoga at home, in their own time. Both studies used waiting-list control groups. This means that people in the control group could go to yoga classes at the end of the study. The American study was funded by the US Government. The Austrailian study was funded by the National Stroke Foundation (Australia). We were able to analyse study data from 69 participants. No significant benefit was found on measures of QoL, balance, strength, endurance, pain, disability scores. No significant benefit was found on measures of movement, although one study reported a significant benefit in improving aspects of range of movement. One study reported a significant benefit in reducing anxiety. Neither study reported on measures of patient harm. We assessed the quality of the evidence using GRADE. Overall, the quality of the evidence was very low, due to the small number of trials included in the review, both of which we judged to be at high risk of bias, particularly in relation to incompleteness of data and selective reporting, and especially regarding the representative nature of the sample in one study. The review could not identify enough high-quality evidence on the benefits and safety of yoga in stroke rehabilitation. More good-quality research studies are needed to be sure that yoga has benefits for stroke survivors. |
Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials. Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta-analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges. | Overall, we judged the quality of the evidence in this review for the main outcome of reduction in seizure frequency to be low due to unclear information in the published papers about how the studies were designed and unclear presentation of results. This review provides no information about the effect of TMS on quality of life. It is important that future studies are larger and measure important outcomes, such as the effect of TMS on reducing seizure frequency, improving quality of life, and any side-effects associated with TMS compared with other available treatments. |
We included 55 studies in the review. Thirty-three studies in 14,174 children provided information for the QCA, and 33 RCTs in 12,623 children measured the effects of interventions. Eleven studies contributed to both the QCA and the analysis of effectiveness. Most studies were conducted in North America in socially disadvantaged populations. High school students were better represented among studies contributing to the QCA than in studies contributing to effectiveness evaluations, which more commonly included younger elementary and junior high school students. The interventions all attempted to improve knowledge of asthma, its triggers, and stressed the importance of regular practitioner review, although there was variation in how they were delivered. QCA results highlighted the importance of an intervention being theory driven, along with the importance of factors such as parent involvement, child satisfaction, and running the intervention outside the child's own time as drivers of successful implementation. Compared with no intervention, school-based self-management interventions probably reduce mean hospitalisations by an average of about 0.16 admissions per child over 12 months (SMD –0.19, 95% CI -0.35 to -0.04; 1873 participants; 6 studies, moderate certainty evidence). They may reduce the number of children who visit EDs from 7.5% to 5.4% over 12 months (OR 0.70, 95% CI 0.53 to 0.92; 3883 participants; 13 studies, low certainty evidence), and probably reduce unplanned visits to hospitals or primary care from 26% to 21% at 6 to 9 months (OR 0.74, 95% CI 0.60 to 0.90; 3490 participants; 5 studies, moderate certainty evidence). Self-management interventions probably reduce the number of days of restricted activity by just under half a day over a two-week period (MD 0.38 days 95% CI -0.41 to -0.18; 1852 participants; 3 studies, moderate certainty evidence). Effects of interventions on school absence are uncertain due to the variation between the results of the studies (MD 0.4 fewer school days missed per year with self-management (-1.25 to 0.45; 4609 participants; 10 studies, low certainty evidence). Evidence is insufficient to show whether the requirement for reliever medications is affected by these interventions (OR 0.52, 95% CI 0.15 to 1.81; 437 participants; 2 studies; very low-certainty evidence). Self-management interventions probably improve children's asthma-related quality of life by a small amount (MD 0.36 units higher on the Paediatric AQLQ(95% CI 0.06 to 0.64; 2587 participants; 7 studies, moderate certainty evidence). School-based asthma self-management interventions probably reduce hospital admission and may slightly reduce ED attendance, although their impact on school attendance could not be measured reliably. They may also reduce the number of days where children experience asthma symptoms, and probably lead to small improvements in asthma-related quality of life. Many of the studies tested the intervention in younger children from socially disadvantaged populations. Interventions that had a theoretical framework, engaged parents and were run outside of children's free time were associated with successful implementation. | We included 55 studies. Thirty three of these studies helped us to gain a better understanding of the best way to deliver an asthma self-management intervention. Thirty three studies helped us to determine whether these interventions are successful in improving children's health and well-being. Eleven studies contributed to both. We included 23 studies in quantitative models measuring children's asthma outcomes (an outcome is something you can measure to find out if an intervention worked). Results show that school-based self-management interventions could improve outcomes such as hospitalisations, emergency department visits, and health-related quality of life. Fewer studies reported improved unplanned medical visits or reduced numbers of days on which children could not do their normal activities. Interventions did not reduce school absences, symptoms, or reliever medication use. The more effective interventions were based on theories about how the intervention might work. Researchers found that including parents in the intervention, making sure children were happy with the intervention, and running the intervention during school hours helped increase fidelity. Studies that measured whether an intervention worked were usually well designed; however sometimes they were difficult to carry out, and some may not have measured outcomes accurately. Reviewers found that some of the studies conducted to understand how an intervention should be delivered were at risk of bias, and certainty of the evidence was generally lower for these studies. Evidence suggests that school-based self-management interventions can help children with asthma and can reduce hospital admissions and trips to the emergency department. Study findings suggest that interventions that were based on a theory about how an intervention can be planned and delivered could prove useful in improving children's outcomes, reaching large numbers of children, and keeping dropout rates low, and indicate that those designing interventions should consider factors such as including parents. This review is current to August 2017. |
We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non-significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G-CSF. G-CSF was associated with a non-significant reduction in early impairment (mean difference (MD) -0.4, 95% CI -1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G-CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G-CSF are ongoing. There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome. | In this analysis, we assessed the effect of CSFs on outcome after stroke using data from clinical trials of people with recent stroke. We included a total of 11 studies and 1275 participants. A higher death rate was observed in participants treated with erythropoietin (EPO) in three trials (782 participants); whether further trials of EPO will be performed early after stroke remains unclear. In eight small trials involving 548 participants, patterns of improvement after a stroke were observed using granulocyte colony stimulating factor (G-CSF) and further trials are ongoing. Currently, there is insufficient evidence to support the use of CSFs in the treatment of people with recent stroke. |
We only identified one trial that met the inclusion criteria but this trial did not have any results so we could not perform the planned subgroup and sensitivity analyses in the absence of data. Two ongoing trials were identified which may provide data for analyses in a later version of this review. The completion date of these trials is currently unknown. The current review failed to find any completed randomised clinical trials with results. Therefore we are unable to conclude whether intensive glycaemic control when compared to conventional glycaemic control has a positive or detrimental effect on the treatment of foot ulcers in people with diabetes. Previous evidence has however highlighted a reduction in risk of limb amputation (from various causes) in people with type 2 diabetes with intensive glycaemic control. Whether this applies to people with foot ulcers in particular is unknown. The exact role that intensive glycaemic control has in treating foot ulcers in multidisciplinary care (alongside other interventions targeted at treating foot ulcers) requires further investigation. | We did not find any trials which have been completed on this topic with available results. The only trial which met our criteria for inclusion had been terminated due to encountering difficulties with recruiting participants. Therefore we cannot be sure whether controlling blood glucose intensively when people have diabetic foot ulcers is beneficial or harmful. The lack of evidence however should not deter efforts to achieve optimal glycaemic control in people with diabetic foot ulcers to encourage healing as is current practice. We believe there are currently two trials underway which may provide some evidence on this topic once completed. This Plain Language Summary is up to date as of 7 December 2015. |
We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two of the trials included children up to 14 years old. Participants in two trials had cirrhosis in addition to chronic hepatitis B. All trials were assessed at high risk of bias, and certainty of the evidence for all outcomes was very low. Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials reported health-related quality of life, hepatitis B-related mortality, or morbidity. Adverse events considered 'not to be serious' was an outcome in 19 trials; nine of these trials had zero events in both groups. Radix Sophorae flavescentis versus placebo or no intervention showed no difference in effects on adverse events considered 'not to be serious' (RR 1.10, 95% CI 0.76 to 1.59; I² = 49%; 10 trials, 1050 participants). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable HBV-DNA (RR 0.61, 95% CI 0.55 to 0.68; I² = 56%; 29 trials, 2914 participants) and in the proportion of participants with detectable HBeAg (hepatitis B e-antigen) (RR 0.71, 95% CI 0.66 to 0.76; I² = 19%; 20 trials, 2129 participants). Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding. Additionally, 432 trials lacked the methodological information needed to ensure inclusion of these trials in our review. The included trials lacked data on health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The effects of Radix Sophorae flavescentis on all-cause mortality and on the proportion of participants with serious adverse events and adverse events considered 'not to be serious' remain unclear. We advise caution in interpreting results showing that Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and detectable HBeAg because the trials reporting on these outcomes are at high risk of bias and both outcomes are non-validated surrogate outcomes. We were unable to obtain information on the design and conduct of a large number of trials; therefore, we were deterred from including them in our review. Undisclosed funding may influence trial results and may lead to poor trial design. Given the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials in which patient-centred outcomes are assessed. | We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two trials assessed children under 14 years of age. Participants in two trials had cirrhosis in chronic hepatitis B (late-stage scarring of the liver). Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding. Undisclosed funding may influence trial results and may lead to poor trial design. Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials assessed health-related quality of life, and no trials followed people who died from hepatitis B or were at risk of dying because of hepatitis B. Adverse events considered 'not to be serious' was an outcome in 19 trials. We cannot say if Radix Sophorae flavescentis versus placebo or no intervention is better or worse regarding the occurrence of adverse events considered 'not to be serious'. Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and also the proportion of people with detectable HBeAg. However, caution is needed to understand these beneficial findings, as these trials were at high risk of bias, and these outcomes have not yet been proven relevant to patients. The 432 trials identified could not be included in the review because of lack of information required for the conduct of this review. Accordingly, more information from properly designed randomised clinical trials is needed before one can determine the benefits or harms of Radix Sophorae flavescentis for people with chronic hepatitis B. 'Certainty of evidence' means "the extent of one's confidence that review results are correct in supporting or rejecting a finding". The certainty of evidence on the use of Radix Sophorae flavescentis for people with chronic HBV in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to HBV infection, and serious adverse events cannot be determined, as only a few trials aimed to explore patient-relevant outcomes. Our certainty in the evidence that Radix Sophorae flavescentis, when compared with no intervention or placebo, decreases or increases adverse events considered not to be serious in people with chronic hepatitis B is very low. Our certainty in the evidence that Radix Sophoae flavescentis decreases the proportion of people with detectable HBV-DNA and the proportion of people with detectable HBeAg is also very low. These assessments of certainty of evidence are due to the poor design and reporting of the included trials. |
We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy. | Our systematic review found 17 controlled studies involving 2596 affected children that used these drugs for a short duration and assessed short-term outcomes. When comparing glucocorticoids to placebo, no differences were found for either hospital admissions or length of hospital stay. There was no substantial benefit in other health outcomes. These findings are consistent and likely to be applicable in diverse settings. Exploratory results from one large high-quality trial suggest that combined treatment of systemic glucocorticoids (dexamethasone) and bronchodilators (epinephrine) may significantly reduce hospital admissions. There were no relevant short-term adverse effects that were any different from those seen with an inactive placebo, while long-term safety was not assessed. Further research is needed to confirm the efficacy, safety and applicability of this promising approach. |
We reran the searches to December 2013 and identified three new studies. These three studies did not fulfil our inclusion criteria. Therefore, no new studies were included in this updated review. In total four randomized trials involving 210 participants were included in this review. We observed no differences in mortality (OR 1.67, 95% CI 0.38 to 7.30; P = 0.50); PHTC (OR 0.80, 95% CI 0.15 to 4.18; P = 0.79); changes in MPAP (treatment effect -2.94 mm Hg, 95% CI -9.28 to 3.40; P = 0.36), MAP (treatment effect -3.55 mm Hg, 95% CI -11.86 to 4.76; P = 0.40), HR (treatment effect 0.02 bpm, 95% CI -8.13 to 8.18; P = 1.00), or PaO2:FiO2 (mean difference 17.18, 95% CI -28.21 to 62.57; P = 0.46). There was a significant increase in the methaemoglobin level (mean difference 0.30%, 95% CI 0.24 to 0.36; P < 0.00001) in patients treated with iNO, although levels did not reach toxicity levels. Data from long-term mortality, neurodevelopmental disability, and length of stay were not available. Two trials had a low risk of bias. Very low quality of the evidence was observed considering grading of the outcomes. We observed no differences with the use of iNO in the outcomes reviewed. No data were available for several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions given concerns regarding methodologic quality, sample size, and heterogeneity. | The evidence was current to December 2013. We found four randomized clinical trials involving 210 participants aged from one day to 17 years with PH either in the preoperative (one study) or postoperative period (three studies). Control groups received conventional management therapy (two trials) or nitrogen gas as placebo (two trials). Two trials compared changes in systemic and pulmonary arterial blood pressure and heart rate (haemodynamics). The other two trials compared the number of pulmonary hypertensive crises and deaths, with changes in haemodynamic measurements as secondary outcomes. We found no differences between the groups of patients who received iNO and those that did not. Two trials reported on deaths before discharge, with none occurring in one of the trials. We observed no differences in the number of deaths (two trials); pulmonary hypertensive crises (one trial); changes in mean pulmonary arterial pressure (three trials), arterial pressure (three trials), or heart rate (HR) (three trials); or changes in oxygenation of the blood (one trial). However, no trials reported long-term deaths or neurodevelopmental disability. In addition, no data were available for analysis of length of hospital stay. Although iNO has been studied as a postsurgical therapy in children with heart disease in order to assist recovery, this review showed no benefits with its use. Two trials had a low risk of bias. The quality of the evidence was, however, very low due to the small number of participants and low event rates. All trials utilized different concentrations of iNO, different durations of administration initiated at different times after the operation, and included patients with diverse congenital heart defects necessitating repair. |
