Does home visiting prevent childhood injury? A systematic review of randomised controlled trials.

OBJECTIVE--To quantify the effectiveness of home visiting programmes in the prevention of child injury and child abuse. DESIGN--Systematic review of 11 randomised controlled trials of home visiting programmes. Pooled odds ratios were estimated as an inverse variance weighted average of the study specific odds ratios. SETTING--Randomised trials that were available by April 1995. SUBJECTS--The trials comprised 3433 participants. RESULTS--Eight trials examined the effectiveness of home visiting in the prevention of childhood injury. The pooled odds ratio for the eight trials was 0.74 (95% confidence interval 0.60 to 0.92). Four studies examined the effect of home visiting on injury in the first year of life. The pooled odds ratio was 0.98 (0.62 to 1.53). Nine trials examined the effect of home visiting on the occurrence of suspected abuse, reported abuse, or out of home placement for child abuse. Because of the potential for bias in outcome reporting in these studies, pooled effect estimates were not calculated. CONCLUSIONS--Home visiting programmes have the potential to reduce significantly the rates of childhood injury. The problem of differential surveillance for child abuse between intervention and control groups precludes the use of reported abuse as a valid outcome measure in controlled trials of home visiting.     

The miracle of DICE therapy for acute stroke: fact or fictional product of subgroup analysis?

OBJECTIVE--To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several randomised trials of an ineffective treatment. DESIGN--44 randomised controlled trials of DICE therapy for stroke were performed (simulated by rolling different coloured dice; two trials per investigator). Each roll of the dice yielded the outcome (death or survival) for that "patient." Publication bias was also simulated. The results were combined in a systematic review. SETTING--Edinburgh. MAIN OUTCOME MEASURE--Mortality. RESULTS--The "hypothesis generating" trial suggested that DICE therapy provided complete protection against death from acute stroke. However, analysis of all the trials suggested a reduction of only 11% (SD 11) in the odds of death. A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9% (22). If the analysis excluded red dice trials and those of poor methodological quality the odds decreased by 22% (13, 2P = 0.09). Analysis of "published" trials showed a decrease of 23% (13, 2P = 0.07) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39% (17, 2P = 0.02). CONCLUSION--The early benefits of DICE therapy were not confirmed by subsequent trials. A plausible (but inappropriate) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality, whereas in truth it was ineffective. Chance influences the outcome of clinical trials and systematic reviews of trials much more than many investigators realise, and its effects may lead to incorrect conclusions about the benefits of treatment.     

Cholesterol lowering and mortality: the importance of considering initial level of risk.

OBJECTIVE--To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN--Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS--Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES--Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS--In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION--Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs should be advocated. Future trials should aim to clarify the level of risk above which treatment is of net benefit.     

Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis

Objective To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS.Data sources Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects.Data extraction Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus.Data synthesis Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be ≥1 or the probability that the mean difference would be ≥0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio ≥1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio ≥1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio ≥1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference ≥0)=97.9%). Steroids were not associated with increase in risk of infection.Conclusions A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.     

Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials

Objective To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts.Design Systematic review of randomised controlled trials.Data sources Medline and the Cochrane Collaboration''s register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group.Selection of studies Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week.Results Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42).Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.     

Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol.

OBJECTIVE: To evaluate the comparative efficacy and tolerability of paracetamol-dextropropoxyphene combination and paracetamol through a systematic overview of randomised controlled trials. DESIGN: Systematic retrieval of trials of paracetamol-dextropropoxyphene, paracetamol, and placebo to allow pooling of results from head to head comparison trials and single active placebo controlled trials. SUBJECTS: 2231 patients with postsurgical pain, arthritis, and musculoskeletal pain reported in 26 randomised controlled trials. MAIN OUTCOME MEASURES: Sum of difference in pain intensity; response rate ratio and difference in response rate with response defined as moderate to excellent pain relief; and rate ratio and rate difference of side effects. RESULTS: The difference in pain intensity between paracetamol-dextropropoxyphene and paracetamol was 7.3% (95% confidence interval -0.2 to 14.9). The response rate ratio for the combination and paracetamol was 1.05 (0.8 to 1.3) on the basis of the head to head trials. Indirect comparisons produced quantitatively consistent results. Compared with placebo, the combination produced more dizziness (3.1; 1.1 to 8.9) whereas paracetamol resulted in more drowsiness (1.8; 1.1 to 2.9). CONCLUSION: On the basis of data on analgesic efficacy and acute safety in both head to head and indirect comparisons, there is little objective evidence to support prescribing a combination of paracetamol and dextropropoxyphene in preference to paracetamol alone in moderate pain such as that after surgery.     

Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis.

