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21 randomized controlled trials (RCTs) in 1,993 patients with primary hypertension met the inclusion criteria for this review - ACEIs (5 trials), CCBs (7 trials), ARBs (6 trials), diuretics (2 trials), alpha-blockers (1 trial), and beta-blockers (1 trial). Meta-analysis showed significant heterogeneity across trials. No RCT reported on all cause mortality, cardiovascular mortality, cardiovascular morbidity and serious adverse events. There was no statistically significant difference for overall adverse events (RR=0.78, 95%CI: 0.37 to 1.65) and withdrawals due to adverse events (RR=0.53, 95%CI: 0.26 to 1.07). No significant differences were noted for morning SBP (-1.62 mm Hg, 95% CI: -4.19 to 0.95) and morning DBP (-1.21 mm Hg, 95% CI: -3.28 to 0.86); but 24-hour BP (SBP: -1.71 mm Hg, 95% CI: -2.78 to -0.65; DBP: -1.38 mm Hg, 95% CI: -2.13 to -0.62) showed a statistically significant difference. No RCT reported on clinically relevant outcome measures - all cause mortality, cardiovascular morbidity and morbidity. There were no significant differences in overall adverse events and withdrawals due to adverse events among the evening versus morning dosing regimens. In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known. | This review examined the administration-time-related effects of once-daily evening versus morning regimen on death, cardiovascular outcomes and blood pressure reduction. The interventions included chronotherapeutic delivery formulations and conventional antihypertensive agents. 21 trials, involving 1,993 patients with primary hypertension were identified. We concluded that evening dosing with antihypertensive drugs had a slightly better blood pressure control than the morning dosing regimen in 24-hour BP, but its effect on death and adverse cardiovascular outcomes is not known. |
We included 17 randomised clinical trials which compared peginterferon alpha-2a plus ribavirin versus peginterferon alpha-2b plus ribavirin in 5847 patients. All trials had a high risk of bias. Very few trials reported data on very few patients for the patient-relevant outcomes all-cause mortality, liver-related morbidity, serious adverse events, and quality of life. Accordingly, we were unable to conduct meta-analyses on all-cause mortality, liver-related morbidity, and quality of life. Twelve trials reported on adverse events leading to discontinuation of treatment without clear evidence of a difference between the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI 0.57 to 1.22; I2 = 44%; low quality evidence). A trial sequential analysis showed that we could exclude a relative risk reduction of 20% or more on this outcome. Peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response in the blood serum compared with peginterferon alpha-2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I2= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype, and treatment history yielded similar results. Trial sequential analyses supported the results in patients with genotypes 1 and 4, but not in patients with genotypes 2 and 3. There is lack of evidence on patient-important outcomes and paucity of evidence on adverse events. Moderate quality evidence suggests that peginterferon alpha-2a is associated with a higher sustained virological response in serum than with peginterferon alpha-2b. This finding may be affected by the high risk of bias of the included studies . The clinical consequences of peginterferon alpha-2a versus peginterferon alpha-2b are unknown, and we cannot translate an effect on sustained virological response into comparable clinical effects because sustained virological response is still an unvalidated surrogate outcome for patient-important outcomes. The lack of evidence on patient-important outcomes and the paucity of evidence on adverse events means that we are unable to draw any conclusions about the effects of one peginterferon over the other. | The review identified 17 randomised clinical trials. The trials reported on patient-relevant outcomes only occasionally. All trials had high risk of bias ie, a trial might systematically overestimate benefits or underestimate harms of the treatments). Both treatments were associated with a high risk of experiencing adverse events, which may lead to discontinuation of the treatment. Twelve trials reported on clearing the virus from blood six months after the end of treatment. A summary of the current evidence in this review suggests that peginterferon alpha-2a has higher chances of clearing the virus from the patient's blood than peginterferon alpha-2b (in 50% compared with 43%). We were unable to identify any evidence on the benefits of one peginterferon over the other on patient-important outcomes. There is lack of data regarding patient-important outcomes on this topic. |
We included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00). There is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed. | Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis. We analysed the results from 15 trials with 2496 participants. The effects of azithromycin on cure, improvement or failure were not better than those of amoxycillin or amoxyclav. However, azithromycin seems to have a lower incidence of adverse events than amoxycillin or amoxyclav but it is not significant. Overall the quality of the evidence for the main outcome is low as only three of 15 included trials showed adequate allocation concealment. Hence, currently, there is insufficient evidence to show conclusively that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. |
Nineteen studies met the inclusion criteria of which 16 contributed data on 267 participants with COPD (mean age 56 to 76 years and 67% were men). Of these 16 studies, seven explored the effect of NMES versus usual care and nine explored the effect of NMES plus conventional exercise training versus conventional exercise training alone. Six studies utilised sham stimulation in the control group. When applied in isolation, NMES produced an increase in peripheral muscle force (SMD 0.34, 95% CI 0.02 to 0.65; low-quality evidence) and quadriceps endurance (SMD 1.36, 95% CI 0.59 to 2.12; low-quality evidence) but the effect on thigh muscle size was unclear (MD 0.25, 95% CI -0.11 to 0.61; low-quality evidence). There were increases in six-minute walk distance (6MWD) (MD 39.26 m, 95% CI 16.31 to 62.22; low-quality evidence) and time to symptom limitation exercising at a submaximal intensity (MD 3.62 minutes, 95% CI 2.33 to 4.91). There was a reduction in the severity of leg fatigue on completion of an exercise test (MD -1.12 units, 95% CI -1.81 to -0.43). The increase in peak rate of oxygen uptake (VO2peak) was of borderline significance (MD 0.10 L/minute, 95% CI 0.00 to 0.19). For NMES with conventional exercise training, there was an uncertain effect on peripheral muscle force (SMD 0.47, 95% CI -0.10 to 1.04; very low-quality evidence) and there were insufficient studies to undertake a meta-analysis on the effect on quadriceps endurance or thigh muscle size. However, there was an increase in 6MWD in favour of NMES combined with conventional exercise training (MD 25.87 m, 95% CI 1.06 to 50.69; very low-quality evidence). In people admitted to either in an intensive care unit or a respiratory high dependency centre, NMES combined with conventional exercise reduced the time taken for participants to first sit out of bed by 4.98 days (95% CI -8.55 to -1.41; very low-quality evidence), although the statistical heterogeneity for this analysis was high (I2 = 60%). For both types of studies (i.e. NMES versus usual care and NMES with conventional exercise training versus conventional exercise training alone), there was no risk difference for mortality or minor adverse events in participants who received NMES. NMES, when applied in isolation, increased quadriceps force and endurance, 6MWD and time to symptom limitation exercising at a submaximal intensity, and reduced the severity of leg fatigue on completion of exercise testing. It may increase VO2peak, but the true effect on this outcome measure could be trivial. However, the quality of evidence was low or very low due to risk of bias within the studies, imprecision of the estimates, small number of studies and inconsistency between the studies. Although there were no additional gains in quadriceps force with NMES plus conventional exercise training, there was evidence of an increase in 6MWD. Further, in people who were the most debilitated, the addition of NMES may have accelerated the achievement of a functional milestone, that is, the first time someone sits out of bed. | Nineteen studies met the inclusion criteria for the review, of which 16 had data on 267 participants that could be included in the analyses. The average age of people in each of the studies ranged from 56 to 76 years and 179 (67%) were men. Seven studies explored the effect of applying electrical stimulation alone and nine studies explored the effect of adding electrical stimulation to an exercise programme. Electrical stimulation was applied in a range of settings, such as at home, in an outpatient hospital department, on a hospital ward or in an intensive care unit. Most studies stimulated the thigh muscles once or twice a day for 30 to 60 minutes on four to seven days each week for four to eight weeks. Studies that explored the effect of applying electrical stimulation alone showed an increase in strength and endurance of the thigh muscles. They showed an increase in some, but not all, measures of exercise capacity and a decrease in the severity of leg fatigue after exercise. Studies that explored the effect of adding electrical stimulation to an exercise programme showed a small increase in the distance walked in six minutes. In people who were most unwell (e.g. in an intensive care unit), adding electrical stimulation to an exercise programme helped people to spend fewer days confined to bed. Electrical stimulation did not increase the risk of side effects. The quality of evidence provided by this review was low. This is because most studies had design problems. The inclusion of future studies into this review is likely to change the results. |
We included 29 trials involving 2612 participants. Twenty-eight trials involved patients undergoing surgery and one trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72; P < 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR) 0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04 to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR 0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P < 0.0001). There was substantial statistical heterogeneity between trials for the blood loss and blood transfusion outcomes. There is reliable evidence that topical application of tranexamic acid reduces bleeding and blood transfusion in surgical patients, however the effect on the risk of thromboembolic events is uncertain. The effects of topical tranexamic acid in patients with bleeding from non-surgical causes has yet to be reliably assessed. Further high-quality trials are warranted to resolve these uncertainties before topical tranexamic acid can be recommended for routine use. | This review looked at trials assessing the effects of topical tranexamic acid in patients who are bleeding. Twenty-nine trials were found; 28 involved patients bleeding during operations and one involved people with nosebleeds. When the results of these trials were gathered together they showed that when tranexamic acid was given topically, it reduced the amount of blood that patients lost and made it less likely that they had a blood transfusion. The authors of this review concluded that topical tranexamic acid reduces bleeding in patients who are having an operation. But because there are no trials, we are not sure if it also reduces bleeding from other causes, such as childbirth or bleeding from stomach ulcers. |
Nineteen trials, of which two were newly included in this update, involving 3044 participants, were included. There was considerable variation in the types of implants and techniques used for both internal fixation and arthroplasty in the included trials. The risk of selection bias was low in just three trials, unclear in 13 trials and high in the three quasi-randomised trials. Just three trials reported assessor blinding of functional outcomes. Length of surgery, operative blood loss, need for blood transfusion and risk of deep wound infection were significantly less for internal fixation compared with arthroplasty. Fixation had a significantly higher re-operation rate in comparison with arthroplasty (40% versus 11%; risk ratio 3.22, 95% CI 2.31 to 4.47, 19 trials). No definite differences for hospital stay, mortality, or regain of pre-injury residential state were found. Limited information from some studies suggested pain was less and function was better for a cemented arthroplasty in comparison with fixation. Internal fixation is associated with less initial operative trauma but has an increased risk of re-operation on the hip. Definite conclusions cannot be made for differences in pain and residual disability between the two groups. Future studies should concentrate on better reporting of final outcome measures and function. There is still a need for studies to define which patient groups are better served by the different treatment methods. | Nineteen trials, of which two were newly included in this update, involving 3044 participants, were included in this review. Some trials had weak methods, which required a more cautious interpretation of their results. There were many different types of devices and methods used to place these devices for both treatments in the included trials. We found that each treatment has its own specific complications. Realigning the bones and fixing the fracture (reduction and internal fixation) is a shorter operation with less blood loss. However, people having internal fixation are more likely to need another operation than those treated with joint replacement (40% versus 11%). The reason for this is mainly from a failure of the bone to heal in those cases treated with fixation. No definite differences were found between the two treatment groups in the numbers of patients who had died by various follow-up times. People who had a replacement with an artificial hip joint that was fixed in place with cement seemed to have less residual pain and better function related to using the hip than those whose fracture was fixed. There is not enough evidence to be sure whether fixation of the bone or replacement with an artificial hip is best for treating fractures of the thigh bone near the hip joint. |
We included 13 studies evaluating 19 interventions from high-income countries (HICs). At update stage (from our 2015 search), one previously included study was removed and three new studies added (since our 2012 search). We found no sufficiently robust evaluations conducted in low- and middle-income countries (LMICs). Study quality overall was low and measurements used by studies variable. Participants were classified as drop-in and shelter-based. No studies measured the primary outcome of reintegration and none reported on adverse effects.We found no consistent results on a range of relevant outcomes within domains of psychosocial health, substance misuse and sexually risky behaviours . Interventions evaluated consisted of time-limited therapeutically based programmes that proved no more effective than standard shelter or drop-in services and other control interventions used for most outcomes in most studies. Favourable changes from baseline were reported for outcomes for most participants following therapy interventions and standard services. We noted considerable heterogeneity between studies and inconsistent reporting of equity data. No studies measured the primary outcome of reintegration or reported on adverse effects. Analysis revealed no consistently significant benefit for focused therapeutic interventions compared with standard services such as drop-in centres, case management and other comparable interventions for street-connected children and young people. Commonly available services, however, were not rigorously evaluated. Robust evaluation of interventions, including comparison with no intervention, would establish a more reliable evidence base to inform service implementation. More robust research is needed in LMICs to examine interventions for street-connected children and young people with different backgrounds and service needs. | Thirteen studies have rigorously evaluated 19 interventions such as services to support street-connected children and youth - all in high-income countries. Most have compared therapy-based services versus usual shelter and drop-in services, or versus other therapeutic/health interventions. We found mixed results among these studies but overall findings suggesting that participants receiving therapy and those provided usual services benefited to a similar level. Future research should consider the benefits of usual drop-in and shelter services, most particularly in low- and middle-income countries, and should focus on street-connected children and young people. None of the studies included participants comparable with street children in low-income countries, who may be on the street primarily to earn a living, or as a result of war, migration or urbanisation. Overall we assessed the quality of the evidence included in this review as low/moderate. |
Six trials involving 1740 children were included. There was no significant reduction in mortality associated with pneumonia in children treated with vitamin A compared to those who were not (pooled odds ratio (OR) 1.29; 95% confidence interval (CI) 0.63 to 2.66). Also, there was no statistically significant difference in duration of hospital stay (mean difference (MD) 0.08; 95% CI -0.43 to 0.59). Disease severity after supplementary high-dose vitamin A was significantly worse compared with placebo. However, low-dose vitamin A significantly reduced the recurrence rate of bronchopneumonia (OR 0.12; 95% CI 0.03 to 0.46). Moderate vitamin A significantly reduced the time to remission of signs in children with normal serum retinol (> 200 ug/L). The evidence does not suggest a significant reduction in mortality, measures of morbidity, nor an effect on the clinical course of pneumonia with vitamin A adjunctive treatment in children with non-measles pneumonia. However, not all studies measured all outcomes, which limited the number of studies that could be incorporated into the meta-analyses, so that there may have been a lack of statistical power to detect statistically significant differences. | We found six trials (1740 participants) that used vitamin A adjunctive therapy in children with non-measles pneumonia. There was no significant reduction in mortality or duration of hospital stay. Supplementary high-dose vitamin A may result in a worsening of the disease, and low-dose vitamin A significantly reduces the recurrence of bronchopneumonia. Moderate-dose vitamin A significantly reduces the time to remission of signs in children with normal serum retinol. The possible reason of the lack of benefit of vitamin A in non-measles pneumonia is that the effects of vitamin A may be disease-specific, with vitamin A only being effective when pneumonia is complicated with measles. Further high-quality research is required. |
The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo. One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions. There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials. | From a wide search, we identified three RCTs that met our selection criteria. The trials involved a total of 530 adults with peripheral neuropathy. Treatments were ascorbic acid (vitamin C) in people with Charcot-Marie-Tooth disease in two trials, and amantadine in Guillain-Barré syndrome in the third. Charcot-Marie-Tooth disease is an inherited nerve disease and Guillain-Barré syndrome is a condition where there is inflammation of the peripheral nerves. We chose measures of fatigue at four to 12 weeks as our preferred measure of the effects of treatment. The amantadine trial but not the ascorbic acid trials provided data at this time point; the ascorbic acid trials provided data more than 12 months after the start of the intervention. There was insufficient evidence to determine the effects of amantadine when compared with an inactive treatment (placebo) for fatigue. and there were no major unwanted effects. We found evidence that ascorbic acid probably has little meaningful benefit for fatigue. No major unwanted effects were identified, but the trials were small. We assessed the quality of this evidence as moderate because the results were imprecise, which means they do not rule out the possibility that the drugs could have an effect. We found no evidence from RCTs on other medicines or treatments for fatigue in peripheral neuropathy. There is insufficient evidence to determine the effect of amantadine for fatigue in GBS and ascorbic acid for fatigue in CMT1A. More high-quality studies are needed to provide evidence on which to base management of feelings of fatigue in peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future RCTs. The evidence in this review is current to November 2013. |
We included nine RCTs with 1069 participants, describing 37 comparisons: six were NSAIDs versus placebo and three were NSAIDs versus NSAIDs. The overall risk of bias in the included studies was mixed. In a pooled analysis, NSAIDs did not significantly reduce the total symptom score (SMD -0.40, 95% CI -1.03 to 0.24, three studies, random-effects model), or duration of colds (MD -0.23, 95% CI -1.75 to 1.29, two studies, random-effects model). For respiratory symptoms, cough did not improve (SMD -0.05, 95% CI -0.66 to 0.56, two studies, random-effects model) but the sneezing score significantly improved (SMD -0.44, 95% CI -0.75 to -0.12, two studies, random-effects model). For outcomes related to the analgesic effects of NSAIDs (headache, ear pain, and muscle and joint pain) the treatment produced significant benefits. The risk of adverse effects was not high with NSAIDs (RR 2.94, 95% CI 0.51 to 17.03, two studies, random-effects model) but it is difficult to conclude that such drugs are no different from placebo. The quality of the evidence may be estimated as 'moderate' because of imprecision. The major limitations of this review are that the results of the studies are quite diverse and the number of studies for one result is quite small. NSAIDs are somewhat effective in relieving the discomfort caused by a cold but there is no clear evidence of their effect in easing respiratory symptoms. The balance of benefit and harms needs to be considered when using NSAIDs for colds. | The evidence is current to April 2015. This review found nine studies (1069 participants of both genders, including children, adults and older people from the USA, Japan, Belgium and Denmark) that compared various NSAIDs either with each other or with an inactive substance that has no treatment value (placebo). Our findings suggest that NSAIDs may improve most analgesia-related symptoms caused by the common cold (headache, ear pain, and muscle and joint pain), but there is no clear evidence that NSAIDs are effective in improving coughs and runny noses caused by the common cold. Some of the included trials reported gastrointestinal complaints, rash and oedema (fluid retention) in the NSAIDs group. The quality of the evidence may be estimated as 'moderate' because of imprecision. The major limitations of this review are that the results of the studies are quite diverse and the number of studies for each outcome is quite small. NSAIDs are somewhat effective in relieving the discomfort caused by a cold but there is no clear evidence of their effect in easing respiratory symptoms. The balance of benefit and harms needs to be considered when using NSAIDs for colds. |
A comprehensive search of the literature yielded the following results: CENTRAL (1022 references), MEDLINE (2874 references), and Embase (2820 references). After de-duplication, we screened titles and abstracts of 4880 references and excluded 4864 that did not meet the review inclusion criteria. Of the 16 references that potentially met the review inclusion, we excluded all 16 reports after reviewing the full texts. We did not identify any ongoing trials. There is currently an absence of evidence to indicate the effectiveness of health education interventions involving healthcare providers or individuals or both to promote early presentation and referral for women with endometrial cancer symptoms. High-quality RCTs are needed to assess whether health education interventions enhance early presentation and referral. If health education interventions can be shown to reduce treatment delays in endometrial cancer, further studies would be required to determine which interventions are most effective. | We planned to include randomised controlled trials (studies in which people or groups of people are allocated by chance to two or more groups, treating them differently). In the absence of randomised controlled trials, we planned to include studies where participants were not randomised but that included an assessment of the benefits of health education compared to no health education. We searched scientific databases and checked the titles and abstracts of 4880 possibly relevant articles and assessed the full text of 16 of these references. However, we found no studies that met our inclusion criteria. There is currently an absence of evidence to indicate whether providing health education to healthcare providers, or individuals or both, promotes early presentation and referral for women with symptoms of endometrial cancer. |
Forty-five studies (3186 participants) met the inclusion criteria; (dietary advice compared with: no advice (1053 participants); with oral nutritional supplements (332 participants); with dietary advice and oral nutritional supplements (731 participants); and dietary advice plus oral nutritional supplements compared with no additional intervention (1070 participants). Follow-up ranged from 18 days to 24 months. No comparison showed a significant difference between groups for mortality or morbidity. There was a significant change in weight found between groups when comparing dietary advice to no advice for interventions lasting greater than 12 months, mean difference 3.75 kg (95% confidence interval 0.97 to 6.53), and when all studies were combined, mean difference 1.47 kg (95% confidence interval 0.32 to 2.61) although there was significant heterogeneity in the combined analysis (I2 = 90%). Similar improvements in weight were found for the comparison of dietary advice with nutritional supplements if required versus no advice, mean difference 2.20 kg (95% confidence interval 1.16 to 3.25). Dietary advice compared with no advice was also associated with significantly improved mid-arm muscle circumference when all studies were combined, but with moderate heterogeneity, mean difference 0.81 mm (95% confidence interval 0.31 to 1.31). Dietary advice given with nutritional supplements compared with dietary advice alone resulted in improvements in: mid-arm muscle circumference, mean difference -0.89 mm (95% confidence interval -1.35 to -0.43); triceps skinfold thickness, mean difference -1.22 mm (95% confidence interval -2.34 to -0.09); and grip strength, mean difference -1.67 kg (95% confidence interval -2.96 to -0.37), although the effects on triceps skinfold thickness and grip strength were heterogeneous. Dietary advice with supplements if required resulted in a significant increase in triceps skinfold thickness compared with no advice, mean difference 0.40 mm (95% confidence interval 0.10 to 0.70), although these results are from a single trial with only 29 participants. Evidence of variable quality suggests that dietary advice with or without oral nutritional supplements may improve weight, body composition and grip strength. We found no evidence of benefit of dietary advice or oral nutritional supplements given alone or in combination on survival. Studies addressing the impact of nutritional interventions on nutritional, functional and patient-centred outcomes are needed. | Forty-five studies with a total of 3186 people are included in this review in four different comparisons: dietary advice to no advice; to oral nutritional supplements; to dietary advice plus oral nutritional supplements; and to dietary advice and nutritional supplements given together compared with no additional help. Follow-up ranged from 18 days to 24 months. There are some significant results for change in weight, muscle bulk and strength suggesting that nutritional intervention is beneficial although for some comparisons there are big differences between the studies. The authors conclude that nutritional intervention appears to be more effective than no help at improving weight, muscle bulk and strength. More research is needed to work out the best ways to help people who are losing weight because of illness in order to improve their clinical outcomes and quality of life. |
978 unique references were identified via the search strategy. All but 50 were excluded by title and abstract screening. Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as information provided was not adequate concerning random sequence generation, allocation concealment, blinding, or completeness of outcome reporting. Results of the meta-analysis remained unchanged from the previous versions of this review and indicated no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence). We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence). This review found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence. | We found only three trials that compared lymphadenectomy with no lymphadenectomy among women with endometrial cancer. One of these trials could not be included in the meta-analysis of this review, as it provided insufficient information about outcomes for women. When we combined findings from the two remaining trials, which included 1945 women, we found no evidence that women who received lymphadenectomy were less likely to die or have a relapse of their cancer. In addition, severe adverse events experienced as a consequence of lymphadenectomy outnumbered those reported when no lymphadenectomy was performed. The overall quality of the evidence for lymphadenectomy versus standard surgery was moderate for survival outcomes and adverse events (other than evidence for presence or absence of lymphoedema or lymphocyst, which was of high quality). The quality of evidence for quality of life was very low, as this outcome was not reported. The uncertainty of whether lymphadenectomy or no lymphadenectomy is best in the management of early-stage endometrial cancer probably reflects the fact that evidence shows no reduction in death or in disease relapse when lymphadenectomy is performed, rather than lack of evidence. In addition, women undergoing lymphadenectomy experienced more severe adverse events than those who did not undergo lymphadenectomy. |
We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients. | We searched the medical literature until 26 March 2015. This review includes one study with 117 participants in which a tooth (117 premolars) received a carbon fibre post, and was restored with either a fused porcelain to metal crown or a routine white filling. The study was of short duration (three years), included a relatively small number of participants, and was assessed to be at a high risk of bias due to missing results for people who dropped out of the study. The evidence produced from one study concluded that none of the 117 root-filled premolars experienced a catastrophic failure (i.e. one that cannot be repaired) after three years, although only 104 teeth were included in the final, three-year assessment. The study concluded there was no difference between treatments for the risk of non-catastrophic failure. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of decay, periodontal health status, and costs. The quality of the evidence is very low. As there is only a single study, which is at high risk of bias, there is insufficient reliable evidence to determine whether single crowns are better than routine fillings. Future research should aim to provide more reliable information that can help clinicians to decide on appropriate treatment whilst taking into consideration the individual circumstances and preferences of their patients. |
In total 437 eligible women were randomised to receive high dose chemotherapy with autograft and 413 were randomised to receive conventional treatment. There were fifteen treatment-related deaths among the high dose group and two in the control (conventional dose) group (RR 4.08, 95% CI 1.40 to 11.93). There was no statistically significant difference in overall survival between the high dose and control groups at three years or five years. At five years of follow up, there was a statistically significant difference in event-free survival, favouring the high dose group (RR 2.84, 95% CI 1.07 to 7.50). Toxicity was more severe in the high dose group. Only one of the trials has followed up all women for five years. Although there is evidence that high dose chemotherapy and autograft significantly improves event-free survival compared to conventional chemotherapy in women with metastatic breast cancer there is no significant evidence of benefit in overall survival. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials. | This review identified six randomised trials including 437 women receiving high dose chemotherapy with autograft and 413 women receiving conventional chemotherapy treatment. In the group receiving the high dose chemotherapy, there were 15 treatment-related deaths as opposed to two in the conventional chemotherapy arm. Although the high-dose treatment did not increase overall survival at 5 years compared with conventional treatment, women on the high-dose treatment survived significantly longer before experiencing recurrence of cancer. Treatment side-effects were worse in the high-dose group. On the basis of this review, the authors conclude that high dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials. |
We identified 11 completed trials (1369 participants) and one ongoing trial. Trials were heterogeneous in participants recruited, qigong duration and length of follow-up periods. We were unable to ascertain the risk of bias in nine trials published in Chinese, as insufficient methodological details were reported and we were unable to contact the study authors to clarify this. We performed no meta-analyses, as trials were small and were at significant risk of bias. Clinical events were detailed in subsequent reports of two trials when statistically significant effects of qigong were seen for all-cause mortality, stroke mortality and stroke incidence at 20 to 30 years after completion of the trials. However, these trials were designed to examine outcomes in the short term, and it is not clear whether qigong was practised during extended periods of follow-up; therefore effects cannot be attributed to the intervention. None of the included studies reported other non-fatal CVD events. Six trials provided data that could be used to examine the effects of qigong on blood pressure. Reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were seen in three and two trials, respectively. Three trials examined the effects of qigong on blood lipids when favourable effects were seen in one trial for total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and two trials showed favourable effects on high-density lipoprotein (HDL) cholesterol. The only trial considered at low risk of selection and detection bias did not demonstrate statistically significant effects on CVD risk factors with qigong, but this study was small and was underpowered. None of the included studies reported incidence of type 2 diabetes (T2D), adverse events, quality of life or costs. Currently, very limited evidence is available on the effectiveness of qigong for the primary prevention of CVD. Most of the trials included in this review are likely to be at high risk of bias, so we have very low confidence in the validity of the results. Publication of the ongoing trial will add to the limited evidence base, but further trials of high methodological quality with sufficient sample size and follow-up are needed to be incorporated in an update of this review before the effectiveness of qigong for CVD prevention can be established. | The evidence is current to November 2014. We included trials with interventions lasting at least three months. We found 11 completed trials (1369 participants). These trials showed variation in participants recruited, duration of qigong and follow-up of the interventions. For two trials that were followed up for many years after trial completion, results showed that qigong had a beneficial effect on all-cause mortality, stroke mortality and stroke incidence, but it is not clear whether this effect can be attributed to qigong, as it is uncertain whether qigong was practised during the years after the trials ended. Some beneficial effects of qigong on blood pressure and blood lipid levels were observed, but these results were based on only a small number of studies with small sample size that were at significant risk of bias. Therefore, additional large, high-quality, long-term trials are needed before we will be able to determine whether qigong is beneficial for the prevention of cardiovascular disease. |