Only one study enrolling 182 patients (reported as an abstract in conference proceedings) was identified and found eligible for inclusion; the authors reported only limited results. The trial was stopped prematurely and was, therefore, under-powered to detect any significant differences and at high risk of bias. The only available outcome of clinical significance was 28-day mortality. There was no statistically significant difference between groups, with a relative risk for 28-day mortality in the partial liquid ventilation group of 1.54 (95% confidence interval 0.82 to 2.9). There is no evidence from RCTs to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome. Adequately powered, high quality RCTs are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of both respiratory support and hospital stay, and long-term neurodevelopmental outcomes). The studies should be published in full. | We found only one multicentre randomized controlled study, reported as an abstract in conference proceedings, that was eligible for inclusion in this updated Cochrane review. The company sponsored study enrolled 182 patients in 65 centres. The trial was stopped early, before recruiting sufficient numbers of participants and before it could detect any clear differences between partial liquid ventilation and conventional mechanical ventilation (the control group). The number of deaths at 28 days was 22% of patients in the partial liquid ventilation group and 14% in the control group, the difference was not statistically significant; there was a wide variation in results and a clinically significant difference could not be excluded. There were other problems with the trial that made its results unreliable in terms of eligible patients, use of other rescue therapies, and that the measured outcomes were altered at least twice during the study; additional therapies such as high frequency ventilation or inhaled nitric oxide were allowed in the control group. |
We included nine studies enrolling 220 dialysis participants. Seven studies were deemed to have moderate to high risk of bias. All studies were small in size and had a short follow-up period (two to six months). Studies evaluated the effects of six different interventions against placebo or standard treatment. The interventions studied included aerobic resistance exercise, gabapentin, ropinirole, levodopa, iron dextran, and vitamins C and E (individually and in combination). Aerobic resistance exercise showed a significant reduction in severity of RLS compared to no exercise (2 studies, 48 participants: MD -7.56, 95% CI -14.20 to -0.93; I2 = 65%), and when compared to exercise with no resistance (1 study, 24 participants: MD -11.10, 95% CI -17.11 to -5.09), however there was no significant reduction when compared to ropinirole (1 study, 22 participants): MD -0.55, 95% CI -6.41 to 5.31). There were no significant differences between aerobic resistance exercise and either no exercise or ropinirole in the physical or mental component summary scores (using the SF-36 form). Improvement in sleep quality varied. There was no significant difference in subjective sleep quality between exercise and no exercise; however one study reported a significant improvement with ropinirole compared to resistance exercise (MD 3.71, 95% CI 0.89 to 6.53). Using the Epworth Sleepiness Scale there were no significant differences between resistance exercise and no exercise, ropinirole, or exercise with no resistance. Two studies reported there were no adverse events and one study did not mention if there were any adverse events. In one study, one patient in each group dropped out but the reason for dropout was not reported. Two studies reported no adverse events and one study did not report adverse events. Gabapentin was associated with reduced RLS severity when compared to placebo or levodopa, and there was a significant improvement in sleep quality, latency and disturbance reported in one study when compared to levodopa. Three patients dropped out due to lethargy (2 patients), and drowsiness, syncope and fatigue (1 patient). Because of a short duration of action, rebound and augmentation were noted with levodopa treatment even though it conferred some benefit in reducing the symptoms of RLS. Reported adverse events were severe vomiting, agitation after caffeine intake, headaches, dry mouth, and gastrointestinal symptoms. One study (25 participants) reported iron dextran reduced the severity of RLS at weeks one and two, but not at week four. Vitamins C, E and C plus E (1 study, 60 participants) helped the symptoms of RLS with minimal side effects (nausea and dyspepsia) but more evidence is needed before any conclusions can be drawn. Given the small size of the studies and short follow-up, it can only be concluded that pharmacological interventions and intra-dialytic exercise programs have uncertain effects on RLS in haemodialysis patients. There have been no studies performed in non-dialysis CKD, peritoneal dialysis patients, or kidney transplant recipients. Further studies are warranted before any conclusions can be drawn. Aerobic resistance exercise and ropinirole may be suitable interventions for further evaluation. | The quality of the studies was deemed to be moderate. Of the nine studies, one was sponsored by a pharmaceutical company and funding sources were reported for only two other studies. The included studies were heterogeneous, small in size and had short follow-up periods. The interventions studied included exercise, gabapentin, ropinirole, levodopa, iron dextran, and vitamins C and E (individually and in combination). All interventions reduced the severity of RLS compared to a control. Intradialytic aerobic exercise reduced the severity of RLS however the safety of this intervention is unclear. Resistance exercise did not improve sleep quality but improved the mental health component on a quality of life questionnaire. This improvement in mental health component was not significant when compared to no exercise or ropinirole. Ropinirole reduced the symptoms of RLS and improved quality of sleep without any reported side effects. Gabapentin and levodopa improved the symptoms of RLS; however there were several adverse events reported included lethargy, drowsiness and fatigue for gabapentin, and vomiting, agitation, headaches, dry mouth, and gastrointestinal symptoms for levodopa. Iron dextran infusion reduced the symptoms of RLS but was only significant up to two weeks after treatment. Vitamin C, E and their combination also reduced RLS symptoms with minimal side effects. Small size and short duration of follow-up were the major drawbacks of these studies. The small number of studies, small sample sizes and short duration of follow up make it difficult to draw any firm conclusions. The effects of aerobic exercise and other pharmacological agents on RLS are uncertain in haemodialysis patients. There is a need to perform high quality randomised studies to establish the best treatment for RLS in patients with CKD. Aerobic exercise and ropinirole may be suitable interventions for further evaluation. |
A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. There is no evidence that bulking agents are effective for treating IBS. There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures. | This review evaluates the effectiveness of medical therapies for patients with irritable bowel syndrome (IBS). We considered studies involving bulking agents (a fibre supplement), antispasmodics (smooth muscle relaxants) or antidepressants (drugs used to treat depression that can also change pain perceptions) that used outcome measures including improvement of abdominal pain, global assessment (overall relief of IBS symptoms) or symptom score. We found that bulking agents are not effective for treating IBS. There is evidence that antispasmodics including cimetropium/dicyclomine peppermint oil, pinaverium and trimebutine are effective for the treatment of IBS. Antidepressants are effective for the treatment of IBS. The side effects of these medications were not evaluated in this review. Physicians should be aware of the limitations of drug therapies and discuss these limitations with their patients before prescribing medication for IBS. |
Twenty studies (732 randomised participants, with data for 547 participants with stroke) met the inclusion criteria for this review. However, only 10 of these studies compared the effect of an intervention with a placebo, control, or no treatment group, and eight had data which could be included in meta-analyses. Only two of these eight studies presented data relating to our primary outcome of functional abilities in activities of daily living. One study reported evidence relating to adverse events. Three studies (88 participants) compared a restitutive intervention with a control, but data were only available for one study (19 participants). There was very low-quality evidence that visual restitution therapy had no effect on visual field outcomes, and a statistically significant effect on quality of life, but limitations with these data mean that there is insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control. Four studies (193 participants) compared the effect of scanning (compensatory) training with a control or placebo intervention. There was low-quality evidence that scanning training was more beneficial than control or placebo on quality of life, measured using the Visual Function Questionnaire (VFQ-25) (two studies, 96 participants, mean difference (MD) 9.36, 95% confidence interval (CI) 3.10 to 15.62). However, there was low or very-low quality evidence of no effect on measures of visual field, extended activities of daily living, reading, and scanning ability. There was low-quality evidence of no significant increase in adverse events in people doing scanning training, as compared to no treatment. Three studies (166 participants) compared a substitutive intervention (a type of prism) with a control. There was low or very-low quality evidence that prisms did not have an effect on measures of activities of daily living, extended activities of daily living, reading, falls, or quality of life, and very low-quality evidence that they may have an effect on scanning ability (one study, 39 participants, MD 9.80, 95% CI 1.91 to 17.69). There was low-quality evidence of an increased odds of an adverse event (primarily headache) in people wearing prisms, as compared to no treatment. One study (39 participants) compared the effect of assessment by an orthoptist to standard care (no assessment) and found very low-quality evidence that there was no effect on measures of activities of daily living. Due to the quality and quantity of evidence, we remain uncertain about the benefits of assessment interventions. There is a lack of evidence relating to the effect of interventions on our primary outcome of functional ability in activities of daily living. There is limited low-quality evidence that compensatory scanning training may be more beneficial than placebo or control at improving quality of life, but not other outcomes. There is insufficient evidence to reach any generalised conclusions about the effect of restitutive interventions or substitutive interventions (prisms) as compared to placebo, control, or no treatment. There is low-quality evidence that prisms may cause minor adverse events. | We included 20 studies (involving 547 stroke participants) that investigated the effect of treatments for visual field defects. However, only 10 of these studies compared the effect of a particular treatment with no treatment. Three of these studies investigated a type of eye movement training designed to improve the lost visual field (a 'restitutive' intervention). Four of the included studies investigated the effect of scanning training, which involves training people to 'scan' across the space in front of them and into the 'lost' visual field, in order to better cope with their lost vision (a 'compensatory' intervention). Three of the included studies investigated the effect of wearing a special prism on a pair of glasses, which increases the amount a person can see on their affected side (a 'substitutive' intervention). One of the studies investigated the effect of specialised assessment by an orthoptist (a hospital-based vision specialist), compared to standard care. We searched for studies up to May 2018. Only two studies presented data relating to how treatment can improve stroke survivors' abilities in activities of daily living, and there was a lack of consistency across studies that limited our ability to draw clear conclusions. There was insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control. There was low or very low-quality evidence that scanning training may help improve quality of life, but may have no effect on other outcomes (including adverse events). There was low or very-low quality evidence that prisms may have an effect on ability to scan (look) for objects, but may cause a range of minor adverse events (particularly headache) and may have no effect on other outcomes. Limitations with the evidence meant that we could not draw any conclusions about the benefits of assessment interventions. The quality of the evidence was low to very low, and in general was insufficient to reach conclusions about the effects of interventions for people with visual field defects. |
Combined results from the 4 eligible randomised controlled trials shows that participants allocated to FOBT screening had a statistically significant 16% reduction in the relative risk of colorectal cancer mortality (RR 0.84; CI: 0.78-0.90). In the 3 studies that used biennial screening (Funen, Minnesota, Nottingham) there was a 15% relative risk reduction (RR 0.85, CI: 0.78-0.92) in colorectal cancer mortality. When adjusted for mean screening attendance in the individual studies, there was a 25% relative risk reduction (RR 0.75, CI: 0.66 - 0.84) for those attending at least one round of screening using the faecal occult blood test. Benefits of screening include a modest reduction in colorectal cancer mortality, a possible reduction in cancer incidence through the detection and removal of colorectal adenomas, and potentially, the less invasive surgery that earlier treatment of colorectal cancers may involve. Harmful effects of screening include the psycho-social consequences of receiving a false-positive result, the potentially significant complications of colonoscopy or a false-negative result, the possibility of overdiagnosis (leading to unnecessary investigations or treatment) and the complications associated with treatment. | The screening test used in these trials to detect colorectal (bowel) cancer was the faecal occult blood test (FOBT). If the FOBT is positive, the bowels are examined closely with further diagnostic test (coloscopy, flexible sigmoidoscopy, double-contrast barium enema), but these tests often cause discomfort and can cause serious adverse consequences. As blood identified in faeces may be due to several reason (unrelated to cancer), it may cause people unnecessary stress and expose them to possible harm. This review found that FOBT screening is likely to avoid approximately 1 in 6 colorectal cancer deaths. |
