Healing by primary closure versus open healing after surgery for pilonidal sinus: systematic review and meta-analysis

Objective To determine the relative effects of open healing compared with primary closure for pilonidal sinus and optimal closure method (midline v off-midline).Design Systematic review and meta-analyses of randomised controlled trials.Data sources Cochrane register of controlled trials, Cochrane Wounds Group specialised trials register, Medline (1950-2007), Embase, and CINAHL bibliographic databases, without language restrictions.Data extraction Primary outcomes were time (days) to healing, surgical site infection, and recurrence rate. Secondary outcomes were time to return to work, other complications and morbidity, cost, length of hospital stay, and wound healing rate.Study selection Randomised controlled trials evaluating surgical treatment of pilonidal sinus in patients aged 14 years or more. Data were extracted independently by two reviewers and assessed for quality. Meta-analyses used fixed and random effects models, dichotomous data were reported as relative risks or Peto odds ratios and continuous data are given as mean differences; all with 95% confidence intervals.Results 18 trials (n=1573) were included. 12 trials compared open healing with primary closure. Time to healing was quicker after primary closure although data were unsuitable for aggregation. Rates of surgical site infection did not differ; recurrence was less likely to occur after open healing (relative risk 0.42, 0.26 to 0.66). 14 patients would require their wound to heal by open healing to prevent one recurrence. Six trials compared surgical closure methods (midline v off-midline). Wounds took longer to heal after midline closure than after off-midline closure (mean difference 5.4 days, 95% confidence interval 2.3 to 8.5), rate of infection was higher (relative risk 4.70, 95% confidence interval 1.93 to 11.45), and risk of recurrence higher (Peto odds ratio 4.95, 95% confidence interval 2.18 to 11.24). Nine patients would need to be treated by an off-midline procedure to prevent one surgical site infection and 11 would need to be treated to prevent one recurrence.Conclusions Wounds heal more quickly after primary closure than after open healing but at the expense of increased risk of recurrence. Benefits were clearly shown with off-midline closure compared with midline closure. Off-midline closure should become standard management for pilonidal sinus when closure is the desired surgical option.     

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.     

Corticosteroids in the Treatment of Community-Acquired Pneumonia in Adults: A Meta-Analysis

Background

The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.

Methods

Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis.

Results

Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37–1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11–0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26–0.97; P = 0.04; I ² = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68–4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41–6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65–2.84; P = 0.41).

Conclusion

Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials.     

Effect of obesity on short- and long-term mortality postcoronary revascularization: a meta-analysis

Objective: Overweight and obesity are often assumed to be risk factors for postprocedural mortality in patients with coronary artery disease (CAD). However, recent studies have described an “obesity paradox”—a neutral or beneficial association between obesity and mortality postcoronary revascularization. We reviewed the effect of overweight and obesity systematically on short‐ and long‐term all‐cause mortality post‐coronary artery bypass grafting (CABG) and post‐percutaneous coronary intervention (PCI). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify cohort, case control, and randomized controlled studies evaluating the effect of obesity on in‐hospital/short‐term (within 30 days) and long‐term (up to 5 years) mortality. Full‐text, published articles reporting all‐cause mortality between individuals with and without elevated BMI were included. Two reviewers independently assessed studies for inclusion and performed data extraction. Results: Twenty‐two cohort publications were identified, reporting results in ten post‐PCI and twelve post‐CABG populations. Compared to individuals with non‐elevated BMI levels, obese patients undergoing PCI had lower short‐ (odds ratio (OR) 0.63; 95% confidence interval (CI) 0.54–0.73) and long‐term mortality (OR 0.65; 95% CI 0.51–0.83). Post‐CABG, obese patients had lower short‐term (OR 0.63; 95% CI 0.56–0.71) and similar long‐term (OR 0.88; 95% CI 0.60–1.29) mortality risk compared to normal weight individuals. Results were similar in overweight patients for both procedures. Conclusions: Compared to non‐obese individuals, overweight and obese patients have similar or lower short‐ and long‐term mortality rates postcoronary revascularization. Further research is needed to confirm the validity of these findings and delineate potential underlying mechanisms.     

Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding

Objectives To review randomised controlled trials of treatment with a proton pump inhibitor in patients with ulcer bleeding and determine the impact on mortality, rebleeding, and surgical intervention.Design Systematic review and meta-analysis.Data sources Cochrane Collaboration''s trials register, Medline, and Embase, handsearched abstracts, and pharmaceutical companies.Review methods Included randomised controlled trials compared proton pump inhibitor with placebo or H₂ receptor antagonist in endoscopically proved bleeding ulcer and reported at least one of mortality, rebleeding, or surgical intervention. Trials were graded for methodological quality. Two assessors independently reviewed each trial, and disagreements were resolved by consensus.Results We included 21 randomised controlled trials comprising 2915 patients. Proton pump inhibitor treatment had no significant effect on mortality (odds ratio 1.11, 95% confidence interval 0.79 to 1.57; number needed to treat (NNT) incalculable) but reduced rebleeding (0.46, 0.33 to 0.64; NNT 12) and surgery (0.59, 0.46 to 0.76; NNT 20). Results were similar when the meta-analysis was restricted to the 10 trials with the highest methodological quality: 0.96, 0.46 to 2.01, for mortality; 0.41, 0.25 to 0.68, NNT 10, for rebleeding; 0.62, 0.46 to 0.83, NNT 25, for surgery.Conclusions Treatment with a proton pump inhibitor reduces the risk of rebleeding and the requirement for surgery after ulcer bleeding but has no benefit on overall mortality.     

Association between statin therapy and outcomes in critically ill patients: a nested cohort study

Background

The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.

Methods

This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.

Results

Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.

Conclusion

Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.     

Withdrawal of inhaled corticosteroids in individuals with COPD - a systematic review and comment on trial methodology

Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately.     

Identification of additional trials in prospective trial registers for cochrane systematic reviews

Background

Publication and selective outcome reporting bias are a threat to the validity of systematic reviews. Extensive searching for additional trials in prospective trial registers could reduce this problem. We have evaluated how authors of Cochrane systematic reviews currently make use of trial registers as an additional source for the identification of potentially eligible trials.

Methodology/Principal Findings

We included 210 systematic Cochrane reviews of interventions published between 2008 and 2010 of which the protocol was first published in 2008. When prospective trial registers were searched we recorded the names of the register(s), the authors'' motive(s) and if they yielded any extra trials.In 80 reviews (38.1%) the authors had searched in one or more prospective trial register(s) of which 55% had searched in overlapping search portals and individual registers. Most frequently assessed were the MetaRegister (66.3%) and Clinicaltrials.gov (60%) which is in sharp contrast of other registers or portals like the WHO ICTRP Search Portal (20%). Reported motives to use registers were to identify ongoing trials (83.3%), to identify unpublished outcomes or trials (23.5%), to identify recently published trials (11.8%), or to identify any relevant trial (3.9%).In 28 reviews (35%) the authors had selected (ongoing) trials identified in trial registers as potentially eligible.

Discussion

Trial registers as an additional source of information are gaining acknowledgement amongst Cochrane reviewers. Nevertheless, searches seem to be inefficient as overlapping databases are frequently consulted, while the WHO ICTRP Search Portal that includes the data from all approved registers worldwide is being underused. Moreover, the emphasis is now on the identification of ongoing trials, although the prospective registers offer a broader potential. Further familiarity of registers and guidance how to search and to report will help to implement this as a common method and utilize the full potential of prospective trial registers for systematic reviews.     

Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials

ObjectiveTo determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes.DesignSystematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials.ResultsEleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046).ConclusionsThere seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.