We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs. Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence). Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour. There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL). The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm. Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH). Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited. Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed. | On 12 November 2015 we searched for evidence from randomised controlled trials and found a single trial conducted across four rural districts in Ghana. The trial randomised 28 community health officers (serving 2404 potentially eligible pregnant women) to the intervention group and 26 community health officers (3515 potentially eligible pregnant women) to the control group. It was uncertain from this trial whether the intervention prevented loss of more than one litre of blood (severe PPH) as the results were variable and suggested anything between a 98% decrease to a 30% increase in blood loss (very low-quality evidence). Because there were no cases of severe maternal illness (for example, because of uterine rupture), or maternal deaths, it was not possible to fully assess the effect of the intervention on those outcomes (thequality of the evidence was very low). The women receiving oxytocin had half the incidence of PPH (> 500 mL) compared with the control group (low-quality evidence). There was little or no difference between the oxytocin and control groups on the rates for transfer or referral of women to a healthcare facility (low-quality evidence), stillbirths (low-quality evidence), or the numbers of babies that died within three days of being born (low-quality evidence). There were no cases of oxytocin use during labour, needle-stick injury or any other major or minor adverse events or unanticipated harmful event. Overall, the quality of the evidence was low/very low because of methodological limitations in the trial and imprecision in the effect estimates for all the important outcomes. It is uncertain if the administration of oxytocin by community health officers without midwifery skills administered in non-health facility settings compared with a control group reduces the incidence of severe PPH, severe maternal illness or maternal deaths when compared with a control group. However, oxytocin probably decreases the incidence of PPH (> 500 mL). Considering the very specific setting where the trial was conducted and the limited role played by the community health officer in the trial, the applicability of the evidence is rather limited. Further high-quality randomised controlled trials are urgently needed to assess the effects of using oxytocin in pre-filled injection devices or other new delivery systems on severe PPH. Similarly, future studies should consider other important outcomes like possible adverse events and the acceptability of the intervention for mothers and other community stakeholders. |
We found one RCT with 174 participants and five CBAs with 48,058 participants assessing the effectiveness of vocational training (n = 1) and antiretroviral therapy (ART) (n = 5). We found no studies assessing psychological interventions. The one RCT was conducted in the United States; the five CBA studies were conducted in South Africa, India, Kenya, and Uganda. We graded all six studies as having a high risk of bias. The effectiveness of vocational intervention was assessed in only one study but we could not infer the intervention effect due to a lack of data. For pharmacological interventions, we found very low-quality evidence for a beneficial effect of ART on employment outcomes in five studies. Due to differences in outcome measurement we could only combine the results of two studies in a meta-analysis. Two studies compared employment outcomes of HIV+ persons on ART therapy to healthy controls. One study found a MD of -1.22 days worked per month (95% confidence interval (CI) -1.74 to -1.07) at 24-months follow-up. The other study found that the likelihood of being employed steadily increased for HIV+ persons compared to healthy individuals from ART initiation (OR 0.35, 95% CI 0.26 to 0.47) to three- to five-years follow-up (OR 0.73, 95% CI 0.42 to 1.28). Three other studies compared HIV+ persons on ART to HIV+ persons not yet on ART. Two studies indicated an increase in the likelihood of employment over time due to the impact of ART for HIV+ persons compared to HIV+ persons pre-ART (OR 1.75, 95% CI 1.44 to 2.12). One study found that the group on ART worked 12.1 hours more (95% CI 6.99 to 17.21) per week at 24-months follow-up than the average of the cohort of ART and pre-ART HIV+ persons which was 20.1 hours. We rated the evidence as very low quality for all comparisons due to a high risk of bias. We found very low-quality evidence showing that ART interventions may improve employment outcomes for HIV+ persons. For vocational interventions, the one included study produced no evidence of an intervention effect. We found no studies that assessed psychological interventions. We need more high-quality, preferably randomized studies to assess the effectiveness of RTW interventions for HIV+ persons. | We found five controlled before-after (CBA) studies from South Africa, India, Uganda, and Kenya and one randomized controlled trial from the USA. The studies included over 48,000 participants. Five studies examined antiretroviral therapy and one study examined vocational interventions as a way of improving return to work in HIV+ people. The five CBA studies found that antiretroviral therapy interventions may increase employment outcomes in HIV+ people. One study assessed the effect of making changes to work tasks or the work environment but did not report enough data to say if it helped or not. We found no studies on psychological support to help HIV+ people cope better. Overall, we found very low-quality evidence because the included studies all had a high risk of bias. We found very low-quality evidence that antiretroviral therapy interventions could improve employment outcomes for HIV+ people. We need high-quality, randomized trials to find out if pharmacological, vocational, and psychological interventions can improve employment outcomes for HIV+ people. |
Nine small trials involving 510 adults with potentially or evidently unstable fractures, were grouped into five comparisons. The interventional, clinical and methodological heterogeneity of trials precluded data pooling. Only one trial had secure allocation concealment. Two trials comparing a bridging (of the wrist) external fixator versus pins and plaster external fixation found no significant differences in function or deformity. One trial found tendencies for more serious complications but less subsequent discomfort and deformity in the fixator group. Three trials compared non-bridging versus bridging fixation. Of the two trials testing uni-planar non-bridging fixation, one found no significant differences in functional or clinical outcomes; the other found non-bridging fixation significantly improved grip strength, wrist flexion and anatomical outcome. The third trial found no significant findings in favour of multi-planar non-bridging fixation of complex intra-articular fractures. One trial using a bridging external fixator found that deploying an extra external fixator pin to fix the 'floating' distal fragment gave superior functional and anatomical results. One trial found no evidence of differences in clinical outcomes for hydroxyapatite coated pins compared with standard uncoated pins. Two trials compared dynamic versus static external fixation. One trial found no significant effects from early dynamism of an external fixator. The poor quality of the other trial undermines its findings of poorer functional and anatomical outcomes for dynamic fixation. There is insufficient robust evidence to determine the relative effects of different methods of external fixation. Adequately powered studies could provide better evidence. | Nine small randomised trials involving 510 adults with potentially or evidently unstable fractures, were grouped into five comparisons. The trials were too different to justify pooling of results. Only one trial used a best-practice method for preventing selection bias. Two trials comparing a bridging (of the wrist) external fixator versus pins and plaster external fixation found no statistically significant differences in function or deformity. One trial found tendencies for more serious complications but less subsequent discomfort and deformity in the fixator group. Three trials compared non-bridging versus bridging fixation, using external fixators. Two trials tested similar non-bridging fixators: one found no significant differences in functional or clinical outcomes, whereas the other found non-bridging fixation significantly improved grip strength, wrist flexion and anatomical outcome. The third trial found no significant findings in favour of multi-planar non-bridging fixation of complex fractures. One trial using a bridging external fixator found that fixing the distal fracture fragment with an extra external fixator pin gave superior functional and anatomical results. One trial found no evidence of differences in clinical outcomes for hydroxyapatite coated pins compared with standard uncoated pins. Two trials compared dynamic versus static external fixation. One trial found no significant effects from the early 'dynamism' of an external fixator. The poor quality of the other trial undermines its findings of poorer results for dynamic fixation. The review concluded that there is insufficient robust evidence to determine the relative effects of the different methods of external fixation. |
We included eight RCTs with 311 participants in this review. After exclusion of five participants, we included 306 participants in one or more outcomes. Five trials (240 participants) investigated the three main treatments: open necrosectomy (121 participants), minimally invasive step-up approach (80 participants), and peritoneal lavage (39 participants) and were included in the network meta-analysis. Three trials (66 participants) investigated the variations in the main treatments: early open necrosectomy (25 participants), delayed open necrosectomy (11 participants), video-assisted minimally invasive step-up approach (12 participants), endoscopic minimally invasive step-up approach (10 participants), minimally invasive step-up approach (planned surgery) (four participants), and minimally invasive step-up approach (continued percutaneous drainage) (four participants). The trials included infected or sterile necrotising pancreatitis of varied aetiology. All the trials were at unclear or high risk of bias and the overall quality of evidence was low or very low for all the outcomes. Overall, short-term mortality was 30% and serious adverse events rate was 139 serious adverse events per 100 participants. The differences in short-term mortality and proportion of people with serious adverse events were imprecise in all the comparisons. The number of serious adverse events and adverse events were fewer in the minimally invasive step-up approach compared to open necrosectomy (serious adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68; 88 participants; 1 study; adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68; 88 participants; 1 study). The proportion of people with organ failure and the mean costs were lower in the minimally invasive step-up approach compared to open necrosectomy (organ failure: OR 0.20, 95% CI 0.07 to 0.60; 88 participants; 1 study; mean difference in costs: USD -11,922; P value < 0.05; 88 participants; 1 studies). There were more adverse events with video-assisted minimally invasive step-up approach group compared to endoscopic-assisted minimally invasive step-up approach group (rate ratio 11.70, 95% CI 1.52 to 89.87; 22 participants; 1 study), but the number of interventions per participant was less with video-assisted minimally invasive step-up approach group compared to endoscopic minimally invasive step-up approach group (difference in medians: 2 procedures; P value < 0.05; 20 participants; 1 study). The differences in any of the other comparisons for number of serious adverse events, proportion of people with organ failure, number of adverse events, length of hospital stay, and intensive therapy unit stay were either imprecise or were not consistent. None of the trials reported long-term mortality, infected pancreatic necrosis (trials that included participants with sterile necrosis), health-related quality of life at any time frame, proportion of people with adverse events, requirement for additional invasive intervention, time to return to normal activity, and time to return to work. Low to very low quality evidence suggested that the minimally invasive step-up approach resulted in fewer adverse events, serious adverse events, less organ failure, and lower costs compared to open necrosectomy. Very low quality evidence suggested that the endoscopic minimally invasive step-up approach resulted in fewer adverse events than the video-assisted minimally invasive step-up approach but increased the number of procedures required for treatment. There is currently no evidence to suggest that early open necrosectomy is superior or inferior to peritoneal lavage or delayed open necrosectomy. However, the CIs were wide and significant benefits or harms of different treatments cannot be ruled out. The TENSION trial currently underway in Netherlands is assessing the optimal way to perform the minimally invasive step-up approach (endoscopic drainage followed by endoscopic necrosectomy if necessary versus percutaneous drainage followed by video-assisted necrosectomy if necessary) and is assessing important clinical outcomes of interest for this review. Implications for further research on this topic will be determined after the results of this RCT are available. | Eight trials including 311 participants met the inclusion criteria for the review, of whom 306 participants were included in various comparisons. The treatments compared in five trials included necrosectomy, peritoneal lavage, and the step-up approach. Three other trials compared variations in timing of necrosectomy and methods of step-up approach. The participants in the trials had infected or sterile pancreatic necrosis resulting from varying causes. Overall, the short-term death rate (mortality over a short time) was 30% and serious adverse events (side effects or complications) rate was 139 per 100 participants. The differences in short-term mortality and percentage of people with serious adverse events were imprecise in all the comparisons. The number of serious adverse events and adverse events were fewer in the minimally invasive step-up approach compared to open necrosectomy. The complications resulting from the disease and treatment included heart failure (heart does not pump enough blood around the body at the correct pressure), lung failure (lungs do not remove waste products from the blood), kidney failure (kidneys do not remove waste products from the blood), and blood poisoning (micro-organisms and their poisons are in the blood). The percentage of people with organ failure and the average costs were lower in the minimally invasive step-up approach compared to open necrosectomy. The number of adverse events were more with the video-assisted minimally invasive step-up approach compared to the endoscopic-assisted minimally invasive step-up approach but the total numbers of procedures performed were less with the video-assisted minimally invasive step-up approach compared to the endoscopic minimally invasive step-up approach. The differences in any of the other comparisons for number of serious adverse events, percentage of people with organ failure, number of adverse events, length of hospital stay, and intensive therapy unit stay were either imprecise or were not consistent. None of the trials reported long-term mortality, infected pancreatic necrosis (in trials that included participants with sterile necrosis), health-related quality of life (which measures physical, mental, emotional, and social functioning), percentage of people with adverse events, requirement for additional invasive intervention, time to return to normal activity, and time to return to work. The overall quality of evidence was low or very low for all the measurement because the trials were at high risk of bias (e.g. prejudice of people who conducted the trial and trial participants who prefer one treatment over another) and were small trials. As a result, further studies are required on this topic. |
We included 18 studies that randomised a total of 2438 participants - both adults and children - and performed comparisons of interest. Included studies assessed higher versus lower doses of prednisolone (n = 4); longer versus shorter courses of prednisolone (n = 3) or dexamethasone (n = 1); tapered versus non-tapered courses of prednisolone (n = 4); and prednisolone versus dexamethasone (n = 6). Follow-up duration ranged from seven days to six months. The smallest study randomised just 15 participants, and the largest 638 (median 93). The varied interventions and outcomes reported limited the number of meaningful meta-analyses that we could perform. For two of our primary outcomes - hospital admission and serious adverse events - events were too infrequent to permit conclusions about the superiority of one treatment over the other, or their equivalence. Researchers in the included studies reported asthma symptoms in different ways and rarely used validated scales, again limiting our conclusions. Secondary outcome meta-analysis was similarly hampered by heterogeneity among interventions and outcome measures used. Overall, we found no convincing evidence of differences in outcomes between a higher dose or longer course and a lower dose or shorter course of prednisolone or dexamethasone, or between prednisolone and dexamethasone. Included studies were generally of reasonable methodological quality. Review authors assessed most outcomes in the review as having low or very low quality, meaning we are not confident in the effect estimates. The predominant reason for downgrading was imprecision, but indirectness and risk of bias also reduced our confidence in some estimates. Evidence is not strong enough to reveal whether shorter or lower-dose regimens are generally less effective than longer or higher-dose regimens, or indeed that the latter are associated with more adverse events. Any changes recommended for current practice should be supported by data from larger, well-designed trials. Varied study design and outcome measures limited the number of meta-analyses that we could perform. Greater emphasis on palatability and on whether some regimens might be easier to adhere to than others could better inform clinical decisions for individual patients. | We included 18 studies involving 2438 adults and children. Studies compared two types of steroid - prednisolone and dexamethasone - or two different doses or durations of either drug. The smallest study included just 15 people, and the largest 638. Studies followed people for between seven days and six months to see what happened to them. The evidence presented here is current to April 2016. It was difficult to combine the results of studies in a useful way because investigators used a variety of doses and durations of steroids and measured their results in different ways. Also, events such as hospital admissions and serious side effects happened very rarely in these studies, making it difficult to tell whether longer or shorter courses or higher or lower doses are better or safer, or if prednisolone is generally better or worse than dexamethasone. Some studies were old and did not use steroid doses or durations used by medical practitioners today. Any changes to the way in which asthma attacks are currently managed with oral steroids would need to be supported by larger studies than have been conducted so far. Evidence presented in this review is generally considered to be of low or very low quality, which means we are not very sure whether the results are accurate, mostly because we have not been able to combine many studies. Some studies did not clearly explain how trial organisers decided which people would receive which dose of steroids, and in some studies, both participants and trial organisers knew which dose they were getting. This may have affected study results. |
In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results. | We searched several electronic databases to find high quality trials about this topic. Two authors independently read reports on the trials to decide whether or not to include them in the review, and they independently extracted the trial data so as not to miss any important information. The search yielded two high quality trials including a total of 381 participants. The statistical analyses resulted in similar rates of pancreatic fistula (about 35%), deaths after surgery (about 1%) and average operation time between the two operation methods. Individual surgeons can choose which closure technique to use after removing of the tail of the pancreas according to their preferences and the participant's anatomic characteristics. More high quality trials on this topic would be beneficial, and studies investigating new methods should compare them either to stapler or hand-sewn closure in order to ensure comparability of results. |
We included five small trials involving 169 participants with patella fractures. Participant age ranged from 16 to 76 years. There were 68 females and 100 males; the gender of one participant was not reported. Two trials were conducted in China and one each in Finland, Mexico and Turkey. All five trials compared different surgical interventions. Two trials compared biodegradable versus metallic implants for treating displaced patella fractures; one trial compared patellectomy with advancement of vastus medialis obliquus versus simple patellectomy for treating comminuted patella fractures; and two trials compared percutaneous osteosynthesis (both procedures were 'novel' and one used a new device) versus open surgery for treating displaced patella fractures. All the trials had design flaws, such as lack of assessor blinding, which put them at high risk of bias, potentially limiting the reliability of their findings. No trial reported on health-related quality of life, return to previous activity or cosmetic appearance. Very low quality evidence from two trials (48 participants) comparing biodegradable versus metallic implants indicated little difference between the two interventions at two-year follow-up in the numbers of participants with occasional knee pain (1/23 versus 2/24), incurring adverse events (3/24 versus 1/24) or with reduced knee motion (2/23 versus 2/24). Neither trial reported patient-rated knee function scores. In one trial, as per routine practice, metallic implants were removed one year after surgery (four participants). The other trial did not report on this aspect. Very low quality evidence from one trial (28 participants) indicated that compared with simple patellectomy, patellectomy with advancement of vastus medialis obliquus surgery for treating comminuted patella fractures resulted in more participants with a 'good' result based on a subjectively rated score (12/12 versus 11/16; risk ratio (RR) 1.42, 95% confidence interval (CI) 1.01 to 2.01), fewer participants experiencing knee pain (5/12 versus 13/16; RR 3.11, 95% CI 1.01 to 9.60) and more participants with unlimited activity and no loss in quadriceps strength at four-year follow-up. The only adverse event reported was a patellar tendon subluxation in the simple patellectomy group. Neither trial comparing percutaneous osteosynthesis (using novel devices or methods) versus open surgery reported on patient-rated knee function scores. Very low quality evidence from two trials (93 participants) showed that percutaneous osteosynthesis improved knee pain measured using visual analogue scale (0 to 10 where 10 is worst pain) at one month (mean difference (MD) -2.24, 95% CI -2.80 to -1.68) and at up to three months (MD -1.87, 95% CI -2.45 to -1.29). This effect did not persist at six months (very low quality evidence from one trial). Very low quality evidence from the two trials showed significantly fewer participants with adverse events (loss of reduction, infection, hardware complications, delayed wound healing) after percutaneous surgery (8/47 versus 28/46; RR 0.28, 95% CI 0.14 to 0.55). Very low quality evidence from the two trials indicated better clinician-rated knee function scores after percutaneous fixation at two to three months and 12 months follow-up; however, the between-group difference was not clinically important at 24 months. Very low quality evidence showed a lower incidence of hardware removal in the percutaneous group at two years; however, the results in the two trials were heterogeneous and the reasons for removal were not given in detail. There is very limited evidence from RCTs about the relative effects of different surgical interventions for treating fractures of the patella in adults. There is no evidence from RCTs evaluating the relative effects of surgical versus conservative treatment or different types of conservative interventions. Based on very low quality evidence, biodegradable implants seem to be no better than metallic implants for displaced patellar fractures; patellectomy with vastus medialis obliquus advancement may give better results than simple patellectomy for comminuted patellar fractures; and two novel methods of percutaneous osteosynthesis may give better results than conventional open surgery. However, until conclusive evidence becomes available, treatment options must be chosen on an individual patient basis, carefully considering the relative benefits and harms of each intervention and patient preferences. Further randomised trials are needed, but in order to optimise research effort, these should be preceded by research that aims to identify priority questions. | We searched the scientific literature up to May 2014 and found five relevant studies with a total of 169 participants. Participants in these studies were aged between 16 and 76 years. There were 68 females and 100 males; the gender of one participant was not reported. Two studies were conducted in China, and one each in Finland, Mexico and Turkey. All five studies compared different types of surgery or surgical devices. Thus, we found no studies comparing different types of conservative treatment or surgery versus conservative treatment. The five studies made three comparisons. We judged the evidence available for each comparison was of very low quality. This was because all the trials had design flaws that put them at high risk of bias and the studies were also too small. What the included studies found None of the studies reported on health-related quality of life, return to previous activity or cosmetic appearance. Two studies comparing biodegradable (non-metallic) versus metallic implants found little difference in outcomes (knee pain, adverse events and function) between the two groups. Neither study reported on patient-rated function. One study compared patellectomy with repositioning of a tendon with simple patellectomy (kneecap is removed) for treating complex kneecap fractures. It found that tendon repositioning resulted in more participants reporting better knee function and fewer participants with pain and limited knee function. One participant had an adverse event. Two studies found that novel methods of percutaneous fixation (surgery using small incisions to insert the fixation devices) resulted in less knee pain and fewer adverse events (mainly relating to the fracture fixation materials) than open surgery (involving wide incisions). Neither study reported on patient-rated function. Conclusions Overall, the evidence is very low quality and is insufficient to draw firm conclusions about the best method of treatment for kneecap fractures. Treatment options must be chosen on an individual patient basis, carefully considering the relative benefits and harms of each intervention and patient preferences. Further research is warranted and should be preceded by research to determine which questions should be prioritised. |
We included 15 studies with 724 participants. We found a range of treatment protocols in terms of duration of care, TENS application times and intensity of application. Briefly, duration of care ranged from four days through to three months. Similarly, we found variation of TENS application times; from 15 minutes up to hourly sessions applied four times daily. We typically found intensity of TENS set to comfortable perceptible tingling with very few studies titrating the dose to maintain this perception. Of the comparisons, we had planned to explore, we were only able to undertake a quantitative synthesis for TENS versus sham TENS. Insufficient data and large diversity in the control conditions prevented us from undertaking a quantitative synthesis for the remaining comparisons. For TENS compared to sham TENS, five studies were suitable for pooled analysis. We described the remainder of the studies in narrative form. Overall, we judged 11 studies at high risk of bias, and four at unclear risk. Due to the small number of eligible studies, the high levels of risk of bias across the studies and small sample sizes, we rated the quality of the evidence as very low for the pooled analysis and very low individual GRADE rating of outcomes from single studies. For the individual studies discussed in narrative form, the methodological limitations, quality of reporting and heterogeneous nature of interventions compared did not allow for reliable overall estimates of the effect of TENS. Five studies (across various neuropathic conditions) were suitable for pooled analysis of TENS versus sham TENS investigating pain intensity using a visual analogue scale. We found a mean postintervention difference in effect size favouring TENS of -1.58 (95% confidence interval (CI) -2.08 to -1.09, P < 0.00001, n = 207, six comparisons from five studies) (very low quality evidence). There was no significant heterogeneity in this analysis. While this exceeded our prespecified minimally important difference for pain outcomes, we assessed the quality of evidence as very low meaning we have very little confidence in this effect estimate and the true effect is likely to be substantially different from that reported in this review. Only one study of these five investigated health related quality of life as an outcome meaning we were unable to report on this outcome in this comparison. Similarly, we were unable to report on global impression of change or changes in analgesic use in this pooled analysis. Ten small studies compared TENS to some form of usual care. However, there was great diversity in what constituted usual care, precluding pooling of data. Most of these studies found either no difference in pain outcomes between TENS versus other active treatments or favoured the comparator intervention (very low quality evidence). We were unable to report on other primary and secondary outcomes in these single trials (health-related quality of life, global impression of change and changes in analgesic use). Of the 15 included studies, three reported adverse events which were minor and limited to 'skin irritation' at or around the site of electrode placement (very low quality evidence). Three studies reported no adverse events while the remainder did not report any detail with regard adverse events. In this review, we reported on the comparison between TENS and sham TENS. The quality of the evidence was very low meaning we were unable to confidently state whether TENS is effective for pain control in people with neuropathic pain. The very low quality of evidence means we have very limited confidence in the effect estimate reported; the true effect is likely to be substantially different. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment modality. | We reviewed all eligible clinical trials comparing TENS to 'fake' TENS (known as 'sham'), usual care or no treatment, or comparing TENS plus usual care versus usual care alone, for neuropathic pain in adults. As of September 2016, we found 15 studies eligible for inclusion. Of these 15 studies, we were able to combine results from five studies to investigate the effect of TENS compared to sham TENS for treatment of pain. The studies involved a range of neuropathic pain problems (e.g. people with spinal cord injury, back pain with nerve involvement, complications associated with diabetes, etc.). We found the quality of the studies overall to be low. We were unable to confidently state whether TENS is effective in relieving pain compared to sham TENS in people with neuropathic pain. This is due to the very low quality of the evidence, which means we have very limited confidence in this result and that future studies are likely to change this result. Lack of reported data meant we were unable to draw any conclusion on the effect of TENS treatment on health related quality of life, pain relieving medicine use or people's impression of how TENS changed their condition. We described the results of 10 further studies comparing TENS against other types of treatment. These 10 studies were quite varied and so we could not combine them and analyse them together. This, together with the very low quality of these 10 studies, meant we were unable to judge pain relief, health related quality of life, pain medication use or impression of change. In three of the 15 studies, some people using TENS experienced skin irritation under the electrode pads. Three studies reported no problems and the remaining studies did not provide any details on side effects. Based on this, it is not realistic to comment on side effects associated with TENS use. |
We included five randomized trials (208 participants, 104 in the intervention group and 104 in the control group). Interventions ranged from three to six months. Four trials reported results in non-Asian populations published in English. One trial reported results in Chinese people published in Chinese. Overall, the risk of bias of included trials was high or unclear. There were no outcome data on death from any cause, morbidity, complications, health-related quality of life and costs. Two trials reported adverse effects, including gastrointestinal discomfort (bloating and constipation) and an increased number of hot flushes. None of the trials found serious adverse events. There was a slight significant effect on triglycerides in favour of isoflavones when compared with placebo (mean difference (MD) -0.46 mmol/L (95% confidence interval (CI) -0.84 to -0.09; P = 0.02; 52 participants; 2 trials). No statistically significant effects on total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were shown in favour of isoflavones. We found no evidence for effects of isoflavones on patient-important outcomes or lowering of cholesterol levels in people with hypercholesterolaemia. Our findings have to be interpreted with caution due to high or unclear risk of bias in several risk of bias domains, and low number of participants in trials. | To assess the effects of isoflavones for the treatment of hypercholesterolaemia, we examined five randomized controlled trials of isoflavones or soy protein containing isoflavones. The trials lasted three to six months and involved 208 participants. There were no outcome data on death from any cause, cardiovascular events such as heart attack or stroke, morbidity, complications, health-related quality of life and costs. Two trials reported adverse effects, including gastrointestinal discomfort (bloating and constipation) and an increased number of hot flushes. They observed no serious adverse events. In our included studies, we found no cholesterol-lowering effect of isoflavones. However, the quality of the included trials had some considerable limitations and the number of the participants was low. Further higher-quality and rigorously performed studies on patient-important outcome measures such as cardiovascular diseases and health-related quality of life are required. |
Eighteen trials met our inclusion criteria. Eleven studies are complete (1392 participants), and seven are ongoing. Of the completed studies, seven interventions are broad, targeting the lifestyle management of CHD, and four focused on physical activity promotion. The comparison group in trials was usual care (n = 6), minimal intervention (n = 3), or traditional cardiac rehabilitation (n = 2). We found no effects of Internet-based interventions for all-cause mortality (odds ratio (OR) 0.27, 95% confidence interval (CI) 0.04 to 1.63; participants = 895; studies = 6; low-quality evidence). There was only one case of cardiovascular mortality in a control group (participants = 895; studies = 6). No incidences of non-fatal re-infarction were reported across any of the studies. We found no effects for revascularisation (OR 0.69, 95% CI 0.37 to 1.27; participants = 895; studies = 6; low-quality evidence). We found no effects for total cholesterol (mean difference (MD) 0.00, 95% CI -0.27 to 0.28; participants = 439; studies = 4; low-quality evidence), high-density lipoprotein (HDL) cholesterol (MD 0.01, 95% CI -0.06 to 0.07; participants = 437; studies = 4; low-quality evidence), or triglycerides (MD 0.01, 95% CI -0.17 to 0.19; participants = 439; studies = 4; low-quality evidence). We did not pool the data for low-density lipoprotein (LDL) cholesterol due to considerable heterogeneity. Two out of six trials measuring LDL cholesterol detected favourable intervention effects, and four trials reported no effects. Seven studies measured systolic and diastolic blood pressure; we did not pool the data due to substantial heterogeneity. For systolic blood pressure, two studies showed a reduction with the intervention, but the remaining studies showed no effect. For diastolic blood pressure, two studies showed a reduction with the intervention, one study showed an increase with the intervention, and the remaining four studies showed no effect. Five trials measured health-related quality of life (HRQOL). We could draw no conclusions from one study due to incomplete reporting; one trial reported no effect; two studies reported a short- and medium-term effect respectively; and one study reported both short- and medium-term effects. Five trials assessed dietary outcomes: two reported favourable effects, and three reported no effects. Eight studies assessed physical activity: five of these trials reported no physical activity effects, and three reported effectiveness. Trials are yet to measure the impact of these interventions on compliance with medication. Two studies measured healthcare utilisation: one reported no effects, and the other reported increased usage of healthcare services compared to a control group in the intervention group at nine months' follow-up. Two trials collected cost data: both reported that Internet-delivered interventions are likely to be cost-effective. In terms of the risk of bias, the majority of studies reported appropriate randomisation and appropriate concealment of randomisation processes. A lack of blinding resulted in a risk of performance bias in seven studies, and a risk of detection bias in five trials. Two trials were at risk of attrition bias, and five were at risk for reporting bias. In general, evidence was of low quality due to lack of blinding, loss to follow-up, and uncertainty around the effect size. Few studies measured clinical events, and of those that did, a very small number of events were reported, and therefore no firm conclusions can be made. Similarly, there was no clear evidence of effect for cardiovascular risk factors, although again the number of studies reporting these was small. There was some evidence for beneficial effects on HRQOL, dietary outcomes, and physical activity, although firm conclusions cannot yet be made. The effects on healthcare utilisation and cost-effectiveness are also inconclusive, and trials are yet to measure the impact of Internet interventions on compliance with medication. The comparison groups differed across trials, and there were insufficient studies with usable data for subgroup analyses. We intend to study the intensity of comparison groups in future updates of this review when more evidence is available. The completion of the ongoing trials will add to the evidence base. | The evidence is current to December 2014. We included 18 studies. Eleven are complete, and seven are ongoing. In the completed studies, 1392 people with coronary heart disease were recruited. The average age of participants ranged from 54.9 to 66.27 years. The majority of people recruited were men. Studies were carried out worldwide, and in a variety of healthcare settings. Seven studies tested broad programmes targeting multiple lifestyle factors related to heart disease. Four studies tested programmes focused only on increasing levels of physical activity. The length of the programmes in the included studies ranged from six weeks to one year. These programmes were compared to no intervention in six studies, some support in three studies, and full traditional rehabilitation in two studies. There is no evidence to date to suggest that Internet-delivered programmes help reduce rates of death or future cardiac surgery, but this was based on a small number of studies. There is also no strong evidence to date suggesting a benefit of these programmes for lipid levels or blood pressure. There is some evidence to suggest improvements in HRQOL and behaviour change, but there is insufficient evidence to date to draw firm conclusions. Studies have not yet measured the impact of Internet-delivered programmes on medication compliance. There was very limited information on healthcare utilisation and cost of interventions. The reporting of the seven ongoing studies will add to the evidence base. The evidence was generally of low quality. The included studies were at some risk of bias, with six studies judged at high risk of bias for some risk of bias domains. The results of this review therefore need to be interpreted cautiously. There is currently limited evidence on the effects of Internet-based interventions for the treatment of coronary heart disease. We identified seven ongoing trials, which we will incorporate into this review when the results are available. |