Fifteen trials were included, six of which were added in this update. Three trials of a nursing intervention to manage breathlessness showed benefit in terms of symptom experience, performance status and emotional functioning. Four trials assessed structured nursing programmes and found positive effects on delay in clinical deterioration, dependency and symptom distress, and improvements in emotional functioning and satisfaction with care. Three trials assessed the effect of different psychotherapeutic, psychosocial and educational interventions in patients with lung cancer. One trial assessing counselling showed benefit for some emotional components of the illness but findings were not conclusive. One trial examined the effects of coaching sensory self monitoring and reporting on pain-related variables and found that although coaching increases the amount of pain data communicated to providers by patients with lung cancer, the magnitude of the effect is small and does not lead to improved efficacy of analgesics prescribed for each patient’s pain level. One trial compared telephone-based sessions of either caregiver-assisted coping skills training (CST) or education/support involving the caregiver and found that patients in both treatment conditions showed improvements in pain, depression, quality of life and self efficacy. Two trials assessed exercise programmes; one found a beneficial effect on self empowerment and the other study showed an increase in quadriceps strength but no significant changes for any measure of quality of life. One trial of nutritional interventions found positive effects for increasing energy intake, but no improvement in quality of life. Two small trials of reflexology showed some positive but short-lasting effects on anxiety and pain intensity. The main limitations of the studies included were the variability of the interventions assessed and the approaches to measuring the considered outcomes, and the lack of data reported in the trials regarding allocation of patients to treatment groups and blinding. Nurse follow-up programmes and interventions to manage breathlessness may produce beneficial effects. Counselling may help patients cope more effectively with emotional symptoms, but the evidence is not conclusive. Other psychotherapeutic, psychosocial and educational interventions can play some role in improving patients' quality of life. Exercise programmes and nutritional interventions have not shown relevant and lasting improvements of quality of life. Reflexology may have some beneficial effects in the short term. | This review found that nursing programmes and interventions to manage breathlessness may produce beneficial effects and that some psychotherapeutic, psychosocial and educational interventions can play some role in improving the quality of life of patients. Counselling may help patients to cope better with emotional symptoms and reflexology can have some short-term beneficial effects. The main limitations of the included studies were the variability of the interventions, the way results were measured and the lack of 'blinding' (ensuring that those who are measuring the patients' outcomes are not aware of which treatment the patient actually received). |
We included two trials with a total of 37 children diagnosed with ASD who were randomised into groups that received either omega-3 fatty acids supplementation or a placebo. We excluded six trials because they were either non-randomised controlled trials, did not contain a control group, or the control group did not receive a placebo. Overall, there was no evidence that omega-3 supplements had an effect on social interaction (mean difference (MD) 0.82, 95% confidence interval (CI) -2.84 to 4.48, I2 = 0%), communication (MD 0.62, 95% CI -0.89 to 2.14, I2 = 0%), stereotypy (MD 0.77, 95% CI -0.69 to 2.22, I2 = 8%), or hyperactivity (MD 3.46, 95% CI -0.79 to 7.70, I2 = 0%). To date there is no high quality evidence that omega-3 fatty acids supplementation is effective for improving core and associated symptoms of ASD. Given the paucity of rigorous studies in this area, there is a need for large well-conducted randomised controlled trials that examine both high and low functioning individuals with ASD, and that have longer follow-up periods. | The purpose of this review was to assess the evidence for the effectiveness of omega-3 supplementation for core features of ASD and associated symptoms. We found only two small randomised controlled trials that evaluated omega-3 fatty acids for ASD. There is insufficient evidence that omega-3 fatty acids supplementation is an effective treatment for ASD. However, high quality large randomised controlled trials are needed before definite recommendations about this treatment can be made. |
A total of 11 trials with 419 participants met our inclusion criteria. In 10 studies the participants were adults and only one was in children. Reporting of study design was inadequate to determine risk of bias for most of the studies and poor availability of data for our key outcomes may indicate some selective outcome reporting. Four studies were parallel-group and the remainder were cross-over studies. Eight studies included people with asthma and three studies included 40 participants with exercise-induced asthma. Five studies reported results using single-dose regimes prior to bronchial challenges or exercise tests. There was marked heterogeneity in vitamin C dosage regimes used in the selected studies, compounding the difficulties in carrying out meaningful analyses. One study on 201 adults with asthma reported no significant difference in our primary outcome, health-related quality of life (HRQL), and overall the quality of this evidence was low. There were no data available to evaluate the effects of vitamin C supplementation on our other primary outcome, exacerbations in adults. One small study reported data on asthma exacerbations in children and there were no exacerbations in either the vitamin C or placebo groups (very low quality evidence). In another study conducted in 41 adults, exacerbations were not defined according to our criteria and the data were not available in a format suitable for evaluation by our methods. Lung function and symptoms data were contributed by single studies. We rated the quality of this evidence as moderate, but further research is required to assess any clinical implications that may be related to the changes in these parameters. In each of these outcomes there was no significant difference between vitamin C and placebo. No adverse events at all were reported; again this is very low quality evidence. Studies in exercise-induced bronchoconstriction suggested some improvement in lung function measures with vitamin C supplementation, but theses studies were few and very small, with limited data and we judged the quality of the evidence to be low. Currently, evidence is not available to provide a robust assessment on the use of vitamin C in the management of asthma or exercise-induced bronchoconstriction. Further research is very likely to have an important impact on our confidence in the estimates of effect and is likely to change the estimates. There is no indication currently that vitamin C can be recommended as a therapeutic agent in asthma. There was some indication that vitamin C was helpful in exercise-induced breathlessness in terms of lung function and symptoms; however, as these findings were provided only by small studies they are inconclusive. Most published studies to date are too small and inconsistent to provide guidance. Well-designed trials with good quality clinical endpoints, such as exacerbation rates and health-related quality of life scores, are required. | Eleven studies on 419 people with asthma or exercise-induced breathlessness were included in this review comparing vitamin C compared to placebo (no vitamin C). Most studies were in adults and one small study was in children. The small number of studies available for review and their different designs meant that we were only able to describe individual studies, rather than pooling the results together to get an average from the trials. The study design was not well described in most study reports and therefore it was impossible to determine risk of bias for most of the studies. There was very little data available in the trials for our key outcomes and this may indicate some selective outcome reporting. There was no indication of benefit from the studies that considered vitamin C in relation to asthma. However, it is not possible to form any clear conclusions on the basis of those studies at this stage. The review concludes that there is insufficient evidence currently available to evaluate the use of vitamin C as a treatment in asthma. Larger, well-designed research is needed to provide clearer guidance. There was some indication that vitamin C was helpful in exercise-induced breathlessness in terms of how easily people breathe and their symptoms; however, as these findings were provided by only very small studies they do not provide complete answers to guide treatment. Details of the way patients were allocated to receive vitamin C or not were not clearly described in 10 of the 11 studies and we considered this carefully in the review in relation to our level of uncertainty in interpreting the results. Taking this into account, together with the imprecision of the results, we judged the estimates of the usefulness of vitamin C as a treatment to be of either low or moderate quality in relation to asthma. Additionally, for exercise-induced breathlessness the three studies providing data to the review were small and we are mindful of the need to draw very cautious conclusions about the results. This plain language summary is current as of December 2012. |
We found only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [summary relative risk 0.45 (0.20 to 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short-term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No long-term outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice. | The review of one small trial found that apnea might be reduced in the first few days after treatment, but there were not enough infants studied to know if this was a significant effect. There is no evidence from this trial on longer term effects or less common adverse effects. More research is needed on the effectiveness, potential harm and long-term benefits or adverse effects of these drugs. |
Ten studies met the inclusion criteria for the review, and nine studies provided information on one or more outcomes for the review. A total of 1014 participants were randomly assigned to the enhanced recovery protocol (499 participants) or standard care (515 participants) in the nine RCTs. Most of the trials included low anaesthetic risk participants with high performance status undergoing different upper gastrointestinal, liver and pancreatic surgeries. Eight trials incorporated more than one element of the enhanced recovery protocol. All of the trials were at high risk of bias. The overall quality of evidence was low or very low. None of the trials reported long-term mortality, medium-term health-related quality of life(three months to one year), time to return to normal activity, or time to return to work. The difference between the enhanced recovery protocol and standard care were imprecise for short-term mortality (enhanced recovery protocol: 4/425 (adjusted proportion = 0.6%); standard care: 1/443 (0.2%); seven trials; 868 participants; RR 2.79; 95% CI 0.44 to 17.73; very low quality evidence), proportion of people with serious adverse events (enhanced recovery protocol: 4/157 (adjusted proportion = 0.6%); standard care: 0/184 (0.0%); two trials; 341 participants; RR 5.57; 95% CI 0.68 to 45.89; very low quality evidence), number of serious adverse events (enhanced recovery protocol: 34/421 (8 per 100 participants); standard care: 46/438 (11 per 100 participants); seven trials; 859 participants; rate ratio 0.72; 95% CI 0.45 to 1.13; very low quality evidence), health-related quality of life (four trials; 373 participants; SMD 0.29; 95% CI -0.04 to 0.62; very low quality evidence) and hospital readmissions (enhanced recovery protocol: 14/355 (adjusted proportion = 3.3%); standard care: 9/378 (2.4%); seven trials; 733 participants; RR 1.4; 95% CI 0.69 to 2.87; very low quality evidence). The enhanced recovery protocol group had a lower proportion of people with mild adverse events (enhanced recovery protocol: 31/254 (adjusted proportion = 10.9%); standard care: 51/271 (18.8%); four trials; 525 participants; RR 0.58; 95% CI 0.39 to 0.85; low quality evidence), fewer number of mild adverse events (enhanced recovery protocol: 69/499 (13 per 100 participants); standard care: 128/515 (25 per 100 participants); nine trials; 1014 participants; rate ratio 0.52; 95% CI 0.39 to 0.70; low quality evidence), shorter length of hospital stay (nine trials; 1014 participants; MD -2.19 days; 95% CI -2.53 to -1.85; low quality evidence) and lower costs (four trials; 282 participants; MD USD -6300; 95% CI -8400 to -4200; low quality evidence) than standard care group. Based on low quality evidence, enhanced recovery protocols may reduce length of hospital stay and costs (primarily because of reduction in hospital stay) in people undergoing major upper gastrointestinal, liver and pancreatic surgeries. However, the validity of the results is uncertain because of the risk of bias in the trials and the way the outcomes were measured. Future RCTs should be conducted with low risk of bias, and measure clinically important outcomes for including the three months to one year period. | Ten studies met the inclusion criteria for the review, and nine studies provided information for the review. A total of 1014 participants received an enhanced recovery protocol (499 participants) or standard care (515 participants) in the nine trials. The decision on whether a participant received an enhanced recovery protocol or standard care was made using methods similar to the toss of a coin, ensuring that the participants in the two groups were similar. One additional trial (including 33 participants) also performed the same comparison but did not provide any information for this review. Most of the trials included persons who were healthy in aspects other than the condition requiring surgery. Eight trials incorporated more than one component of the enhanced recovery protocol. None of the trials reported long-term deaths, medium-term health-related quality of life (three months to one year), time to return to normal activity, or time to return to work. The difference between enhanced recovery protocols and standard care was imprecise for short-term deaths, percentage of people with major complications, total number of major complications, health-related quality of life and hospital readmissions. Enhanced recovery protocols had a lower percentage of people with minor complications, fewer minor complications, shorter length of hospital stay (approximately two days shorter hospital stay per person) and lower costs (cost savings of approximately USD 6300 per person) compared to standard care. Because the trials were of poor quality and did not include clinically important end points, future high quality studies are needed in this field. The quality of evidence was low or very low. As a result, there is a lot of uncertainty regarding the results. |
Only one trial was found and this showed that rescue HFOV caused a reduction in any new pulmonary air leak (PAL) [RR 0.73 (95% CI 0.55,0.96), RD -0.17 (95% CI -0.32, -0.03)]. The number of infants that needed to be treated (NNT) to prevent one infant having any PAL was six (95% CI 3, 37). There was no significant difference in the rate of PIE or of gross pulmonary air leak, such as pneumomediastinum or pneumothorax. There was no significant effect on mortality or the use of IPPV at 30 days. The rate of intraventricular haemorrhage (IVH) of any grade was increased in infants treated with HFOV, [RR 1.77 (95% CI 1.06, 2.96), RD 0.16 (95% CI 0.02, 0.29)]. Thus, for every six infants (95% CI 3, 50) given rescue HFOV, one infant developed IVH of any grade. There was a stronger, but non-significant trend towards an increase in severe IVH (grades 3 or 4 IVH). There is insufficient information on the use of rescue HFOV to make recommendations for practice. The small amount of data that exists suggest that harm might outweigh any benefit. Any future use of HFOV as rescue therapy for preterm infants with severe RDS should be within randomised controlled trials and address important outcomes such as longer term pulmonary and neurological function. | This review of the evidence from one randomised controlled trial suggests there might be less short-term lung injury from high frequency oscillatory ventilation. However, more babies in this group developed haemorrhage in and around the fluid spaces in the brain (cerebral ventricles) and this harm might outweigh any benefit. More information is needed to clarify the balance between benefits and harms of high frequency oscillatory ventilation instead of conventional positive pressure ventilation for preterm infants with severe lung disease. |
Eleven randomised trials with 1205 participants with asymptomatic or mild-to-moderate cholelithiasis were included. None of the randomised clinical trials compared a single Chinese medicinal herb with a Western medicine or with surgery. No placebo-controlled trials were identified. In the trials comparing one Chinese herbal medicine (Gandanxiaoshi tablet) versus another (Aihuodantong tablet), there was no significant difference in the improvement of upper abdominal pain after the end of treatment (RR 1.21; 95% CI 0.71 to 2.05), and the heterogeneity among trials was not substantial. No other outcomes could be assessed. The remaining trials of Chinese medicinal herbs (Qingdan capsule, Danshu capsule, Paishi capsule, Rongdanpaishi capsule), did not offer specific data on symptoms, signs, or change in gallstones that would permit assessment of significant differences in curative effects between the treatment and control groups. No serious adverse events were reported. This review reveals no strong evidence that the analysed Chinese medicinal herbs have any beneficial effects on asymptomatic or mild-to-moderate cholelithiasis. Definitive conclusions will require much better designed randomised trials to reduce risk of bias and allow detailed assessment of clinical outcomes. | The objective of this review was to evaluate the benefits and harms of Chinese medicinal herbs for people with cholelithiasis. Though some Chinese medicinal herbs appear to be safe for people with asymptomatic, mild, or moderate disease, they have not been conclusively shown to have curative effects on gallstones due to the low methodological quality (high risk of bias) of the included trials. Thus, randomised clinical trials with low risk of bias should be conducted to assess the effects of Chinese medicinal herbs before they can be used widely in the clinic. |