What is already known on this topic

Enteral feeding within 24 hours after gastrointestinal surgery is toleratedTheoretically, early enteral feeding improves tissue healing and reduces septic complications after gastrointestinal surgery

What this study adds

There is no benefit in keeping patients “nil by mouth” after gastrointestinal surgerySeptic complications and length of hospital stay were reduced in those patients who received early enteral feedingIn patients who received early enteral feeding there were no significant reductions in incidence of anastomotic dehiscence, wound infection, pneumonia, intra-abdominal abscess, and mortality     

Effectiveness of physiotherapy exercise after knee arthroplasty for osteoarthritis: systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the effectiveness of physiotherapy exercise after elective primary total knee arthroplasty in patients with osteoarthritis.Design Systematic review.Data sources Database searches: AMED, CINAHL, Embase, King''s Fund, Medline, Cochrane library (Cochrane reviews, Cochrane central register of controlled trials, DARE), PEDro, Department of Health national research register. Hand searches: Physiotherapy, Physical Therapy, Journal of Bone and Joint Surgery (Britain) Conference Proceedings.Review methods Randomised controlled trials were reviewed if they included a physiotherapy exercise intervention compared with usual or standard physiotherapy care, or compared two types of exercise physiotherapy interventions meeting the review criteria, after discharge from hospital after elective primary total knee arthroplasty for osteoarthritis.Outcome measures Functional activities of daily living, walking, quality of life, muscle strength, and range of motion in the knee joint. Trial quality was extensively evaluated. Narrative synthesis plus meta-analyses with fixed effect models, weighted mean differences, standardised effect sizes, and tests for heterogeneity.Results Six trials were identified, five of which were suitable for inclusion in meta-analyses. There was a small to moderate standardised effect size (0.33, 95% confidence interval 0.07 to 0.58) in favour of functional exercise for function three to four months postoperatively. There were also small to moderate weighted mean differences of 2.9 (0.61 to 5.2) for range of joint motion and 1.66 (−1 to 4.3) for quality of life in favour of functional exercise three to four months postoperatively. Benefits of treatment were no longer evident at one year.Conclusions Interventions including physiotherapy functional exercises after discharge result in short term benefit after elective primary total knee arthroplasty. Effect sizes are small to moderate, with no long term benefit.     

Psychosocial and psychological interventions for prevention of postnatal depression: systematic review

Objective To assess the effects of psychosocial and psychological interventions compared with usual antepartum, intrapartum, or postpartum care on the risk of postnatal depression.Data sources Medline, Embase, CINAHL, Cochrane central register of controlled trials, Cochrane pregnancy and childbirth group trials register, Cochrane depression, anxiety, and neurosis trials register, secondary references and review articles, and experts in the field.Study selection All published and unpublished randomised controlled trials of preventive psychosocial or psychological interventions in which the primary or secondary aim was a reduction in the risk of postnatal depression. All trials recruited pregnant women or new mothers less than six weeks postpartum. Eligible studies were abstracted, assessed for methodological quality, and pooled with relative risk for categorical data and weighted mean difference for continuous data.Results Fifteen trials with 7697 women were included. Although there was no overall statistically significant effect on the prevention of postnatal depression in the meta-analysis of all types of interventions (15 trials, n = 7697; relative risk 0.81, 95% confidence interval 0.65 to 1.02), these results suggest a potential reduction in postnatal depression. The only intervention to have a clear preventive effect was intensive postpartum support provided by a health professional (0.68, 0.55 to 0.84). Identifying women “at risk” assisted in the prevention of postnatal depression (0.67, 0.51 to 0.89). Interventions with only a postnatal component were more beneficial (0.76, 0.58 to 0.98) than interventions that incorporated an antenatal component. In addition, individually based interventions were more effective (0.76, 0.59 to 1.00) than group based interventions (1.03, 0.65 to 1.63).Conclusions Diverse psychosocial or psychological interventions do not significantly reduce the number of women who develop postnatal depression. The most promising intervention is the provision of intensive, professionally based postpartum support.     