We included 24 trials involving 23,748 participants. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence relates to the effects of anticoagulant therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on eight trials (22,125 participants), there was no evidence that early anticoagulation reduced the odds of being dead or dependent at the end of follow-up (OR 0.99; 95% CI 0.93 to 1.04). Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99). Since the last version of the review, no new relevant studies have been published and so there is no additional information to change the conclusions. Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any of the currently available anticoagulants in acute ischaemic stroke. | This systematic review was designed to find out whether people treated with anticoagulants soon after having a stroke got better or not, and whether they had problems with bleeding. There is a lot of information in this systematic review - 23,748 people with stroke have been involved in 24 included randomised trials to answer this question. People treated with anticoagulants did not have less long-term disability, and experienced more bleeding. Anticoagulant treated patients had less chance of developing blood clots in their legs and in their lungs following their stroke, but these benefits were offset by the increased number of bleeds. This review did not provide any evidence that the early use of anticoagulants is of overall benefit to people with strokes caused by blood clots. More research is needed to find out if there are ways to select the people with stroke who will benefit from anticoagulants without suffering the bleeding complications. |
We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered. We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants). Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality). There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine. | We identified 26 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), involving 1728 opioid-dependent participants. The studies were undertaken in 12 different countries and involved treatment with an alpha2-adrenergic agonist (clonidine, lofexidine, guanfacine, and in one study, tizanidine) compared with reducing doses of methadone (12 studies), placebo (six studies), or symptomatic medications (four studies). Five studies compared different alpha2-adrenergic agonists. Treatment was scheduled to last for one to two weeks in most studies; the shortest duration was three days, and the longest was 30 days. Six studies received some financial support from a pharmaceutical company. Opioid withdrawal was similar with alpha2-adrenergic agonists and reducing doses of methadone, but the duration of treatment was longer and there were fewer adverse effects with methadone. Withdrawal signs and symptoms occurred earlier with alpha2-adrenergic agonists, within a few days of cessation of the opioid drugs. The chances of completing withdrawal treatment were similar. Clonidine and lofexidine were more effective than placebo in managing withdrawal from heroin or methadone, and were associated with higher chances of completing treatment. Lofexidine had less effect on blood pressure than clonidine. For alpha2-adrenergic agonists compared with placebo, the evidence was very low to moderate quality, indicating that further evidence would be likely to change the estimates of relative effect made in this review. However, the evidence is sufficient to indicate that alpha2-adrenergic agonists are more effective than placebo, making further comparisons of this nature inappropriate on ethical grounds. For the comparison of alpha2-adrenergic agonists with reducing doses of methadone, the evidence was low to moderate quality. The key reasons for the low quality were small numbers of studies reporting some outcomes, low rates of occurrence of some events (for example drop-out due to adverse effects), and variability between studies. |
Twelve RCTs and three CCTs were identified, all focusing on BN, BED, EDNOS or combinations of these, in adults, using manual-based PSH/GSH across various settings. Primary comparisons: At end of treatment, PSH/GSH did not significantly differ from waiting list in abstinence from bingeing (RR 0.72, 95% CI 0.47 to 1.09), or purging (RR 0.86, 95% CI 0.68 to 1.08), although these treatments produced greater improvement on other eating disorder symptoms, psychiatric symptomatology and interpersonal functioning but not depression. Compared to other formal psychological therapies, PSH/GSH did not differ significantly at end of treatment or follow-up in improvement on bingeing and purging (RR 0.99, 95% CI 0.75 to 1.31), other eating disorder symptoms, level of interpersonal functioning or depression. There were no significant differences in treatment dropout. Secondary comparisons: One small study in BED found that cognitive-behavioural GSH compared to a non-specific control treatment produced significantly greater improvements in abstinence from bingeing and other eating disorder symptoms. Studies comparing PSH with GSH found no significant differences between treatment groups at end of treatment or follow-up. Comparison between different types of PSH/GSH found significant differences on eating disorder symptoms but not on bingeing/purging abstinence rates. PSH/GSH may have some utility as a first step in treatment and may have potential as an alternative to formal therapist-delivered psychological therapy. Future research should focus on producing large well-conducted studies of self-help treatments in eating disorders including health economic evaluations, different types and modes of delivering self-help (e.g. computerised versus manual-based) and different populations and settings. | This review aimed to evaluate pure self-help (PSH) and guided self-help (GSH) interventions for eating disorders for all ages and genders, compared to psychological, pharmacological or control treatments and waiting list. Fifteen trials were identified, all focused on BN, BED or EDNOS, using manual-based self-help. There is some evidence that PSH/GSH reduce eating disorder and other symptoms in comparison to waiting list or control treatment and may produce comparable outcomes to formal therapist-delivered psychological therapies. PSH/GSH may have some utility as a first step in treatment. In the future there need to be large well-conducted effectiveness studies of self-help treatments with or without guidance incorporating cost evaluations and investigation of different types of self-help in different populations and settings. |
We included 10 randomised clinical trials with 934 participants, but only five trials with 490 participants provided data for analysis. All the trials compared Xiao Chai Hu Tang formula with no intervention. All trials appeared to have been conducted and published only in China. The included trials assessed heterogeneous forms of Xiao Chai Hu Tang formula, administered for three to eight months. One trial included participants with hepatitis B and comorbid tuberculosis, and one trial included participants with hepatitis B and liver cirrhosis. The remaining trials included participants with hepatitis B only. All the trials were at high risk of bias, and the certainty of evidence for all outcomes that provided data for analyses was very low. We downgraded the evidence by one or two levels because of outcome risk of bias, inconsistency or heterogeneity of results (opposite direction of effect), indirectness of evidence (use of surrogate outcomes instead of clinically relevant outcomes), imprecision of results (the CIs were wide), and publication bias (small sample size of the trials). Additionally, 47 trials lacked the necessary methodological information needed to ensure the inclusion of these trials in our review. None of the included trials aimed to assess clinically relevant outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. The effects of Xiao Chai Hu Tang formula on the proportion of participants with adverse events considered 'not to be serious' is uncertain (RR 0.43, 95% CI 0.02 to 11.98; I2 = 69%; very low-certainty evidence). Only three trials with 222 participants reported the proportion of people with detectable hepatitis B virus DNA (HBV-DNA), but the evidence that Xiao Chai Hu Tang formula reduces the presence of HBV-DNA in the blood (a surrogate outcome) is uncertain (RR 0.62, 95% CI 0.45 to 0.85; I2 = 0%; very low-certainty evidence). Only two trials with 160 participants reported the proportion of people with detectable hepatitis B virus e-antigen (HBeAg; a surrogate outcome) (RR 0.72, 95% CI 0.50 to 1.02; I2 = 38%; very low-certainty evidence) and the evidence is uncertain. The evidence is also uncertain for separately reported adverse events considered 'not to be serious'. Funding: two of the 10 included trials received academic funding from government or hospital. None of the remaining eight trials reported information on funding. The clinical effects of Xiao Chai Hu Tang formula for chronic hepatitis B remain unclear. The included trials were small and of low methodological quality. Despite the wide use of Xiao Chai Hu Tang formula, we lack data on all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The evidence in this systematic review comes from data obtained from a maximum three trials. We graded the certainty of evidence as very low for adverse events considered not to be serious and the surrogate outcomes HBeAg and HBV-DNA. We found a large number of trials which lacked clear description of their design and conduct, and hence, these trials are not included in the present review. As all identified trials were conducted in China, there might be a concern about the applicability of this review outside China. Large-sized, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding are lacking. | We included 10 randomised clinical trials (studies where people are randomly put into one of two or more treatment groups) with 934 participants. All trials compared Xiao Chai Hu Tang formula with no treatment. The trials assessed different formulas and doses for three to eight months. One trial included participants with tuberculosis (a disease of the lungs that can make you cough mucous), and one trial included participants with liver cirrhosis (scarring). Only five trials with 490 participants provided data for analysis Two of the 10 included trials reported receiving academic funding. None of the remaining eight trials reported information of support or funding. None of the 10 included trials reported data on all-cause mortality (death from any cause), serious side effects (untoward medical occurrences that result in serious outcomes such as death or disability), health-related quality of life (a measure of physical, mental, emotional, and social functioning a measure of a person's satisfaction with their life and health), hepatitis B-related death, and hepatitis B-related morbidity. We are uncertain whether Xiao Chai Hu Tang formula versus no intervention has a positive or negative effect regarding side effects considered 'not to be serious', the proportion of people with detectable HBeAg (a hepatitis B viral protein that indicates active viral replication), and separately reported side effects considered 'not to be serious'. Xiao Chai Hu Tang formula compared with no intervention seems to reduce the proportion of people with detectable HBV-DNA (which is used to indicate how much hepatitis B virus is in the blood) but the reliability of this finding is low. Surrogate outcomes are markers that are used in research as a substitute for a clinically meaningful measure that directly measures patient outcomes. We cannot always be certain that such surrogate outcomes are reliable substitutes for important outcomes as they need to be officially examined. Caution is needed with this beneficial finding as the trials are at high risk of bias, and this outcome has not yet been proven relevant to patients. We identified an additional 47 studies as potential randomised clinical trials, but the data they reported were of no use. Accordingly, properly designed randomised clinical trials are needed before the benefits and harms of Xiao Chai Hu Tang formula for chronic hepatitis B can be determined. The reliability of the evidence on the use of Xiao Chai Hu Tang formula in people with chronic hepatitis B virus in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to hepatitis B virus infection, and serious side effects cannot be determined as no trials aimed to explore these. The reliability of the evidence that Xiao Chai Hu Tang formula, when compared with no intervention, in terms of side effects considered 'not to be serious', the proportion of people with detectable HBV-DNA, and the proportion of people with detectable HBeAg is very low. These assessments of the reliability of the evidence are due to the poor design and reporting of the included trials. |
A total of 12 studies involving 2342 children were included. Eleven out of 12 trials were conducted in North America, within urban or suburban settings involving vulnerable populations. The studies were overall of good methodological quality. They differed markedly in terms of age, severity of asthma, context and content of the educational intervention leading to substantial clinical heterogeneity. Due to this clinical heterogeneity, we did not pool results for our primary outcome, the number of patients with exacerbations requiring emergency department (ED) visit. The mean number of exacerbations requiring ED visits per person at six months was not significantly different between the home-based intervention and control groups (N = 2 studies; MD 0.04; 95% confidence interval (CI) -0.20 to 0.27). Only one trial contributed to our other primary outcome, exacerbations requiring a course of oral corticosteroids. Hospital admissions also demonstrated wide variation between trials with significant changes in some trials in both directions. Quality of life improved in both education and control groups over time. A table summarising some of the key components of the education programmes is included in the review. We found inconsistent evidence for home-based asthma educational interventions compared to standard care, education delivered outside of the home or a less intensive educational intervention delivered at home. Although education remains a key component of managing asthma in children, advocated in numerous guidelines, this review does not contribute further information on the fundamental content and optimum setting for such educational interventions. | The included studies varied in the characteristics of children (e.g. age, severity of asthma), the education delivered and the way each outcome was reported. This made it difficult to compare the results and provide overall conclusions and we did not pool results for most of the outcomes. There was also diversity in the findings of the individual trials. We were able to combine the results of two studies reporting the average number of emergency department visits per child, which was not different at six months between the home education group and the group receiving the usual care. Only one trial contributed to our other primary outcome, exacerbations (flare-ups) requiring a course of oral corticosteroids. Hospital admissions also demonstrated wide variation between trials with significant changes in some trials in both directions. Quality of life improved in both education and control groups over time. |
We included 12 studies, involving 622 participants with 648 fractures. Eight studies were randomised placebo-controlled trials, two were randomised controlled trials without placebo controls, one was a quasi-randomised placebo-controlled trial and one was a quasi-randomised controlled trial without placebo control. Eleven trials tested LIPUS and one trial tested ECSW. Four trials included participants with conservatively treated upper limb complete fractures and six trials included participants with lower limb complete fractures; these were surgically fixed in four trials. The remaining two trials reported results for conservatively treated tibial stress fractures. 'Risk of bias' assessment of the included studies was hampered by the poor reporting of methods, frequently resulting in the risk of bias of individual domains being judged as ‘unclear’. Both quasi-randomised studies were at high risk of bias, including selection and attrition bias. Three studies were at low risk of selection bias relating to allocation concealment the majority of studies were at low risk of performance bias as they employed a form of intervention blinding. Only limited data were available from three of only four studies reporting on functional outcome. One study of complete fractures found little evidence of a difference between the two groups in the time to return to work (mean difference (MD) 1.95 days favouring control, 95% confidence interval (CI) -2.18 to 6.08; 101 participants). Pooled data from two studies found LIPUS did not significantly affect the time to return to training or duty in soldiers or midshipmen with stress fractures (MD -8.55 days, 95% CI -22.71 to 5.61; 93 participants). We adopted a conservative strategy for data analysis that was more likely to underestimate than to overestimate a benefit of the intervention. After pooling results from eight studies (446 fractures), the data showed no statistically significant reduction in time to union of complete fractures treated with LIPUS (standardised mean difference (SMD) -0.47, 95% CI -1.14 to 0.20). This result could include a clinically important benefit or harm, and should be seen in the context of the highly significant statistical heterogeneity (I² = 90%). This heterogeneity was not explained by the a priori subgroup analyses (upper limb versus lower limb fracture, smoking status). An additional subgroup analysis comparing conservatively and operatively treated fractures raised the possibility that LIPUS may be effective in reducing healing time in conservatively managed fractures, but the test for subgroup differences did not confirm a significant difference between the subgroups. Pooled results from five of the eight trials (333 fractures) reporting proportion of delayed union or non-union showed no significant difference between LIPUS and control (10/168 versus 13/165; RR 0.75; 95% CI 0.24 to 2.28). Adverse effects directly associated with LIPUS and associated devices were found to be few and minor, and compliance with treatment was generally good. One study reporting on pain scores found no difference between groups at eight weeks (101 participants). One quasi-randomised study found no significant difference in non-union at 12 months between internal fixation supplemented with ECSW and internal fixation alone (3/27 versus 6/30; RR 0.56, 95% CI 0.15 to 2.01). There was a clinically small but statistically significant difference in the visual analogue scores for pain in favour of ECSW at three month follow-up (MD -0.80, 95% CI -1.23 to -0.37). The only reported complication was infection, with no significant difference between the two groups. While a potential benefit of ultrasound for the treatment of acute fractures in adults cannot be ruled out, the currently available evidence from a set of clinically heterogeneous trials is insufficient to support the routine use of this intervention in clinical practice. Future trials should record functional outcomes and follow-up all trial participants. | This is an update of a review previously published in February 2012. We did a new literature search up till 2 June 2014 but did not find any new studies. There are 12 studies, involving 622 participants with 648 fractures, included in this review. In all the studies we included, participants were assigned randomly to one of two groups, one group receiving treatment by ultrasound and the other group receiving no treatment or sham treatment. Most participants had a recent complete fracture of a single bone. The participants of two trials had 110 incomplete or stress fractures that resulted from heavy exercise. Four trials tested the effects of ultrasound on healing of 203 upper limb fractures and the other trials, on 130 lower limb fractures. The most commonly investigated bone was the tibia (shin bone). Eleven trials tested low-intensity pulsed ultrasound and one trial with 59 fractures tested shockwave therapy. Most trials compared a working ultrasound device with a sham device and thus protected against placebo effects. The placebo effect is a phenomenon whereby patients experience a treatment effect that is not objectively attributable to the treatment itself. However, studies varied substantially in terms of quality and risk of having biased results. In many cases the quality of reporting was poor, which made it difficult to determine which biases might have affected each study. The risk of bias across many domains therefore had to be judged as 'unclear'. The results of many trials were probably biased because of missing data from several trial participants. Additionally, the trials were very different from each other; for example, they varied in the bone that was broken and whether or not the fractures were also treated surgically. Based on analyses that adjusted for these missing data, the available evidence did not confirm that ultrasound improved the time taken for bone healing or prevented the problem of the bone failing to heal at all (eight trials with 333 fractures). The results from one low quality trial (with 59 fractures) testing shockwave therapy were inconclusive. Few complications were reported in any of the studies and these were not related to the ultrasound or shockwave therapy. While a potential benefit of ultrasound for the treatment of acute fractures in adults cannot be ruled out, the currently available evidence from 12 quite different trials is insufficient to support the routine use of ultrasound in clinical practice. Future studies should measure return to full function and normal activity and should try to ensure all participants are followed up. |
We included 40 new trials bringing the total to 87 included trials (7140 randomised teeth) for this update. All were small, single-centre trials (median number of randomised teeth = 68). All trials were assessed at unclear or high risk of bias. The 87 trials examined 125 different comparisons: 75 comparisons of different medicaments or techniques for pulpotomy; 25 comparisons of different medicaments for pulpectomy; four comparisons of pulpotomy and pulpectomy; and 21 comparisons of different medicaments for direct pulp capping. The proportion of clinical failures and radiological failures was low in all trials. In many trials, there were either no clinical failures or no radiographic failures in either study arm. For pulpotomy, we assessed three comparisons as providing moderate-quality evidence. Compared with formocresol, MTA reduced both clinical and radiological failures, with a statistically significant difference at 12 months for clinical failure and at six, 12 and 24 months for radiological failure (12 trials, 740 participants). Compared with calcium hydroxide, MTA reduced both clinical and radiological failures, with statistically significant differences for clinical failure at 12 and 24 months. MTA also appeared to reduce radiological failure at six, 12 and 24 months (four trials, 150 participants) (low-quality evidence). When comparing calcium hydroxide with formocresol, there was a statistically significant difference in favour of formocresol for clinical failure at six and 12 months and radiological failure at six, 12 and 24 months (six trials (one with no failures), 332 participants). Regarding pulpectomy, we found moderate-quality evidence for two comparisons. The comparison between Metapex and zinc oxide and eugenol (ZOE) paste was inconclusive, with no clear evidence of a difference between the interventions for failure at 6 or 12 months (two trials, 62 participants). Similarly inconclusive, there was no clear evidence of a difference in failure between Endoflas and ZOE (outcomes measured at 6 months; two trials, 80 participants). There was low-quality evidence of a difference in failure at 12 months that suggested ZOE paste may be better than Vitapex (calcium hydroxide/iodoform) paste (two trials, 161 participants). Regarding direct pulp capping, the small number of studies undertaking the same comparison limits any interpretation. We assessed the quality of the evidence as low or very low for all comparisons. One trial appeared to favour formocresol over calcium hydroxide; however, there are safety concerns about formocresol. Pulp treatment for extensive decay in primary teeth is generally successful. Many included trials had no clinical or radiological failures in either trial arm, and the overall proportion of failures was low. Any future trials in this area would require a very large sample size and follow up of a minimum of one year. The evidence suggests MTA may be the most efficacious medicament to heal the root pulp after pulpotomy of a deciduous tooth. As MTA is relatively expensive, future research could be undertaken to confirm if Biodentine, enamel matrix derivative, laser treatment or Ankaferd Blood Stopper are acceptable second choices, and whether, where none of these treatments can be used, application of sodium hypochlorite is the safest option. Formocresol, though effective, has known concerns about toxicity. Regarding pulpectomy, there is no conclusive evidence that one medicament or technique is superior to another, and so the choice of medicament remains at the clinician's discretion. Research could be undertaken to confirm if ZOE paste is more effective than Vitapex and to evaluate other alternatives. Regarding direct pulp capping, the small number of studies and low quality of the evidence limited interpretation. Formocresol may be more successful than calcium hydroxide; however, given its toxicity, any future research should focus on alternatives. | Review authors working with Cochrane Oral Health carried out this review of randomised controlled trials. The evidence is current up to August 2017. We included 87 trials that investigated the success of pulp treatment of milk teeth. The trials were published between 1989 and 2017 and provided 125 comparisons of different treatment options. Pulp treatment for extensive decay in primary teeth is generally successful. The proportion of treatment failures was low, with many of the included trials having no failures with either of the treatments being compared. After a pulpotomy, mineral trioxide aggregate (MTA) seems to be the best material (in terms of biocompatibility and efficacy) to put into contact with the remaining root dental nerve. The evidence showed it to be less likely to fail than either calcium hydroxide or formocresol. After pulpectomy, it is not clear whether any medicament is superior to another. ZOE paste may give better results than Vitapex (calcium hydroxide/iodoform) paste, but more studies are needed to confirm this and to explore other treatment options. Regarding direct pulp capping, the small number of studies undertaking the same comparison limits any interpretation. Formocresol may be superior to calcium hydroxide in terms of clinical and radiological failure, but because of toxic effects associated with formocresol, safer alternatives should be evaluated. We judged the quality of the evidence suggesting the superiority of MTA over calcium hydroxide or formocresol after pulpotomy to be moderate. For other comparisons, the quality of the evidence is low or very low, which means we cannot be certain about the findings. The low quality is due to shortcomings in the methods used within the individual trials, the small number of children included in the trials and the short-term follow-up after treatment. Future trials to evaluate which healing agents are best for the three pulp treatments would require a very large sample size and should follow up the participants of a minimum of one year. |
We included 26 trials (2756 participants), all conducted in China. All participants were inpatients within the first few days after stroke onset (mean age 58 to 75 years and male proportion 45% to 80%). Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days. The study quality was generally poor and many trials were poorly reported. Only one trial reported long-term death and disability, where stroke survivors in the buflomedil group had a lower risk of suffering 'death or disability' than those in the control group (200 participants, RR 0.71, 95% confidence interval (CI) 0.53 to 0.94). All 26 trials assessed outcomes by the end of treatment (eight trials with 1056 participants reported death, one trial with 85 participants reported disability, and 26 trials with 2756 participants reported neurological deficits), but there was no robust evidence for any of these short-term outcomes. Seventeen trials (1899 participants) investigated the presence of adverse events during the treatment, of which six trials (853 participants) reported "no significant adverse event in any participants" and the other 11 trials (1046 participants) reported a total of 38 adverse events in the buflomedil group and two events in the control group. In general, for each of these outcomes the quality of evidence was low according to the GRADE principles. There is insufficient evidence on the efficacy or safety of buflomedil to support its use for the treatment of acute ischaemic stroke. Given these uncertainties, the data support the rationale for an adequately powered RCT of buflomedil in people with acute ischaemic stroke. | The evidence is current to September 2014. We found 26 randomised controlled trials with 2756 participants. All these trials were conducted in China with adult stroke patients of both sexes. All participants were in hospital and within the first few days after the onset of their stroke. Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days. There was insufficient evidence to show whether buflomedil reduced the chance of dying or having less long-term disability in stroke survivors. Although all trials assessed outcomes immediately at the end of treatment, there was no robust evidence on the effects of buflomedil on any short-term outcomes. Also, there was insufficient evidence on the harms that the drug might cause. The quality of evidence was generally low. There were not enough data and most trials had poor study design or incomplete reporting of relevant information. To provide evidence for the use of buflomedil as a routine treatment for acute ischaemic stroke, high quality randomised trials are needed. |
We included 12 eligible trials with a total of 1450 mothers and 1204 known infants. Eleven trials administered probiotics to mothers during pregnancy and one trial administered probiotics to mothers after birth of their preterm infants. No studies compared maternal probiotic administration directly with neonatal administration. Included prenatal trials were highly variable in the indication for the trial, the gestational age and duration of administration of probiotics, as well as the dose and formulation of the probiotics. The pregnant women included in these trials were overall at low risk for preterm birth. In a meta-analysis of trial data, oral probiotic administration to pregnant women did not reduce the incidence of preterm birth < 37 weeks (typical risk ratio (RR) 0.92, 95% confidence interval (CI) 0.32 to 2.67; 4 studies, 518 mothers and 506 infants), < 34 weeks (typical risk difference (RD) 0.00, 95% CI -0.02 to 0.02; 2 studies, 287 mothers and infants), the incidence of infant mortality (typical RD 0.00, 95% CI -0.02 to 0.02; 2 studies, 309 mothers and 298 infants), or the gestational age at birth (mean difference (MD) 0.15, 95% CI -0.33 to 0.63; 2 studies, 209 mothers with 207 infants). One trial studied administration of probiotics to mothers after preterm birth and included 49 mothers and 58 infants. There were no significant differences in the risk of any NEC (RR 0.44, 95% CI 0.13 to 1.46; 1 study, 58 infants), surgery for NEC (RR 0.15, 95% CI 0.01 to 2.58; 1 study, 58 infants), death (RR 0.66, 95% CI 0.06 to 6.88; 1 study, 58 infants), and death or NEC (RR 0.53, 95% CI 0.19 to 1.49; 1 study, 58 infants). There was an improvement in time to reach 50% enteral feeds in infants whose mothers received probiotics, but the estimate is imprecise (MD -9.60 days, 95% CI -19.04 to -0.16 days; 58 infants). No other improvement in any neonatal outcomes were reported. The estimates were imprecise and do not exclude the possibility of meaningful harms or benefits from maternal probiotic administration. There were no cases of culture-proven sepsis with the probiotic organism. The GRADE quality of evidence was judged to be low to very low due to inconsistency and imprecision. There is insufficient evidence to conclude whether there is appreciable benefit or harm to neonates of either oral supplementation of probiotics administered to pregnant women at low risk for preterm birth or oral supplementation of probiotics to mothers of preterm infants after birth. Oral supplementation of probiotics to mothers of preterm infants after birth may decrease time to 50% enteral feeds, however, this estimate is extremely imprecise. More research is needed for post-natal administration of probiotics to mothers of preterm infants, as well as to pregnant mothers at high risk for preterm birth. | Twelve eligible trials with a total of 1450 mothers and 1204 known infants were included from searches, up to date as of March 2017. Eleven trials gave probiotics to mothers during pregnancy and one trial gave probiotics to mothers after the birth of their preterm infants. No studies compared maternal probiotic administration directly versus neonatal administration.The studies of pregnant women focused on various aspects of the studies with different probiotics given at different times. The pregnant women included in these trials were overall at low risk for preterm birth. The one trial with mothers given probiotics after birth was to mothers of infants who weighed less than 1500 g at birth. There is insufficient evidence to conclude whether there is appreciable benefit or harm to neonates of either oral supplementation of probiotics administered to pregnant women at low risk for preterm birth or oral supplementation of probiotics to mothers of preterm infants after birth. There were no trials that gave mothers at high risk for having a premature infant probiotics, so the effects of probiotics given to those mothers is unknown. More studies are needed to know if probiotics given to mothers of preterm infants decreases death, necrotizing enterocolitis, or other problems related to prematurity. In general, the evidence was of low to very low quality due to imprecision (small sample sizes) and indirectness (enrolled mothers were not necessarily at high risk for delivering their babies early). |