OBJECTIVE--To examine whether tricyclic antidepressants are superior to placebo in the treatment of child and adolescent depression. DESIGN--Meta-analysis of 12 randomised controlled trials comparing the efficacy of tricyclic antidepressants with placebo in depressed subjects aged 6-18 years. MAIN OUTCOME MEASURES--Most studies employed several depression rating scales. For each study the "best available" measure was chosen by using objective criteria, and individual and pooled effect sizes were calculated as the number of standard deviations by which the change scores for the treatment groups exceeded those for the control groups. Where authors had reported numbers "responding" to treatment we calculated individual and pooled ratios for the odds of improvement in treated compared with control subjects. RESULTS--From the six studies presenting data which enabled an estimation of effect size the pooled effect size was 0.35 standard deviations (95% confidence interval of -0.16 to 0.86) indicating no significant benefit of treatment. From the five studies presenting data on the number of "responders" in each group, the ratio of the odds of a response in the treated compared with the control subjects was calculated and the pooled odds ratio was 1.08 (95% confidence interval of 0.53 to 2.17); again indicating no significant benefit of treatment. The pooled sample had more than an 80% chance of detecting a treatment effect of 0.5 standard deviations or greater. There was an inverse relation between study quality and estimated treatment effect. CONCLUSIONS--Tricyclic antidepressants appear to be no more effective than placebo in the treatment of depression in children and adolescents.     

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis

Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation.Design Systematic review and meta-analysis.Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists.Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients.Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77).Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.     

Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed

     

Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis.

OBJECTIVE: To determine the effect of antibiotic treatment for acute otitis media in children. DESIGN: Systematic search of the medical literature to identify studies that used antibiotics in randomised controlled trials to treat acute otitis media. Studies were examined blind, and the results of those of satisfactory quality of methodology were pooled. SUBJECTS: Six studies of children aged 7 months to 15 years. MAIN OUTCOME MEASURES: Pain, deafness, and other symptoms related to acute otitis media or antibiotic treatment. RESULTS: 60% of placebo treated children were pain free within 24 hours of presentation, and antibiotics did not influence this. However, at 2-7 days after presentation, by which time only 14% of children in control groups still had pain, early use of antibiotics reduced the risk of pain by 41% (95% confidence interval 14% to 60%). Antibiotics reduced contralateral acute otitis media by 43% (9% to 64%). They seemed to have no influence on subsequent attacks of otitis media or deafness at one month, although there was a trend for improvement of deafness at three months. Antibiotics were associated with a near doubling of the risk of vomiting, diarrhoea, or rashes (odds ratio 1.97 (1.19 to 3.25)). CONCLUSIONS: Early use of antibiotics provides only modest benefit for acute otitis media: to prevent one child from experiencing pain by 2-7 days after presentation, 17 children must be treated with antibiotics early.     

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation

ObjectiveTo examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients with non-rheumatic atrial fibrillation.MethodsMeta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects.ResultsNo trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others.ConclusionsThe heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.     

Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group.

OBJECTIVE--To determine the clinical benefits of selective decontamination of the digestive tract in patients treated in intensive care units. DESIGN--Meta-analysis of 22 randomised trials that compared different combinations of oral non-absorbable antibiotics, with or without a systemic component, with no treatment in controls. SUBJECTS--4142 patients seen in general and specialised intensive care units around the world. 2047 received some form of antibiotic treatment, the remainder no prophylaxis. DATA ANALYSIS--Each trial was reviewed through direct contact with study investigators. Data collected were: the randomisation procedure, number of patients, number excluded from the analysis, and numbers of respiratory tract infections and deaths. Data were combined according to an intention to treat analysis with the Mantel-Haenszel-Peto method. MAIN OUTCOME MEASURES--Respiratory tract infections and total mortality. RESULTS--Selective decontamination of the digestive tract significantly reduced respiratory tract infections (odds ratio 0.37; 95% confidence interval 0.31 to 0.43). The value of the common odds ratio for total mortality (0.90; 0.79 to 1.04) suggested at best a moderate treatment effect, reaching statistical significance only when the subgroup of trials of topical and systemic treatment combined was considered separately (odds ratio 0.80; 0.67 to 0.97). No firm conclusions could be drawn owing to large variations in patient mix and severity within and between trials. CONCLUSIONS--The findings strongly indicate that selective decontamination significantly reduces infection related morbidity in patients receiving intensive care. They also highlight why definite conclusions about the effect of prophylaxis on mortality cannot be drawn despite the large number of trials available. Based on the most favourable results obtained by pooling data from trials in which combined topical and systemic treatment was used it may be estimated that 6 (range 5-9) and 23 (13-139) patients would need to be treated to prevent one respiratory tract infection and one death respectively.     

Beta-blocker use and COPD mortality: a systematic review and meta-analysis

ABSTRACT: BACKGROUND: Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial. Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD. METHODS: We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD. Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies. Publication bias was assessed using a funnel plot. RESULTS: Our search identified nine retrospective cohort studies that met the study inclusion criteria. The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%). CONCLUSION: The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality. Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded. The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials.     

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.