Occupational therapy for patients with problems in personal activities of daily living after stroke: systematic review of randomised trials

Objective To determine whether occupational therapy focused specifically on personal activities of daily living improves recovery for patients after stroke.Design Systematic review and meta-analysis.Data sources The Cochrane stroke group trials register, the Cochrane central register of controlled trials, Medline, Embase, CINAHL, PsycLIT, AMED, Wilson Social Sciences Abstracts, Science Citation Index, Social Science Citation, Arts and Humanities Citation Index, Dissertations Abstracts register, Occupational Therapy Research Index, scanning reference lists, personal communication with authors, and hand searching.Review methods Trials were included if they evaluated the effect of occupational therapy focused on practice of personal activities of daily living or where performance in such activities was the target of the occupational therapy intervention in a stroke population. Original data were sought from trialists. Two reviewers independently reviewed each trial for methodological quality. Disagreements were resolved by consensus.Results Nine randomised controlled trials including 1258 participants met the inclusion criteria. Occupational therapy delivered to patients after stroke and targeted towards personal activities of daily living increased performance scores (standardised mean difference 0.18, 95% confidence interval 0.04 to 0.32, P=0.01) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio 0.67, 95% confidence interval 0.51 to 0.87, P=0.003). For every 100 people who received occupational therapy focused on personal activities of daily living, 11 (95% confidence interval 7 to 30) would be spared a poor outcome.Conclusions Occupational therapy focused on improving personal activities of daily living after stroke can improve performance and reduce the risk of deterioration in these abilities. Focused occupational therapy should be available to everyone who has had a stroke.     

Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis

Background

Uncertainly prevails with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. The meta-analysis with sequential analysis was designed to evaluate the efficacy and safety of airway administration (inhalation or instillation) of corticosteroids for preventing bronchopulmonary dysplasia (BPD) in premature infants.

Methods

We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to February 2017. All published randomized controlled trials (RCTs) evaluating the effect of airway administration of corticosteroids (AACs) vs placebo or systemic corticosteroid in prematurity were included. All meta-analyses were performed using Review Manager 5.3.

Results

Twenty five RCTs retrieved (n?=?3249) were eligible for further analysis. Meta-analysis and trial sequential analysis corrected the 95% confidence intervals estimated a lower risk of the primary outcome of BPD (relative risk 0.71, adjusted 95% confidence interval 0.57–0.87) and death or BPD (relative risk 0.81, adjusted 95% confidence interval 0.71–0.97) in AACs group than placebo and it is equivalent for preventing BPD than systemic corticosteroids. Moreover, AACs fail to increasing risk of death compared with placebo (relative risk 0.90, adjusted 95% confidence interval 0.40–2.03) or systemic corticosteroids (relative risk 0.81, 95% confidence interval 0.62–1.06).

Conclusions

Our findings suggests that AACs (especially instillation of budesonide using surfactant as a vehicle) are an effective and safe option for preventing BPD in preterm infants. Furthermore, the appropriate dose and duration, inhalation or instillation with surfactant as a vehicle and the long-term safety of airway administration of corticosteroids needs to be assessed in large trials.

     

Prophylactic corticosteroid to prevent pain flare in bone metastases treated by radiotherapy

BackgroundThe aim of this study was to evaluate the effectiveness of prophylactic corticosteroids to prevent pain flare (PF) in bone metastases treated with radiotherapy performing a meta-analysis of randomized clinical trials (RCT).Materials and methodsRCTs were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-analysis was performed to assess if corticosteroids reduce the PF, pain progression, and the mean of days with PF compared with the placebo. A p-value < 0.05 was considered significant.ResultsThree RCTs with a total of 713 patients treated were included. The corticosteroids reduced the occurrence of early PF 20.5% (51/248) versus 32% (80/250) placebo, OR = 0.55 (95% CI: 0.36–0.82, p = 0.002). The mean days of PF were reduced to 1.6 days (95% CI: 1.3–1.9, p = 0.0001). Prophylactic corticosteroids had more patients with no PF and no pain progression, OR = 1.63 (95% CI: 1.14–2.32, p = 0.007). No significant corticosteroids effect was observed for pain progression (p = ns) and late PF occurrence (p = ns).ConclusionProphylactic corticosteroids reduced the incidence of early PF, the days with PF, resulting in a superior rate of patients with no PF and no pain progression, but with no significant benefit for reducing pain progression or late PF occurrence.     