We identified and included 22 RCTs randomly assigning 8641 people with COPD to either once-daily LABA/LAMA FDC (6252 participants) or placebo (3819 participants); nine studies had a cross-over design. Studies had a duration of between three and 52 weeks (median 12 weeks). The mean age of participants across the included studies ranged from 59 to 65 years and in 21 of 22 studies, participants had GOLD stage II or III COPD. Concomitant inhaled corticosteroid (ICS) use was permitted in all of the included studies (where stated); across the included studies, between 28% to 58% of participants were using ICS at baseline. Six studies evaluated the once-daily combination of IND/GLY (110/50 μg), seven studies evaluated TIO/OLO (2.5/5 or 5/5 μg), eight studies evaluated UMEC/VI (62.5/5, 125/25 or 500/25 μg) and one study evaluated ACD/FOR (200/6, 200/12 or 200/18 μg); all LABA/LAMA combinations were compared with placebo. The risk of bias was generally considered to be low or unknown (insufficient detail provided), with only one study per domain considered to have a high risk of bias except for the domain 'other bias' which was determined to be at high risk of bias in four studies (in three studies, disease severity was greater at baseline in participants receiving LABA/LAMA compared with participants receiving placebo, which would be expected to shift the treatment effect in favour of placebo). Compared to the placebo, the pooled results for the primary outcomes for the once-daily LABA/LAMA arm were as follows: all-cause mortality, OR 1.88 (95% CI 0.81 to 4.36, low-certainty evidence); all-cause serious adverse events (SAEs), OR 1.06 (95% CI 0.88 to 1.28, high-certainty evidence); acute exacerbations of COPD (AECOPD), OR 0.53 (95% CI 0.36 to 0.78, moderate-certainty evidence); adjusted St George's Respiratory Questionnaire (SGRQ) score, MD -4.08 (95% CI -4.80 to -3.36, high-certainty evidence); proportion of SGRQ responders, OR 1.75 (95% CI 1.54 to 1.99). Compared with placebo, the pooled results for the secondary outcomes for the once-daily LABA/LAMA arm were as follows: adjusted trough forced expiratory volume in one second (FEV1), MD 0.20 L (95% CI 0.19 to 0.21, moderate-certainty evidence); adjusted peak FEV1, MD 0.31 L (95% CI 0.29 to 0.32, moderate-certainty evidence); and all-cause AEs, OR 0.95 (95% CI 0.86 to 1.04; high-certainty evidence). No studies reported data for the 6-minute walk test. The results were generally consistent across subgroups for different LABA/LAMA combinations and doses. Compared with placebo, once-daily LABA/LAMA (either IND/GLY, UMEC/VI or TIO/OLO) via a combination inhaler is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild-to-moderate COPD; UMEC/VI appears to reduce the rate of exacerbations in this population. These conclusions are supported by moderate or high certainty evidence based on studies with an observation period of up to one year. | Twenty-two studies (including 8641 people with COPD) compared once-daily LABA/LAMA in a single inhaler with a dummy inhaler. People were allowed to continue to use their inhaled corticosteroids (ICS) during the studies; approximately a third to a half of people were using their ICS at the beginning of each study. The evidence presented in this review is current up to December 2018. The majority of people who took part in the studies had mild-to-moderate COPD and the average age of people in each study ranged from 59 to 65 years. Six studies evaluated the once-daily combination of indacaterol/glycopyrronium, seven studies evaluated tiotropium/olodaterol, eight studies evaluated umeclidinium/vilanterol and one study evaluated aclidinium/formoterol. People who took once-daily LABA/LAMA using a single inhaler showed a greater improvement in quality of life than those taking placebo in a dummy inhaler; lung function was also improved in people taking once-daily LABA/LAMA. People taking umeclidinium/vilanterol had fewer flare-ups (exacerbations). There was no significant difference between groups (LABA/LAMA versus placebo) in the number of people who died, or in the number of people who experienced serious adverse events or any adverse event. The results were similar for the different LABA/LAMA combinations and doses that we evaluated. The included studies were generally well designed and well reported. People in the studies and those performing the research did not know which treatment people were receiving, which ensures a fair evaluation of the treatments. In three of the studies, people who were taking once-daily LABA/LAMA had more severe COPD at the start of the study than people taking dummy inhalers; this could have reduced the treatment effect seen with LABA/LAMA in these studies so we can be confident that our findings do not overestimate the effect seen with once-daily LABA/LAMA. One of the outcomes of interest (how far a person is able to walk in six minutes) was not reported by any of the included studies. Overall, we can be confident in the conclusions of this review. |
Eighteen studies were identified by the searches. Only one study could be included which reported results from 17 participants aged 10 to 41 years with an infective exacerbation of Pseudomonas aeruginosa. All their 31 admissions (18 hospital and 13 at home after two to four days of hospital treatment) were analysed as independent events. Outcomes were measured at 0, 10 and 21 days after initiation of treatment. Home participants underwent fewer investigations than hospital participants (P < 0.002) and general activity was higher in the home group. No significant differences were found for clinical outcomes, adverse events, complications or change of intravenous lines,or time to next admission. Home participants received less low-dose home maintenance antibiotic. Quality of life measures showed no significant differences for dyspnoea and emotional state, but fatigue and mastery were worse for home participants, possibly due to a higher general activity and need of support. Personal, family, sleeping and eating disruptions were less important for home than hospital admissions. Home therapy was cheaper for families and the hospital. Indirect costs were not determined. Current evidence is restricted to a single randomized clinical trial. It suggests that, in the short term, home therapy does not harm individuals, entails fewer investigations, reduces social disruptions and can be cost-effective. There were both advantages and disadvantages in terms of quality of life. The decision to attempt home treatment should be based on the individual situation and appropriate local resources. More research is urgently required. | We found one study with 17 people aged 10 to 41 years who had a flare up of infection with Pseudomonas aeruginosa. The people taking part were assigned to either home antibiotics or hospital antibiotics at random. Those who had home antibiotics initially spent up to four days in hospital and were taught to prepare and administer their own intravenous antibiotics. They were discharged with enough medication and equipment for the course of treatment and were visited at home. All participants received the same type of antibiotic and the course lasted at least 10 days. There were no differences found for clinical outcomes, adverse events, or complications linked to intravenous treatment. People at home were more tired and found the treatment more difficult to master. This may be due to them being more active and needing more support. Home therapy was cheaper for families and the hospital. There were no details about indirect costs. We conclude that treatment at home does not harm people in the short term and does reduce social disruption. However, the decision in favour of this option must be made on an individual basis. The evidence is very limited and more research is strongly needed to recommend its use. |
From 85 papers describing IQCODE, we included three papers, representing data from 626 individuals. Of this total, 22% (N = 135/626) were excluded because of prevalent dementia. There was substantial attrition; 47% (N = 295) of the study population received reference standard assessment at first follow-up (three to six months) and 28% (N = 174) received reference standard assessment at final follow-up (one to three years). Prevalence of dementia ranged from 12% to 26% at first follow-up and 16% to 35% at final follow-up. The three studies were considered to be too heterogenous to combine, so we did not perform meta-analyses to describe summary estimates of interest. Included patients were poststroke (two papers) and hip fracture (one paper). The IQCODE was used at three thresholds of positivity (higher than 3.0, higher than 3.12 and higher than 3.3) to predict those at risk of a future diagnosis of dementia. Using a cut-off of 3.0, IQCODE had a sensitivity of 0.75 (95%CI 0.51 to 0.91) and a specificity of 0.46 (95%CI 0.34 to 0.59) at one year following stroke. Using a cut-off of 3.12, the IQCODE had a sensitivity of 0.80 (95%CI 0.44 to 0.97) and specificity of 0.53 (95C%CI 0.41 to 0.65) for the clinical diagnosis of dementia at six months after hip fracture. Using a cut-off of 3.3, the IQCODE had a sensitivity of 0.84 (95%CI 0.68 to 0.94) and a specificity of 0.87 (95%CI 0.76 to 0.94) for the clinical diagnosis of dementia at one year after stroke. In generaI, the IQCODE was sensitive for identification of those who would develop dementia, but lacked specificity. Methods for both excluding prevalent dementia at baseline and assessing for the development of dementia were varied, and had the potential to introduce bias. Included studies were heterogenous, recruited from specialist settings, and had potential biases. The studies identified did not allow us to make specific recommendations on the use of the IQCODE for the future diagnosis of dementia in clinical practice. The included studies highlighted the challenges of delayed verification dementia research, with issues around prevalent dementia assessment, loss to follow-up over time, and test non-completion potentially limiting the studies. Future research should recognise these issues and have explicit protocols for dealing with them. | We found three relevant studies, all of which were carried out in specific hospital settings. Two papers only included patients with acute stroke, and the other included those who had sustained a hip fracture. The papers differed in many other ways, so we we were unable to estimate a summary of their combined results. In general, a 'positive' IQCODE picked up patients who would go on to develop dementia (good sensitivity), but mislabelled a number who did not develop dementia (poor specificity). We cannot make recommendations for current practice, based on the studies we reviewed. The included studies demonstrated some of the challenges of research that follows people at risk of dementia over time. Not all the studies had a robust method of ensuring that none of the included participants had dementia at the start of the study, and that only new cases were identified. Similarly, many of the participants included at the start of the study were not available for re-assessment, due to death or other illness. The review was performed by a team based in research centres in the UK (Glasgow, Edinburgh, Oxford). We had no external funding specific to this study, and we have no conflicts of interest that may have influenced our assessment of the research data. |
Three studies met the inclusion criteria for the review. Two studies were based on oral sensorimotor interventions for participants with cerebral palsy compared to standard care and a third study trialled lip strengthening exercises for children with myotonic dystrophy type 1 compared to no treatment (Sjogreen 2010). A meta-analysis combining results across the three studies was not possible because one of the studies had participants with a different condition, and the remaining two, although using oral sensorimotor treatments, used vastly different approaches with different intensities and durations. The decision not to combine these was in line with our protocol. In this review, we present the results from individual studies for four outcomes: physiological functions of the oropharyngeal mechanism for swallowing, the presence of chest infection and pneumonia, diet consistency, and changes in growth. However, it is not possible to reach definitive conclusions on the effectiveness of particular interventions for oropharyngeal dysphagia based on these studies. One study had a high risk of attrition bias owing to missing data, had statistically significant differences (in weight) across experimental and control groups at baseline, and did not describe other aspects of the trial sufficiently to enable assessment of other potential risks of bias. Another study was at high risk of detection bias as some outcomes were assessed by parents who knew whether their child was in the intervention or control group. The third study overall seemed to be at low risk of bias, but like the other two studies, suffered from a small sample size. The review demonstrates that there is currently insufficient high-quality evidence from randomised controlled trials or quasi-randomised controlled trials to provide conclusive results about the effectiveness of any particular type of oral-motor therapy for children with neurological impairment. There is an urgent need for larger-scale (appropriately statistically powered), randomised trials to evaluate the efficacy of interventions for oropharyngeal dysphagia. | This review examined the effectiveness of interventions for oropharyngeal dysphagia in children with neurological impairment. The three studies included in the review examined oral sensorimotor treatments and lip strengthening interventions. We were interested in three primary outcomes, which were physiological functions of the oropharyngeal mechanism for swallowing (for example, lip seal maintenance), the presence of chest infection and pneumonia, and diet consistency, and three secondary outcomes, which were changes in growth, child's level of participation in the mealtime routine, and the level of parent or carer stress associated with feeding. We concluded that there is currently not enough high-quality evidence from randomised controlled trials or quasi-randomised controlled trials for any particular type of oropharyngeal dysphagia intervention in this population of children. There is a need for larger-scale randomised controlled trials to evaluate the effects of interventions for oropharyngeal dysphagia in children with neurological impairment. |
Three studies involving 1257 women met our inclusion criteria. Cord drainage reduced the length of the third stage of labour (mean difference (MD) -2.85 minutes, 95% confidence interval (CI) -4.04 to -1.66; three trials, 1257 women (heterogeneity: T² = 0.87; Chi²P=17.19, I² = 88%)) and reduced the average amount of blood loss (MD -77.00 ml, 95% CI -113.73 to -40.27; one trial, 200 women). No incidence of retained placenta at 30 minutes after birth was observed in the included studies, therefore, it was not possible to compare this outcome. The differences between the cord drainage and the control group were not statistically significant for postpartum haemorrhage or manual removal of the placenta. None of the included studies reported fetomaternal transfusion outcomes and there were no data relating to maternal pain or discomfort during the third stage of labour. There was a small reduction in the length of the third stage of labour and also in the amount of blood loss when cord drainage was applied compared with no cord drainage. The clinical importance of such observed statistically significant reductions, is open to debate. There is no clear difference in the need for manual removal of placenta, blood transfusion or the risk of postpartum haemorrhage. Due to small trials with medium risk of bias, the results should be interpreted with caution. | This review included three studies involving 1257 birthing women. The findings showed that placental cord drainage in the management of third stage of labour reduced the length of third stage of labour by a mean of about three minutes and reduced blood loss by average of 77 ml. There was no clear difference in the manual removal of placenta or the risk of postpartum haemorrhage or incidence of blood transfusion. The trials did not report on maternal pain or discomfort during the third stage of labour. Some of the outcomes were not reported in the same way in all trials, limiting the amount of information available for analysis. Other desired outcomes were either not reported or were not reported in an appropriate way for statistical analysis (e.g. placenta not delivered within 30 minutes after birth, maternal haemoglobin changes). Further investigation of the effect of placental cord drainage on maternal outcomes would be useful although it is not a priority area for maternity research. |
Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly more frequent in naltrexone depot groups compared to placebo. In alcohol dependent samples only, adverse effects appeared to be significantly more frequent in the low-dose naltrexone depot groups compared to placebo (RR 1.18, 95% CI 1.02 to 1.36, p=0.02). In the opioid dependent sample, group differences were not statistically significant. Reports on systematic assessment of side effects and adverse events were scarce. There is insufficient evidence to evaluate the effectiveness of sustained-release naltrexone for treatment of opioid dependence. For naltrexone injections, administration site-related adverse effects appear to be frequent, but of moderate intensity and time limited. For a harm-benefit evaluation of naltrexone implants, more data on side effects and adverse events are needed. | There is insufficient evidence from randomised controlled trials to evaluate the effectiveness of sustained-release naltrexone. In the one controlled study that met inclusion criteria, 60 outpatients were randomised to one of three groups that received two sequential depot injections of naltrexone (192 or 384 mg) or placebo injections. The mean dropout time was 48 days with high dose naltrexone compared with 27 days on placebo; an increase in treatment of 21 days (range 11 to 31 days). The lower depot dose gave a lesser benefit. The number retained in treatment at eight weeks did not show a clear difference and ranged from a mean of 68% to 39% of participants in the different groups. 'Wanting heroin' did not differ on naltrexone but 'needing heroin' scored significantly lower with depot naltrexone compared to placebo. The most prominent adverse effects were general symptoms of fatigue and pain at the injection site. Seventeen reports met inclusion criteria for assessing adverse effects. Seven looked specifically at naltrexone implants for treatment of opioid dependence and wound infection, allergic reaction to the implant and number of implants removed. The majority of the trials did not have a control group and systematic assessment of adverse effects was lacking. |
We included one trial with a total of 60 children with a diagnosis of ASD who randomly received hyperbaric oxygen therapy or a sham treatment. Using GRADE criteria, we rated the quality of the evidence as low because of the small sample size and wide confidence intervals (CIs). Other problems included selection bias and short duration or follow-up. Overall, study authors reported no improvement in social interaction and communication, behavioral problems, communication and linguistic abilities, or cognitive function. With regard to the safety of hyperbaric oxygen therapy (adverse events), they reported minor-grade ear barotrauma events. Investigators found significant differences between groups in total number of side effect events (Peto odds ratio (OR) 3.87, 95% CI 1.53 to 9.82) and in the number of children who experienced side effects (Peto OR 4.40, 95% CI 1.33 to 14.48). To date, there is no evidence that hyperbaric oxygen therapy improves core symptoms and associated symptoms of ASD. It is important to note that adverse effects (minor-grade ear barotrauma events) can occur. Given the absence of evidence of effectiveness and the limited biological plausibility and possible adverse effects, the need for future RCTs of hyperbaric oxygen therapy must be carefully considered. | We searched electronic databases and identified randomized controlled trials (in which participants are randomly allocated to one of two or more treatment groups) consisting of participants who received high-pressure oxygen therapy or room air or no treatment as a control. The evidence is current up to December 2015. We found a single, small study of 60 children that evaluated high-pressure oxygen therapy for ASD. There was no evidence that high-pressure oxygen therapy improved social interaction, behavioral problems, speech or language communication, or mental function in children with ASD. However, children who received high-pressure (hyperbaric) oxygen therapy showed an increased occurrence of ear barotrauma events when compared with those in the control group. The quality of the evidence is low. Evidence is insufficient to confirm that high-pressure oxygen is an effective treatment for individuals with ASD. |
We included four trials. One trial evaluated mass treatment of all individuals in a particular community. The other three trials evaluated various combinations of improved syndromic STI management in clinics, STI counselling, and STI treatment. In the mass treatment trial in rural southwestern Uganda, after three rounds of treatment of all community members for STIs, the adjusted rate ratio (aRR) of incident HIV infection was 0.97 (95% CI 0.81 - 1.2), indicating no effect of the intervention. The three STI management intervention studies were all conducted in rural parts of Africa. One study, in northern Tanzania, showed that the incidence of HIV infection in the intervention groups (strengthened syndromic management of STIs in primary care clinics) was 1.2% compared with 1.9% in the control groups (aRR = 0.58, 95% CI 0.42 - 0.79), corresponding to a 42% reduction (95% CI 21.0% - 58.0%) in HIV incidence in the intervention group. Another study, conducted in rural southwestern Uganda, showed that the aRR of behavioural intervention and STI management compared to control on HIV incidence was 1.00 (95% CI 0.63 - 1.58). In the third STI management trial, in eastern Zimbabwe, there was no effect of the intervention on HIV incidence (aRR = 1.3, 95% CI 0.92 - 1.8). These are consistent with data from the mass treatment trial showing no intervention effect. Overall, pooling the data of the four studies showed no significant effect of any intervention (rate ratio [RR] = 0.97, 95% CI 0.78 - 1.2). Combining the mass treatment trial and one of the STI management trials, we find that there is a significant 12.0% reduction in the prevalence of syphilis for those receiving a biomedical STI intervention (RR 0.88, 95% CI 0.80 - 0.96). For gonorrhoea, we find a statistically significant 51.0% reduction in its prevalence in those receiving any of these interventions (RR 0.49, 95% CI 0.31 - 0.77). Finally, for chlamydia, we found no significant difference between any biomedical intervention and control (RR 1.03, 95% CI 0.77 - 1.4). We failed to confirm the hypothesis that STI control is an effective HIV prevention strategy. Improved STI treatment services were shown in one study to reduce HIV incidence in an environment characterised by an emerging HIV epidemic (low and slowly rising prevalence), where STI treatment services were poor and where STIs were highly prevalent; Incidence was not reduced in two other settings. There is no evidence for substantial benefit from a presumptive treatment intervention for all community members. There are, however, other compelling reasons why STI treatment services should be strengthened, and the available evidence suggests that when an intervention is accepted it can substantially improve quality of services provided. | Subsequent trials, however, failed to confirm these findings and also failed to show a substantial benefit for community-wide presumptive treatment for STIs. This is likely due to the endemic nature of HIV and relatively low incidence of STIs in these populations. There are, however, other good reasons as to why STI treatment services should be strengthened and the available evidence suggests that when an intervention is applied and accepted in a community, it can improve the quality of services provided. The trial in Masaka District, Uganda showed an increase in the use of condoms, a marker for less risky sexual behaviours, although a newer study by Gregson conducted in Zimbabwe suggested no effect. With the last three trials having shown disappointing results with respect to HIV prevention, it is unlikely that further community trials will be conducted, let alone yield different results. Future trials of biomedical interventions that involve individual randomisation, however, may represent an opportunity to reexamine presumptive treatment of STIs. Such trials should also aim to measure a range of factors that include health-seeking behaviour and quality of treatment, as well as HIV, STI and other biological endpoints. |
We found six Cochrane systematic reviews and judged them to be of high methodological quality. They included 148 randomised controlled trials (RCTs) in 98,093 participants. Compared with usual care alone, the addition of exercise-based cardiac rehabilitation in low-risk people after myocardial infarction or percutaneous coronary intervention or with heart failure appeared to have no impact on mortality, but did reduce hospital admissions and improved health-related quality of life. Psychological- and education-based interventions alone appeared to have little or no impact on mortality or morbidity but may have improved health-related quality of life. Home- and centre-based programmes were equally effective in improving quality of life outcomes at similar healthcare costs. Selected interventions can increase the uptake of cardiac rehabilitation programmes whilst there is currently only weak evidence to support interventions that improve adherence to cardiac rehabilitation programmes. The quality of the primary RCTs in the included systematic reviews was variable, and limitations in the methodological quality of the RCTs led to downgrading of the quality of the evidence, which varied widely by review and by outcome. Exercise-based cardiac rehabilitation is an effective and safe therapy to be used in the management of clinically stable people following myocardial infarction or percutaneous coronary intervention or who have heart failure. Future RCTs of cardiac rehabilitation need to improve their reporting methods and reflect the real world practice better including the recruitment of higher risk people and consideration of contemporary models of cardiac rehabilitation delivery, and identify effective interventions for enhancing adherence to rehabilitation. | We searched for Cochrane reviews that analysed the data from randomised controlled trials (RCT; experiments that randomly allocate participants to one of two or more treatment groups), which looked at the effectiveness of CR in adults with heart disease and compared patient outcomes with a no-exercise control group. This overview summarised the findings from these reviews. We found six high-quality Cochrane reviews that included 148 RCTs in 98,093 people who primarily had experienced a heart attack, had undergone cardiac surgery or had chronic heart failure. The findings of this overview showed important benefits of CR participation that included a reduction in the risk of hospital admissions, as well as improvements in health-related quality of life compared with not undertaking rehabilitation. The quality of the RCTs in the included systematic reviews was variable, and limitations in their methodological quality led to downgrading of the quality of the evidence, which varied widely by review and outcome. We make the following recommendations for the future conduct and reporting of systematic reviews of CR. • The scope of CR reviews needs to reflect current guidelines that recommend that CR should be based on an individually prescribed programme of exercise training with appropriate co-interventions. • Future CR reviews need to explore the complexity of CR using appropriate approaches to explore the association between intervention characteristics and outcomes across trials. • Future Cochrane CR reviews need to standardise their methods and reporting. |
Two trials enrolling 54 infants in total, fulfilled the inclusion criteria. Both reported only the short term results (4 to 6 hours) of the interventions. Only one infant (randomised to NCPAP) required intubation during this period. In a cross-over study of 20 infants, Ryan 1989 showed no significant difference in rates of apnea (events/hr) between the two interventions [WMD -0.10 (-0.53,0.33)]. Lin (1998) randomised 34 infants and demonstrated a greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP [WMD -1.19 (-2.31,-0.07)]. Meta-analysis of both trials showed no difference in pC02 (mmHg) at the end of the 4-6 hour study period [WMD 0.95 (-3.05,4.94)]. No data were reported on gastrointestinal complications. Implications for practice: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea. Implications for research: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment. | This review of two small trials suggests that nasal intermittent positive pressure ventilation (NIPPV) delivered via nasal prongs may be more effective than NCPAP alone in preterm babies whose apneas are frequent or severe. Further research is needed to confirm effectiveness and safety as few babies have been studied so far. |
We included nine trials of 4433 participants. Odds ratios for mortality after stenting compared to balloon angioplasty at 30 days, 6 and 12 months were 1.16 (95% CI 0.78 to 1.73), 1.27 (95% CI 0.89 to 1.83), and 1.06 (95% CI 0.77 to 1.45). At 30 days, 6 and 12 months odds ratios for reinfarction after stenting compared to balloon angioplasty were 0.52 (95% CI 0.31 to 0.87), 0.67 (95% CI 0.45 to 1.00), and 0.67 (95% CI 0.45-0.98) and odds ratio for target vessel revascularization after stenting compared to balloon angioplasty were 0.45 (95%CI 0.34 to 0.60), 0.42 (95% CI 0.35 to 0.51), and 0.47 (95% CI 0.38 to 0.57). The odds ratio for post-interventional bleeding complications after stenting compared to balloon angioplasty was 1.34 (95% CI 0.95 to 1.88; test of heterogeneity p > 0.1). There is no evidence to suggest that primary stenting reduces mortality when compared to balloon angioplasty. Stenting seems to be associated with a reduced risk of reinfarction and target vessel revascularization, but potential confounding due to unbalanced post-interventional antithrombotic/anticoagulant therapies can not be ruled out on basis of this review. | This review compared these treatments and found both were equally effective at preventing death but using stents was better than balloon angioplasty because fewer arteries needed to be re-cleared and stents prevented more heart attacks than balloon angioplasty. |
We included seventeen trials with overall 2134 participants. We performed two separate meta-analyses: one that evaluated the use of systemic prophylactic antibiotics and another that evaluated the use of antibiotic-impregnated systems. All studies included shunt infection in their primary outcome. We could not analyse all-cause mortality regarding systemic antibiotics due to lack of data. No significant differences were found (odds ratio (OR): 1.47, 95% confidence intervals (CI) 0.83 to 2.62) for this outcome regarding the use of antibiotic-impregnated catheters compared with standard ones. The use of systemic antibiotic prophylaxis and the use of antibiotic-impregnated catheters were associated with a decrease in shunt infection (OR: 0.52, 95% CI 0.36 to 0.74 and OR: 0.21, 95% CI 0.08 to 0.55 respectively). We found no significant benefit for shunt revision in both meta-analyses that evaluated systemic antibiotics and impregnated-shunt systems. We found no significant differences between the subgroups evaluated: type of shunt (internal/external, ventriculoperitoneal/ventriculoatrial), age and duration of the administration of antibiotics. We could demonstrate a benefit of systemic prophylactic antibiotics for the first 24 hours postoperatively to prevent shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after this period remains uncertain. However this data derives from the rate of shunt infection, which is an intermediary outcome. Future trials should evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, and should include all-cause mortality, shunt revision and adverse events as additional outcomes. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection although more well-designed clinical trials testing the effect of antibiotic-impregnated shunts are required to confirm their net benefit. | Our review included randomized controlled trials that compared the incidence of shunt infection in patients who were given preventive antibiotic therapy with those who did not receive these drugs. We also included trials comparing antibiotic-impregnated shunt systems with those who received non-antibiotic impregnated shunts. We included seventeen trials in our review. Although the available data does not provide much detail on mortality or the adverse events caused by antibiotics (an adverse event is an incident in which harm resulted to a person receiving the health care) it does support the use of preventative systemic prophylactic antibiotics for the first 24 hours postoperatively following an intracranial ventricular shunt operation or the use of antibiotic-impregnated catheters. However this data was obtained from an intermediary outcome which is the rate of shunt infections. Therefore although the evidence suggests that the use of antibiotics is beneficial in reducing the incidence of shunt infection more research is needed to confirm their benefit. |
From the 468 references identified after removing duplicates, we found two trials comprising 86 participants that met our inclusion criteria. Both trials included participants with Brugada syndrome who were randomized to ICD versus β-blocker therapy for secondary prevention for sudden cardiac death. Both studies were small, were performed by the same investigators, and exhibited a high risk of bias across multiple domains. In the group randomized to ICD therapy, there was a nine-fold lower risk of mortality compared with people randomized to medical therapy (0% with ICD versus 18% with medical therapy; RR 0.11, 95% CI 0.01 to 0.83; 2 trials, 86 participants). There was low quality evidence of a difference in the rates of combined fatal and non-fatal cardiovascular events, and the results were imprecise (26% with ICD versus 18% with medical therapy; RR 1.49, 95% CI 0.66 to 3.34; 2 trials, 86 participants). The rates of adverse events were higher in the ICD group, but these results were imprecise (28% with ICD versus 10% with medical therapy; RR 2.44, 95% CI 0.92 to 6.44; 2 trials, 86 participants). For secondary outcomes, the risk of non-fatal cardiovascular events was higher in the ICD group, but these results were imprecise and were driven entirely by appropriate ICD-termination of cardiac arrhythmias (26% with ICD versus 0% with medical therapy; RR 11.4, 95% CI 1.57 to 83.3; 2 trials, 86 participants). Approximately 25% of the ICD group experienced inappropriate ICD firing, all of which was corrected by device reprogramming. No data were available for quality of life or cost. We considered the quality of evidence low using the GRADE methodology, due to study limitations and imprecision of effects. Among people with Brugada syndrome who have survived a prior episode of sudden cardiac death, ICD therapy appeared to reduce mortality when compared to β-blocker therapy, but the true magnitude may be substantially different from the estimate of the effect because of study limitations and imprecision. Due to the large magnitude of effect, it is unlikely that there will be additional studies evaluating the role of ICDs for secondary prevention in this population. Further studies are necessary to determine the optimal treatment, if any, to prevent an initial episode of sudden cardiac death in people with cardiac ion channelopathies. | We searched scientific databases and found two randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) including 86 adults that met our inclusion criteria. Both trials compared implantable cardioverter defibrillators with medical therapy in people with Brugada syndrome who had already survived a sudden cardiac arrest event. We found no studies in people who had not experienced such an event or with other abnormalities. These two studies were small, were performed by the same investigators from Thailand, were funded by a device company, and had major methodological limitations, including being stopped early. Nearly all (98%) participants were men who had an average age of 44 years old. All-cause mortality (death from any cause) was lower in people who received the implantable cardioverter defibrillator. Rates of survived sudden cardiac arrest, heart attack, and stroke were higher, primarily due to differences in survived sudden cardiac arrest rates. Implantable cardioverter defibrillators had a higher rate of side effects compared with medical therapy, including receiving inappropriate shocks from their defibrillators, which required reprogramming of these devices. There was low quality evidence that implantable cardioverter defibrillators lower mortality in people with inherited heart rate abnormalities who have survived a sudden cardiac arrest event because of few, small, low quality studies. These devices carry a higher risk of side effects than medical therapy. Further research is very likely to have an important impact on our confidence in the results. |
Sixteen trials, with a combined total of 3299 participants fulfilled our inclusion criteria. According to GRADE, the quality of evidence was moderate for recurrent VTE, low for major bleeding, and moderate for mortality. We downgraded the quality of the evidence for imprecision (recurrent VTE, mortality) and for risk of bias and inconsistency (major bleeding). We found no clear differences in recurrent VTE between LMWH and VKA (Peto OR 0.83, 95% confidence interval (CI) 0.60 to 1.15; P = 0.27; 3299 participants; 16 studies; moderate-quality evidence). We found less bleeding with LMWH than with VKA (Peto OR 0.51, 95% CI 0.32 to 0.80; P = 0.004; 3299 participants; 16 studies; low-quality evidence). However, when comparing only high-quality studies for bleeding, we observed no clear differences between LMWH and VKA (Peto OR 0.62, 95% CI 0.36 to 1.07; P = 0.08; 1872 participants; seven studies). We found no clear differences between LMWH and VKA in terms of mortality (Peto OR 1.08, 95% CI 0.75 to 1.56; P = 0.68; 3299 participants; 16 studies; moderate-quality evidence). Moderate-quality evidence shows no clear differences between LMWH and VKA in preventing symptomatic VTE and death after an episode of symptomatic DVT. Low-quality evidence suggests fewer cases of major bleeding with LMWH than with VKA. However, comparison of only high-quality studies for bleeding shows no clear differences between LMWH and VKA. LMWH may represent an alternative for some patients, for example, those residing in geographically inaccessible areas, those who are unable or reluctant to visit the thrombosis service regularly, and those with contraindications to VKA. | The quality of evidence for the outcomes recurrent blood clots and death was moderate. The quality of this evidence was downgraded because of the small number of events reported, leading to imprecision. For the outcome bleeding, the quality of evidence was low because of inconsistency between studies and risk of bias. Continued research into long term treatment of blood clots in the veins with LMWH and VKA is needed. This review found no clear differences in recurrent blood clots and death between LMWH and VKA, and fewer bleeding episodes with LMWH than with VKA. However, when only high-quality studies were compared for bleeding, no clear differences were observed between LMWH and VKA. LMWH may offer an alternative for some patients, for example, those in geographically inaccessible areas, those unable or reluctant to visit the thrombosis service regularly, and those for whom taking VKA may be harmful. |
