Substantial Statistical Heterogeneity Research Articles

Endometrial scratching prior to IVF; does it help and for whom? A systematic review and meta-analysis.

STUDY QUESTIONWhat is the effect of endometrial scratching in patients with or without prior failed ART cycles on live birth (LBR) and clinical pregnancy rates (CPR)?SUMMARY ANSWERIt remains unclear if endometrial scratching improves the chance of pregnancy and, if so, for whom.WHAT IS KNOWN ALREADYEndometrial scratching is hypothesized to improve embryo implantation in ART. Multiple studies have been published, but it remains unclear if endometrial scratching actually improves pregnancy rates and, if so, for which patients.STUDY DESIGN, SIZE, DURATIONFor this review, a systematic search for published articles on endometrial scratching and ART was performed on 12 February 2018, in Pubmed, Embase and the Cochrane Library.PARTICIPANTS/MATERIALS, SETTING, METHODSRandomized controlled trials (RCTs) that evaluated endometrial scratching in the cycle prior to the stimulation cycle and reported CPR or LBR were included. RCTs investigating the effect of scratching during the stimulation cycle, or prior to cryo-thaw cycles were excluded. Studies were assessed using the Cochrane Risk of Bias tool. The effect of scratching was assessed for three different patient groups: patients with no prior IVF/ICSI treatment (Group 0), patients with one failed full IVF/ICSI cycle, including cryo-thaw cycles (Group 1) and patients with two or more failed full IVF/ICSI cycles (Group 2). A meta-analysis was performed when statistical heterogeneity was low; otherwise, a descriptive analysis was performed.MAIN RESULTS AND THE ROLE OF CHANCEFourteen RCTs involving 2537 participants were included. Most RCTs contained a high or unclear risk of bias on one or more items. Substantial clinical and statistical heterogeneity was present; therefore meta-analysis for LBR and CPR could only be performed on Group 1. For this group, no differences between scratch and control were found for both LBR (risk ratio (RR) 1.01 [95%CI 0.68–1.51]) and CPR (RR 1.04 [95%CI 0.74–1.45]). For Groups 0 and 2, pooled analysis could not be performed, and for both groups the results of the individual RCTs were negative, neutral and positive. Miscarriage and multiple pregnancy rates were evaluated for the three groups (0, 1 and 2) together. Both outcomes were not significantly different between scratch and control (miscarriage rate RR 0.82 [95%CI 0.57–1.17] and multiple pregnancy rate RR 1.06 [95%CI 0.84–1.35]). Subgroup analysis, excluding trials with a risk of unintentional endometrial injury in the control group, was performed for Group 0 and 2 for LBR and CPR, and for the overall groups for miscarriage rate and multiple pregnancy rate. This reduced the heterogeneity and allowed for pooled analysis in these subgroups. Results of pooled analysis for the subgroups of Group 0 and 2 showed no significant difference for LBR, but CPR was significantly improved after endometrial scratching (Group 0 RR 1.28 [95%CI 1.02–1.62] and Group 2 RR 2.03 [95%CI 1.20–3.43]). Subgroup analysis of the overall groups showed no significant difference for miscarriage and multiple pregnancy rate.LIMITATIONS REASONS FOR CAUTIONThe main limitations were that many RCTs had a high or unclear risk of bias on one or several items, clinical heterogeneity was still present despite categorizing into three populations, and that not all RCTs could be included in the analyses because separate data for our three groups could not be provided.WIDER IMPLICATIONS OF THE FINDINGSIt remains unclear if endometrial scratching improves the chance of pregnancy for women undergoing ART and, if so, for whom. This means endometrial scratching should not be offered in daily practice until results from large and well-designed RCTs and an individual patient data analysis become available.STUDY FUNDING/COMPETING INTERESTSNo specific funding was sought for the study. The Department of Reproductive Medicine and Gynaecology funds of the University Medical Center of Utrecht were used to support the authors throughout the study period and preparation of the manuscript. None of the authors has a conflict of interest to declare.REGISTRATION NUMBERNot applicable.

Role of diffusional kurtosis imaging in grading of brain gliomas: a protocol for systematic review and meta-analysis

IntroductionCentral nervous system (CNS) gliomas are the most common primary intra-axial brain tumours and pose variable treatment response according to their grade, therefore, precise staging is mandatory. Histopathological analysis of...

Caseworker-assigned discharge plans to prevent hospital readmission for acute exacerbations in children with chronic respiratory illness.