Long term pharmacotherapy for obesity and overweight: updated meta-analysis

Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.Design Updated meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006.Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer.Results 30 trials of one to four years’ duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine lowered concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate. Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.Conclusions Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.     

Adjunctive Corticotherapy for Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background

Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP.

Methods

We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications.

Results

14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96).

Conclusion

Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.     

Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials

Objective To evaluate the addition of methylxanthines to standard treatments in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD).Design Meta-analysis of randomised controlled trials.Data source The Cochrane airways review group''s COPD register. Two reviewers independently selected articles for inclusion, assessed methodological quality, and extracted data.Selection of studies Four trials met the inclusion criteria, with 169 patients.Main outcome measures Mean change in spirometry, clinical end points, symptom scores, and adverse events.Results Mean change in forced expiratory volume at one second at two hours was similar in methylxanthine and placebo groups but transiently increased with methylxanthines at three days. Non-significant reductions in admissions to hospital and length of stay were offset by a non-significant increase in relapses at one week. Changes in symptom scores did not reach significance. Methylxanthines caused more nausea and vomiting than placebo (odds ratio 4.6, 95% confidence interval 1.7 to 12.6), and non-significant increases in tremor, palpitations, and arrhythmias were also observed.Conclusions The available data do not support the use of methylxanthines for the treatment of exacerbations of chronic obstructive pulmonary disease. Potential benefits of methylxanthines for lung function and symptoms were generally not confirmed at standard levels of significance, whereas the potentially important adverse events of nausea and vomiting were significantly increased in patients receiving methylxanthines.     

Different Sodium-Glucose Cotransporter-2 Inhibitors: Can They Prevent Death?

ObjectiveSodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcome trials (CVOTs) demonstrate cardiovascular (CV) safety and benefits. Some dedicated randomized controlled trials (RCTs) demonstrate benefit in terms of renal outcomes and hospitalization due to heart failure (HF). RCTs report differences in the secondary outcomes with respect to mortality (CV and/or all-cause). We undertook a meta-analysis of all SGLT2is for which in addition to CVOT, HF outcome/renal outcome studies are available to establish whether individual SGLT2is were able to prevent death.MethodsWe included available event-driven randomized, placebo-controlled CVOTs and dedicated RCTs of SGLT2is exploring renal outcomes and HF. We included 3 trials of empagliflozin, 3 of dapagliflozin, 2 of canagliflozin, and 2 of sotagliflozin. The efficacy outcomes included all-cause mortality and CV mortality. Hazard ratios (HRs) with 95% CIs were pooled for individual molecules.ResultsThe HR for all-cause mortality including all trials was 0.86 (0.80-0.93). The HRs for all-cause mortality in empagliflozin (N = 16 738), dapagliflozin (N = 26 208), canagliflozin (N = 14 543), and sotagliflozin (N = 11 806) were 0.86 (0.69-1.08), 0.83 (0.72-0.97), 0.86 (0.75-0.97), and 0.95 (0.81-1.11), respectively. The HR for CV mortality including all trials was 0.85 (0.78-0.92). The HRs for CV mortality in empagliflozin, dapagliflozin, sotagliflozin, and canagliflozin were 0.81 (0.63-1.03), 0.88 (0.78-1.00), 0.89 (0.74-1.07), and 0.84 (0.72-0.98), respectively.ConclusionSGLT2is as a class reduce both all-cause mortality and CV mortality. Canagliflozin possibly reduces both all-cause mortality and CV mortality, whereas dapagliflozin may reduce all-cause mortality but not CV mortality. Empagliflozin and sotagliflozin may reduce neither.     

The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is the 4^th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD.

Methods

Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus.

Results

Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality.

Conclusions

A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.     

Terlipressin versus Norepinephrine in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis

Background

Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS.

Methods

We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events.

Results

Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83).

Conclusions

Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.