Seventeen RCTs with 1103 participants were included. These studies differed in the both thrombolytic agent used and in the technique used to deliver it. Systemic, loco-regional and catheter-directed thrombolysis (CDT) were all included. Fourteen studies were rated as low risk of bias and three studies were rated as high risk of bias. We combined the results as any (all) thrombolysis compared to standard anticoagulation. Complete clot lysis occurred significantly more often in the treatment group at early follow-up (RR 4.91; 95% CI 1.66 to 14.53, P = 0.004) and at intermediate follow-up (RR 2.44; 95% CI 1.40 to 4.27, P = 0.002; moderate quality evidence). A similar effect was seen for any degree of improvement in venous patency. Up to five years after treatment significantly less PTS occurred in those receiving thrombolysis (RR 0.66, 95% CI 0.53 to 0.81; P < 0.0001; moderate quality evidence). This reduction in PTS was still observed at late follow-up (beyond five years), in two studies (RR 0.58, 95% CI 0.45 to 0.77; P < 0.0001; moderate quality evidence). Leg ulceration was reduced although the data were limited by small numbers (RR 0.87; 95% CI 0.16 to 4.73, P = 0.87). Those receiving thrombolysis had increased bleeding complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006; moderate quality evidence). Three strokes occurred in the treatment group, all in trials conducted pre-1990, and none in the control group. There was no significant effect on mortality detected at either early or intermediate follow-up. Data on the occurrence of pulmonary embolism (PE) and recurrent DVT were inconclusive. Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included two trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion. Thrombolysis increases the patency of veins and reduces the incidence of PTS following proximal DVT by a third. Evidence suggests that systemic administration and CDT have similar effectiveness. Strict eligibility criteria appears to improve safety in recent studies and may be necessary to reduce the risk of bleeding complications. This may limit the applicability of this treatment. In those who are treated there is a small increased risk of bleeding. Using GRADE assessment, the evidence was judged to be of moderate quality due to many trials having low numbers of participants. However, the results across studies were consistent and we have reasonable confidence in these results. | The review results are based on 17 controlled trials that randomised a total of 1103 people with acute DVT (within 21 days of onset of symptoms) to receive thrombolysis or anticoagulant treatment. Trials were carried out principally in the USA, Scandinavia, Germany and the UK. All trials included men and women ranging in age from 18 to 75 years with a preponderance of older adults. The present review (current until February 2016) showed that thrombolysis may have advantages over standard anticoagulation treatment. Thrombolysis effectively dissolved the clot so that complete clot breakdown occurred more often with thrombolysis than with standard anticoagulant therapy. Blood flow in the affected vein (venous patency) was also better maintained. Three trials (306 participants) continued for over six months and found that fewer people developed PTS when treated with thrombolysis, 45% compared with 66% in the standard anticoagulation treatment group. Two trials (211 participants) which continued for over five years also showed that fewer people developed PTS when treated with thrombolysis. Those receiving thrombolysis had more bleeding complications than with standard anticoagulation (10% versus 8%). Most bleeding episodes and deaths occurred in the older studies. Use of strict eligibility criteria appears to have improved the safety of this treatment, which is effective delivered directly to the clot by catheter or via bloodstream from another vein. Qualitity of the evidence Using GRADE assessment, the evidence was judged to be of moderate quality due to many trials having low numbers of participants. However, the results across studies were consistent and we have reasonable confidence in these results. |
We included two randomised controlled trials with a total of 80 participants in this review. 1. Early versus delayed open appendicectomy for appendiceal phlegmon Forty participants (paediatric and adults) with appendiceal phlegmon were randomised either to early appendicectomy (appendicectomy as soon as appendiceal mass resolved within the same admission) (n = 20), or to delayed appendicectomy (initial conservative treatment followed by interval appendicectomy six weeks later) (n = 20). The trial was at high risk of bias. There was no mortality in either group. There is insufficient evidence to determine the effect of using either early or delayed open appendicectomy onoverall morbidity (RR 13.00; 95% CI 0.78 to 216.39; very low-quality evidence), the proportion of participants who developed wound infection (RR 9.00; 95% CI 0.52 to 156.91; very low quality evidence) or faecal fistula (RR 3.00; 95% CI 0.13 to 69.52; very low quality evidence). The quality of evidence for increased length of hospital stay and time away from normal activities in the early appendicectomy group (MD 6.70 days; 95% CI 2.76 to 10.64, and MD 5.00 days; 95% CI 1.52 to 8.48, respectively) is very low quality evidence. The trial reported neither quality of life nor pain outcomes. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess Forty paediatric participants with appendiceal abscess were randomised either to early appendicectomy (emergent laparoscopic appendicectomy) (n = 20) or to delayed appendicectomy (initial conservative treatment followed by interval laparoscopic appendicectomy 10 weeks later) (n = 20). The trial was at high risk of bias. The trial did not report on overall morbidity or complications. There was no mortality in either group. We do not have sufficient evidence to determine the effects of using either early or delayed laparoscopic appendicectomy for outcomes relating to hospital stay between the groups (MD −0.20 days; 95% CI −3.54 to 3.14; very low quality of evidence). Health-related quality of life was measured with the Pediatric Quality of Life Scale-Version 4.0 questionnaire (a scale of 0 to 100 with higher values indicating a better quality of life). Health-related quality of life score measured at 12 weeks after appendicectomy was higher in the early appendicectomy group than in the delayed appendicectomy group (MD 12.40 points; 95% CI 9.78 to 15.02) but the quality of evidence was very low. This trial reported neither the pain nor the time away from normal activities. It is unclear whether early appendicectomy prevents complications compared to delayed appendicectomy for people with appendiceal phlegmon or abscess. The evidence indicating increased length of hospital stay and time away from normal activities in people with early open appendicectomy is of very low quality. The evidence for better health-related quality of life following early laparoscopic appendicectomy compared with delayed appendicectomy is based on very low quality evidence. For both comparisons addressed in this review, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities, quality of life and the length of hospital stay. | We searched for all relevant randomised controlled trials up to 23 August 2016. We identified two trials involving 80 participants. One compared early versus delayed open appendicectomy in 40 children and adults with appendiceal phlegmon. The other trial compared early versus delayed keyhole (laparoscopic) appendicectomy (where surgery is performed through a very small incision) in 40 children with appendiceal abscess. Studies took place in the USA and India. The age of the individuals in the trials varied between 1 year and 84 years, and 27.5% were females. Both two studies were small and had a number of limitations so we cannot be certain about how the effects of the two surgical approaches compare. From one trial in children and adults comparing open with delayed appendicectomy, there was insufficient evidence to show the effect of using either approach on the overall complication rate or the proportion of participants who developed wound infection. Our certainty in a longer stay in hospital stay and time away from normal activities with open appendicectomy is very low. There were no deaths in the study. Quality of life, and pain were not reported in this trial. The other trial in children with appendiceal abscess receiving either early or delayed keyhole appendicectomy did not report on overall complication rates. The trial did not provide enough evidence to show the effect of using either approach on the length of hospital stay among participants. We have very low certainty that children who had early keyhole appendicectomy had better quality of life compared with children who had delayed keyhole appendicectomy. The study did not report if there were any deaths, and did not provide information on pain, or time away from normal activities. At present the benefits and harms of early versus delayed appendicectomy are not well understood because the current information is based upon very low quality evidence. Both trials were at a high risk of bias. Overall, we judged the quality of the evidence to be very low. Thus, further well-designed trials are urgently needed. |
Fifteen trials met the inclusion criteria. The overall methodology of all the trials assessed was either low or very low GRADE level. None of the trials were of strong to moderate GRADE level. The results showed very low level evidence that certain massage techniques (traditional Chinese massage, classical and modified strain/counterstrain technique) may have been more effective than control or placebo treatment in improving function and tenderness. There was very low level evidence that massage may have been more beneficial than education in the short term for pain bothersomeness. Along with that, there was low level evidence that ischaemic compression and passive stretch may have been more effective in combination rather than individually for pain reduction. The clinical applicability assessment showed that only 4/15 trials adequately described the massage technique. The majority of the trials assessed outcomes at immediate post-treatment, which is not an adequate time to assess clinical change. Due to the limitations in the quality of existing studies, we were unable to make any firm statement to guide clinical practice. We noted that only five of the 15 studies reported side effects. All five studies reported post-treatment pain, discomfort and soreness as a side effect and one study (Irnich 2001) showed that 22% of the participants experienced low blood pressure following treatment. No recommendations for practice can be made at this time because the effectiveness of massage for neck pain remains uncertain. As a stand-alone treatment, massage for MND was found to provide an immediate or short-term effectiveness or both in pain and tenderness. Additionally, future research is needed in order to assess the long-term effects of treatment and treatments provided on more than one occasion. | We included 15 trials in this review that assessed whether massage could help reduce neck pain and improve function. Results showed that massage is safe, and any side effects were temporary and benign. However, massage did not show a significant advantage over other comparison groups. Massage was compared with no treatment, hot packs, active range-of-movement exercises, acupuncture, exercises, sham laser, manual traction, mobilization, and education. There were a number of challenges with this review. Overall, the quality of the studies was poor and the number of participants in most trials was small. Most studies lacked a clear definition, description, or rationale for the massage technique used. Details on the credentials or experience of the person giving the massage were often missing. There was such a range of massage techniques and comparison treatments in the studies that we could not combine the results to get an overall picture of the effectiveness of massage. Therefore, no firm conclusions could be drawn and the effectiveness of massage for improving neck pain and function remains unclear. |
We included two RCTs in this review, in which 2343 participants with AMD were randomised to receive either omega 3 fatty acid supplements or a placebo. The trials, which had a low risk of bias, were conducted in the USA and France. Overall, there was no evidence that people who took omega 3 fatty acid supplements were at decreased (or increased risk) of progression to advanced AMD (pooled hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.84 to 1.10, high quality evidence). Similarly, people taking these supplements were no more (or less) likely to lose 15 or more letters of visual acuity (USA study HR 0.96, 95% CI 0.84 to 1.10; French study at 36 months risk ratio (RR) 1.25, 95% CI 0.69 to 2.26, participants = 230). The number of adverse events was similar in the intervention and placebo groups (USA study participants with one or more serious adverse event RR 1.00, 95% CI 0.91 to 1.09, participants = 2080; French study total adverse events RR 1.05, 95% CI 0.97 to 1.13, participants = 263). This review found that omega 3 LCPUFA supplementation in people with AMD for periods up to five years does not reduce the risk of progression to advanced AMD or the development of moderate to severe visual loss. No published randomised trials were identified on dietary omega 3 fatty acids for primary prevention of AMD. Currently available evidence does not support increasing dietary intake of omega 3 LCPUFA for the explicit purpose of preventing or slowing the progression of AMD. | We searched for studies up to 2 February 2015. We identified two trials with a total of 2343 participants. The trials were conducted in the USA and France and investigated the use of fish oil supplements in people with AMD who were at high risk of progressing to advanced disease. We judged the studies to be at low risk of bias. One study was funded by government grants and the other study was funded by the manufacturer of the dietary supplement. These studies found that omega 3 supplementation for periods up to five years did not reduce the rate of progression to advanced AMD or reduce significant visual loss compared to a placebo. The incidence of adverse effects was similar in the intervention and placebo groups. We judged the quality of the evidence on rate of progression to AMD to be high, and the quality of the evidence for other outcomes to be moderate because the estimates were imprecise. |
Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day). Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain. | In this review involving 1010 adults and children with asthma, we found that tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide (compared to clinical symptoms with or without spirometry/peak flow) was beneficial in reducing the final (but not the overall) daily inhaled corticosteroid doses in adults. However in children inhaled corticosteroid dose was increased when exhaled nitric oxide guided strategy was used. There was no difference between groups in other asthma outcomes (exacerbations, spirometry, FeNO or symptom control). Thus tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide cannot be routinely advocated. |
We identified five RCTs that randomised 544 children (three studies) and 205 adults (exclusively from two studies). They all compared saline irrigation to routine care or other nose sprays, rather than placebo. We included two new trials in this update, which did not contribute data of sufficient size or quality to materially change the original findings. Most trials were small and we judged them to be of low quality, contributing to an unclear risk of bias. Most outcome measures differed greatly between included studies and therefore could not be pooled. Most results showed no difference between nasal saline treatment and control. However, one larger trial, conducted with children, did show a significant reduction in nasal secretion score (mean difference (MD) -0.31, 95% confidence interval (CI) -0.48 to -0.14) and nasal breathing (obstruction) score (MD -0.33, 95% CI -0.47 to -0.19) in the saline group. However, a MD of -0.33 on a four-point symptom scale may have minimal clinical significance. The trial also showed a significant reduction in the use of decongestant medication by the saline group. Minor nasal discomfort and/or irritation was the only side effect reported by a minority of participants. Nasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs. However, the included trials were generally too small and had a high risk of bias, reducing confidence in the evidence supporting this. Future trials should involve larger numbers of participants and report standardised and clinically meaningful outcome measures. | We identified five studies, with a total of 749 participants enrolled and 565 participants providing data, which addressed the research question and met the inclusion criteria. They all compared saline irrigation with routine care or other nose sprays. These studies covered a wide range of ages, countries, sample sizes, dosing methods and frequency, and time since onset of URTI symptoms. They were also highly variable in their design and the symptoms that were measured. This is not surprising due to the lack of consistent measures of URTI symptoms and signs. This resulted in very few common outcome measures that could be combined across these five studies. The evidence is current to August 2014. The two additional studies included since the original systematic review have not contributed data of sufficient size or quality to materially change the original findings. Only the largest study, which studied 401 children aged 6 to 10 years, found significant reductions in a number of symptoms, including nasal secretions, sore throat, nasal breathing score and nasal obstruction, as well as reduced use of additional nasal decongestant medications. It also reported a significant improvement in the health status score. There was a reduction in the outcome of time to resolution of symptoms, which was reported in two trials on adult participants, but the difference was not clinically significant. Nasal saline is safe but may cause minor adverse effects, such as irritation or a burning sensation, particularly with products using higher flows or concentrations. Most studies were small and had significant shortcomings in the design or implementation of the research. Further studies, preferably larger in size and using common outcome measures, are needed to establish the potential for the role of nasal saline irrigation in reducing the severity and duration of acute URTI symptoms, secondary infections and possibly antibiotic usage. |
We included two RCTs and one non-randomized study, involving a total of 181 participants. Both RCTs were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other involving 76 participants with postherpetic neuralgia. Study phases were 20 days and approximately eight weeks, respectively. The non-randomized study retrospectively evaluated 86 outpatients over an average of 8.8 ± 6.3 months. One RCT reported average pain intensity and pain relief, and found statistically significant improvements versus placebo for both outcomes, with 10 mg and 20 mg daily doses of methadone. The second RCT reported differences in pain reduction between methadone and morphine and found morphine to be statistically superior. The non-randomized study found that in patients initially prescribed methadone it was effective in fewer participants than in those initially prescribed other long-acting opioids (28% versus 42%, 33% and 50% for morphine, oxycodone and transdermal fentanyl, respectively). One RCT compared incidences for several individual adverse events, but found a difference between methadone and placebo for only one event, dizziness (P = 0.041). The three studies provide very limited evidence of the efficacy of methadone for CNCP, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments. | The three studies included in our review provide very limited evidence of the effectiveness of methadone for chronic non-cancer pain. We were unable to combine results statistically, and there were too few participants in each study to be confident in their results. No conclusions can be made regarding differences in effectiveness or side effects between methadone and placebo, other opioids, or other treatments. |
Six RCTs with a total of 1211 participants were eligible; five trials evaluated oral aciclovir, and one, with 419 participants, evaluated oral famciclovir. We were able to conduct meta-analyses as there were sufficient similarities in the included studies, such as the reporting of the presence of PHN, duration of rash before treatment initiation and treatment regimen. For our primary outcome, based on three trials (609 participants) we found no significant difference between the aciclovir and control groups in the incidence of PHN four months after the onset of the acute herpetic rash (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.51 to 1.11), nor was there a significant difference at six months (RR 1.05, 95% CI 0.87 to 1.27, two trials, 476 participants). In four of the trials (692 participants), there was some evidence for a reduction in the incidence of pain four weeks after the onset of rash. In the trial of famciclovir versus placebo, neither 500 mg nor 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly. The most commonly reported adverse events were nausea, vomiting, diarrhoea and headache for aciclovir, and headache and nausea for famciclovir. For neither treatment was the incidence of adverse events significantly different from placebo. None of the studies were at high risk of bias, although the risk of bias was unclear in at least one domain for all but one study. We found no new RCTs when we updated the searches in April 2013. There is high quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments; therefore, further well-designed RCTs are needed to investigate famciclovir or other new antiviral agents in preventing PHN. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different subgroups of people, such as people who are immunocompromised. | We identified six clinical trials that met our standards for inclusion in the review. They included a total of 1319 participants. We decided that our main measure of whether antiviral medicines work in preventing PHN would be whether or not PHN had developed six months after a first attack of shingles (some of the studies we included of aciclovir measured PHN at four months). Aciclovir, which is an antiviral medicine, was used in five trials (900 participants) and was not better than a placebo (dummy pill) in preventing PHN. In the other trial (419 participants), famciclovir, which is another antiviral drug, was no better than placebo in preventing pain following healing of the shingles rash. The number of side effects with aciclovir and famciclovir was not very different from the number with placebo. The trials did not have any major problems of design or conduct that put the results in doubt, although most of the reports did not provide enough information to fully assess every aspect. We conclude that according to high quality evidence, oral aciclovir was ineffective in reducing the incidence of PHN and there is not enough evidence on other antiviral treatments. There need to be further well-designed trials of famciclovir or other new antiviral agents with a greater number of participants. Future trials should pay more attention to the severity of pain and quality of life of participants, and should include different groups of people, such as those who have lowered immunity. The evidence is current to April 2013, when the searches were last updated. Because new evidence on this topic is slow to emerge, we have scheduled the next update of this review for 2017. |
We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear. Since the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear. | We identified three randomised controlled trials (RCTs), which are studies that randomly assign participants into different treatment groups, that looked at whether adding focused (targeted) radiation (radiosurgery) to WBRT is beneficial to people with brain metastases. Overall, participants who underwent WBRT and SRS did not survive longer than participants who were treated with WBRT alone. However, participants with high functional status to perform activities of daily life and those with a single metastasis did survive longer after SRS and WBRT. Participants treated with WBRT and SRS did experience improved local control and performance status, as well as decreased steroid use compared to participants treated with WBRT alone. The overall quality of the evidence was moderate based on the GRADE assessments for our outcomes of interest, and the overall risk of bias was unclear. Most of our conclusions are based on the results of one large trial with unclear risk of bias and therefore, we cautiously make the following remarks: we found that when radiosurgery was added to WBRT, there was no evidence to suggest that people lived any longer than if they had WBRT alone, except for people with only one brain metastasis (who may live longer if they receive the combination treatment). People having combination treatment also seemed to function better in daily life, their treated tumors were associated with having less chance of growing back, and they had to take less steroid medication. The side effects of combined therapy and WBRT alone were similar. |
We included 56 trials with 3105 participants in this updated review. The average age of the participants was 60 years, and the studies were carried out in both inpatient and outpatient settings. All participants had at least some walking difficulties and many could not walk without assistance. Overall, the use of treadmill training did not increase the chances of walking independently compared with other physiotherapy interventions (risk difference (RD) -0.00, 95% confidence interval (CI) -0.02 to 0.02; 18 trials, 1210 participants; P = 0.94; I² = 0%; low-quality evidence). Overall, the use of treadmill training in walking rehabilitation for people after stroke increased the walking velocity and walking endurance significantly. The pooled mean difference (MD) (random-effects model) for walking velocity was 0.06 m/s (95% CI 0.03 to 0.09; 47 trials, 2323 participants; P < 0.0001; I² = 44%; moderate-quality evidence) and the pooled MD for walking endurance was 14.19 metres (95% CI 2.92 to 25.46; 28 trials, 1680 participants; P = 0.01; I² = 27%; moderate-quality evidence). Overall, the use of treadmill training with body weight support in walking rehabilitation for people after stroke did not increase the walking velocity and walking endurance at the end of scheduled follow-up. The pooled MD (random-effects model) for walking velocity was 0.03 m/s (95% CI -0.05 to 0.10; 12 trials, 954 participants; P = 0.50; I² = 55%; low-quality evidence) and the pooled MD for walking endurance was 21.64 metres (95% CI -4.70 to 47.98; 10 trials, 882 participants; P = 0.11; I² = 47%; low-quality evidence). In 38 studies with a total of 1571 participants who were independent in walking at study onset, the use of treadmill training increased the walking velocity significantly. The pooled MD (random-effects model) for walking velocity was 0.08 m/s (95% CI 0.05 to 0.12; P < 0.00001; I2 = 49%). There were insufficient data to comment on any effects on quality of life or activities of daily living. Adverse events and dropouts did not occur more frequently in people receiving treadmill training and these were not judged to be clinically serious events. Overall, people after stroke who receive treadmill training, with or without body weight support, are not more likely to improve their ability to walk independently compared with people after stroke not receiving treadmill training, but walking speed and walking endurance may improve slightly in the short term. Specifically, people with stroke who are able to walk (but not people who are dependent in walking at start of treatment) appear to benefit most from this type of intervention with regard to walking speed and walking endurance. This review did not find, however, that improvements in walking speed and endurance may have persisting beneficial effects. Further research should specifically investigate the effects of different frequencies, durations, or intensities (in terms of speed increments and inclination) of treadmill training, as well as the use of handrails, in ambulatory participants, but not in dependent walkers. | We identified 56 relevant trials, involving 3105 participants, up to March 2017. Twenty-six studies (1410 participants) compared treadmill training with body weight support to another physiotherapy treatment; 20 studies (889 participants) compared treadmill training without body weight support to other physiotherapy treatment, no treatment, or sham treatment; two studies (100 participants) compared treadmill training with body weight support to treadmill training without body weight support; and four studies (147 participants) did not state whether they used body weight support or not. The average age of the participants was 60 years, and the studies were carried out in both inpatient and outpatient settings. The results of this review were partly inconclusive. People after stroke who receive treadmill training with or without body weight support are not more likely to improve their ability to walk independently. The quality of this evidence was low. However, treadmill training with or without body weight support may improve walking speed and walking capacity compared with people not receiving treadmill training. The quality of this evidence was moderate. More specifically, people after stroke who are able to walk at the start of therapy appear to benefit most from this type of intervention, but people who are not able to walk independently at therapy onset do not benefit. This review found that improvements in walking speed and endurance in people who can walk have no lasting positive effect. Unwanted events such as falls and dropouts were not more common in people receiving treadmill training. Further analysis showed that treadmill training in the first three months after stroke produces only modest improvements in walking speed and endurance. For people treated at a later stage (more than six months after their stroke) the effects were smaller. More frequent treadmill training (for example, five times per week) appears to produce greater effects on walking speed and endurance; however, this was not conclusive. Brief periods of treadmill training (duration of four weeks) provided a modest improvement in walking speed but not enough to be clinically important. Effects of the age of participants or the type of stroke were not investigated in this review. In practice, it appears that people who can walk after stroke, but not those who cannot, may profit from treadmill training (with and without body weight support) to improve their walking abilities. Further research should specifically investigate the effects of different frequencies, durations or intensities (in terms of speed increments and inclination) of treadmill training, as well as the use of handrails. Future trials should include people who can already walk, but not dependent walkers who are unable to walk unaided. Future research should analyse age groups, gender, and type of stroke to see who might benefit most from this treatment. The quality of evidence for treadmill training for walking after stroke was low to moderate. It was moderate for walking speed and walking endurance at the end of treatment and low for improving the ability to walk independently. |
This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain. We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder. There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI. Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation. It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I2 = 82%). Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols. The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias. In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias. Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form. It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out. | We conducted a literature review up to March 2017 and three studies were included according to our selection criteria. The three studies reported data on 110 participants. All three studies investigated whether introducing probiotics directly into the bladder to create a non-harmful colony will prevent urinary tract infections in people with bladder dysfunction, predominantly people with spinal cord injury. Two studies reported that this method was generally safe. This review found that generally, the studies were poor quality with high risk of bias. We found the effectiveness of colonisation with probiotics in preventing bladder infection in people with bladder dysfunction is uncertain. Furthermore, the success of colonisation was variable, and the colonisation process is invasive and demands a high level of commitment on the part of the participant. We did not identify any studies investigating whether other probiotics and other administration routes is effective in preventing urinary tract infections in people with bladder dysfunction. It is uncertain if probiotics prevent urine infections in people with bladder dysfunction after a nervous system injury. Further robustly designed studies are necessary. |
In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk. | In this review we included 142 studies with more than 1.1 million participants looking for an association between green tea consumption and cancers of the digestive tract and the female reproductive system, breast, prostate, kidney and urinary tract, nasopharynx, lung, blood, skin, thyroid and brain. The majority of the studies were of medium to high quality in terms of how they were conducted. Overall, the evidence from the studies showed that the consumption of green tea consumption to reduce the risk of cancer was inconsistent. Some studies suggested a beneficial effect on cancer risk, while others indicated no effect, and even suggested a slightly increased cancer risk. In particular, results from experimental studies suggested that green tea extract supplementation yielded a decreased risk for prostate cancer, but increased risk for gynaecological cancers. For non-melanoma skin cancer no difference in cancer cases emerged. Green tea supplementation seemed to slightly improve quality of life compared with placebo, although it was associated with some adverse effects including gastrointestinal disorders, higher levels of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin reactions. In nonexperimental studies, comparing people consuming the highest amount of green tea to those in the lowest category of consumption, we found an indication of a lower occurrence of new cases of overall types of cancer, while no difference emerged for lethal cases. However, results according to the type of cancer and study design were inconsistent. A beneficial effect of green tea consumption on cancer prevention remains unproven so far. Caution is advised regarding supplementation with high-dose green tea extracts due to the possible adverse effects. |
We identified 22 new trials for inclusion in this update. In total, the evidence of this review rests on 52 trials with a total of 3731 participants. We included music therapy interventions offered by trained music therapists, as well as music medicine interventions, which are defined as listening to pre-recorded music, offered by medical staff. We categorized 23 trials as music therapy trials and 29 as music medicine trials. The results suggest that music interventions may have a beneficial effect on anxiety in people with cancer, with a reported average anxiety reduction of 8.54 units (95% confidence interval (CI) −12.04 to −5.05, P < 0.0001) on the Spielberger State Anxiety Inventory - State Anxiety (STAI-S) scale (range 20 to 80) and −0.71 standardized units (13 studies, 1028 participants; 95% CI −0.98 to −0.43, P < 0.00001; low quality evidence) on other anxiety scales, a moderate to strong effect. Results also suggested a moderately strong, positive impact on depression (7 studies, 723 participants; standardized mean difference (SMD): −0.40, 95% CI −0.74 to −0.06, P = 0.02; very low quality evidence), but because of the very low quality of the evidence for this outcome, this result needs to be interpreted with caution. We found no support for an effect of music interventions on mood or distress. Music interventions may lead to small reductions in heart rate, respiratory rate and blood pressure but do not appear to impact oxygen saturation level. We found a large pain-reducing effect (7 studies, 528 participants; SMD: −0.91, 95% CI −1.46 to −0.36, P = 0.001, low quality evidence). In addition, music interventions had a small to moderate treatment effect on fatigue (6 studies, 253 participants; SMD: −0.38, 95% CI −0.72 to −0.04, P = 0.03; low quality evidence), but we did not find strong evidence for improvement in physical functioning. The results suggest a large effect of music interventions on patients' quality of life (QoL), but the results were highly inconsistent across studies, and the pooled effect size for the music medicine and music therapy studies was accompanied by a large confidence interval (SMD: 0.98, 95% CI −0.36 to 2.33, P = 0.15, low quality evidence). A comparison between music therapy and music medicine interventions suggests a moderate effect of music therapy interventions for patients' quality of life (QoL) (3 studies, 132 participants; SMD: 0.42, 95% CI 0.06 to 0.78, P = 0.02; very low quality evidence), but we found no evidence of an effect for music medicine interventions. A comparison between music therapy and music medicine studies was also possible for anxiety, depression and mood, but we found no difference between the two types of interventions for these outcomes. The results of single studies suggest that music listening may reduce the need for anesthetics and analgesics as well as decrease recovery time and duration of hospitalization, but more research is needed for these outcomes. We could not draw any conclusions regarding the effect of music interventions on immunologic functioning, coping, resilience or communication outcomes because either we could not pool the results of the studies that included these outcomes or we could only identify one trial. For spiritual well-being, we found no evidence of an effect in adolescents or young adults, and we could not draw any conclusions in adults. The majority of studies included in this review update presented a high risk of bias, and therefore the quality of evidence is low. This systematic review indicates that music interventions may have beneficial effects on anxiety, pain, fatigue and QoL in people with cancer. Furthermore, music may have a small effect on heart rate, respiratory rate and blood pressure. Most trials were at high risk of bias and, therefore, these results need to be interpreted with caution. | We identified 22 new studies, so the evidence in this review update now rests on 52 studies with 3731 participants. The findings suggest that music therapy and music medicine interventions may have a beneficial effect on anxiety, pain, fatigue, heart rate, respiratory rate and blood pressure in people with cancer. Because of the very low quality of the evidence for depression, it is unclear what impact music interventions may have. Music therapy but not music medicine interventions may improve patients' quality of life. We did not find evidence that music interventions improve mood, distress or physical functioning, but only a few trials studied these outcomes. We could not draw any conclusions about the effect of music interventions on immunologic functioning, coping, resilience or communication outcomes because there were not enough trials looking at these aspects. Therefore, more research is needed. No adverse effects of music interventions were reported. Most trials were at high risk of bias, so these results need to be interpreted with caution. We did not identify any conflicts of interests in the included studies. We conclude that music interventions may have beneficial effects on anxiety, pain, fatigue and quality of life (QoL) in people with cancer. Furthermore, music may have a small positive effect on heart rate, respiratory rate and blood pressure. Reduction of anxiety, fatigue and pain are important outcomes for people with cancer, as they have an impact on health and overall QoL. Therefore, we recommend considering the inclusion of music therapy and music medicine interventions in psychosocial cancer care. |