The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use. | We included 20 studies (1936 participants) in this review which compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other nebulised medications through the different types of nebuliser. Some conventional nebuliser systems have faster air flows and smaller medication droplets. These systems decrease treatment time and deliver more medication into the lung than other conventional nebulisers which have slower air flows and larger medication droplets. Nebulisers using newer technologies, e.g. adaptive aerosol delivery or vibrating mesh technology, deliver the medication faster and may deliver more of the medication into the lung. These systems appear safe when used with the correct amount of medication, which may be different to that used in a conventional nebuliser system. Some studies suggest that people with cystic fibrosis may prefer these newer systems and may take more of their medication when using them. More research is needed into what dose of medication is needed and how these newer nebuliser technologies affect quality of life, burden of treatment, additional treatment needed and treatment costs. |
We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in health care. We found 72 comparisons, but just three are supported by high-certainty evidence according to GRADE. 1. Open trials rather than blinded, placebo trials. The absolute improvement was 10% (95% CI 7% to 13%). 2. Telephone reminders to people who do not respond to a postal invitation. The absolute improvement was 6% (95% CI 3% to 9%). This result applies to trials that have low underlying recruitment. We are less certain for trials that start out with moderately good recruitment (i.e. over 10%). 3. Using a particular, bespoke, user-testing approach to develop participant information leaflets. This method involved spending a lot of time working with the target population for recruitment to decide on the content, format and appearance of the participant information leaflet. This made little or no difference to recruitment: absolute improvement was 1% (95% CI −1% to 3%). We had moderate-certainty evidence for eight other comparisons; our confidence was reduced for most of these because the results came from a single study. Three of the methods were changes to trial management, three were changes to how potential participants received information, one was aimed at recruiters, and the last was a test of financial incentives. All of these comparisons would benefit from other researchers replicating the evaluation. There were no evaluations in paediatric trials. We had much less confidence in the other 61 comparisons because the studies had design flaws, were single studies, had very uncertain results or were hypothetical (mock) trials rather than real ones. The literature on interventions to improve recruitment to trials has plenty of variety but little depth. Only 3 of 72 comparisons are supported by high-certainty evidence according to GRADE: having an open trial and using telephone reminders to non-responders to postal interventions both increase recruitment; a specialised way of developing participant information leaflets had little or no effect. The methodology research community should improve the evidence base by replicating evaluations of existing strategies, rather than developing and testing new ones. | The 68 included studies covered a very wide range of disease areas, including antenatal care, cancer, home safety, hypertension, podiatry, smoking cessation and surgery. Primary, secondary and community care were included. The size of the studies ranged from 15 to 14,467 participants. Studies came from 12 countries; there was also one multinational study involving 19 countries. The USA and UK dominated with 25 and 22 studies, respectively. The next largest contribution came from Australia with eight studies. Our search updated our 2010 review and is current to February 2015. We also identified six studies published after 2015 outside the search. The review includes 24 mock trials where the researchers asked people about whether they would take part in an imaginary trial. We have not presented or discussed their results because it is hard to see how the findings relate to real trial decisions. |
Thirteen trials met the inclusion criteria. Two hundred ninety-four individuals randomized to anabolic steroid therapy and 238 individuals randomized to placebo were included in the analysis of efficacy for change from baseline in lean body mass. Three hundred forty-three individuals randomized to anabolic steroid and 286 randomized to placebo were included in the analysis of efficacy for change from baseline in body weight. The mean methodologic quality of the included studies was 4.1, of a maximum 5 points. Although significant heterogeneity was present for both outcomes, the average change in lean body mass was 1.3 kg (95% CI: 0.6, 2.0), while the average change in total body weight was 1.1 kg (95% CI: 0.3, 2.0). A total of eight deaths occurred during the treatment period; four in the anabolic steroid treatment groups and four in the placebo-treatment groups (risk difference 0.00, 95% CI -0.03, 0.03). The risk difference for withdrawals or discontinuations of study medication due to adverse events was 0.00 (95% CI: -0.02, 0.03). Although the results of the trials were heterogeneous, on average, the administration of anabolic steroids appeared to result in a small increase in both lean body mass and body weight as compared with placebo. While these results suggest that anabolic steroids may be useful in the treatment of weight loss in HIV infected individuals, due to limitations, treatment recommendations cannot be made. Further information is required regarding the long-term benefit and adverse effects of anabolic steroid use, the specific populations for which anabolic steroid therapy may be most beneficial, and the optimal regime. In addition, the correlation of improvement in lean body mass with more clinically relevant endpoints, such as physical functioning and survival, needs to be determined. | The purpose of this review was to evaluate anabolic steroids as a means of treatment of weight loss in individuals with HIV infection. The review includes 13 randomized clinical trials in the primary analysis. The results suggested that anabolic steroids increased both lean body mass and body weight. However, the results were not consistent among individual trials and the average increase was small and may not be clinically relevant. Furthermore, the results need to be interpreted with caution as this meta-analysis was limited due to small sample sizes; short duration of treatment and of follow-up; and heterogeneity of the study populations, the anabolic interventions, and concomitant therapies. |
A total of 501 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in 12 trials to various experimental interventions and control interventions. The proportion of genotype I varied between 49% and 100% in the seven trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. Ten trials including 441 liver transplant recipients provided data for this review. There were no significant differences in the 90-day mortality (1 trial; 81 participants; 5/35 (adjusted proportion: 14.2%) in interferon group versus 5/46 (10.9%) in control group; RR 1.31; 95% CI 0.41 to 4.19); mortality at maximal follow-up (2 trials; 105 participants; 7/47 (adjusted proportion: 14.8%) in interferon group versus 10/58 (17.2%) in control group; RR 0.86; 95% CI 0.36 to 2.08); long-term mortality (1 trial; 81 participants; HR 0.45; 95% CI 0.13 to 1.56); mortality at maximal follow-up (1 trial; 54 participants; 1/26 (3.9%) in pegylated interferon group versus 2/28 (7.1%) in control group; RR 0.54; 95% CI 0.05 to 5.59); 90-day mortality (1 trial; 115 participants; 5/55 (9.1%) in pegylated interferon plus ribavirin group versus 3/60 (5.0%) in control group; RR 1.82; 95% 0.46 to 7.25); 90-day mortality (3 trials; 53 participants; 3/37 (adjusted proportion: 4.3%) in HCV antibody group versus 1/16 (6.3%) in placebo group; RR 0.69; 95% CI 0.15 to 3.11); or 90-day mortality (2 trials; 31 participants; 2/14 (adjusted proportion: 16.2%) in HCV antibody high-dose group versus 1/17 (5.9%) in HCV antibody low-dose group; RR 2.75; 95% CI; 0.30 to 25.35). There were no significant differences in the retransplantation at maximal follow-up (2 trials; 105 participants; 2/47 (adjusted proportion: 4.0%) in interferon group versus 2/58 (3.4%) in control group; RR 1.17; 95% CI 0.22 to 6.2); 90-day retransplantation (1 trial; 18 participants; 1/12 (8.3%) in HCV antibody group versus 0/6 (0%) in control group; RR 1.71; 95% CI 0.09 to 32.93); or 90-day retransplantation (1 trial; 12 participants; 1/6 (17.7%) in HCV antibody high-dose group versus 0/6 (0%) in HCV antibody low-dose group; RR 3.00; 95% CI 0.15 to 61.74). There were no significant differences in serious adverse events, graft rejection, worsening of fibrosis, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver decompensation, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in either group in any of the comparisons. There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or retransplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary. | Ten trials including 441 liver transplant recipients provided data for this review. The patients were randomised to receive different treatments or no treatment in these 10 trials. We found two other trials, but data were not provided. There were no significant differences in the proportion of patients who died or required retransplantation within 90 days or at maximal follow-up between the different treatment groups for any of the comparisons. There were no significant differences in serious complications, graft rejection, microscopic features of liver damage, or evidence of chronic hepatitis C recurrence between the different treatment groups or no treatment in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver failure, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in any of the comparisons. There is currently no evidence to recommend preventive antiviral treatment to prevent recurrence of chronic HCV infection either in primary liver transplantation or retransplantation. All the trials were at high risk of systematic errors (ie, there was potential to arrive at wrong conclusions because of the way the trial was conducted) and random errors (there was potential to arrive at the wrong conclusions because of the play of chance). Overall, the quality of evidence was very low. Further randomised clinical trials with low risk of random errors and systematic errors are necessary to assess the long-term survival benefits for various treatment options in these patients. Such trials should include patient-oriented outcomes such as mortality, graft failure, graft rejections, and quality of life. |
We included 11 trials, with a total of 1,126 participants. The majority of participants were female (mean = 80.6% in 10 trials reporting gender). All trials were of psychosocial interventions; there were none of pharmacological treatments. With the exception of dialectical behaviour therapy for adolescents (DBT-A) and group-based therapy, assessments of specific interventions were based on single trials. We downgraded the quality of evidence owing to risk of bias or imprecision for many outcomes. Therapeutic assessment appeared to increase adherence with subsequent treatment compared with TAU (i.e., standard assessment; n = 70; k = 1; OR = 5.12, 95% CI 1.70 to 15.39), but this had no apparent impact on repetition of SH at either 12 (n = 69; k = 1; OR 0.75, 95% CI 0.18 to 3.06; GRADE: low quality) or 24 months (n = 69; k = 1; OR = 0.69, 05% CI 0.23 to 2.14; GRADE: low quality evidence). These results are based on a single cluster randomised trial, which may overestimate the effectiveness of the intervention. For patients with multiple episodes of SH or emerging personality problems, mentalisation therapy was associated with fewer adolescents scoring above the cut-off for repetition of SH based on the Risk-Taking and Self-Harm Inventory 12 months post-intervention (n = 71; k = 1; OR = 0.26, 95% CI 0.09 to 0.78; GRADE: moderate quality). DBT-A was not associated with a reduction in the proportion of adolescents repeating SH when compared to either TAU or enhanced usual care (n = 104; k = 2; OR 0.72, 95% CI 0.12 to 4.40; GRADE: low quality). In the latter trial, however, the authors reported a significantly greater reduction over time in frequency of repeated SH in adolescents in the DBT condition, in whom there were also significantly greater reductions in depression, hopelessness, and suicidal ideation. We found no significant treatment effects for group-based therapy on repetition of SH for individuals with multiple episodes of SH at either the six (n = 430; k = 2; OR 1.72, 95% CI 0.56 to 5.24; GRADE: low quality) or 12 month (n = 490; k = 3; OR 0.80, 95% CI 0.22 to 2.97; GRADE: low quality) assessments, although considerable heterogeneity was associated with both (I2 = 65% and 77% respectively). We also found no significant differences between the following treatments and TAU in terms of reduced repetition of SH: compliance enhancement (three month follow-up assessment: n = 63; k = 1; OR = 0.67, 95% CI 0.15 to 3.08; GRADE: very low quality), CBT-based psychotherapy (six month follow-up assessment: n = 39; k = 1; OR = 1.88, 95% CI 0.30 to 11.73; GRADE: very low quality), home-based family intervention (six month follow-up assessment: n = 149; k = 1; OR = 1.02, 95% CI 0.41 to 2.51; GRADE: low quality), and provision of an emergency card (12 month follow-up assessment: n = 105, k = 1; OR = 0.50, 95% CI 0.12 to 2.04; GRADE: very low quality). No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported. There are relatively few trials of interventions for children and adolescents who have engaged in SH, and only single trials contributed to all but two comparisons in this review. The quality of evidence according to GRADE criteria was mostly very low. There is little support for the effectiveness of group-based psychotherapy for adolescents with multiple episodes of SH based on the results of three trials, the evidence from which was of very low quality according to GRADE criteria. Results for therapeutic assessment, mentalisation, and dialectical behaviour therapy indicated that these approaches warrant further evaluation. Despite the scale of the problem of SH in children and adolescents there is a paucity of evidence of effective interventions. Further large-scale trials, with a range of outcome measures including adverse events, and investigation of therapeutic mechanisms underpinning these interventions, are required. It is increasingly apparent that development of new interventions should be done in collaboration with patients to ensure that these are likely to meet their needs. Use of an agreed set of outcome measures would assist evaluation and both comparison and meta-analysis of trials. | There have been surprisingly few investigations of treatments for SH in children and adolescents, despite the size of this problem in many countries. Providing therapeutic assessment may improve attendance at subsequent treatment sessions. Only one therapeutic approach - mentalisation - was associated with a reduction in frequency of repetition of SH. However this effect was only modest and the trial was small, which prevents us from being able to make firm conclusions about the effectiveness of this treatment. There was no clear evidence of effectiveness for compliance enhancement, individual cognitive behavioral therapy (CBT)-based psychotherapy, home-based family intervention, or provision of an emergency card, nor was there clear evidence for group therapy for adolescents with a history of multiple episodes of SH. Therapeutic assessment, mentalisation, and dialectical behaviour therapy warrant further investigation. While in a single small study, individual CBT-based psychotherapy appeared ineffective, further evaluation of this treatment is also desirable given the favourable results found in adults who SH. Given the extent of SH in children and adolescents, greater attention should be paid to the development and evaluation of specific therapies for this population. |