Chronic respiratory conditions are major causes of mortality and morbidity. Children with chronic health conditions have increased morbidity associated with their physical, emotional, and general well-being. Acute respiratory exacerbations (AREs) are common in children with chronic respiratory disease, often requiring admission to hospital. Reducing the frequency of AREs and recurrent hospitalisations is therefore an important goal in the individual and public health management of chronic respiratory illnesses in children. Discharge planning is used to decide what a person needs for transition from one level of care to another and is usually considered in the context of discharge from hospital to the home. Discharge planning from hospital for ongoing management of an illness has historically been referral to a general practitioner or allied health professional or self management by the individual and their family with limited communication between the hospital and patient once discharged. Effective discharge planning can decrease the risk of recurrent AREs requiring medical care. An individual caseworker-assigned discharge plan may further decrease exacerbations. To evaluate the efficacy of individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, in preventing hospitalisation for AREs in children with chronic lung diseases such as asthma and bronchiectasis. We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials registries, and reference lists of articles. The latest searches were undertaken in November 2017. All randomised controlled trials comparing individual caseworker-assigned discharge planning compared to traditional discharge-planning approaches (including self management), and their effectiveness in reducing the subsequent need for emergency care for AREs (hospital admissions, emergency department visits, and/or unscheduled general practitioner visits) in children hospitalised with an acute exacerbation of chronic respiratory disease. We excluded studies that included children with cystic fibrosis. We used standard Cochrane Review methodological approaches. Relevant studies were independently selected in duplicate. Two review authors independently assessed trial quality and extracted data. We contacted the authors of one study for further information. We included four studies involving a total of 773 randomised participants aged between 14 months and 16 years. All four studies involved children with asthma, with the case-planning undertaken by a trained nurse educator. However, the discharge planning/education differed among the studies. We could include data from only two studies (361 children) in the meta-analysis. Two further studies enrolled children in both inpatient and outpatient settings, and one of these studies also included children with acute wheezing illness (no previous asthma diagnosis); the data specific to this review could not be obtained. For the primary outcome of exacerbations requiring hospitalisation, those in the intervention group were significantly less likely to be rehospitalised (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.16 to 0.50) compared to controls. This equates to 189 (95% CI 124 to 236) fewer admissions per 1000 children. No adverse events were reported in any study. In the context of substantial statistical heterogeneity between the two studies, there were no statistically significant effects on emergency department (OR 0.37, 95% CI 0.04 to 3.05) or general practitioner (OR 0.87, 95% CI 0.22 to 3.44) presentations. There were no data on cost-effectiveness, length of stay of subsequent hospitalisations, or adherence to medications. One study reported quality of life, with no significant differences observed between the intervention and control groups.We considered three of the studies to have an unclear risk of bias, primarily due to inadequate description of the blinding of participants and investigators. The fourth study was assessed as at high risk of bias as a single unblinded investigator was used. Using the GRADE system, we assessed the quality of the evidence as moderate for the outcome of hospitalisation and low for the outcomes of emergency department visits and general practitioner consultations. Current evidence suggests that individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma. There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma, and there is an absence of data for children with other chronic respiratory conditions. Given the potential benefit and cost savings to the healthcare sector and families if hospitalisations and outpatient attendances can be reduced, there is a need for further randomised controlled trials encompassing different chronic respiratory illnesses, ethnicity, socio-economic settings, and cost-effectiveness, as well as defining the essential components of a complex intervention.

Information or education interventions for adult intensive care unit (ICU) patients and their carers.

Information or education interventions for adult intensive care unit (ICU) patients and their carers.

Does perioperative intravenous dextrose reduce postoperative nausea and vomiting? A systematic review and meta-analysis.

PurposePerioperative dextrose-containing fluid administration has been used as a non-pharmacologic preventive measure against postoperative nausea and vomiting (PONV), a common and distressing complication of anesthesia. However, its efficacy remains unclear as previous studies reported inconsistent results. Our objective was to compare dextrose-containing fluid with non-dextrose-containing fluid in terms of PONV for 24 hours after surgery under general anesthesia. The effects of dextrose according to different types of surgery and the fluid volume were also examined.MethodsWe performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing dextrose-containing fluid with non-dextrose-containing fluids after general anesthesia in terms of PONV incidence and the need for rescue anti-emetic therapies for 24 hours after surgery. A literature search was performed, using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus, up to February 2018.ResultsWe included seven RCTs. Compared with the control group, perioperative dextrose administration did not reduce the risk for PONV, with a relative risk (RR) of 0.72 (95% CI: 0.50–1.03). However, perioperative dextrose reduced the requirement for anti-emetics, compared with the control group, with a RR of 0.60 (95% CI: 0.44–0.83). The quality of evidence in this meta-analysis was poor due to high risks of selection and performance biases and substantial statistical heterogeneity. After subgroup analysis, the risk for PONV was reduced in patients who had undergone laparoscopic cholecystectomy, but not other surgeries, and the effects of dextrose on the risk for PONV did not differ according to the fluid volume administered.ConclusionPerioperative intravenous (i.v.) dextrose did not reduce the risk for PONV. However, it did reduce the need for anti-emetics after general anesthesia. Furthermore, the effects of dextrose varied according to the surgery type. Further studies are needed to determine the benefits of perioperative i.v. dextrose administration as a preventive measure against PONV.