We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine whether there was any difference in the number of participants with severe or life-threatening bleeding between a therapeutic-only transfusion policy and a prophylactic platelet transfusion policy (two RCTs; 801 participants; risk ratio (RR) 4.91, 95% CI 0.86 to 28.12; low-quality evidence). Two RCTs (801 participants) reported time to first bleeding episode. As there was considerable heterogeneity between the studies, we were unable to perform a meta-analysis. Both studies individually found that time to first bleeding episode was shorter in the therapeutic-only group compared with the prophylactic platelet transfusion group. There was insufficient evidence to determine any difference in all-cause mortality within 30 days of the start of the study using a therapeutic-only platelet transfusion policy compared with a prophylactic platelet transfusion policy (two RCTs; 629 participants). Mortality was a rare event, and therefore larger studies would be needed to establish the effect of these alternative strategies. There was a clear reduction in the number of platelet transfusions per participant in the therapeutic-only arm (two RCTs, 991 participants; standardised mean reduction of 0.50 platelet transfusions per participant, 95% CI -0.63 to -0.37; moderate-quality evidence). None of the studies reported quality of life. There was no evidence of any difference in the frequency of adverse events, such as transfusion reactions, between a therapeutic-only and prophylactic platelet transfusion policy (two RCTs; 991 participants; RR 1.02, 95% CI 0.62 to 1.68), although the confidence intervals were wide. We found low- to moderate-grade evidence that a therapeutic-only platelet transfusion policy is associated with increased risk of bleeding when compared with a prophylactic platelet transfusion policy in haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT. There is insufficient evidence to determine any difference in mortality rates and no evidence of any difference in adverse events between a therapeutic-only platelet transfusion policy and a prophylactic platelet transfusion policy. A therapeutic-only platelet transfusion policy is associated with a clear reduction in the number of platelet components administered. | The evidence is current to July 2015. In this update, we identified seven randomised controlled trials that compared only giving platelet transfusions to treat bleeding versus giving platelet transfusions to prevent and treat bleeding . One trial is still recruiting participants and has not been completed. We reviewed six randomised controlled trials with a total of 1195 participants. These trials were conducted between 1978 and 2013. Five of the trials included adults who were receiving chemotherapy or a stem cell transplantation as treatment for blood cancers. One of the trials included children receiving chemotherapy for leukaemia. Four of the six studies reported funding sources; these were charitable foundations or government funds. Giving platelet transfusions to prevent and treat bleeding in patients with low platelet counts due to blood cancers or their treatments may result in a reduction in bleeding when compared with giving platelet transfusions only to treat bleeding. There may not be an increased risk of death or adverse events if platelet transfusions are only given to treat bleeding versus giving platelet transfusions to prevent and treat bleeding, but there was not enough evidence to be certain about this. Giving platelet transfusions only when bleeding occurs probably reduces the number of platelets given. None of the six studies reported any quality-of-life outcomes. The evidence for most of the findings was of low or moderate quality, as patients and their doctors knew which study arm the patient had been put in; outcomes reported in the studies were difficult to compare because bleeding was measured and reported differently; and some outcomes were imprecise, because the outcome did not happen very often (such as death). |
Five RCTs met the pre-specified inclusion criteria for this review. No trials evaluated strict glycaemic control in the immediate pre-operative period or outside the intensive care unit. Due to heterogeneity in patient populations, peri-operative period, glycaemic target, route of insulin administration, and definitions of outcome measures, combination of the results of the five included trials into a meta-analysis was not appropriate. The methodological quality of the trials was variable. In terms of outcomes, only one trial demonstrated a significant reduction in SSIs with strict glycaemic control, but the quality of this trial was difficult to assess as a result of poor reporting; furthermore the baseline rate of SSIs was high (30%). The other trials were either underpowered to detect a difference in SSIs, due to a low baseline rate (less than or equal to 5%), or did not report SSIs as a single outcome but as part of a composite. Of the three trials reporting hypoglycaemia (which was not consistently defined) all had a higher rate in the strict glycaemic control group but none attributed significant morbidity to the hypoglycaemia. Adequacy of glucose control between groups was measured differently among studies. Studies could not be compared due to differences in target ranges, and were susceptible to measurement bias due to differences in frequency of measurement and lack of blinding by the providers following the glycaemic protocols. Infection-related mortality was not reported in any of the trials, and no trials demonstrated a significant difference in all-cause mortality. Length of hospital stay was significantly reduced in the strict glycaemic control groups in only one trial. There is insufficient evidence to support strict glycaemic control versus conventional management (maintenance of glucose < 200 mg/dL) for the prevention of SSIs. No trials were found that evaluated strict glycaemic control in the immediate pre-operative period or outside the setting of an intensive care unit. The trials were limited by small sample size, inconsistencies in the definitions of the outcome measures and methodological quality. Further large randomised trials are required to address this question and may be most appropriately performed in patients at high risk for SSIs. | Previous studies have suggested that decreasing blood glucose levels to within a low, narrow range (strict control) around the time of surgery may decrease infections and improve outcome. However, concerns about side effects from low glucose levels, such as seizures and increased risk of death, have prevented widespread use of this strategy. There are only five trials comparing strict control strategies with the conventional strategy of treating blood glucose levels only when they become high. These trials differ significantly in patient characteristics, glucose targets, medications and methods used to lower glucose levels, as well as the outcomes measured. Furthermore, the individual studies, which are small and/or flawed, do not demonstrate a significant decrease in surgical site infections. There are insufficient data to support the routine adoption of strict blood glucose control around the time of operation to prevent surgical site infections. |
We included seven RCTS in the review; we included six of these, totalling 485 couples, in the meta-analysis. No trials reported the primary outcome of live birth. The evidence was of very low-quality. The main limitations were (unclear) risk of bias, signs of imprecision and inconsistency in results among studies and the small number of studies/participants included. Swim-up versus gradient technique Considering the quality of evidence, we are uncertain whether there was a difference between clinical pregnancy rates (CPR) for swim-up versus a gradient technique (odds ratio (OR) 0.83, 95% CI 0.51 to 1.35; I² = 71%; 4 RCTs, 370 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a gradient technique is assumed to be 24%, the chance of pregnancy after using the swim-up technique is between 14% and 30%. We are uncertain whether there was a real difference between ongoing pregnancy rates per couple (OR 0.39, 95% CI 0.19 to 0.82; heterogeneity not applicable; 1 RCT, 223 participants; very low-quality evidence). Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates (MPR) per couple comparing a swim-up versus gradient technique (MPR per couple 0% versus 0%; 1 RCT, 25 participants; very low-quality of evidence). Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates (MR) per couple comparing a swim-up versus gradient technique (OR 0.85, 95% CI 0.28 to 2.59; I² = 44%; 3 RCTs, 330 participants; very low-quality evidence). No studies reported on ectopic pregnancy rate, fetal abnormalities or infection rate. Swim-up versus wash technique Considering the quality of evidence, we are uncertain whether there is a difference in clinical pregnancy rates after a swim-up technique versus wash and centrifugation (OR 0.41, 95% CI 0.15 to 1.13; I² = 55%; 2 RCTs, 78 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 38%, the chance of pregnancy after using the swim-up technique is between 9% and 41%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates between swim-up technique versus wash technique (OR 0.49, 95% CI 0.02 to 13.28; heterogeneity not applicable; 1 RCT, 26 participants; very low-quality evidence). Miscarriage rate was only reported by one study: no miscarriages were reported in either treatment arm. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. Gradient versus wash technique Considering the quality of evidence, we are uncertain whether there is a difference in clinical pregnancy rates after a gradient versus wash and centrifugation technique (OR 1.78, 95% CI 0.58 to 5.46; I² = 52%; 2 RCTs, 94 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 13%, the chance of pregnancy after using the gradient technique is between 8% and 46%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates per couple between the treatment groups (OR 0.33, 95% CI 0.01 to 8.83; very low-quality evidence). Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates per couple between the treatment groups (OR 6.11, 95% CI 0.27 to 138.45; very low-quality evidence). No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. The very low quality of the available evidence means we cannot be certain about the relative effectiveness of the different semen preparation techniques: swim-up versus gradient versus wash and centrifugation technique. No studies reported on live birth rates. We are uncertain whether there is a difference in clinical pregnancy rates, ongoing pregnancy rates, multiple pregnancy rates or miscarriage rates per couple between the three sperm preparation techniques. Further randomised trials are warranted that report live birth data | We found six randomised controlled trials comparing a gradient, swim-up or wash technique, in a total of 485 couples undergoing IUI. The evidence is current to March 2019. We are uncertain whether there is a difference in pregnancy outcomes between the three sperm preparation techniques for subfertile couples undergoing IUI. No studies reported on live birth rates. Considering the quality of evidence (very low), we are uncertain whether there was a difference between clinical pregnancy rates (CPR) for swim-up versus a gradient technique. The results suggest that if the chance of pregnancy after the use of a gradient technique is assumed to be 24%, the chance of pregnancy after using the swim-up technique is between 14% and 30%. We are uncertain whether there was a difference between ongoing pregnancy rates per couple, multiple pregnancy rates (MPR) per couple or miscarriage rates (MR) per couple when comparing a swim-up versus gradient technique. The quality of the evidence for these outcomes was very low. No studies reported on ectopic pregnancy rate, fetal abnormalities or infection rate. Considering the quality of evidence (very low), we are uncertain whether there is a difference in clinical pregnancy rates after a swim-up technique versus wash and centrifugation. The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 38%, the chance of pregnancy after using the swim-up technique is between 9% and 41%. Considering the very low-quality evidence, we are uncertain whether there was a difference between multiple pregnancy rates between swim-up technique versus wash technique. Miscarriage rate was only reported by one study: no miscarriages were reported in either treatment arm. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. Considering the quality of evidence (very low), we are uncertain whether there is a difference in clinical pregnancy rates after a gradient versus wash and centrifugation technique. The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 13%, the chance of pregnancy after using the gradient technique is between 8% and 46%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates per couple between the treatment groups. Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates per couple between the treatment groups. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. The quality of the evidence was very low. The main limitations were (unclear) risk of bias, signs of imprecision (small number of studies/participants included) and inconsistency in results among studies. |
We included 21 randomised studies involving 1,690 caregivers; 19 studies compared telephone support interventions and usual care, of which 18 contributed data to the analyses. Two studies compared telephone and non-telephone professional support interventions. Caregiver ages ranged from 19 years to 87 years across studies. The majority of participants were female (> 70.53%), with two trials including females only. Most caregivers were family members, educated beyond secondary or high school level or had the equivalent in years of education. All caregivers were based in the community. Overall risk of bias was high for most studies. The results demonstrated that there is probably little or no difference between telephone support interventions and usual care for the primary outcome of quality of life at the end of intervention (SMD -0.02, 95% CI -0.24 to 0.19, 4 studies, 364 caregivers) (moderate-certainty evidence) or burden at the end of intervention (SMD -0.11, 95% CI -0.30 to 0.07, 9 studies, 788 caregivers) (low-certainty evidence). For one study where quality of life at the end of intervention was reported narratively, the findings indicated that a telephone support intervention may result in slightly higher quality of life, compared with usual care. Two further studies on caregiver burden were reported narratively; one reported that telephone support interventions may decrease burden, the other reported no change in the intervention group, compared with usual care. We are uncertain about the effects of telephone support interventions on caregiver depression at the end of intervention (SMD -0.37, 95% CI -0.70 to -0.05, 9 studies, 792 caregivers) due to very low-certainty evidence for this outcome. Depression was reported narratively for three studies. One reported that the intervention may reduce caregiver depression at the end of intervention, but this effect was not sustained at short-term follow-up. The other two studies reported there may be little or no difference between telephone support and usual care for depression at the end of intervention. Six studies measured satisfaction with the intervention but did not report comparative data. All six reported high satisfaction scores with the intervention. No adverse events, including suicide or suicide ideation, were measured or reported by any of the included studies. Our analysis indicated that caregiver anxiety may be slightly reduced (MD -6.0, 95% CI -11.68 to -0.32, 1 study, 61 caregivers) and preparedness to care slightly improved (SMD 0.37, 95% CI 0.09 to 0.64, 2 studies, 208 caregivers) at the end of intervention, following telephone-only support interventions compared to usual care. Findings indicated there may be little or no difference between telephone support interventions and usual care for all of the following outcomes at the end of intervention: problem-solving, social activity, caregiver competence, coping, stress, knowledge, physical health, self-efficacy, family functioning, and satisfaction with supports (practical or social). There may also be little or no effect of telephone support interventions for quality of life and burden at short-term follow-up or for burden and depression at medium-term follow-up. Litttle or no difference was found between groups for any of the reported outcomes in studies comparing telephone and non-telephone professional support interventions. We are uncertain as to the effects of telephone support interventions compared to non-telephone support interventions for caregiver burden and depression at the end of intervention. No study reported on quality of life or satisfaction with the intervention and no adverse events were reported or noted in the two studies reporting on this comparison. Although our review indicated slight benefit may exist for telephone support interventions on some outcomes (e.g. anxiety and preparedness to care at the end of intervention), for most outcomes, including the primary outcomes, telephone-only interventions may have little or no effect on caregiver outcomes compared to usual care. The findings of the review were mainly based on studies with overall high risk of bias, and few participants. Further high-quality trials, with larger sample sizes are required. | We included 21 studies involving 1,690 caregivers caring for persons with a range of diagnosed conditions. Caregiver ages ranged from 19 years to 87 years. Most were female and caring for a family member. The majority were spouses, in particular wives, except for one study that mainly focused on adult children. Most caregivers had greater than secondary school education. Eighteen studies reported funding from reputable sources. Key results Nineteen studies (18 studies contributing data) compared telephone support interventions and usual care. Telephone support interventions probably have little or no effect on caregiver quality of life (4 studies, 364 caregivers) and may have little effect on burden (9 studies, 788 caregivers) compared to usual care on completion of the intervention. Although anxiety may be slightly reduced and preparedness to care slightly improved following the intervention, we are uncertain about the effects on depression and overall, telephone interventions may have little or no effect on the outcomes assessed by this review. High satisfaction with the intervention was reported in six studies that measured this outcome, but no comparative data from usual care groups was reported. Two studies compared telephone and non-telephone-based support interventions. There may be little or no evidence of an effect of telephone support when compared non-telephone-based support interventions for any reported outcome. No adverse events were measured or reported in any of the included studies. Quality of evidence The quality of the evidence was assessed as very low to moderate across outcomes, thus reducing confidence in the findings. Many of the results were based on data from single studies with few participants. Larger well-designed studies are required to determine the effects of telephone support interventions. |
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56). In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections. | Therefore, we conducted a systematic review assessing the influence of CSFs on disease and infection-related outcomes. Our review showed that the addition of CSFs to chemotherapy in AML patients affected neither overall survival, nor the achievement of disease remission or the rate of relapse. Importantly, they did not affect the rate of infections in this population. We concluded that CSFs post-chemotherapy should not be given routinely in AML patients. However, their administration could be considered on an individual basis. |
Over 4600 women were recruited into the 15 trials included in the review, however two trials did not contribute any outcome data to the review. The trials had a moderate risk of bias. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of death prior to hospital discharge (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.86 to 1.27, six trials, 3694 infants), neonatal respiratory distress syndrome (average RR 1.05, 95% CI 0.91 to 1.22, nine trials, 3833 infants), or chronic lung disease (RR 1.01, 95% CI 0.85 to 1.19, five trials, 2511 infants), and did not improve any of the secondary fetal, neonatal or childhood outcomes assessed by intention-to-treat analyses. Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side effects reported (nausea, vomiting, light headedness, urgency of micturition, facial flushing) were significantly more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of needing respiratory support (RR 1.16, 95% CI 1.03 to 1.29, three trials, 1969 infants), and of having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, three trials, 1969 infants). Only three trials provided data on childhood follow-up, and while one trial suggested poorer outcomes for infants who were exposed to prenatal TRH, the other two trials, that assessed infants using an established developmental instrument, showed no clear differences between groups in follow-up outcomes. Sensitivity analyses by trial quality, or subgroups with differing times from entry to birth, or different dose regimens of TRH, did not change these findings. Prenatal TRH in addition to corticosteroids, given to women at risk of preterm birth, does not improve infant outcomes and can cause maternal side effects. | This review included 15 trials, of a moderate risk of bias, that involved over 4600 women and their babies. In this review, TRH, given with corticosteroids to women at risk of early birth, was not shown to further reduce the breathing difficulties for the babies. Babies born to mothers who had received TRH with corticosteroids, were more likely to require support for breathing than babies born to mothers who received only corticosteroids. Women receiving TRH were more likely to experience adverse side effects, such as nausea, vomiting and flushing than women who only received corticosteroids. Therefore, based on the current available evidence, TRH is not recommended to be given to women at risk of preterm birth for preventing neonatal respiratory disease. |
We included four trials published between 1996 to 2000 that randomized 563 children (465 evaluable) aged five months to 15 years to intermittent twice-weekly versus daily anti-TB treatment. Two trials were from India, one from South Africa, and one from Turkey. All trials used rifampicin and isoniazid, three trials used pyrazinamide, and one trial used streptomycin. The drug combination, and the duration of intermittent and daily treatments differed between trials, and no trials used drug combinations and schedules currently recommended for childhood TB. No trial reported if any child was HIV-positive. In comparisons of twice-weekly versus daily anti-TB treatment regimens, the trials did not detect differences in the number of patients cured, but trials were small, and the comparator regimens were not standard (four trials, 465 children; very low quality evidence). Trials were underpowered to provide estimates for death (two trials, 213 participants, very low quality evidence), relapse (one trial, 214 participants,very low quality evidence), and treatment limiting adverse events (four trials, 441 participants, very low quality evidence) Reported adherence to treatment was similar (87% versus 84%; four trials, 458 children, very low quality evidence) We did not find trials comparing the commonly used thrice-weekly anti-TB short-course regimen with the daily treatment regimen. Trials conducted to date are insufficient to support or refute the use of intermittent twice- or thrice-weekly, short-course treatment regimens over daily short-course treatment in children with TB. Further randomized trials conducted in high TB-transmission settings will help inform policy and practice. | In this Cochrane review, the review authors compared children given intermittent anti-TB treatment to those given daily treatment. They examined the evidence up to 30 May 2013 and included four randomized trials that compared twice-weekly treatment with daily doses of anti-TB drugs, but none evaluated thrice-weekly dosing. The four trials included 563 children aged five months to 15 years, not known to be resistant to TB drugs. The trials were published over 12 years ago and the regimens used are not those currently recommended. The trials were small, and did not detect a difference between twice-weekly or daily treatment in the number of children who were cured, died, relapsed, reported taking most or all of the drugs, or had adverse effects. Whether regimens of drugs two or three times a week are as good as regimens with daily doses remains unclear, as the evidence base to date is small, and the regimens tested are not the same as currently currently recommended drug combinations. |
Eight studies met the inclusion criteria. Three papers compared the effects of anticholinergic drugs with placebo, and a meta-analysis of these results demonstrated no statistically significant benefit of the use of anticholinergic drugs over placebo in any of the outcome measures used. The results of one of these trials could not be included in the meta-analysis but the authors did report significantly lower symptom scores with inhaled anticholinergics compared with placebo. However, there was no significant difference between ipratropium bromide and placebo in the percentage of symptom-free nights or days. Two trials studied the effects of anticholinergics on bronchial hyper responsiveness to histamine, by measuring the provocation dose of histamine needed to cause a fall of 20 % in FEV1 (PD 20). One study (comparing anticholinergics with placebo) reported a statistically significant increase in PD 20 but this was not found in another study (comparing anticholinergics with a beta-2 agonist). Both trials also examined the effect of anticholinergic drugs on diurnal variation in peak expiratory flow rate (PEFR) and reported no significant effect. Two studies compared the addition of an anticholinergic drug to a beta-2 agonist with the beta-2 agonist alone. Both trials failed to show any significant benefit from the long term use of combined anticholinergics with beta-2 agonists compared with beta-2 agonists alone. One trial compared the effects of oral and inhaled anticholinergic drugs with placebo. No statistically significant differences were found in any of the outcome measures except for a higher FEV1 / VC ratio and RV / TLC ratio with oral anticholinergic therapy when compared with placebo. The present review summarises the best evidence available to date. Although there were some small beneficial findings in favour of anticholinergic therapy, there is insufficient data to support the use of anticholinergic drugs in the maintenance treatment of chronic asthma in children. | This study undertook a comprehensive search of the literature unrestricted by country of publication or language. Unfortunately small numbers of relevant trials were found and these were of variable quality. This review found that although anticholinergic drugs are well tolerated, in children over two years of age, there is not enough data to be sure if they are better than placebo in terms of effects on lung function or symptoms. |
Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD - 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD - 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD - 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765). Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment. | 50 studies with 7793 participants were included in the review, in most studies treatment was provided over a period of three months. The review shows that more patients who took naltrexone were able to reduce the amount and frequency of drinking than those who took an identical appearing, but inert substance (placebo). On average, one out of nine patients was helped by naltrexone. Naltrexone does not have serious side effects, but gastrointestinal symptoms like nausea, stomach pain and loss of appetite are common. Some patients also get tired from naltrexone. For injectable formulations of naltrexone, which can be advantageous for patients who have problems with taking their medication on schedule, and the second opioid antagonist nalmefene, the database is still too sparse to allow final conclusions. Nevertheless, the available studies indicate that these drugs might have comparable effects on drinking than oral naltrexone has. Naltrexone does not cause dependency and unlike disulfiram, another medicine that is sometimes used to treat alcohol dependence, it does not make patients feel sick if they drink alcohol while taking it. |
Of the 12 records retrieved by the search, three trials published in 2001, 2003 and 2007, involving 80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric facility and followed up for a period nine weeks to 26 weeks, were included. Overall, pyridoxal 5 phosphate produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to 139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n = 60, MD -4.07, CI -6.36 to -1.79, low quality evidence). It was unclear whether pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20 to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from the study because they were not willing to take more medications while none of the participants taking placebo discontinued their medications (n = 65, 2 RCTs, RR 8.72, CI 0.51 to 149.75, low quality evidence). There was no significant difference in the endpoint positive and negative psychiatric symptoms scores, measured using the Positive and Negative symptoms Scale (PANSS) between participants taking pyridoxal 5 phosphate and those taking placebo. For the positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72, low quality evidence). Pyridoxal 5 phosphate may have some benefits in reducing the severity of tardive dyskinesia symptoms among individuals with schizophrenia. However, the quality of evidence supporting the effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low, based on few studies, short follow-up periods, small sample sizes and inadequate adherence to standardised reporting guidelines for randomised controlled trials among the included studies. | . A search for relevant randomised studies was conducted in January 2013. The review includes three studies with 80 participants. All participants had tardive dyskinesia as a result of taking antipsychotic medication and were randomised into treatment groups. One group received pyridoxal 5 phosphate, the other group received a placebo. Antipsychotic treatment continued as usual throughout the trials. . People taking pyridoxal 5 phosphate in these studies experienced more than 40% improvement in their tardive dyskinesia compared to those on placebo, so had less severe tardive dyskinesia. Experience of side effects were similar between treatment groups with participants taking pyridoxal 5 phosphate experiencing no more or less side effects than participants in the placebo group and they did not experience greater worsening of their psychiatric symptoms than those on placebo. Evidence from the studies is weak, but suggests pyridoxal 5 phosphate may be effective in the treatment of tardive dyskinesia. . Evidence is weak. The number of studies and participants is few. The quality of studies is low. Better evidence could be gathered by better designed, conducted and reported trials. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/. |
Only four studies met the criteria for inclusion, with a total of 274 participants. Four pharmacological agents were investigated: modafinil (51 participants); (−)-OSU6162, a monoamine stabiliser (12 participants of which six had a TBI); atomoxetine (60 participants); and rivastigmine (157 participants). A meta-analysis could not be performed due to the small number and heterogeneity of the studies. All studies examined cognitive performance, with the majority of the psychometric sub-tests showing no difference between treatment and placebo (n = 274, very low quality evidence). For (−)-OSU6162 modest superiority over placebo was demonstrated on three measures, but markedly inferior performance on another. Rivastigmine was better than placebo on one primary measure, and a single cognitive outcome in a secondary analysis of a subgroup with more severe memory impairment at baseline. The study of modafinil assessed clinical global improvement (n = 51, low quality evidence), and did not find any difference between treatment and placebo. Safety, as measured by adverse events, was reported by all studies (n = 274, very low quality evidence), with significantly more nausea reported by participants who received rivastigmine compared to placebo. There were no other differences in safety between treatment and placebo. No studies reported any deaths. There is insufficient evidence to determine whether pharmacological treatment is effective in chronic cognitive impairment in TBI. Whilst there is a positive finding for rivastigmine on one primary measure, all other primary measures were not better than placebo. The positive findings for (−)-OSU6162 are interpreted cautiously as the study was small (n = 6). For modafinil and atomoxetine no positive effects were found. All four drugs appear to be relatively well tolerated, although evidence is sparse. | Method: We reviewed randomised controlled trials investigating the efficacy of any of the drugs commonly used to treat cognitive impairment after TBI. We included only studies which started treatment at least 12 months after the injury; by this time the cognitive impairment is usually stable. Results: We identified only four trials for inclusion. These investigated four different drugs—modafinil; the experimental drug (−)-OSU6162; atomoxetine; and rivastigmine—against placebo. On most measures there was no difference between treatment and placebo. Furthermore, the quality of the evidence was assessed as very low. The experimental drug called (−)-OSU6162 was better than placebo on three cognitive measures, although this was a small study with only six participants with TBI. Modafinil, atomoxetine and rivastigmine were not found to be better than placebo. No difference between modafinil and placebo was found on assessment of clinical global improvement. Compared to placebo, more participants on modafinil and fewer on rivastigmine dropped out of the trials. More people taking modafinil, atomoxetine and rivastigmine experienced adverse effects than those on placebo, although the difference is most likely due to chance. Only nausea was statistically more likely in those taking rivastigmine. In the study of (−)-OSU6162, one participant of three given placebo experienced adverse effects requiring a dose reduction, with no drop-outs reported. No studies reported any deaths. Conclusion: Recommendations for, or against, drug treatment of chronic cognitive impairment in TBI cannot be made on the basis of current evidence. |
Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam. Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06). Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization. Although this review suggests that diazepam alone compared with combination of phenobarbitone and chlorpromazine may be more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of this observation should be moderated by local needs and circumstances, pending the availability of better evidence. We recommend a reinforcement of preventive measures against tetanus infection and it is hoped that in the light of clear evidence about the preventive efficacy of tetanus toxoid immunization, concerted efforts should be made towards preventive interventions and ultimate eradication such that there will not be enough case materials for a trial. In the event of a need for a trial, a large prospective, multicenter, randomized controlled trial, which compares diazepam alone with combinations of other drugs (excluding diazepam) will be ideal. | The review authors searched the medical literature and identified two randomised controlled trials with a total of 134 hospitalized neonates and older children who had tetanus from Nigeria (19 neonates, seven children aged between one month and 10 years of age) and Indonesia (74 neonates, 34 children aged between three days and 12 years). All drugs were given orally as medications and feeds are usually given via nasogastric tube in the settings where the disease burden is high. Neither study provided information on the safety of the interventions or followed up survivors beyond discharge from hospital. |
It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease. | It was not possible to extract the results from the first phases of two included crossover studies of D-cycloserine for Alzheimer's disease and therefore the meta-analyses are based on the included two parallel group 6-month studies. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease. |