OBJECTIVE--To assess the effects of calcium channel blockers on development of infarcts, reinfarction, and mortality. DESIGN--A systematic overview of all randomised trials of calcium channel blockers in myocardial infarction and unstable angina. PATIENTS--19,000 Patients in 28 randomised trials. RESULTS--In the trials of myocardial infarction 873 deaths occurred among 8870 patients randomised to active treatment compared with 825 deaths among 8889 control patients (odds ratio of 1.06, 95% confidence interval of 0.96 to 1.18). There was no evidence of a beneficial effect on development and size of infarcts or rate of reinfarction. The results were similar in short term trials in which treatment was confined to the acute phase and those in which treatment was started some weeks later and continued for a year or two. There was no evidence of heterogeneity among different calcium channel blockers in their effects on any end point. The results were similar in the unstable angina trials (110 out of 561 patients treated with calcium channel blocker compared with 104 out of 548 controls developed a myocardial infarction; 14 out of 591 treated compared with nine out of 578 controls died). CONCLUSIONS--Calcium channel blockers do not reduce the risk of initial or recurrent infarction or death when given routinely to patients with acute myocardial infarction or unstable angina.     

Lower versus Higher Oxygen Concentration for Delivery Room Stabilisation of Preterm Neonates: Systematic Review

Background

Emerging evidence suggests that initiating delivery room respiratory support or resuscitation for term infants using lower rather than higher concentrations of oxygen reduces mortality and the risk of serious morbidity. Uncertainty exists with regard to applicability of this strategy for preterm infants who have different underlying reasons for respiratory distress and risks for harm at birth than term infants.

Methods

We performed a systematic review and meta-analysis of randomised controlled trials to determine the effect on mortality and morbidity of using lower (21– 50%) versus higher (>50%) oxygen concentrations for delivery room transition support of preterm infants.

Results

We identified six randomised controlled trials in which a total of 484 infants participated. Most participants were preterm infants born before 32 weeks’ gestation. One trial was quasi-randomised and in one trial allocation concealment was not described. Clinicians and investigators were aware of the interventions in all but one trial. Meta-analyses found a statistically significant reduction in the risk of death pooled risk ratio 0.65 (95% confidence interval 0.43, 0.98), but this effect disappeared when only the four trials with adequate allocation concealment were included [pooled risk ratio 1.0 (95% confidence interval 0.45, 2.24)]. None of the trials has evaluated any neuro-developmental outcomes.

Conclusions

The available trial data do not provide strong evidence that using lower versus higher oxygen concentrations for delivery room transition support for preterm infants confers important benefits or harms. Lack of allocation concealment and blinding of clinicians and assessors are the major sources of bias in the existing trials. Further, large, good-quality trials are needed to resolve on-going uncertainties and inform clinical practice.     

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed.

Key messages

• A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome
• Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm
• Assertive outreach can help to keep patients in treatment
• Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences
• There is an urgent need for large trials of promising therapies for this substantial clinical population

     

Mitochondrial dysfunction early after traumatic brain injury in immature rats

Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. Rates of phosphorylating (State 3) and resting (State 4) respiration were measured with and without bovine serum albumin. The respiratory control ratio was calculated (State 3/State 4). Rates of mitochondrial H(2)O(2) production, pyruvate dehydrogenase complex enzyme activity, and cytochrome c content were measured. Mitochondrial State 4 rates (ipsilateral/contralateral ratios) were higher after TBI at 1 h, which was reversed with bovine serum albumin. Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (相似文献   

Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis

ObjectivesTo evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis.DesignQuantitative systematic review of randomised controlled trials.Subjects6038 patients with plaque psoriasis reported in 37 trials.ResultsCalcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol.ConclusionsCalcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life.     

Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study

Objective To examine whether the association of inadequate or unclear allocation concealment and lack of blinding with biased estimates of intervention effects varies with the nature of the intervention or outcome.Design Combined analysis of data from three meta-epidemiological studies based on collections of meta-analyses.Data sources 146 meta-analyses including 1346 trials examining a wide range of interventions and outcomes.Main outcome measures Ratios of odds ratios quantifying the degree of bias associated with inadequate or unclear allocation concealment, and lack of blinding, for trials with different types of intervention and outcome. A ratio of odds ratios <1 implies that inadequately concealed or non-blinded trials exaggerate intervention effect estimates.Results In trials with subjective outcomes effect estimates were exaggerated when there was inadequate or unclear allocation concealment (ratio of odds ratios 0.69 (95% CI 0.59 to 0.82)) or lack of blinding (0.75 (0.61 to 0.93)). In contrast, there was little evidence of bias in trials with objective outcomes: ratios of odds ratios 0.91 (0.80 to 1.03) for inadequate or unclear allocation concealment and 1.01 (0.92 to 1.10) for lack of blinding. There was little evidence for a difference between trials of drug and non-drug interventions. Except for trials with all cause mortality as the outcome, the magnitude of bias varied between meta-analyses.Conclusions The average bias associated with defects in the conduct of randomised trials varies with the type of outcome. Systematic reviewers should routinely assess the risk of bias in the results of trials, and should report meta-analyses restricted to trials at low risk of bias either as the primary analysis or in conjunction with less restrictive analyses.     

Phenytoin versus Leviteracetam for Seizure Prophylaxis after brain injury – a meta analysis

Background

Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.

Methods

An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.

Results

The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate’s Odds Ratio 1.12 (95% CI?=?0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7?days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI?=?0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6?months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI?=?0.24, 3.79).

Conclusions

Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.