We identified three prospective RCTs for inclusion in this review (319 participants available to assess the primary outcome of anxiety). The studies included people from the outpatient setting, with the majority of participants being male. All three studies assessed psychological therapy (cognitive behavioural therapy) plus co-intervention versus co-intervention alone. We assessed the quality of evidence contributing to all outcomes as low due to small sample sizes and substantial heterogeneity in the analyses. Two of the three studies had prespecified protocols available for comparison between prespecified methodology and outcomes reported within the final publications. We observed some evidence of improvement in anxiety over 3 to 12 months, as measured by the Beck Anxiety Inventory (range from 0 to 63 points), with psychological therapies performing better than the co-intervention comparator arm (mean difference (MD) -4.41 points, 95% confidence interval (CI) -8.28 to -0.53; P = 0.03). There was however, substantial heterogeneity between the studies (I2 = 62%), which limited the ability to draw reliable conclusions. No adverse events were reported. We found only low-quality evidence for the efficacy of psychological therapies among people with COPD with anxiety. Based on the small number of included studies identified and the low quality of the evidence, it is difficult to draw any meaningful and reliable conclusions. No adverse events or harms of psychotherapy intervention were reported. A limitation of this review is that all three included studies recruited participants with both anxiety and depression, not just anxiety, which may confound the results. We downgraded the quality of evidence in the 'Summary of findings' table primarily due to the small sample size of included trials. Larger RCTs evaluating psychological interventions with a minimum 12-month follow-up period are needed to assess long-term efficacy. | This systematic review found three studies with a total of 319 participants with COPD and coexisting anxiety. All three studies assessed psychotherapy (CBT) with a co-intervention, versus the co-intervention alone. There was limited evidence showing some improvements in reduced levels of anxiety and improved quality of life in the psychotherapy group. It is important to note that the overall quality of the evidence was low and hence further research is needed to increase our confidence in this effect. A limitation of this review is that all three included studies recruited participants with both anxiety and depression, not just anxiety, which may confound the results. Further research is needed to establish whether this therapy will reduce hospital admissions and length of hospital stays, as this was not assessed in the current evidence base. Larger studies of longer duration need to be conducted. There are at least two more clinical trials currently ongoing for this question. Once they are published, the evidence from them could increase or decrease our confidence in the findings of this review. |
We found 9 RCTs involving a total of 421 participants of which 6 were studies of egg and milk exclusion (N=288), 1 was a study of few foods (N=85) and 2 were studies of an elemental diet (N=48). There appears to be no benefit of an egg and milk free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet compared to normal diet (RR 1.51, 95% CI 1.07 to 2.11) and change in surface area and severity score was significantly improved in the exclusion diet compared to the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19 to 10.81) and end of treatment (MD 6.10, 95% CI 0.06 to12.14). Methodological difficulties have made it difficult to interpret these studies. Poor concealment of randomisation allocation, lack of blinding and high dropout rates without an intention-to-treat analysis indicates that these studies should be interpreted with great caution. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs. Little evidence supports the use of various exclusion diets in unselected people with atopic eczema, but that may be because they were not allergic to those substances in the first place. Lack of any benefit may also be because the studies were too small and poorly reported. Future studies should be appropriately powered focusing on participants with a proven food allergy. In addition a distinction should be made between young children whose food allergies improve with time and older children/adults. | The general quality of the studies was poor. The main findings of the review suggest that there is some evidence from one study for the use of an egg-free diet in infants with a suspected egg allergy who have positive specific IgE antibodies to eggs in their blood. Other studies that compared a dietary exclusion with ordinary diets did not test the people taking part to see if they were allergic to the foods concerned. There appears to be little benefit in eliminating cows milk from the diet or using an elemental (liquid diet containing only amino acids, carbohydrates, fat, minerals and vitamins) or 'few foods diet' for improving atopic eczema in people who have not undergone any form of testing. Three of the studies used soya based substitute which itself can be allergenic to people with atopic eczema. Adhering to elimination diets is difficult. The studies were performed in different populations with only one study describing the severity of the atopic eczema. The clinical relevance of changes in severity scores obtained in many studies is unknown. |
Two trials with a total of 69 participants met the inclusion criteria. The first study considered the treatment of 403 people but only included 44 participants in the surgical trial, who were randomised into surgical and non-surgical groups. However, the report did not provide information on the method of randomisation. The second study randomly allocated 25 participants into surgical or control groups using statistical charts. There was no attempt in either study to conceal allocation. Neither participants nor outcome assessors were blind to the interventions, in either study. The first study lost seven participants to follow-up and there were no losses to follow-up in the second study. Surgeons in both studies decompressed the nerves of all the surgical group participants using a retroauricular approach. The primary outcome was recovery of facial palsy at 12 months. The first study showed that the operated group and the non-operated group (who received oral prednisolone) had comparable facial nerve recovery at nine months. This study did not statistically compare the groups but the scores and size of the groups suggested that statistically significant differences are unlikely. The second study reported no statistically significant differences between the operated and control (no treatment) groups. One operated participant in the first study had 20 dB sensorineural hearing loss and persistent vertigo. We identified no new studies when we updated the searches in October 2012. There is only very low quality evidence from randomised controlled trials and this is insufficient to decide whether surgical intervention is beneficial or harmful in the management of Bell's palsy. Further research into the role of surgical intervention is unlikely to be performed because spontaneous recovery occurs in most cases. | After a wide search for randomised controlled trials, we found two studies to include in our review, which together involved 69 people with Bell's palsy. Our main measure of the effects of surgery was to be the recovery of paralysis at 12 months. The first study compared surgery with a steroid medicine and the second study compared surgery with no treatment. In the first study the surgery and no surgery groups appeared to have similar facial nerve recovery at nine months. The second study found no differences in recovery of the facial paralysis after one year, between the participants who had an operation and those who had no treatment. One participant who had surgery in the first study had mild hearing loss and vertigo (dizziness) afterwards. Both studies had limitations that could have affected the results. This review was first published in 2011. We updated the searches in October 2012 and found no new relevant studies. The review found that there was only very low quality evidence and that this was insufficient to decide whether an operation would be helpful or harmful for people with Bell's palsy. There is unlikely to be further research into the role of an operation because Bell's palsy usually recovers without treatment. |
We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients. | We included randomized studies of critically ill adults receiving treatment in intensive care units and in other critical care areas. We selected studies that included lateral positioning after a single turn or following repetitive turns. The duration of each body position was 10 minutes or longer. Comparisons included the other lateral position (opposite side), as well as supine (lying on your back), semi recumbent (lying on your back with your upper body elevated to a 45-degree angle) and prone (lying on your stomach) positions. Results We found 24 eligible studies. No studies reported on mortality. Two studies reported on pulmonary morbidity following cardiac surgery, but available data were insufficient for analysis. The other studies reported measures that we included to identify clinical adverse events. Most of these studies did not report results in a way that could be combined for review of evidence, and trial design was often dissimilar. We compared two studies of critically ill adults with unilateral lung disease (one 'bad lung' and one 'good lung'). Oxygen levels within the blood were lower for 'bad lung down' (side lying with the 'bad lung' lowermost). However, the sample was small, both studies were of poor quality and very low oxygen levels in the blood were not consistently found across studies. Therefore, results need to be viewed with caution. Conclusion We found no clear evidence on the effectiveness of routine lateral repositioning or the effects of a single turn for critically ill patients. Good quality studies are needed to find out whether routine lateral repositioning is still recommended for most critically ill patients, and whether one body position is best avoided for some. |
Four studies evaluating rimonabant 20 mg versus rimonabant 5 mg versus placebo in addition to a hypocaloric diet lasting at least one year were included. Compared with placebo, rimonabant 20 mg produced a 4.9 kg greater reduction in body weight in trials with one-year results. Improvements in waist circumference, high-density lipoprotein cholesterol, triglyceride levels and systolic and diastolic blood pressure were also seen. However, the results with rimonabant 5 mg demonstrated a weight reduction which was only 1.3 kg greater when compared with placebo. No clinically relevant effects on plasma lipids and blood pressure were found. Rimonabant 20 mg caused significant more adverse effects both of general and serious nature, especially of nervous system, psychiatric or gastro-intestinal origin. Attrition rates were approximately 40% at the end of one year. The use of rimonabant after one year produces modest weight loss of approximately 5%. Even modest amounts of weight loss may be potentially beneficial. The observed results should be interpreted with some caution, though, since the evaluated studies presented some deficiencies in methodological quality. Studies with longer follow-ups after the end of treatment and of more rigorous quality should be done before definitive recommendations can be made regarding the role of this new medication in the management of overweight or obese patients. | Rimonabant is the first drug of a new class of medications that seems to reduce body weight and improve risk factors for diseases of the blood vessels and heart in people who are overweight or obese. We found four studies which evaluated weight loss, occurrence of disorders and adverse effects of treatment. The four studies involved 6625 people comparing rimonabant 20 mg with rimonabant 5 mg and placebo, in combination with a hypocaloric diet after one or two years of treatment. Greater weight loss and improvement in risk factors were seen after 20 mg of rimonabant. These results have to be interpreted with caution though, due to high discontinuation rates of study participants and the overall low quality of the included studies. We conclude that: 1. average weight loss with rimonabant appears modest, and 2. more rigorous studies examining the efficacy and safety of rimonabant are required to fully evaluate the benefit risk ratio of this new drug. In Europe, rimonabant is contraindicated for patients with severe depression and/or patients who are treated with antidepressive medications. Rimonabant is furthermore not recommended for patients with other untreated psychiatric conditions. |
Two studies, enrolling 97 participants, met our inclusion criteria. The studies differed significantly in terms of study populations, natural history of AKI (multifactorial AKI in patients with native kidneys versus delayed graft function associated with acute tubular necrosis in transplant recipients), and study interventions; hence, data were not meta-analysed. One study reported a significant increase in the risk of all-cause mortality associated with thyroid hormone interventions compared with placebo (59 participants, RR 3.32, 95% CI 1.21 to 9.12); no deaths were reported in the other study. Both studies reported no significant difference in the need for RRT associated with thyroid hormone therapy when compared to placebo. Neither study reported incidence of progression to ESKD. There was a significantly longer duration of AKI (MD 2.00 days, 95% CI 0.18 to 3.82) and RRT (5.00 days, 95% CI 2.05 to 7.95) associated with thyroid hormone therapy compared with placebo in one study; no differences in durations of AKI (MD 2.00 days, 95% CI -3.53 to 7.53) and RRT (MD 2.00 days, 95% CI -2.36 to 6.36) were noted in the other study. One study reported similar lengths of stay in the intensive care unit and hospital in both intervention and control arms (MD -0.20 days, 95% CI -8.17 to 7.77); the other did not report this outcome. No adverse events were noted to be associated with thyroid hormone therapy in either study. Adequate data were not available to assess changes in kidney function or numbers of RRT sessions. Both included studies were small and methodological quality was suboptimal. We found a paucity of large, high quality studies to inform analysis of thyroid hormone interventions for the treatment of people with AKI. Current evidence suggested that thyroid hormone therapy may be associated with worse outcomes for patients with established AKI; therefore, its use for these patients should be avoided. The role of thyroid hormone therapy in preventing AKI has not been adequately investigated and may be considered in future clinical studies. | We searched the medical literature to investigate the benefits and harms of thyroid hormone therapy for adults with AKI of any cause who were in hospital and found two studies that involved 97 people. There were many differences between study populations, particularly participants' kidney history (some had their own kidneys; others had transplants); and the drugs that were investigated. These differences meant that we were unable to statistically evaluate (meta-analyse) study data. We found that risk of death from any cause was much higher among people with AKI who received thyroid hormone therapy compared with those who received placebo in one study; no deaths were reported in the second study. Thyroid hormone therapy was found to be no better or worse than placebo in changing patients' needs for kidney dialysis or transplant. People with AKI who received thyroid hormone therapy needed dialysis for longer than those who received placebo in one study, but no differences in AKI and dialysis durations were noted in the other. Lengths of stay in intensive care units and hospital were similar in both those who received thyroid hormone therapy and placebo in one study; but not reported in the other study. Neither study reported if any participants progressed to end-stage kidney disease. We had planned to analyse changes in kidney function and numbers of dialysis sessions, but data reporting was insufficient to make assessments. The included studies were few in number, small in size, and low in methodological quality. The available evidence suggested that use of thyroid hormone therapy was associated with worse outcomes in patients with established AKI, and therefore, use of these therapies should be avoided for these people. |