We identified two new studies for inclusion in the review update; the review now includes seven trials with 622 participants who presented to an emergency department with SVT. All included studies were RCTs, but only three described the randomisation process, and none had blinded participants, personnel, or outcome assessors to the intervention given. Moderate-quality evidence shows no differences in the number of people reverting to sinus rhythm who were treated with adenosine or CCA (89.7% vs 92.9%; OR 1.51, 95% confidence interval (CI) 0.85 to 2.68; participants = 622; studies = 7; I2 = 36%). Low-quality evidence suggests no appreciable differences in major adverse event rates between CCAs and adenosine. Researchers reported only one case of hypotension in the CCA group and none in the adenosine group (0.66% vs 0%; OR 3.09, 95% CI 0.12 to 76.71; participants = 306; studies = 3; I2 = 0%). Included trials did not report length of stay in hospital nor patient satisfaction. Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no appreciable differences in the incidence of hypotension. A study comparing patient experiences and prospectively studied adverse events would provide evidence on which treatment is preferable for management of SVT. | This review compares effectiveness and side effects of adenosine and CCAs in terminating SVT episodes. We included in the review seven trials involving 622 patients. Evidence is current to July 2017. Combined analysis of these trials showed no differences between adenosine and CCAs in successfully treating SVT. This finding is based on moderate-quality evidence. A temporary drop in blood pressure that did not require treatment was reported in only one of 152 study participants treated with CCAs, and low-quality evidence suggests that no patients treated with adenosine experienced low blood pressure. We have no data on length of stay in hospital nor on patient satisfaction. Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no differences in cases of hypotension. None of these trials examined patient preferences, which is an important factor in deciding which drug is the 'best' treatment. |
Twelve randomised clinical trials (RCTs) met our predefined review protocol criteria for analysis. We found only one trial to be at low risk of bias, considering the remaining trials to be at high risk of bias. The risk of selection bias in nine studies was unclear due to poor reporting, leading to uncertainty in the pooled effect estimates. Five trials compared NSAIDs versus placebo, four trials compared NSAID versus opioids, and four trials compared NSAID versus spasmolytic drugs (one of the 12 trials was a three-arm study comparing NSAIDs versus both opioids and spasmolytic drugs). There were 828 randomised participants (minimum 30 and maximum 324 per trial), of whom 416 received NSAIDs and 412 received placebo, spasmolytic drugs, or opioids. Twenty-four per cent of the participants were males. The age of the participants in the trials ranged from 18 to 86 years. All people were admitted to emergency departments for acute biliary pain. There was no mortality. When compared with placebo, NSAIDs obtained a significantly lower proportion of participants without complete pain relief (RR 0.27, 95% confidence interval (CI) 0.19 to 0.40; I2 = 0%; 5 trials; moderate-quality evidence), which was confirmed by Trial Sequential Analysis, but not regarding participants with complications (RR 0.66, 95% CI 0.38 to 1.15; I2 = 26%; 3 trials; very low-quality evidence). NSAIDs showed more pain control than spasmolytic drugs (RR 0.51, 95% CI 0.37 to 0.71; I2 = 0%; 4 trials; low-quality evidence), which was not confirmed by Trial Sequential Analysis, and a significantly lower proportion of participants with complications (RR 0.27, 95% CI 0.12 to 0.57; I2 = 0%; 2 trials; low-quality evidence), which was also not confirmed by Trial Sequential Analysis. We found no difference in the proportions of participants without complete pain relief when comparing NSAIDs versus opioids (RR 0.98, 95% CI 0.47 to 2.07; I2 = 52%), suggesting moderate heterogeneity among trials (4 trials; very low-quality evidence). Only one trial comparing NSAIDs versus opioids reported results on complications, finding no significant difference between treatments. None of the included trials reported severe adverse events. Seven out of the 12 trials assessed non-severe adverse events: in two out of the seven trials, adverse events were not observed, and minor events were reported in the remaining five trials. In addition, we found one ongoing RCT assessing the analgesic efficacy of intravenous ibuprofen in biliary colic. NSAIDs have been assessed in relatively few trials including a limited number of participants for biliary colic, considering its common occurrence. We found only one trial to be at low risk of bias. There was no mortality. None of the included trials reported quality of life. The generalisability of the review is low as most of the RCTs included neither elderly people nor participants with comorbidities, who are more prone to complications as compared to others with biliary colic. The beneficial effect of NSAIDs compared with placebo on pain relief was confirmed when we applied Trial Sequential Analysis. The quality of evidence according to GRADE criteria was moderate for the comparison of NSAIDs versus placebo regarding the outcome lack of pain relief and low or very low for the other outcomes and comparisons. We found only one trial at low risk of bias, following the predefined 'Risk of bias' domains. We found the risk of selection bias to be unclear in nine studies due to poor reporting, leading to uncertainty in the pooled effect estimates. | We searched for randomised clinical trials recruiting participants presenting with biliary colic and comparing NSAIDs versus no intervention, placebo, or other drugs. We included 12 randomised clinical trials with 828 participants, of whom 416 received NSAIDs and 412 received placebo, spasmolytic drugs, or opioids, in the review. Considering the common occurrence of biliary colic, these numbers of trials and participants are insufficient. Elderly participants and participants with co-morbidities were poorly represented in the trials. Twenty-four per cent of the participants were males. The age of participants ranged from 18 to 86 years. All people were admitted to emergency department for acute biliary pain. There was no mortality. None of the included trials reported quality of life. We found that NSAIDs significantly reduced biliary pain when compared with placebo and spasmolytic drugs. NSAIDs also significantly reduced cholelithiasis-related complications (e.g. acute cholecystitis, acute pancreatitis, jaundice, cholangitis) as compared to placebo and spasmolytic drugs. One trial comparing NSAIDs versus opioids reported results on complications, finding no significant difference between treatments. None of the trials reported major adverse events. Seven out of 12 trials reported minor adverse events; in two out of the eight trials adverse events were not observed, and minor events were reported in the remaining five trials. We found one ongoing randomised clinical trial aimed at assessing the analgesic effectiveness of intravenous ibuprofen in biliary colic. The trials appeared to be free of industry sponsorship or other type of for-profit support that may manipulate the trial design, conductance, results, or conclusions of the trial. The quality of evidence according to GRADE criteria (a system developed to grade evidence and recommendations in health care) was moderate for the comparison NSAIDs versus placebo for the outcome lack of pain relief and low or very low for the other outcomes and comparisons. Only one of 12 trials was at low risk of bias following predefined 'Risk of bias' domains. The results of the present systematic review with meta-analysis suggest that NSAIDs can be used for pain relief, but further randomised clinical trials are warranted, and NSAIDs should be used with care in certain patient groups, such as the elderly and people with co-morbidities. |
We included 12 studies (803 children) in this review and meta-analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I2 = 90%; very low-quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I2 = 67%; low-quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I2 = 0%; low-quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low-quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low-quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low-quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low-quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. | We reviewed the evidence on how effective indirect laryngoscopy, or videolaryngoscopy, is when compared with direct laryngoscopy for intubation in children from 28 days to 18 years old. We found 12 randomized controlled trials (803 children) that met our inclusion criteria. The evidence is current to November 2015. We reran the search in January 2017 and will include the three studies awaiting classification when we update the review. For intubation, use of indirect laryngoscopy, or videolaryngoscopy, took longer and was more likely to be unsuccessful (very low-quality evidence). No significant difference was found between direct and indirect laryngoscopy when success of the first attempt at intubation was assessed (low-quality evidence). Only a few studies reported the effect of intubation on adverse haemodynamic response, including changes in oxygen saturation, heart rate, and trauma to the mouth and windpipe. Therefore, it was difficult to conclude on the overall adverse effect (very low-quality evidence). Indirect laryngoscopy might provide better views of the vocal cords. We found considerable variation in results from included studies in terms of assessment of intubation time, number of attempts at intubation, number of unsuccessful intubations, adverse effects, and assessments of how well the vocal cords were seen. None of the included studies was funded by a laryngoscope manufacturer, hence minimizing the risk of other bias. The quality of the studies varied, and only a few were of highest quality. For these reasons, we graded the overall quality of evidence as very low. |
We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%. No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence). Investigators reported few minor adverse events. Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI 0.08 to 0.93, respectively) for both follow-up values and change from baseline scores. However, evidence of heterogeneity across trials was due to variation in intervention components (i.e. mode, frequency, intensity, duration of intervention and sessions) and measures used to assess outcomes. All trials reviewed were at high risk of performance bias, and most were also at high risk of detection, attrition, and selection bias. In light of the aforementioned issues, we determined that the evidence was of very low, low, or moderate quality. No conclusions regarding breast cancer-related and all-cause mortality or breast cancer recurrence were possible. However, physical activity interventions may have small-to-moderate beneficial effects on HRQoL, and on emotional or perceived physical and social function, anxiety, cardiorespiratory fitness, and self-reported and objectively measured physical activity. The positive results reported in the current review must be interpreted cautiously owing to very low-to-moderate quality of evidence, heterogeneity of interventions and outcome measures, imprecision of some estimates, and risk of bias in many trials. Future studies with low risk of bias are required to determine the optimal combination of physical activity modes, frequencies, intensities, and durations needed to improve specific outcomes among women who have undergone adjuvant therapy. | We included only studies consisting of women with breast cancer who had completed active cancer treatment. These studies compared outcomes of women involved in PA interventions versus outcomes of those who were offered usual care or no PA. Participants must have been assigned to a group in random or somewhat random fashion. The evidence is current to September 2015. This review includes 63 trials involving 5761 participants. Most trials (28) consisted of aerobic exercise (e.g. walking, cycling, dance), whereas seven trials included a resistance training-only group, and 21 trials included a combined aerobic exercise and resistance training group. One in five participants placed in a PA intervention group dropped out before the end of the study, and on average one-quarter of target PA sessions were missed by participants. We found no studies that looked at effects of PA after cancer treatment on risk of recurrence or dying from breast cancer or any other cause. We found that participants performing PA had more favourable values by the end of the intervention and experienced greater positive changes over the intervention period in terms of QoL, views on their emotional health and physical ability, social function, feelings of worry, stamina, PA levels, body fat, and strength of muscles, compared with usual care participants. Researchers found no effects on perceived health, ability to sleep, feelings of pain, sexual function, body mass index, waist-to-hip girth ratio, and bone health of the upper and lower spine or hip. At least three months after completion of the intervention, actual values and changes from the start of the intervention in feelings of tiredness, stamina, and self-reported PA levels remained more favourable in participants given PA intervention than in those given usual care. Both aerobic exercise only and combined aerobic and resistance training interventions improved QoL and stamina. Aerobic exercise improved views on perceived emotional health and physical ability, as well as social function and self-reported PA levels, whereas resistance training resulted in greater improvement in muscle strength. Combined aerobic and resistance training interventions led to reduced feelings of tiredness. Trialists reported few minor adverse events among those given PA interventions. We rated the quality of evidence related to various aspects of health as very low, low, or moderate. We noted wide variation among the interventions that we looked at in terms of types of PA, frequency of sessions per week, levels of effort among participants, and session and intervention duration. Also, researchers measured aspects of health in many different ways. Other problems with eligible studies included lack of information on how study authors placed participants in groups at random, whether researchers who were carrying out the tests knew which group the person being tested belonged to, and how researchers dealt with data missing from their studies. In many aspects, we could not rule out the chance that positive effects observed were small enough that they were not important. It is also possible that smaller studies that have not found favourable effects of PA in women with breast cancer after treatment have not been published, because study authors often find it difficult to publish studies that have not found beneficial effects. |
Three RCTs randomising 853 women, of whom 781 were evaluated, met the inclusion criteria. Meta-analysis of three trials for overall survival (OS) found no statistically significant difference between IDS and chemotherapy alone (hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.61 to 1.06, I² = 58%). Subgroup analysis for OS in two trials, where the primary surgery was not performed by gynaecologic oncologists or was less extensive, showed a benefit of IDS (HR = 0.68, 95% CI 0.53 to 0.87, I² = 0%). Meta-analysis of two trials for PFS found no statistically significant difference between IDS and chemotherapy alone (HR = 0.88, 95% CI 0.57 to 1.33, I² = 83%). Rates of toxic reactions to chemotherapy were similar in both arms (risk ratio = 1.19, 95% CI 0.53 to 2.66, I² = 0%), but little information was available for other adverse events or quality or life (QoL). We found no conclusive evidence to determine whether IDS between cycles of chemotherapy would improve or decrease the survival rates of women with advanced ovarian cancer, compared with conventional treatment of primary surgery followed by adjuvant chemotherapy. IDS appeared to yield benefit only in women whose primary surgery was not performed by gynaecologic oncologists or was less extensive. Data on QoL and adverse events were inconclusive. | This review compares the survival of women with advanced epithelial ovarian cancer, who had IDS performed between cycles of chemotherapy after primary surgery, with survival of women who had conventional treatment (primary debulking surgery and adjuvant chemotherapy). It found similar survival rates in women who did and did not receive IDS. Not enough information about adverse effects was available. Information on quality of life of the women was also inconclusive. |
Twelve trials (seven with duration of at least three months) met the inclusion criteria, with 19,715 participants randomised. The two largest trials that were conducted in the USA (SELECT and NPC) reported clinical events. There were no statistically significant effects of selenium supplementation on all cause mortality (RR 0.97, 95% CI 0.88 to 1.08), CVD mortality (RR 0.97, 95% CI 0.79 to 1.2), non-fatal CVD events (RR 0.96, 95% CI 0.89 to 1.04) or all CVD events (fatal and non-fatal) (RR 1.03, 95% CI 0.95 to 1.11). There was a small increased risk of type 2 diabetes with selenium supplementation but this did not reach statistical significance (RR 1.06, 95% CI 0.97 to 1.15). Other adverse effects that increased with selenium supplementation, as reported in the SELECT trial, included alopecia (RR 1.28, 95% CI 1.01 to 1.62) and dermatitis grade 1 to 2 (RR 1.17, 95% CI 1.0 to 1.35). Selenium supplementation reduced total cholesterol but this did not reach statistical significance (WMD - 0.11 mmol/L, 95% CI - 0.3 to 0.07). Mean high density lipoprotein (HDL) levels were unchanged. There was a statistically significant reduction in non-HDL cholesterol (WMD - 0.2 mmol/L, 95% CI - 0.41 to 0.00) in one trial of varying selenium dosage. None of the longer term trials examined effects on blood pressure. Overall, the included studies were regarded as at low risk of bias. The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD. | This review assessed the effects of providing selenium supplements to healthy adults in order to prevent the occurrence of cardiovascular disease. Whether selenium supplements would reduce the risk factors associated with heart disease was also examined. We found 12 trials in which 19,715 healthy adults were randomly assigned to receive selenium supplements or placebo. The vast majority of participants involved in these trials were male individuals from the US, where people are already well nourished and take large amounts of selenium from natural foods. Overall, the included studies were regarded as at low risk of bias. In our review, providing selenium supplements to healthy adults did not prevent the occurrence of major cardiovascular disease. The increased risk of developing type 2 diabetes when taking selenium supplements, as suggested in some previous studies, could not definitely be ruled out in our review. In summary, this review of the available evidence to date suggests that taking selenium supplements is neither beneficial nor harmful for cardiovascular disease, but it is probably unnecessary for those who are already well nourished and who take large amounts of selenium from natural foods. |
Since only one small study (n = 40) was included, no meta-analysis could be performed. The included randomised controlled study was of parallel design and undertaken at two paediatric hospitals in Australia. The study evaluated the effects of a singing program on the quality of life and respiratory muscle strength of hospitalised children with cystic fibrosis (mean age 11.6 years, 35% male). While the singing group received eight individual singing sessions, the control group participated in preferred recreational activities, such as playing computer games or watching movies. This study was limited by a small sample size (51 participants) and a high drop-out rate (21%). There were no differences between the groups at either post-intervention or follow-up; although by the end of treatment there were some improvements in some of the domains of the quality of life questionnaire Cystic Fibrosis Questionnaire-Revised (e.g. emotional, social and vitality domains) for both singing and control groups. For the respiratory muscle strength indices, maximal expiratory pressure at follow-up (six to eight weeks post-intervention) was higher in the singing group, mean difference 25.80 (95% confidence interval 5.94 to 45.66). There was no difference between groups for any of the other respiratory function parameters (maximal inspiratory pressure, spirometry) at either post-intervention or follow-up. No adverse effects were observed in the singing group; adverse events for the control group were not reported in the paper. There is insufficient evidence to determine the effects of singing on quality of life or on the respiratory parameters in people with cystic fibrosis. However, there is growing interest in non-medical treatments for cystic fibrosis and researchers may wish to investigate the impact of this inexpensive therapy on respiratory function and psychosocial well-being further in the future. | The review includes one study with 40 children with cystic fibrosis aged between seven and 17 years of age. This study compared a specially designed singing intervention with other non-physical leisure activities (recreation) and children were selected for the singing or the recreation program randomly. The study lasted two weeks and children were followed up for between six and eight weeks. The study assessed the impact of singing on respiratory muscle strength, quality of life and lung function tests. Participants from both the singing and recreation groups reported some improvement in quality of life measurements. Participants in the singing group showed a greater increase in maximal expiratory pressure (a substitute measure of respiratory muscle strength test), while there was no improvement in this outcome for those in the recreation group. No adverse events were reported. There is currently not enough evidence to assess the effect of singing on clinical outcomes in people with cystic fibrosis. Future studies using robust methods are needed to assess the possible effects of singing for people with cystic fibrosis The included study was limited by the small number of participants (only 51 participants enrolled and only 40 were analysed) and a high drop-out rate (21%). We also think the fact that the young people who were enrolled in the study were keen to sing, could have affected the study results. |
Fifteen studies (8 parallel, 7 crossover; 352 patients) were included. Only one study enrolled women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. PDE5i significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (2 studies, 101 patients, MD 10.65, 95% CI 5.34 to 15.96), all its individual domains and the complete 15-item IIEF tool (1 study, 41 patients, MD 2.64, 95% CI 1.32 to 3.96). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients, MD 0.21 ng/mL, 95% CI -2.14 to 2.55) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients, SMD 1.62, 95% CI 0.58 to 2.66). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Only sparse data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or psychosexual therapies in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden. | We identified 15 studies enrolling 352 patients with only one study enrolling both men and women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. In two studies (101 patients) PDE5i significantly increased the individual domains and the overall International Index of Erectile Function-5 (IIEF-5) score and the complete 15-item IIEF tool (1 study, 41 patients). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Little data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or behavioural therapy in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD however evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden. |
Seven studies with a total of 2422 participants were included in this systematic review. Meta-analysis could be performed with the data of four included studies, with a total of 1382 participants. The methodological quality of the included trials was relatively low. Evidence of a beneficial effect of culturing in low oxygen concentration was found for live birth rate (OR 1.39; 95% CI 1.11 to 1.76; P = 0.005; I2 = 0%); this would mean that a typical clinic could improve a 30% live birth rate using atmospheric oxygen concentration to somewhere between 32% and 43% by using a low oxygen concentration. The results were very similar for ongoing and clinical pregnancy rates. There was no evidence that culturing embryos under low oxygen concentrations resulted in higher numbers of adverse events such as multiple pregnancies, miscarriages or congenital abnormalities. The results of this systematic review and meta-analysis suggest that culturing embryos under conditions with low oxygen concentrations improves the success rates of IVF and ICSI, resulting in the birth of more healthy newborns. | The results of clinical studies that have been undertaken to study the effect on the outcomes of IVF and ICSI procedures of culturing embryos under low oxygen concentrations have been conflicting. Therefore, we performed a systematic review and meta-analysis of the literature to find the best available evidence. It has shown that culturing embryos under low oxygen concentrations does indeed improve clinical outcomes after IVF and ICSI, such as number of deliveries (live birth rate) and ongoing and clinical pregnancy rates. Furthermore, no evidence was found of an increased risk of adverse events such as multiple pregnancies, miscarriages and congenital abnormalities. We concluded that culturing embryos under low oxygen concentrations seems beneficial with an increase in the number of newborns, but more studies are needed to strongly prove this effect. |
Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between rTMS and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS. The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit. | It has been used for physiological studies and it has also been proposed as a treatment for depression. Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between repetitive (rTMS) and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS. |
We identified 42 eligible studies in 2433 participants: antimicrobial agents (36 studies); urokinase (4 studies), peritoneal lavage (1 study), and IP immunoglobulin (1 study). We did not identify any optimal antibiotic agent or combination of agents. IP glycopeptides (vancomycin or teicoplanin) had uncertain effects on primary treatment response, relapse rates, and need for catheter removal compared to first generation cephalosporins, although glycopeptide regimens were more likely to achieve a complete cure (3 studies, 370 episodes: RR 1.66, 95% CI 1.01 to 2.72). For relapsing or persistent peritonitis, simultaneous catheter removal and replacement was better than urokinase at reducing treatment failure rates (RR 2.35, 95% CI 1.13 to 4.91) although evidence was limited to a single small study. Continuous and intermittent IP antibiotic dosing schedules had similar treatment failure and relapse rates. IP antibiotics were superior to IV antibiotics in reducing treatment failure in one small study (RR 3.52, 95% CI 1.26 to 9.81). Longer duration treatment (21 days of IV vancomycin and IP gentamicin) had uncertain effects on risk of treatment relapse compared with 10 days treatment (1 study, 49 patients: RR 1.56, 95% CI 0.60 to 3.95) although may have increased ototoxicity. In general, review conclusions were based on a small number of studies with few events in which risk of bias was generally high; interventions were heterogeneous, and outcome definitions were often inconsistent. There were no RCTs evaluating optimal timing of catheter removal and data for automated PD were absent. Many of the studies evaluating treatment of PD-related peritonitis are small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. IP administration of antibiotics was superior to IV administration for treating PD-associated peritonitis and glycopeptides appear optimal for complete cure of peritonitis, although evidence for this finding was assessed as low quality. PD catheter removal may be the best treatment for relapsing or persistent peritonitis. Evidence was insufficient to identify the optimal agent, route or duration of antibiotics to treat peritonitis. No specific antibiotic appears to have superior efficacy for preventing treatment failure or relapse of peritonitis, but evidence is limited to few trials. The role of routine peritoneal lavage or urokinase is uncertain. | This review of interventions for PD-associated peritonitis identified 42 studies (2433 participants). Many studies were small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. In general, information about the best treatment of peritonitis in people on PD may be insufficient to guide therapy. We found that intraperitoneal antibiotics appear to improve treatment responses compared with IV antibiotics. Glycopeptides may increase likelihood of cure compared with first generation cephalosporins. There appears to be no certain role for routine peritoneal lavage (washing) or use of clot-breaking (fibrinolytic) agents. New and larger randomised controlled trials that compare the effects of IV versus intraperitoneal antibiotics and different antibiotic types on patient-relevant outcomes including adequate assessment of treatment harms are still needed. |
The search identified 281 trials. Only two studies involving a total of 157 participants were confirmed to be authentic RCTs (Li 2004c; Zhao 2000). Both were of poor methodological quality with a high risk of conflicted interest and potential for bias in favour of the intervention. We could not reach a definitive conclusion from the results. The pooled result showed that adding a Western medicine to CHM resulted in a significantly higher treatment success rate than with CHM alone (RR 1.33, 95% CI 1.08 to 1.63). When CHM plus Western medicine was compared to CHM alone for the time to disappearance of abdominal pain, again the results favoured the arm that included Western medicine (RR -2.09, 95% CI -4.14 to -0.04). Results were inconsistent for the time required for human chorionic gonadotropin (beta-hCG) to return to normal. One study favoured CHM plus Western medicine over Western medicine (with or without placebo) (MD -6.68, 95% CI -11.49 to -1.87); when CHM plus Western medicine was compared to CHM alone the results favoured the arm that included Western medicine (MD -8.12, 95% CI -10.89 to -5.53). We have not found any well-designed trials investigating Chinese herbal medicines in the treatment of ectopic pregnancy. We cannot support or refute any CHM preparation for clinical use on the basis of evidence from randomised controlled trials. | The review authors investigated 281 studies that claimed to be randomised controlled trials and that used Chinese herbal medicines in the treatment of ectopic pregnancy.Only two of these studies were confirmed to be randomised controlled trials. Both trials were of poor quality in terms of design and how they were conducted.These studies did not provide clear evidence that CHM is beneficial in the treatment of ectopic pregnancy. |
We included eight RCTs (474 randomised participants), which compared oral corticosteroids with placebo or no intervention. All trials only recruited adults with chronic rhinosinusitis with nasal polyps. All trials reported outcomes at two to three weeks, at the end of the short-course oral steroid treatment period. Three trials additionally reported outcomes at three to six months. Two of these studies prescribed intranasal steroids to patients in both arms of the trial at the end of the oral steroid treatment period. Oral steroids versus placebo or no intervention Disease-specific health-related quality of life was reported by one study. This study reported improved quality of life after treatment (two to three weeks) in the group receiving oral steroids compared with the group who received placebo (standardised mean difference (SMD) -1.24, 95% confidence interval (CI) -1.92 to -0.56, 40 participants, modified RSOM-31), which corresponds to a large effect size. We assessed the evidence to be low quality (we are uncertain about the effect estimate; the true effect may be substantially different from the estimate of the effect). Disease severity as measured by patient-reported symptom scores was reported by two studies, which allowed the four key symptoms used to define chronic rhinosinusitis (nasal blockage, nasal discharge, facial pressure, hyposmia) to be combined into one score. The results at the end of treatment (two to three weeks) showed an improvement in patients receiving oral steroids compared to placebo, both when presented as a mean final value (SMD -2.84, 95% CI -4.09 to -1.59, 22 participants) and as a change from baseline (SMD -2.28, 95% CI -2.76 to -1.80, 114 participants). These correspond to large effect sizes but we assessed the evidence to be low quality. One study (114 participants) followed patients for 10 weeks after the two-week treatment period. All patients in both arms received intranasal steroids at the end of the oral steroid treatment period. The results showed that the initial results after treatment were not sustained (SMD -0.22, 95% CI -0.59 to 0.15, 114 participants, percentage improvement from baseline). This corresponds to a small effect size and we assessed the evidence to be low quality. There was an increase in adverse events in people receiving orals steroids compared with placebo for gastrointestinal disturbances (risk ratio (RR) 3.45, 95% CI 1.11 to 10.78; 187 participants; three studies) and insomnia (RR 3.63, 95% CI 1.10 to 11.95; 187 participants; three studies). There was no significant impact of oral steroids on mood disturbances at the dosage used in the included study (risk ratio (RR) 2.50, 95% CI 0.55 to 11.41; 40 participants; one study). We assessed the evidence to be low quality due to the lack of definitions of the adverse events and the small number of events or sample size, or both). Other comparisons No studies that compared short-course oral steroids with other treatment for chronic rhinosinusitis met the inclusion criteria. At the end of the treatment course (two to three weeks) there is an improvement in health-related quality of life and symptom severity in patients with chronic rhinosinusitis with nasal polyps taking oral corticosteroids compared with placebo or no treatment. The quality of the evidence supporting this finding is low. At three to six months after the end of the oral steroid treatment period, there is little or no improvement in health-related quality of life or symptom severity for patients taking an initial course of oral steroids compared with placebo or no treatment. The data on the adverse effects associated with short courses of oral corticosteroids indicate that there may be an increase in insomnia and gastrointestinal disturbances but it is not clear whether there is an increase in mood disturbances. All of the adverse events results are based on low quality evidence. More research in this area, particularly research evaluating patients with chronic rhinosinusitis without nasal polyps, longer-term outcomes and adverse effects, is required. There is no evidence for oral steroids compared with other treatments. | This review includes evidence up to 11 August 2015. We included eight randomised controlled trials with a total of 474 participants. All of the patients were adults who had chronic rhinosinusitis with nasal polyps. All of the studies followed patients until the end of treatment (two to three weeks) and three studies (210 participants) followed up people for three to six months after the initial treatment had ended. Five of the eight reports mentioned how the trial was funded. None of the funding sources were pharmaceutical companies. At the end of a two- or three-week treatment course, people who took oral steroids may have had a better quality of life, less severe symptoms and smaller nasal polyps than people who had placebo or did not receive any treatment. After three to six months, there was little or no difference in quality of life, symptom severity or nasal polyps between the people who had oral steroids and the people who had placebo or no intervention. The people who took oral steroids may have had more gastrointestinal disturbances and insomnia than the people who had placebo or no intervention. It is not clear if the people who took oral steroids had more mood disturbances than the people who had placebo or no intervention. We judged the quality of the evidence for oral steroids plus intranasal steroids for adults with nasal polyps to be low (further research is very likely to have an important impact on our confidence in the effect estimate and is likely to change the estimate), as the some of the results are only from one or two studies, which do not have a lot of participants. Most of the trials do not have a high risk of bias, but only people with nasal polyps were included in the review. |
We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). For other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes) , we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35). To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed. | Searching for studies up to May 2014, we found two high quality trials involving 2193 participants that tested beta-blockers after stroke in people with a recent stroke or TIA. No clear evidence indicated that beta-blockers reduced the risk of stroke, heart attack, or death from vascular disease. Participants who received beta blockers instead of placebo showed significantly more adverse effects. More studies with larger samples are needed. |
Four trials (one on slings, three on strapping - 142 participants) met the inclusion criteria. One trial testing a hemisling versus no device reported that no participants had subluxation greater than 10 mm, the same number had lost more than 30 degrees of shoulder external rotation (Peto odds ratio (OR) 1.00, 95% confidence interval (CI) 0.1 to 9.3), and more participants in the hemisling group had pain (Peto OR 8.7, 95% CI 1.1 to 67.1). The other three showed that strapping was effective in delaying the onset of pain (weighted mean difference (WMD) 14 days, 95% CI 9.7 to 17.8), but was ineffective in reducing pain severity (WMD -0.7 cm on a visual analogue scale, 95% CI -2.0 to 0.7), increasing upper limb function (WMD 0.8, 95% CI -1.5 to 3.1) or affecting the degree of contracture (WMD -1.4 degrees, 95% CI -10.9 to 8.1) at the shoulder. There is insufficient evidence to conclude whether slings and wheelchair attachments prevent subluxation, decrease pain, increase function or adversely increase contracture in the shoulder after stroke. There is some evidence that strapping the shoulder delays the onset of pain but does not decrease it, nor does it increase function or adversely increase contracture. | This review of four trials found insufficient evidence to conclude whether supportive devices prevent subluxation or not and found no evidence to conclude whether supportive devices can reposition the head of humerus in the glenoid fossa of an already subluxed shoulder. |