We included 10 RCTs that enrolled a total of 1629 participants. The characteristics of all studies matched the requirements to compare the two types of surgical reconstruction following pancreatoduodenectomy. All studies reported incidence of postoperative pancreatic fistula (the main complication) and postoperative mortality. Overall, the risk of bias in included studies was high; only one included study was assessed at low risk of bias. There was little or no difference between PJ and PG in overall risk of postoperative pancreatic fistula (PJ 24.3%; PG 21.4%; RR 1.19, 95% CI 0.88 to 1.62; 7 studies; low-quality evidence). Inclusion of studies that clearly distinguished clinically significant pancreatic fistula resulted in us being uncertain whether PJ improved the risk of pancreatic fistula when compared with PG (19.3% versus 12.8%; RR 1.51, 95% CI 0.92 to 2.47; very low-quality evidence). PJ probably has little or no difference from PG in risk of postoperative mortality (3.9% versus 4.8%; RR 0.84, 95% CI 0.53 to 1.34; moderate-quality evidence). We found low-quality evidence that PJ may differ little from PG in length of hospital stay (MD 1.04 days, 95% CI -1.18 to 3.27; 4 studies, N = 502) or risk of surgical re-intervention (11.6% versus 10.3%; RR 1.18, 95% CI 0.86 to 1.61; 7 studies, N = 1263). We found moderate-quality evidence suggesting little difference between PJ and PG in terms of risk of any surgical complication (46.5% versus 44.5%; RR 1.03, 95% CI 0.90 to 1.18; 9 studies, N = 1513). PJ may slightly improve the risk of postoperative bleeding (9.3% versus 13.8%; RR 0.69, 95% CI: 0.51 to 0.93; low-quality evidence; 8 studies, N = 1386), but may slightly worsen the risk of developing intra-abdominal abscess (14.7% versus 8.0%; RR 1.77, 95% CI 1.11 to 2.81; 7 studies, N = 1121; low quality evidence). Only one study reported quality of life (N = 320); PG may improve some quality of life parameters over PJ (low-quality evidence). No studies reported cost analysis data. There is no reliable evidence to support the use of pancreatojejunostomy over pancreatogastrostomy. Future large international studies may shed new light on this field of investigation. | We included 10 randomized controlled studies (1629 participants) that compared PJ and PG in people undergoing Whipple surgery. The studies' features were adequate to make feasible and the planned comparison between the two surgical techniques. The primary outcomes were pancreatic fistula and death. Secondary outcomes were duration of hospitalization, surgical re-intervention, overall complications, bleeding, abdominal abscess, quality of life, and costs. We could not demonstrate that one surgical procedure is better than the other. PJ may have little or no difference from PG in overall postoperative pancreatic fistula rate (PJ 24.3%; PG 21.4%), duration of hospitalization, or need for surgical re-intervention (11.6% versus 10.3%). Only seven studies clearly distinguished clinically significant pancreatic fistula which required a change in the patient's management. We are uncertain whether PJ improves the risk of clinically significant pancreatic fistula when compared with PG (19.3% versus 12.8%). PJ probably has little or no difference from PG in rates of death (3.9% versus 4.8%) or complications (46.5% versus 44.5%). The risk of postoperative bleeding in participants undergoing PJ was slightly lower than those undergoing PG (9.3% versus 13.8%), but this benefit appeared to be balanced with a higher risk of developing an abdominal abscess in PJ participants (14.7% versus 8.0%). Only one study reported quality of life; PG may be better than PJ in some quality of life parameters. Cost data were not reported in any studies. Most studies had flaws in methodological quality, reporting or both. Overall, the quality of evidence was low. |
Thirty-two studies were eligible for inclusion. Six were short-term biochemical tolerance studies, one was in infants at > 35 weeks' gestation, one in term surgical newborns, and three yielding no usable data. The 21 remaining studies reported clinical outcomes in very preterm or low birth weight infants for inclusion in meta-analysis for this review. Higher AA intake had no effect on mortality before hospital discharge (typical RR 0.90, 95% CI 0.69 to 1.17; participants = 1407; studies = 14; I2 = 0%; quality of evidence: low). Evidence was insufficient to show an effect on neurodevelopment and suggest no reported benefit (quality of evidence: very low). Higher AA intake was associated with a reduction in postnatal growth failure (< 10th centile) at discharge (typical RR 0.74, 95% CI 0.56 to 0.97; participants = 203; studies = 3; I2 = 22%; typical RD -0.15, 95% CI -0.27 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 4 to 50; quality of evidence: very low). Subgroup analyses found reduced postnatal growth failure in infants that commenced on high amino acid intake (> 2 to ≤ 3 g/kg/day); that occurred with increased amino acid and non-protein caloric intake; that commenced on intake at < 24 hours' age; and that occurred with early lipid infusion. Higher AA intake was associated with a reduction in days needed to regain birth weight (MD -1.14, 95% CI -1.73 to -0.56; participants = 950; studies = 13; I2 = 77%). Data show varying effects on growth parameters and no consistent effects on anthropometric z-scores at any time point, as well as increased growth in head circumference at discharge (MD 0.09 cm/week, 95% CI 0.06 to 0.13; participants = 315; studies = 4; I2 = 90%; quality of evidence: very low). Higher AA intake was not associated with effects on days to full enteral feeds, late-onset sepsis, necrotising enterocolitis, chronic lung disease, any or severe intraventricular haemorrhage, or periventricular leukomalacia. Data show a reduction in retinopathy of prematurity (typical RR 0.44, 95% CI 0.21 to 0.93; participants = 269; studies = 4; I2 = 31%; quality of evidence: very low) but no difference in severe retinopathy of prematurity. Higher AA intake was associated with an increase in positive protein balance and nitrogen balance. Potential biochemical intolerances were reported, including risk of abnormal blood urea nitrogen (typical RR 2.77, 95% CI 2.13 to 3.61; participants = 688; studies = 7; I2 = 6%; typical RD 0.26, 95% CI 0.20 to 0.32; number needed to treat for an additional harmful outcome (NNTH) 4; 95% CI 3 to 5; quality of evidence: high). Higher amino acid intake in parenteral nutrition was associated with a reduction in hyperglycaemia (> 8.3 mmol/L) (typical RR 0.69, 95% CI 0.49 to 0.96; participants = 505; studies = 5; I2 = 68%), although the incidence of hyperglycaemia treated with insulin was not different. Low-quality evidence suggests that higher AA intake in parenteral nutrition does not affect mortality. Very low-quality evidence suggests that higher AA intake reduces the incidence of postnatal growth failure. Evidence was insufficient to show an effect on neurodevelopment. Very low-quality evidence suggests that higher AA intake reduces retinopathy of prematurity but not severe retinopathy of prematurity. Higher AA intake was associated with potentially adverse biochemical effects resulting from excess amino acid load, including azotaemia. Adequately powered trials in very preterm infants are required to determine the optimal intake of AA and effects of caloric balance in parenteral nutrition on the brain and on neurodevelopment. | The review included 21 studies that reported clinical outcomes in very preterm or low birth weight infants. Reporting was incomplete for all outcomes. Searches for studies were conducted in June 2017. Higher amino acid intake did not affect survival in preterm or low birth weight infants. Not enough information is available to determine whether this had an effect on neurodevelopment. Higher amino acid intake was associated with lower rates of growth failure, increased head growth, and fewer premature eye problems (eye problems were not severe). Higher amino acid intake was also associated with increased levels of protein breakdown products (urea) and a lower incidence of high blood glucose levels. Higher amino acid intake did not affect survival but reduced the incidence of growth failure up to the time of hospital discharge. Higher amino acid intake may produce other effects, including an increase in head growth and a reduction in eye problems (retinopathy of prematurity), although these effects are uncertain. Evidence suggests that high amino acid intake may not be tolerated by all infants. Further research is needed to determine the optimal amino acid intake for parenteral nutrition and nutritional balance in preterm infants. Low-quality evidence suggests that higher AA intake in parenteral nutrition does not affect mortality. Very low-quality evidence suggests that higher AA intake reduces the incidence of postnatal growth failure, and that higher AA intake reduces retinopathy of prematurity, but not severe retinopathy. Evidence was insufficient to show whether higher AA intake had an effect on neurodevelopment. |
There was no significant heterogeneity of outcome amongst individual drugs, or of drug classes either for the primary efficacy analysis (death or dependence) or for mortality at final follow up. For the primary efficacy analysis, odds of death or dependence were 1.03 (95% confidence interval (CI) 0.96 to 1.12), and for mortality 1.02 (0.92 to 1.12). Neither ion channel modulators (death or dependence 1.02 (0.90 to 1.16)) nor NMDA antagonists (death or dependence 1.05 (0.95 to 1.16)) differed from the principal analysis including all compounds. Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 (0.81 to 1.74)), aptiganel (OR 1.32 (0.91 to 1.93)) and gavestinel (OR 1.12 (0.95 to 1.32)) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 (0.96 to 1.23)). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 (0.88 to 1.65)) although this was not the case for either of the other two compounds. No statistically significant detriment of psychotomimetic NMDA antagonists was found, although a trend towards higher mortality in this sub-group was seen (OR 1.25 (0.96 to 1.64)). There was no evidence of significant benefit or harm from drugs modulating excitatory amino acid action. Reduction of death or dependence by 8% or more has been excluded for gavestinel and lubeluzole, which contribute most of the data for this review. However, mechanistic understanding of neuroprotection is too poor to extrapolate from these two failed development plans to all glutamate modulators. Further clinical trials of neuroprotective agents remain justified, since confidence limits around estimates of effect remain wide for most agents, and cannot reliably exclude benefit. Although numbers of patients are too small to confirm or refute a trend towards increased mortality with some NMDA antagonists, further commercial development of these agents is exceedingly unlikely. | These drugs were highly effective in animal studies. Individual clinical trials in stroke patients did not confirm benefit for any of the drugs, however. This review confirms that there are no overall benefits for these drugs in stroke, although only two of them have been tested in a large enough population to be reasonably confident that they have no major effects. Some drugs may be harmful. Over 11,000 patients have participated in trials of 13 different drugs that inhibit glutamate release or binding, but two-thirds of all data are from trials of just two drugs. For most drugs in this class, trials have been too small to provide conclusive evidence of harm or benefit. Major differences among individual drugs mean that it is impossible to conclude that all drugs with this mode of action are ineffective. Further trials remain justified, and several are ongoing. |
Forty-nine trials involving 8763 women were included. The data were combined to calculate hazard ratios (HR) for survival on an intention-to-treat basis. For single non-platinum versus platinum combination chemotherapy the overall HR for survival was 0.93, 95% confidence interval (CI) 0.83 to1.05 favouring platinum-based combination chemotherapy. For non-platinum regimens compared with the same regimen plus cisplatin the survival HR was 0.88, 95% CI 0.79 to 0.98 in favour of adding platinum to drug regimens. Single platinum compared with platinum combination gave a HR of 0.91, 95% CI 0.79 to 1.05 favouring combination chemotherapy. Cisplatin versus carboplatin gave a HR of 1.02, 95% CI 0.93 to 1.12. Sub-group analyses for age, stage, grade, histology, resection, bulk of residual tumour and performance status were undertaken for cisplatin versus carboplatin only. No difference in effect was found. Available evidence, although not conclusive, suggests platinum-based chemotherapy is better than non-platinum therapy. There is some evidence that combination therapy improves survival compared with platinum alone. No difference in effect has been shown between cisplatin and carboplatin. | This review found a small benefit in platinum-based chemotherapy over non-platinum therapy. It also found that platinum combinations may offer improved survival over single platinum and that cisplatin and carboplatin are equally effective. The trials were done when paclitaxel (an effective new drug) was not used routinely. The results therefore, will need to be looked at in the light of new evidence from paclitaxel trials. |
Eight randomized trials, including 9598 patients, tested adjusted-dose warfarin versus aspirin (in dosages ranging from 75 to 325 mg/day) in AF patients without prior stroke or TIA. The mean overall follow up was 1.9 years/participant. Oral anticoagulants were associated with lower risk of all stroke (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.54 to 0.85), ischemic stroke (OR 0.53, 95% CI 0.41 to 0.68) and systemic emboli (OR 0.48, 95% CI 0.25 to 0.90). All disabling or fatal strokes (OR 0.71, 95% CI 0.59 to 1.04) and myocardial infarction (OR 0.69, 95% CI 0.47 to 1.01) were substantially but not significantly reduced by oral anticoagulants. Vascular death (OR 0.93, 95% CI 0.75 to 1.15) and all cause mortality (OR 0.99, 95% CI 0.83 to 1.18), were similar with these treatments. Intracranial hemorrhages (OR 1.98, 95% CI 1.20 to 3.28) were increased by oral anticoagulant therapy. Adjusted-dose warfarin and related oral anticoagulants reduce stroke, disabling stroke and other major vascular events for those with non-valvular AF by about one third when compared with antiplatelet therapy. | Atrial fibrillation (AF) is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the bloodstream to the brain and cause a stroke. Drugs that slow clotting, such as oral anticoagulants (warfarin and other coumarin derivates) and antiplatelet agents (aspirin and others), reduce the risk of stroke in patients with atrial fibrillation. In this review of eight randomized trials, including 9598 patients, oral anticoagulants are shown to reduce the risk of stroke in patients with non-valvular AF and with no prior stroke or transient ischemic attack by one-third when compared with antiplatelet agents alone. Antiplatelet agents reduce stroke by about 20% in AF patients compared with no therapy, offering a less efficacious therapeutic option for those deemed not eligible for anticoagulation therapy. The threshold of absolute benefit that warrants anticoagulation remains controversial and depends on patient's preferences and availability of optimal anticoagulation monitoring. |
Twenty-one studies were eligible for inclusion (1745 participants; 19 in adults, 2 in adolescents). Most studies used multimodular approaches. The risk of bias was high for all studies. In adults, psychotherapy had no effect on quality of life at around 12 months (3 studies, 235 patients, SMD -0.07; 95% CI -0.33 to 0.19), emotional status (depression, 4 studies, 266 patients, SMD 0.03; 95% CI -0.22 to 0.27) or proportion of patients not in remission (5 studies, 287 patients, OR 0.85; 95% CI 0.48 to 1.48). Results were similar at 3 to 8 months. There was no evidence for statistical heterogeneity or subgroup effects based on type of disease or intensity of the therapy. In adolescents, there were positive short term effects of psychotherapy on most outcomes assessed including quality of life (2 studies, 71 patients, SMD 0.70; 95% CI 0.21 to 1.18) and depression (1 study, 41 patients, SMD -0.62; 95% CI -1.25 to 0.01). Educational interventions had no effect on quality of life at 12 months (5 studies, 947 patients, SMD 0.11; 95% CI -0.02 to 0.24), depression (3 studies, 378 patients, SMD -0.08; 95% CI -0.29 to 0.12) and proportion of patients not in remission (3 studies, 434 patients, OR 1.00; 95% CI 0.65 to 1.53). No adverse events were reported in any of the included studies. There is no evidence for efficacy of psychological therapy in adult patients with IBD in general. In adolescents, psychological interventions may be beneficial, but the evidence is limited. Further evidence is needed to assess the efficacy of these therapies in subgroups identified as being in need of psychological interventions, and to identify what type of therapy may be most useful. | This review examined the effect of psychological interventions in patients with inflammatory bowel diseases (Crohn's disease and ulcerative colitis) on health related quality of life, emotional state and disease activity. Overall, 21 studies were included in the review, but not all provided sufficient data for the different study questions. All studies were of low methodological quality. Most studies examined combination therapies, often aimed at improving stress management. For example, a therapy might include patient information sessions, training in relaxation techniques and psychotherapy sessions, such as group therapy. Others were restricted to just providing information materials to patients. None of the included studies reported any side effects of psychological interventions. In adults, psychotherapy was not effective at 6 and 12 months for all outcomes (quality of life, emotional status/depression and relapse/disease activity), based on 3 studies. There was no difference by type of disease (Crohn's disease versus ulcerative colitis) or intensity of the therapy. In adolescents, there was a small positive effect for all outcomes (quality of life, coping, depression and anxiety), but only short term effects were reported in this group. Disease activity and relapse rates were not examined in adolescents. In adults, educational interventions were also not effective to improve quality of life and the course of the disease over 1 year, based on 5 studies. Generally, at this moment, it can not be recommended that all patients with IBD receive psychotherapy. We assume that adolescents, and patients with special needs (e.g. emotional problems) may benefit from psychological therapy. More research is needed to examine the effect of psychotherapy focusing on the individual psychological situation of IBD patients. |
Three randomised controlled trials met the inclusion criteria for our systematic review - the studies randomised a total of 524 women. We assessed the three included studies as being at a low to moderate risk of bias; the nature of the intervention made it difficult to achieve blinding of participants and personnel and none of the trial reports contained information about methods of allocation concealment (and were therefore assessed as being at an unclear risk of selection bias). In all studies, the intervention was the use of fetal biometry on ultrasound to identify fetuses displaying signs of fetal macrosomia, and the use of this information to indicate the use of medical anti-hyperglycaemic treatments. Those pregnancies were subject to more stringent blood glucose targets than those without signs of fetal macrosomia. Maternal outcomes The use of fetal biometry in addition to maternal blood glucose concentration (compared with maternal blood glucose concentration alone) may make little or no difference to the incidence of caesarean delivery (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.10; 2 trials, 428 women; low-certainty evidence). We are unclear about the results for hypertensive disorders of pregnancy (RR 0.80, 95% CI 0.34 to 1.89; 2 trials, 325 women) due to very low-certainty evidence. The included trials did not report on development of type 2 diabetes in the mother or maternal hypoglycaemia. Fetal and neonatal outcomes The use of fetal biometry may make little or no difference to the incidence of neonatal hypoglycaemia (RR 0.90, 95% CI 0.57 to 1.42; 3 trials, 524 women; low-certainty evidence). Very low-certainty evidence means that we are unclear about the results for large-for-gestational age (RR 0.81, 95% CI 0.38 to 1.74; 3 trials, 524 women); shoulder dystocia (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women); a composite measure of perinatal morbidity or mortality (RR 1.00, 95% CI 0.21 to 4.71; 1 study, 96 women); or perinatal mortality (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women). This review is based on evidence from three trials involving 524 women. The trials did not report some important outcomes of interest to this review, and the majority of our secondary outcomes were also unreported. The available evidence ranged from low- to very low-certainty, with downgrading decisions based on limitations in study design, imprecision and inconsistency. There is insufficient evidence to evaluate the use of fetal biometry (in addition to maternal blood glucose concentration values) to assist in guiding the medical management of GDM, on either maternal or perinatal health outcomes, or the associated costs. More research is required, ideally larger randomised studies which report the maternal and infant short- and long-term outcomes listed in this review, as well as those outcomes relating to financial and resource implications. | We searched for evidence on the 29th of January 2019 and identified three small randomised controlled trials (involving a total of 524 women) for inclusion in our review. The overall trial quality was low to moderate. The trials did not report the majority of outcomes of interest in this review, including outcomes relating to cost or use of resources. Compared with monitoring the mothers' blood glucose levels alone, the addition of ultrasound may make little or no difference to the risk of having a caesarean birth (2 trials, 428 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about the results relating to the risks of the mother having blood pressure disorders during pregnancy (2 trials, 325 women). The included trials did not report on the important maternal outcomes of low blood glucose, or development of type 2 diabetes. Using ultrasound in addition to monitoring the mother's blood glucose levels may make little or no difference to the risk of the newborn baby having low blood glucose levels (3 trials, 524 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about results relating to the risks of: having a baby that is large for gestational age (3 trials, 524 women); the baby's shoulders becoming entrapped in the birth canal (1 trial, 96 women); death or illness in the newborn baby (1 trial, 96 women); or the baby dying during pregnancy or birth (1 trial, 96 women). This review was based on limited evidence from three trials (involving 524 women). The trials did not report some important outcomes of interest to this review, and the majority of our secondary outcomes were also unreported. The certainty of the available evidence ranged from low to very low. There was insufficient evidence to evaluate the use of ultrasound (in addition to maternal blood glucose concentration values) to assist in guiding the medical management of GDM, and the effect on important short- and long-term outcomes for the mother or her baby, or the associated costs. Large, randomised trials are needed. Such trials could consider important short- and long-term outcomes (as listed in this review) for the mother, her baby, and resource use. |
We screened 17,055 records identified through searches of databases. We obtained 746 full-text articles and assessed them for relevance. We scrutinised 49 studies to establish their eligibility for inclusion in the review and excluded 48, primarily because participants were not patients presenting solely with exertional leg pain, investigators used no reference standard or investigators used neither angiography nor duplex ultrasonography as the reference standard. We excluded most studies for more than one reason. Only one study met the eligibility criteria and provided limb-level accuracy data from just 85 participants (158 legs). This prospective study compared the manual doppler method of obtaining an ABI (performed by untrained personnel) with the automated oscillometric method. Limb-level data, as reported by the study, indicated that the accuracy of the ABI in detecting significant arterial disease on angiography is superior when stenosis is present in the femoropopliteal vessels, with sensitivity of 97% (95% confidence interval (CI) 93% to 99%) and specificity of 89% (95% CI 67% to 95%) for oscillometric ABI, and sensitivity of 95% (95% CI 89% to 97%) and specificity of 56% (95% CI 33% to 70%) for doppler ABI. The ABI threshold was not reported. Investigators attributed the lower specificity for doppler to the fact that a tibial or dorsalis pedis pulse could not be detected by doppler in 12 of 27 legs with normal vessels or non-significant lesions. The superiority of the oscillometric (automated) method for obtaining an ABI reading over the manual method with a doppler probe used by inexperienced operators may be a clinically important finding. Evidence about the accuracy of the ankle brachial index for the diagnosis of PAD in people with leg pain on exercise that is alleviated by rest is sparse. The single study included in our review provided only limb-level data from a few participants. Well-designed cross-sectional studies are required to evaluate the accuracy of ABI in patients presenting with early symptoms of peripheral arterial disease in all healthcare settings. Another systematic review of existing studies assessing the use of ABI in alternative patient groups, including asymptomatic, high-risk patients, is required. | The ABI test is non-invasive and inexpensive and is widely used clinically; therefore, we have reviewed all available reports obtained from a wide search of databases of medical literature to estimate its accuracy in identifying PAD in people who experience pain on walking that goes away after rest. Two review authors independently assessed studies that met inclusion criteria of the review, including use of a cross-sectional study design; enrolment of participants with pain on walking that got better with rest; and use of duplex ultrasonography or angiography to check that results of the ABI test were accurate. One study met our criteria and provided data from 85 participants (158 limbs). Investigators compared the manual doppler method of measuring ABI with the automated method. Researchers provided only data for legs as opposed to data for patients; we were therefore unable to recalculate the analysis at the whole-participant level. In conclusion, we found little evidence about the accuracy of the ankle brachial index for diagnosing PAD in people presenting with exertional leg pain. The study included in our review had some flaws, and well-designed cross-sectional studies are needed to measure the accuracy of the ABI for diagnosing PAD in patients with early symptoms. |
Three RCTs met our inclusion criteria, with the asexual infection in both the tafenoquine and comparator arm treated with chloroquine, and in all trials G6PD deficiency patients were excluded. Tafenoquine dose comparisons Three of the included trials compared eight different dosing regimens. Tafenoquine doses of 300 mg and above resulted in fewer relapses than no hypnozoite treatment over six months follow-up in adults (300 mg single dose: RR 0.19, 95% CI 0.08 to 0.41, one trial, 110 participants, moderate quality evidence; 500 to 600 mg single dose: RR 0.14, 95%CI 0.06 to 0.34, two trials, 122 participants, moderate quality evidence; 1800 mg to 3000 mg in divided doses: RR 0.05, 95% CI 0.01 to 0.23, two trials, 63 participants, low quality evidence). In people with normal G6PD status, there may be little or no difference in serious adverse events (three trials, 358 participants, low quality evidence); or any adverse event (one trial, 272 participants, low quality evidence). Tafenoquine versus primaquine Two of the included trials compared four different dosing regimens of tafenoquine against the standard primaquine regimen of 15 mg/day for 14 days. A single tafenoquine dose of 600 mg may be more effective than primaquine in relation to relapses at six months follow-up (RR 0.29, 95% CI 0.10 to 0.84, two trials, 98 participants, low quality evidence) In people with normal G6PD status, there may be little or no difference for serious adverse events (two trials, 323 participants, low quality evidence) or any adverse event (two trials, 323 participants, low quality evidence) between tafenoquine and primaquine. Tafenoquine prevents relapses after clinically and parasitologically confirmed P. vivax malaria. The drug is untested in pregnancy, children and in G6PD-deficient people. The shorter treatment course is an important practical advantage in people who do not have G6PD deficiency, but the longer half-life may have more substantive consequences if given inadvertently to people with G6PD deficiency. | Researchers in the Cochrane Collaboration examined the research published up to 13 April 2015. We identified three trials conducted in Thailand, India, Peru and Brazil on adults with confirmedP. vivax malaria that randomized 453 participants. All adults received chloroquine (to clear the parasites in the blood) and some groups received either tafenoquine, primaquine or no further treatment. All were observed for recurrences of P. vivax malaria (up to six months) and all trials tested people for G6PD enzyme, and excluded patients who were deficient. Adults receiving tafenoquine at doses greater than 300 mg had fewer relapses than adults who had no further treatment (moderate quality evidence). Tafenoquine 600 mg may be better in relapse prevention than standard primaquine doses (low quality evidence). In patients who do not have G6PD deficiency, there may be little or no difference in adverse effects (low quality evidence). The drug is untested in children and pregnant women. The shorter treatment course is a practical advantage, but the longer half-life could may have more substantive consequences if given inadvertently to people with G6PD deficiency. |
We included seven trials involving 447 infants younger than two years with respiratory distress secondary to viral bronchiolitis. All children were recruited from a paediatric intensive care unit (PICU; 378 infants), except in one trial (emergency department; 69 infants). All children were younger than two (under nine months in two trials and under three months in one trial). Positive tests for respiratory syncytial virus (RSV) were required for inclusion in five trials. The two other trials were carried out in the bronchiolitis seasons. Seven different protocols were used for inhalation therapy with heliox. When heliox was used in the PICU, we observed no significant reduction in the rate of intubation: risk ratio (RR) 2.73 (95% confidence interval (CI) 0.96 to 7.75, four trials, 408 infants, low quality evidence). When heliox inhalation was used in the emergency department, we observed no increase in the rate of discharge: RR 0.51 (95% CI 0.17 to 1.55, one trial, 69 infants, moderate quality evidence). There was no decrease in the length of treatment for respiratory distress: mean difference (MD) -0.19 days (95% CI -0.56 to 0.19, two trials, 320 infants, moderate quality evidence). However, in the subgroup of infants who were started on nasal continuous positive airway pressure (nCPAP) right from the start, because of severe respiratory distress, heliox therapy reduced the length of treatment: MD -0.76 days (95% CI -1.45 to -0.08, one trial, 21 infants, low quality evidence). No adverse events related to heliox inhalation were reported. We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation: MD -1.04 (95% CI -1.60 to -0.48, four trials, 138 infants, moderate quality evidence). This outcome had statistical heterogeneity, which remained even after removing the study using a standard high-concentration reservoir mask. Several factors may explain this heterogeneity, including first the limited number of patients in each trial, and the wide differences in the baseline severity of disease between studies, with the modified Wood Clinical Asthma Score (m-WCAS) in infants treated with heliox ranging from less than two to more than seven. Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. We noticed this beneficial effect regardless of which heliox inhalation protocol was used. Nevertheless, there was no reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress. Heliox could reduce the length of treatment in infants requiring CPAP for severe respiratory distress. Further studies with homogeneous logistics in their heliox application are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid inclusion of children with mild bronchiolitis who may not benefit from heliox inhalation. Such studies would provide the necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis. | We retrieved seven trials involving 447 infants requiring hospitalisation for marked breathing difficulties. Six trials recruited infants from paediatric intensive care units and one trial from the emergency department. Four trials were supported in part by unrestricted grants from a manufacturer with a commercial interest in the results. The evidence is current to March 2015. Pooled results failed to demonstrate a reduction in the rate of emergency department discharge, in the rate of intubation to achieve respiratory support, or in the length of respiratory support. However, four trials involving 138 infants used a clinical respiratory score system, with increased severity receiving a higher score. The pooled results show that infants treated with heliox inhalation had a reduction in this respiratory score in the first hour. In a small subgroup of infants who were started on a nasal device providing a continuous positive airway pressure right from the start, because of the severity of their disease, heliox inhalation could reduce length of treatment. Each trial included in this review used a different method for delivering heliox. They also used different thresholds of clinical respiratory score for inclusion, and were often underpowered for the major endpoints. Further studies using a valid method of heliox application in addition to standard medical care are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid the inclusion of children who are not very sick, who may not benefit from heliox inhalation. Such studies would provide necessary information about the appropriate place of heliox in the management of seasonal pulmonary infection in infants. |