We identified 1995 references and included10 RCTs (2745 workers). Two studies were assessed with low risk of bias. Most trials (N = 8) examined office workers. Few workers were sick-listed. Thus, WIs were seldom designed to improve return-to-work. Overall, there was low quality evidence that showed no significant differences between WIs and no intervention for pain prevalence or severity. If present, significant results in favour of WIs were not sustained across follow-up times. There was moderate quality evidence (1 study, 415 workers) that a four-component WI was significantly more effective in reducing sick leave in the intermediate-term (OR 0.56, 95% CI 0.33 to 0.95), but not in the short- (OR 0.83, 95% CI 0.52 to 1.34) or long-term (OR 1.28, 95% CI 0.73 to 2.26). These findings might be because only a small proportion of the workers were sick-listed. Overall, this review found low quality evidence that neither supported nor refuted the benefits of any specific WI for pain relief and moderate quality evidence that a multiple-component intervention reduced sickness absence in the intermediate-term, which was not sustained over time. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. There is an urgent need for high quality RCTs with well designed WIs. | Studies have shown that musculoskeletal disorders are the most common cause of sick-leave and disability in many industrial countries. Neck pain is more common in the general population than previously known.This Cochrane review presents what we know from research about the effect of workplace interventions for workers with neck pain who, for the most part, are not sick-listed. Ten trials with 2745 participants were included in this review. Two studies were rated as having low risk of bias. The workplace interventions comprised education about stress management, principles of ergonomics, anatomy, musculoskeletal disorders, and the importance of physical activity. They taught 'pause gymnastics', how to use a relaxed work posture, proper positioning, the importance of rest breaks, and strategies to improve relaxation. Some studies also included how to modify work tasks, work load, working techniques, working positions, and working hours. Several studies suggested how to make adjustments and recommended alternatives to the existing furniture and equipment at the workplace. The present review found low quality evidence that those who received workplace interventions did not get more pain relief than those who received no interventions. We found moderate quality evidence (1 trial, 415 workers) that workplace interventions reduced sick leave among the workers at six month-, but not at three- and 12-month follow-ups. This could be due to the fact that few participants in the study were sick-listed. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate for both pain and sickness absence. |
We have added four new trials to this update. This review now includes 21 trials involving 2289 patient and 1290 carer participants. Nine trials evaluated a passive and 12 trials an active information intervention. Meta-analyses showed a significant effect in favour of the intervention on patient knowledge (standardised mean difference (SMD) 0.29, 95% confidence interval (CI) 0.12 to 0.46, P < 0.001), carer knowledge (SMD 0.74, 95% CI 0.06 to 1.43, P = 0.03), one aspect of patient satisfaction (odds ratio (OR) 2.07, 95% CI 1.33 to 3.23, P = 0.001), and patient depression scores (mean difference (MD) -0.52, 95% CI -0.93 to -0.10, P = 0.01). There was no significant effect (P > 0.05) on number of cases of anxiety or depression in patients, carer mood or satisfaction, or death. Qualitative analyses found no strong evidence of an effect on other outcomes. Post-hoc subgroup analyses showed that active information had a significantly greater effect than passive information on patient mood but not on other outcomes. There is evidence that information improves patient and carer knowledge of stroke, aspects of patient satisfaction, and reduces patient depression scores. However, the reduction in depression scores was small and may not be clinically significant. Although the best way to provide information is still unclear there is some evidence that strategies that actively involve patients and carers and include planned follow-up for clarification and reinforcement have a greater effect on patient mood. | Studies have shown that stroke survivors and their carers often report they have not been given enough information about stroke and feel unprepared for life after discharge from hospital. However, the best way to provide information after stroke is unclear. The authors of this review looked at the evidence for the effectiveness of providing information to patients, or carers of patients, who have had a stroke or transient ischaemic attack (TIA), sometimes called a mini-stroke. They examined randomised trials (studies) in which one group of stroke patients or carers who were given the intervention being tested (such as a course of lectures) was compared with a group of stroke patients or carers who received standard care. Twenty-one studies, involving 2289 patients and 1290 carers, are now included in this updated review. Overall, the studies showed that providing information to patients and carers improved their knowledge of stroke and increased patient satisfaction with some, but not all, of the information they received about stroke. There was also an effect on reducing patient depression, although the reduction was small and may not be enough to seem meaningful to patients. When information was provided in a way that more actively involved patients and carers, for example by offering repeated opportunities to ask questions, it had more effect on patient mood than information which was given on one occasion only. There is not much evidence that providing information had effects on other aspects of patient or carer stroke recovery such as independence or social activities. |
We included five RCTs (1218 participants) in the review. Three trials focused on the prophylaxis of MRONJ. Two trials investigated options for the treatment of established MRONJ. The RCTs included only participants treated with bisphosphonates and, thus, did not cover the entire spectrum of medications associated with MRONJ. Prophylaxis of MRONJ One trial compared standard care with regular dental examinations in three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ: RR 0.10; 95% CI 0.02 to 0.39 (253 participants; low-quality evidence). Secondary outcomes were not evaluated. As dentoalveolar surgery is considered a common predisposing event for developing MRONJ, one trial investigated the effect of plasma rich in growth factors (PRGF) for preventing MRONJ in people with cancer undergoing dental extractions. There was insufficient evidence to support or refute a benefit of PRGF on MRONJ incidence when compared with standard treatment (RR 0.08, 95% CI 0.00 to 1.51; 176 participants; very low-quality evidence). Secondary outcomes were not reported. In another trial comparing wound closure by primary intention with wound closure by secondary intention after dental extractions in people treated with oral bisphosphonates (700 participants), no cases of intraoperative complications or postoperative MRONJ were observed. QoL was not investigated. Treatment of MRONJ One trial analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone. HBO in addition to standard care did not significantly improve healing from MRONJ compared with standard care alone (at last follow-up: RR 1.56; 95% CI 0.77 to 3.18; 46 participants included in the analysis; very low-quality evidence). QoL data were presented qualitatively as intragroup comparisons; hence, an effect estimate of treatment on QoL was not possible. Other secondary outcomes were not reported. The other RCT found no significant difference between autofluorescence- and tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ at any timepoint (at one-year follow-up: RR 1.05; 95% CI 0.86 to 1.30; 34 participants included in the analysis; very low-quality evidence). Secondary outcomes were not reported. Prophylaxis of MRONJ One open-label RCT provided some evidence that dental examinations in three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of MRONJ in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be low. There is insufficient evidence to either claim or refute a benefit of either of the interventions tested for prophylaxis of MRONJ (i.e. PRGF inserted into the postextraction alveolus during dental extractions, and wound closure by primary or secondary intention after dental extractions). Treatment of MRONJ Available evidence is insufficient to either claim or refute a benefit for hyperbaric oxygen therapy as an adjunct to conventional therapy. There is also insufficient evidence to draw conclusions about autofluorescence-guided versus tetracycline fluorescence-guided bone surgery. | Working with Cochrane Oral Health, we searched for studies that had been published up to November 2016. We found three studies that focused on the prevention of MRONJ and two studies that tested treatments for MRONJ. The studies involved 1218 adults, with the smallest study having 40 participants and the largest study having 700 participants. Most study participants were women, but one study was of men with prostate cancer receiving bisphosphonate infusions (given by drip into a vein). All studies included only participants treated with bisphosphonates (used to support treatment and reduce risk of fracture and bone pain), although several other drugs are also known to induce MRONJ. One study provided low-quality evidence that dental examinations at three-month intervals and preventive treatments (antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) are more effective than standard care for reducing the number of cases with MRONJ in a group of people receiving intravenous bisphosphonates for cancer-related conditions. In the experimental group (which received preventive care consisting of antibiotics and specific wound closure), fewer people developed MRONJ (2 participants per 100 who underwent close monitoring) compared with the control group (23 participants per 100 who had standard care). There was insufficient evidence to conclude that the use of the other interventions investigated would reduce the risk of MRONJ or would improve healing of MRONJ. The quality of evidence was low or very low. This was due to limitations in how the studies were designed and run. For example, some participants changed groups during the study, some participants did not finish the study, and the outcomes were measured at different follow-up times. |
We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving. For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence). For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) –0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI –0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI –0.10 to 0.10; very low-quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI –0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI –0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI –0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available. No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence. | We searched scientific databases for clinical trials comparing baclofen with placebo (a pretend treatment) or another potentially useful medicine in people with AWS. We included four randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 189 participants. One study from the USA compared baclofen to placebo given over at least 72 hours. The 31 participants were mainly men with the average age 47 years. Two studies with 85 participants compared baclofen to diazepam (a calming medicine) for 10 consecutive days, or for 10-day inpatient stay with flexibility to allow negotiation of the discharge date between day 10 and day 15. One study compared baclofen to chlordiazepoxide given for nine days, in which the 60 participants were all men with an average age of 38 years. None of studies reported any conflict of interest. Addolorato 2006 was supported by Associazione Ricerca in Medicina, Italy. Girish 2016 was supported by KIMS Hospital and Research Centre (Bangalore, India). Jhanwar 2014 reported no funding source. Lyon 2011 was supported by Duluth Clinic Foundation (MN, USA). None of the included studies assess the main outcomes of the review, that is, alcohol withdrawal seizures (fits), alcohol withdrawal delirium (confused thinking and awareness), and craving. We are uncertain whether baclofen improves withdrawal symptoms and signs, and reduces side effects when compared with placebo or other medicines as the quality of the evidence was very low. The quality of the evidence from the studies was very low and results should be interpreted with caution. In the future, well-designed, double-blind (where neither the participant nor the researcher knows which treatment has been given until after the results have been collected) RCTs with large numbers of participants are required to test how effective and well tolerated baclofen is in people with AWS. |
We included six trials, involving a total of 636 women with a twin or triplet pregnancy (total of 1298 babies). We assessed all of the included trials as having a low risk of bias for random sequence generation. Apart from one trial with an unclear risk of bias, we judged all remaining trials to be of low risk of bias for allocation concealment. Five trials (495 women and 1016 babies) compared strict bed rest in hospital with no activity restriction at home. There was no difference in the risk of very preterm birth (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.66 to 1.58, five trials, 495 women, assuming complete correlation between twins/triplets, low-quality evidence), perinatal mortality (RR 0.65, 95% CI 0.35 to 1.21, five trials, 1016 neonates, assuming independence between twins/triplets, low-quality evidence) and low birthweight (RR 0.95, 95% CI 0.75 to 1.21, three trials, 502 neonates, assuming independence between twins/triplets, low-quality evidence). We observed no differences for the risk of small-for-gestational age (SGA) (RR 0.75, 95% CI 0.56 to 1.01, two trials, 293 women, assuming independence between twins/triplets, low-quality evidence) and prelabour preterm rupture of the membrane (PPROM) (RR 1.30, 95% CI 0.71 to 2.38, three trials, 276 women, low-quality evidence). However, strict bed rest in hospital was associated with increased spontaneous onset of labour (RR 1.05, 95% CI 1.02 to 1.09, P = 0.004, four trials, 488 women) and a higher mean birthweight (mean difference (MD) 136.99 g, 95% CI 39.92 to 234.06, P = 0.006, three trials, 314 women) compared with no activity restriction at home. Only one trial (141 women and 282 babies) compared partial bed rest in hospital with no activity restriction at home. There was no evidence of a difference in the incidence of very preterm birth (RR 2.30, 95% CI 0.84 to 6.27, 141 women, assuming complete correlation between twins, low-quality evidence) and perinatal mortality (RR 4.17, 95% CI 0.90 to 19.31, 282 neonates, assuming complete independence twins, low-quality evidence) between the intervention and control group. Low birthweight was not reported in this trial. We found no differences in the risk of PPROM and SGA between women receiving partial bed rest and the control group (low-quality evidence). Women on partial bed rest in hospital were less likely to develop gestational hypertension compared with women without activity restriction at home (RR 0.30, 95% CI 0.16 to 0.59, P = 0.0004, 141 women). Strict or partial bed rest in hospital was found to have no impact on other secondary outcomes. None of the trials reported on costs of the intervention or adverse effects such as the development of venous thromboembolism or psychosocial effects. The evidence to date is insufficient to inform a policy of routine bed rest in hospital or at home for women with a multiple pregnancy. There is a need for large-scale, multicenter randomised controlled trials to evaluate the benefits, adverse effects and costs of bed rest before definitive conclusions can be drawn. | We searched for evidence on 30 May 2016. We identified six randomised controlled trials involving a total of 636 women and 1298 babies. The women were at 17 to 33 weeks pregnant when they entered the trials. The overall risk of bias of the trials was low and the evidence in general was of low quality. Advising women with a multiple pregnancy to either continuously rest in bed (five trials, 495 women and 1016 babies) or rest in bed for several hours during the day but with some physical activity allowed (one trial, 141 women and 282 babies) in hospital did not reduce the risk of very preterm birth (birth before 34 weeks of gestation), infant deaths before or up to one week after the birth or, low birthweight babies (strict bed rest only) compared with women who maintained daily activities at home. Women receiving strict bed rest in hospital were more likely to go into labour normally (four trials, 488 women) and had babies with a higher mean birthweight (three trials, 314 women) compared with women without activity restrictions at home. Partial bed rest in hospital reduced the number of pregnant women developing high blood pressure (one trial, 141 women, low-quality evidence) but the same benefit was not observed with strict bed rest (five trials, 495 women). Adverse effects such as the development of venous thromboembolism or mental, emotional, social and spiritual well-being (psychosocial) effects, and women’s views and experiences of bed rest were not reported in the included trials. Neither were the costs of the intervention reported on. We did not find sufficient evidence to support or refute bed rest for women with a multiple pregnancy as a way of preventing preterm birth and other pregnancy complications. |
We included 10 studies involving 632 participants. One new trial (19 participants) was added for this update. One trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias. We included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence). Two trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse. We found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline. None of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants). There were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence). There is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality. People with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS. The overall conclusions of the review have not changed since 2013 and the number of available trials remains low. | Overall, evidence was low- or very low-quality. This means we have limited or little confidence in the results, and that it is possible that other similar research could find something different. The main reasons for this assessment were that there were few studies that included few people, and a risk that results were not fully reported. All included studies had problems recruiting enough participants, making it more difficult for them to detect effects of stopping antipsychotics. Limited evidence suggests that stopping long-term antipsychotic drug use in older people with dementia and NPS may be done without making their behaviour worse. There may be benefits especially for those with milder NPS. There may be people with more severe symptoms who benefit from continuing treatment, but more research in people with both milder and more severe NPS is needed to be sure about this. The overall conclusions have not changed since the last version of this review and the number of included trials is still low. |
We included 65 randomised controlled trials from 12 countries involving patients undergoing a variety of procedures in hospitals. Nine thousand and twenty one patients were randomised and entered into these studies. Interventions used various designs and formats but the main data for results were from studies using written materials, audio-visual materials and decision aids. Some interventions were delivered before admission to hospital for the procedure while others were delivered on admission. Only one study attempted to measure the primary outcome, which was informed consent as a unified concept, but this study was at high risk of bias. More commonly, studies measured secondary outcomes which were individual components of informed consent such as knowledge, anxiety, and satisfaction with the consent process. Important but less commonly-measured outcomes were deliberation, decisional conflict, uptake of procedures and length of consultation. Meta-analyses showed statistically-significant improvements in knowledge when measured immediately after interventions (SMD 0.53 (95% CI 0.37 to 0.69) I2 73%), shortly afterwards (between 24 hours and 14 days) (SMD 0.68 (95% CI 0.42 to 0.93) I2 85%) and at a later date (15 days or more) (SMD 0.78 (95% CI 0.50 to 1.06) I2 82%). Satisfaction with decision making was also increased (SMD 2.25 (95% CI 1.36 to 3.15) I2 99%) and decisional conflict was reduced (SMD -1.80 (95% CI -3.46 to -0.14) I2 99%). No statistically-significant differences were found for generalised anxiety (SMD -0.11 (95% CI -0.35 to 0.13) I2 82%), anxiety with the consent process (SMD 0.01 (95% CI -0.21 to 0.23) I2 70%) and satisfaction with the consent process (SMD 0.12 (95% CI -0.09 to 0.32) I2 76%). Consultation length was increased in those studies with continuous data (mean increase 1.66 minutes (95% CI 0.82 to 2.50) I2 0%) and in the one study with non-parametric data (control 8.0 minutes versus intervention 11.9 minutes, interquartile range (IQR) of 4 to 11.9 and 7.2 to 15.0 respectively). There were limited data for other outcomes. In general, sensitivity analyses removing studies at high risk of bias made little difference to the overall results. Informed consent is an important ethical and practical part of patient care. We have identified efforts by researchers to investigate interventions which seek to improve information delivery and consideration of information to enhance informed consent. The interventions used consistently improve patient knowledge, an important prerequisite for informed consent. This is encouraging and these measures could be widely employed although we are not able to say with confidence which types of interventions are preferable. Our results should be interpreted with caution due to the high levels of heterogeneity associated with many of the main analyses although we believe there is broad evidence of beneficial outcomes for patients with the pragmatic application of interventions. Only one study attempted to measure informed consent as a unified concept. | We searched the scientific literature to identify randomised controlled trials (RCTs) of interventions designed to improve informed consent in clinical practice. We wanted to determine primarily whether these interventions improved all components of ‘informed consent’ (understanding, deliberation and communication of decision). Other individual outcomes of direct relevance to patients (e.g. recall/knowledge, understanding, satisfaction and anxiety), those related to healthcare professionals (e.g. ease of use of intervention, satisfaction) and system outcomes (e.g. cost, rates of procedural uptake) were also assessed. We included 65 studies involving a total of 9021 patients. The studies varied according to the type of intervention, the procedure for which consent was sought, the clinical setting and the outcomes measured. Most interventions were written or audio-visual. Only one study assessed all the elements of informed consent, but the design was not robust; all other studies assessed only components of informed consent. When the results of multiple studies were combined, we found that interventions improved knowledge of the planned procedure, immediately (up to 24 hours), in the short term (1 to 14 days) and the long term (more than 14 days). Satisfaction with decision making was increased; decisional conflict was reduced; and consultation length may be increased. There were no differences between the intervention and control for the outcomes of generalised anxiety, and either anxiety or satisfaction associated with the consent process. Limitations of the review include difficulties combining the results of studies due to variation in the procedures undergone by patients, the interventions used and outcomes measured. This means that we are uncertain as to which specific interventions are most effective but pragmatic steps to improve information delivery and consideration of the information are likely to benefit patients. |
We included 37 studies involving a total of 4129 participants. Risk of bias across the included studies was variable. We judged the GRADE quality of evidence to be very low or low for the primary outcomes where data were available. The majority of participants were over 65 years of age with mild to moderate adult-onset hearing loss. There was a mix of new and experienced hearing aid users. Six of the studies (287 participants) assessed long-term outcomes. All 37 studies tested interventions that could be classified using the CCM as self-management support (ways to help someone to manage their hearing loss and hearing aid(s) better by giving information, practice and experience at listening/communicating or by asking people to practise tasks at home) and/or delivery system design interventions (just changing how the service was delivered). Self-management support interventions We found no studies that investigated the effect of these interventions on adherence, adverse effects or hearing aid benefit. Two studies reported daily hours of hearing aid use but we were unable to combine these in a meta-analysis. There was no evidence of a statistically significant effect on quality of life over the medium term. Self-management support reduced short- to medium-term hearing handicap (two studies, 87 participants; mean difference (MD) -12.80, 95% confidence interval (CI) -23.11 to -2.48 (0 to 100 scale)) and increased the use of verbal communication strategies in the short to medium term (one study, 52 participants; MD 0.72, 95% CI 0.21 to 1.23 (0 to 5 scale)). The clinical significance of these statistical findings is uncertain. It is likely that the outcomes were clinically significant for some, but not all, participants. Our confidence in the quality of this evidence was very low. No self-management support studies reported long-term outcomes. Delivery system design interventions These interventions did not significantly affect adherence or daily hours of hearing aid use in the short to medium term, or adverse effects in the long term. We found no studies that investigated the effect of these interventions on quality of life. There was no evidence of a statistically or clinically significant effect on hearing handicap, hearing aid benefit or the use of verbal communication strategies in the short to medium term. Our confidence in the quality of this evidence was low or very low. Long-term outcome measurement was rare. Combined self-management support/delivery system design interventions One combined intervention showed evidence of a statistically significant effect on adherence in the short term (one study, 167 participants, risk ratio (RR) 1.06, 95% CI 1.00 to 1.12). However, there was no evidence of a statistically or clinically significant effect on daily hours of hearing aid use over the long term, or the short to medium term. No studies of this type investigated adverse effects. There was no evidence of an effect on quality of life over the long term, or short to medium term. These combined interventions reduced hearing handicap in the short to medium term (14 studies, 681 participants; standardised mean difference (SMD) -0.26, 95% CI -0.50 to -0.02). This represents a small-moderate effect size but there is no evidence of a statistically significant effect over the long term. There was evidence of a statistically, but not clinically, significant effect on long-term hearing aid benefit (two studies, 69 participants, MD 0.30, 95% CI 0.02 to 0.58 (1 to 5 scale)), but no evidence of an effect over the short to medium term. There was evidence of a statistically, but not clinically, significant effect on the use of verbal communication strategies in the short term (four studies, 223 participants, MD 0.45, 95% CI 0.15 to 0.74 (0 to 5 scale)), but not the long term. Our confidence in the quality of this evidence was low or very low. We found no studies that assessed the effect of other CCM interventions (decision support, the clinical information system, community resources or health system changes). There is some low to very low quality evidence to support the use of self-management support and complex interventions combining self-management support and delivery system design in adult auditory rehabilitation. However, effect sizes are small. The range of interventions that have been tested is relatively limited. Future research should prioritise: long-term outcome assessment; development of a core outcome set for adult auditory rehabilitation; and study designs and outcome measures that are powered to detect incremental effects of rehabilitative healthcare system changes. | The evidence is up to date as of June 2016. We found 37 studies involving a total of 4129 people. Most of the people in the studies were aged over 65. There was a mix of new and experienced hearing aid users. Seven studies funded by the United States Veterans Association dominate the evidence. The 1297 people in these studies were serving in the military or military veterans. All but two of the other studies included fewer than 100 people in each study. Thirty-three of the 37 studies looked at ways to help someone to manage their hearing loss and hearing aid(s) better by giving information, practice and experience at listening/communicating or by asking people to practise tasks at home. These are forms of self-management support. Most of these studies also changed how the self-management support was provided, for example by changing the number of appointment sessions or using telephone or email follow-up. Six studies looked at the effect of just changing how the service was delivered. No studies looked at the effect of using guidelines or standards, computerised medical record systems, community resources or changing the health system. We found no evidence that the interventions helped people to wear their hearing aids for more hours per day over the short, medium or long term. One study that used interactive videos to give information after hearing aid fitting encouraged more people to wear their hearing aids. We found no evidence of adverse effects of any of the interventions, but it was rare for studies to look for adverse effects. Giving self-management support meant that people reported less hearing handicap and improved verbal communication over the short term. When this was combined with changing how the support was delivered people also reported slightly more hearing aid benefit over the long term. Only six studies (287 people) looked at how people were doing after a year or more. Complex interventions that deliver self-management support in different ways improve some outcomes for some people with hearing loss who use hearing aids. We found no interventions that increased self-reported daily hours of hearing aid use. Few studies measured how many people use hearing aids compared to how many are fitted (adherence). Many things that might increase daily hours of hearing aid use or encourage more people to wear the hearing aids they have been fitted with have not been tested. It was difficult to combine data across different studies because many outcome measures were used and results were not always fully reported. In future it would be helpful if researchers: - used existing guidelines for presenting their results; - agreed a set of outcome measures for use in this type of study; and - focused on long-term outcomes where people are followed up for at least a year. We judged the evidence to be of very low or low quality. There was risk of bias in the way many of the studies were carried out or reported. The largest studies included only military veterans. We do not know whether studies would find the same results in more mixed populations. Most of the other studies had small sample sizes. Very few studies measured long-term outcomes. |
We included one study from the USA (re-analysed as an ITS) involving one hospital and an unknown number of nurses and patients. The study evaluated the effects of a standardised evidence-based nursing procedure on nursing care for patients at risk of developing healthcare-acquired pressure ulcers (HAPUs). If a patient's admission Braden score was below or equal to 18 (i.e. indicating a high risk of developing pressure ulcers), nurses were authorised to initiate a pressure ulcer prevention bundle (i.e. a set of evidence-based clinical interventions) without waiting for a physician order. Re-analysis of data as a time series showed that against a background trend of decreasing HAPU rates, if that trend was assumed to be real, there was no evidence of an intervention effect at three months (mean rate per quarter 0.7%; 95% confidence interval (CI) 1.7 to 3.3; P = 0.457). Given the small percentages post intervention it was not statistically possible to extrapolate effects beyond three months. Despite extensive searching of published and unpublished research we identified only one low-quality study; we excluded many studies due to non-eligible study design. If policy-makers and healthcare organisations wish to promote evidence-based nursing successfully at an organisational level, they must ensure the funding and conduct of well-designed studies to generate evidence to guide policy. | We searched the literature for robust evaluations of the effectiveness of organisational interventions in promoting EBP in nursing. We included one study from the USA which involved one hospital and for which the number of nurses was not reported. The study evaluated the effects of a standardised evidence-based nursing procedure on improved nursing care for patients at risk of developing healthcare-acquired pressure ulcers (HAPUs), as measured by the HAPU rate. If a patient's admission Braden score was lower than or equal to 18, nurses were authorised to initiate a prevention pressure ulcer care bundle, without a physician order. The Braden scale is a tool used to assess a patient's risk of developing pressure ulcers. An adult with a score below or equal to 18 is considered to have a high risk for developing a pressure ulcer. Re-analysis of the HAPU data, as an interrupted time series, was suggestive of a trend in rates prior to intervention and, if that trend was assumed to be real, there was no evidence of an intervention effect at three months (mean rate per quarter 0.7%; 95% confidence interval (CI) 1.7 to 3.3; P = 0.457). Given the small percentages post intervention it was not statistically possible to extrapolate effects beyond three months. Considering the importance placed on organisational change in promoting EBP in nursing, it is surprising that eight years after the previous empty Cochrane review was published, appropriately evaluated organisational infrastructure interventions are still lacking. If policy-makers and healthcare organisations wish to promote evidence-based nursing at an organisational level successfully, they must ensure the funding and conduct of well-designed studies to generate evidence to guide policy. |
In total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery. There was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I2 = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I2 = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I2 = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I2 = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I2 = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I2 = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I2 = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups. Based on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement. | We identified 13 eligible studies (2794 participants) for this review. One trial did not report any information that we sought. Information on 213 participants was not reported because of various reasons, the common reason being that they did not receive the planned treatment. A total of 2528 participants received either laparoscopic gastrectomy (1288 participants) or open gastrectomy (1240 participants). The decision on whether a participant received laparoscopic or open gastrectomy was made using methods similar to the toss of a coin. This process ensures that the participants in the two groups are similar. All the participants were suitable for major surgery. There was no difference between laparoscopic and open gastrectomy in short-term deaths (laparoscopic gastrectomy: 6 deaths in 1000 operations versus open gastrectomy: 3 deaths in 1000 operations). There is a certain amount of uncertainty when predicting the number of deaths or outcomes based on information in the trials. Because of this uncertainty, we were able to conclude that there was no difference in short-term deaths between the groups, although the deaths in laparoscopic gastrectomy was twice that in open gastrectomy. None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term deaths, serious complications within three months (laparoscopic gastrectomy: 36 complications per 1000 operations versus open gastrectomy: 60 complications per 1000 operations), all complications within three months (laparoscopic gastrectomy: 161 complications per 1000 operations versus open gastrectomy: 253 complications in 1000 operations, short-term and long-term recurrence of cancer, number of people who required blood transfusion, amount of blood transfused during or within one week of surgery, and length of hospital stay were imprecise. As a result, significant benefits or harms of laparoscopic gastrectomy compared to open gastrectomy cannot be ruled out. Further well designed trials are necessary to compare the benefits and harms of laparoscopic and open gastrectomy. The quality of evidence was very low for all outcomes, apart from short-term mortality, which was low. As a result, there is a lot of uncertainty regarding the results. |
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