We included eight RCTs of 1562 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for upper respiratory tract infections (URTIs). Four treatment studies examined the effect on URTI recovery, and four studies investigated the effect on preventing URTIs after one to three months of treatment, followed up for the remainder of the year. Two treatment and two prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products. We found several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many had additional domains with unclear risk of bias. Three studies received funding from homeopathy manufacturers; one support from a non-government organisation; two government support; one was cosponsored by a university; and one did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products; trials at uncertain and high risk of bias reported beneficial effects. We found low-quality evidence that non-individualised homeopathic medicinal products confer little preventive effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence from two individualised prevention studies that homeopathy has little impact on the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also assessed adverse events, hospitalisation rates and length of stay, days off school (or work for parents), and quality of life, but were not able to pool data from any of these secondary outcomes. There is insufficient evidence from two pooled individualised treatment studies (N = 155) to determine the effect of homeopathy on short-term cure (OR 1.31 favouring placebo, 95% CI 0.09 to 19.54; very low-quality evidence) and long-term cure rates (OR 0.99, 95% CI 0.10 to 9.67; very low-quality evidence). Adverse events were reported inconsistently; however, serious events were not reported. One study found an increase in the occurrence of non-severe adverse events in the treatment group. Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn. | We included eight studies involving 1562 children that compared oral homeopathic treatment to either placebo or standard treatment to prevent or treat respiratory infections in children. All studies investigated upper respiratory tract (from the nose to the windpipe (trachea)) infections, but one combined reporting of upper and lower respiratory tract (from the windpipe to the lungs and pleura (membranes covering the lungs)) infections, so the numbers of children with upper or lower infections is unknown. Three studies received funding from homeopathy manufacturers; one reported support from a non-government organisation; two received government support; one was cosponsored by a university; and one did not report funding support. Studies investigated a range of interventions for various illnesses and populations using different outcome measures, so only a small number could be combined for analysis. All moderate-quality studies (low risk of bias) showed little or no beneficial effects for homeopathic medicinal products, whether individualised by a trained homeopath or a standard, non-individualised commercially available therapy. Where results could be combined, there was probably little or no difference in benefit on short- or long-term cure, or in prevention of ARTI. Two low-quality studies (unclear or high risk of bias) showed some benefit of homeopathic medicinal products for a limited number of outcomes. One study showed a reduction in disease severity for the homeopathy group at some time points. The other study showed a reduction in number of respiratory infections over the following year in the treatment groups, although more than a quarter of participants were not accounted for in the results. There was no difference between homeopathy and placebo groups for parents' time off work, antibiotic use, or adverse effects. Consequently, there is no convincing evidence homeopathic medicinal products are effective in treating ARTIs in children. We are unsure about safety because data on adverse events were poorly reported. We rated evidence as moderate or low quality for most outcomes. Three outcomes provided very low-quality evidence because study populations and results differed significantly among studies; there were significant limitations in study design and reporting; and sample sizes were small. |
The search identified 60 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used. Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval (CI) 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months. One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% CI 0.02 to 0.79). One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non-inferiority or equivalence . A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups. A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures. An analysis performed in this review (not adjusted for age) showed fewer participants in the cycled therapy group with one or more isolates of Pseudomonas aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28). Using GRADE, the quality of evidence for outcomes was downgraded to moderate to very low. Downgrading decisions for Pseudomonas aeruginosa eradication and lung function were based on applicability (participants mostly children) and limitations in study design, with imprecision an additional limitation for lung function, growth parameters and adverse effects. We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials comparing two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis. | We included seven trials with 744 people with cystic fibrosis of both sexes, any age and both mild and more severe lung disease. The trials lasted from 28 days to 27 months. We could not combine many results as trials used different treatments. Two trials compared tobramycin to placebo (a dummy treatment). Three trials combined oral ciprofloxacin and inhaled colistin in the experimental group but used different comparators - one compared the antibiotic combination to no treatment, one to inhaled tobramycin and the third to oral ciprofloxacin with inhaled tobramycin. Another trial considered inhaled tobramycin and compared 28 days of treatment to 56 days. The final trial compared regular cycles of inhaled tobramycin (plus oral ciprofloxacin or placebo) to only treating with inhaled tobramycin (plus oral ciprofloxacin or placebo) based on the results of cultures grown in the laboratory. Two small trials (38 people) treating early infection showed that after two months inhaled antibiotics were better than no treatment and eliminated Pseudomonas aeruginosa in most people. One of these trials reported for longer and suggested that this effect may last for up to 12 months. Another small trial (26 people) which lasted two years showed that treating early infection with a combination of inhaled and oral antibiotics was better than no treatment for eliminating Pseudomonas aeruginosa. A trial comparing 28 days of nebulised tobramycin solution for inhalation (88 people) to 56 days showed both were equally tolerated and successful at eliminating Pseudomonas aeruginosa. Four direct comparisons of oral or inhaled antibiotics (or combinations of both), including one with 223 people, did not find a difference between different antibiotic combinations. A recent trial in 306 children (aged up to 12 years) compared a regular cycle of inhaled tobramycin (with either oral ciprofloxacin or placebo) to treatment only when it was shown that a child was infected with Pseudomonas aeruginosa and showed that when children were given a regular cycle of inhaled tobramycin (with either oral ciprofloxacin or placebo) fewer of them grew Pseudomonas aeruginosa from their sputum. The trial report made an adjustment for age and did not show any difference in the number of times Pseudomonas aeruginosa was grown from samples between the groups, nor was there any difference in the length of time until the children had their next chest infection. Some trials were conducted up to 20 years ago and the results may not be applicable today. Some trials were small. All the trials had quite a short follow-up period, so we could not show whether treatment made people with cystic fibrosis feel better or live longer. Given the treatments compared in most of the trials, it would have been easy for people to guess which treatment they were receiving, which might have influenced some of the results. Two trials were supported by the pharmaceutical industry. Further research is still needed to see whether eliminating the bacteria completely improves the well-being and quality of life in people with cystic fibrosis and to establish which antibiotic combination provides the best way of eliminating Pseudomonas aeruginosa. Overall the quality of evidence was moderate to very low, meaning that further research is likely to change the estimate of the size of the treatment effect. Future, larger trials (with greater power) may show one treatment is more effective in eradicating Pseudomonas aeruginosa than another. |
We included two trials with 493 randomised participants with various Child-Pugh scores. The trials had a low risk of bias. The rHuFVIIa administration did not reduce the risk of mortality within five days (21/288 (7.3%) versus 15/205 (7.3%); risk ratio (RR) 0.88, 95% confidence interval (CI) 0.48 to 1.64, I2 = 49%) and within 42 days (5/286 (1.7%) versus 36/205 (17.6%); RR 1.01, 95% CI 0.55 to 1.87, I2 = 55%) when compared with placebo. Trial sequential analysis demonstrated that there is sufficient evidence to exclude that rHuFVIIa decreases mortality by 80%, but there is insufficient evidence to exclude smaller effects. The rHuFVIIa did not increase the risk of adverse events by number of patients (218/297 (74%) and 164/210 (78%); RR 0.94, 95% CI 0.84 to 1.04, I2 = 1%), serious adverse events by adverse events reported (164/590 (28%) versus 123/443 (28%); RR 0.91, 95% CI 0.75 to 1.11, I2 = 0%), and thromboembolic adverse events (16/297 (5.4%) versus 14/210 (6.7%); RR 0.80, 95% CI 0.40 to 1.60, I2 = 0%) when compared with placebo. We found no evidence to support or reject the administration of rHuFVIIa for patients with liver disease and upper gastrointestinal bleeding. Further adequately powered randomised clinical trials are needed in order to evaluate the proper role of rHuFVIIa for treating upper gastrointestinal bleeding in patients with liver disease. Although the results are based on trials with low risk of bias, the heterogeneity and the small sample size result in rather large confidence intervals that cannot exclude the possibility that the intervention has some beneficial or harmful effect. Further trials with alow risk of bias are required to make more confident conclusions about the effects of the intervention. | The review includes two randomised clinical trials with 493 participants. The risk of bias was low. Both trials compared recombinant human activated factor VII with placebo. The meta-analysis showed that the recombinant human activated factor VII does not seem to reduce mortality in patients with liver disease and suffering from upper gastrointestinal bleeding, irrespective of the grade of liver damage. The current evidence is insufficient to support or reject recombinant human activated factor VII for these patients. |
Three randomised clinical trials, including 430 participants, met the inclusion criteria for this review; however, data from two trials with 412 participants could be included in only one primary outcome (i.e. mortality). All three trials were at high risk of bias. All three trials included supportive care as cointervention. The comparisons included in the two trials reporting on mortality were: systemic chemotherapy with sorafenib versus no active intervention; and transarterial chemoembolisation plus systemic chemotherapy with sorafenib versus transarterial chemoembolisation alone. The trials did not report the duration of follow-up; however, it appeared that the participants were followed up for a period of about 18 to 30 months. The majority of the participants in the trials had cirrhotic livers. The trials included participants with intermediate-stage hepatocellular carcinoma arising from viral and non-viral aetiologies. The trials did not report the portal hypertension status of the participants. The mortality was 50% to 70% over a median follow-up period of 18 to 30 months. There was no evidence of difference in mortality at maximal follow-up between systemic chemotherapy versus no chemotherapy (hazard ratio 0.85, 95% CI 0.60 to 1.18; participants = 412; studies = 2; I2 = 0%; very low quality evidence). A subgroup analysis performed by stratifying the analysis by the presence or absence of transarterial chemoembolisation as cointervention did not alter the results. None of the trials reported on serious adverse events other than mortality, health-related quality of life, recurrence of hepatocellular carcinoma, or length of hospital stay. One of the trials providing data was funded by the pharmaceutical industry, the other did not report the source of funding, and the trial with no data for the review was also funded by the pharmaceutical industry. We found two ongoing trials. Currently, there is no evidence from randomised clinical trials that people with intermediate-stage hepatocellular carcinoma would benefit from systemic chemotherapy with sorafenib either alone or when transarterial chemoembolisation was used as a cointervention (very low quality evidence). We need high-quality randomised clinical trials designed to measure differences in clinically important outcomes (e.g. all-cause mortality or health-related quality of life). | Only three trials with 430 participants met our inclusion criteria; however, two of the trials (412 participants) only reported death and no other measures of how well the treatments worked. All three trials included supportive care (treatment to prevent, control, or relieve complications and side effects and improve comfort and quality of life) as a co-intervention. The trials assessed transarterial chemoembolisation (where anti-cancer drugs block the blood supply and treat the cancer through the vessels supplying the cancer), chemotherapy using sorafenib (a drug which blocks cancer growth), or a combination of transarterial chemoembolisation and sorafenib. It appeared that the trials followed participants for about 18 to 30 months from the initiation of treatment. Two trials were funded by the pharmaceutical industry; one trial did not report the source of funding. Over 18 to 30 months, 50% to 75% of participants died. There was no evidence of any difference between the people who received chemotherapy and those who did not receive chemotherapy. None of the trials reported complications, health-related quality of life (a measure of a person's satisfaction with their life and health), cancer recurrence, or length of hospital stay. Overall, there is currently no evidence for benefit of any active treatment in addition to supportive treatment for intermediate-stage hepatocellular carcinoma. There is significant uncertainty on this and further high-quality randomised clinical trials are required. The overall quality of evidence was low or very low and all the trials were at high risk of bias, which means that there is possibility of making the wrong conclusions, overestimating benefits, or underestimating harms of one treatment or the other because of the way that the trials were conducted. |
A total of 43 trials were identified with 1673 participants. All trials used small patient numbers (average trial size of 39 participants); the methods of randomisation and concealment of allocation were poor or not stated in most trials. Blinded assessors were used in just over half of the trials and only 10 stated that they used intention-to-treat analysis. A wide variety of validated and customised outcome measures were used to assess the effectiveness of physiotherapy interventions. The most frequently reported physiotherapy outcomes were gait speed and timed up and go, in 19 and 15 trials respectively. Only five of the 43 trials reported data on falls (12%). The motor subscales of the Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Questionnaire-39 were the most commonly reported clinician-rated disability and patient-rated quality of life outcome measures, used in 22 and 13 trials respectively. The content and delivery of the physiotherapy interventions varied widely in the trials included within this review, so no quantitative meta-analysis could be performed. Considering the small number of participants examined, the methodological flaws in many of the studies, the possibility of publication bias, and the variety of interventions, formal comparison of the different physiotherapy techniques could not be performed. There is insufficient evidence to support or refute the effectiveness of one physiotherapy intervention over another in PD. This review shows that a wide range of physiotherapy interventions to treat PD have been tested . There is a need for more specific trials with improved treatment strategies to underpin the most appropriate choice of physiotherapy intervention and the outcomes measured. | Only randomised controlled trials were included in this review. These were studies where a group of participants were given one physiotherapy intervention and were compared with another group who received a different physiotherapy intervention. The participants were assigned to a group in a random fashion to reduce the potential for bias. A total of 43 randomised trials involving 1673 participants (average trial size of just 39 participants) were identified as suitable for this review. The trials assessed various physiotherapy interventions, so they were grouped according to the type of intervention being used (general physiotherapy, exercise, treadmill training, cueing, dance or martial arts). However, despite this grouping, the physiotherapy interventions delivered and the outcomes assessed varied so much that the results of the individual trials could not be combined. This review highlights that a wide range of different physiotherapy techniques have been tested to treat PD. Considering the small number of participants, the wide variety of physiotherapy interventions and the outcomes assessed, there is insufficient evidence to support the use of one approach of physiotherapy intervention over another for the treatment of PD. |
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