Epidural versus non-epidural or no analgesia for pain management in labour.

Epidural versus non-epidural or no analgesia for pain management in labour.

Interventions for implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism.

Background Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost‐effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system‐wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers’ behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted.

The effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and Trial Sequential Analysis.

BackgroundAtrial fibrillation and atrial flutter may be managed by either a rhythm control strategy or a rate control strategy but the evidence on the clinical effects of these two intervention strategies is unclear. Our objective was to assess the beneficial and harmful effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter.MethodsWe searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS, Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible trials comparing any rhythm control strategy with any rate control strategy in patients with atrial fibrillation or atrial flutter published before November 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were stroke and ejection fraction. We performed both random-effects and fixed-effect meta-analysis and chose the most conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. Statistical heterogeneity was assessed by visual inspection of forest plots and by calculating inconsistency (I2) for traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and subgroup analyses were conducted to explore the reasons for substantial statistical heterogeneity. We assessed the risk of publication bias in meta-analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We used GRADE to assess the quality of the body of evidence.Results25 randomized clinical trials (n = 9354 participants) were included, all of which were at high risk of bias. Meta-analysis showed that rhythm control strategies versus rate control strategies significantly increased the risk of a serious adverse event (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2 = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA-adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not seem to be caused by any single component of the composite outcome. Meta-analysis showed that rhythm control strategies versus rate control strategies were associated with better SF-36 physical component score (mean difference (MD), 6.93 points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8 trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 = 79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both meta-analysis and TSA showed no significant differences on all-cause mortality, SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire, and stroke.ConclusionsRhythm control strategies compared with rate control strategies seem to significantly increase the risk of a serious adverse event in patients with atrial fibrillation. Based on current evidence, it seems that most patients with atrial fibrillation should be treated with a rate control strategy unless there are specific reasons (e.g., patients with unbearable symptoms due to atrial fibrillation or patients who are hemodynamically unstable due to atrial fibrillation) justifying a rhythm control strategy. More randomized trials at low risk of bias and low risk of random errors are needed.Trial registrationPROSPERO CRD42016051433

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis.

AIMTo perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI).METHODSWe conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS).RESULTSFifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002).CONCLUSIONThis meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Psychological interventions for coronary heart disease.

Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease.To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD).We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought.RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately.Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information.Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life.Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.

Multiple-micronutrient supplementation for women during pregnancy.

Multiple-micronutrient supplementation for women during pregnancy.

Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis

BackgroundReports of frequent manifestation of allergic diseases in children with attention deficit hyperactivity disorder (ADHD) have been the subject of mounting clinical interest. However, evidence supporting the association between ADHD and allergies is inconsistent and has yet to be systematically reviewed. The objective of this study was to compile and assess available studies on the association between ADHD and allergic diseases in children.MethodsA comprehensive search using MEDLINE, EMBASE, the Cochrane library, and CINAHL databases was completed in 23 November 2015. The inclusion criteria for studies were that the research assessed allergic diseases in children, 18 years of age and younger, with a diagnosis of ADHD and that a distinct comparison group was incorporated. Any comparative studies, encompassing both randomized controlled trials and observational studies, were considered for inclusion. Two review authors independently assessed the quality of the selected studies by the use of validated assessment tools, performed data extraction and conducted meta-analysis according to Cochrane Collaboration guidelines.ResultsFive eligible studies were included in this systematic review. Of these studies, three were case-control and two were cross sectional studies. A majority of information from the five studies was classified as having low or unclear risk of bias. The meta-analysis showed an association between children with ADHD and asthma compared with the control groups (OR: 1.80, 95% CI: 1.57 - 2.07; five studies, low quality of evidence), but did not indicate an association between food allergy and ADHD (OR: 1.13, 95% CI: 0.88 - 1.47; three studies very low quality of evidence). The odds of experiencing allergic rhinitis, atopic dermatitis, and allergic conjunctivitis were slightly higher in children with ADHD compared with control groups, though a substantial statistical heterogeneity was notable in the overall effect estimates.ConclusionsThe findings from this review and meta-analysis show that children with ADHD are more likely to have asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis than their counterparts. Interventions including strategies for managing allergies in children with ADHD would be beneficial.

Endometrial thickness in women undergoing IUI with ovarian stimulation. How thick is too thin? A systematic review and meta-analysis.

Is pre-ovulatory endometrial thickness (EMT) in women with unexplained subfertility undergoing IUI with ovarian stimulation (OS) associated with pregnancy chances? We found no evidence for an association between EMT and pregnancy chances. It has been suggested that OS with clomiphene citrate (CC) results in a lower EMT than with gonadotrophins or aromatase inhibitors, but the clinical consequences in terms of pregnancy are unclear. We performed a systematic review and meta-analysis of studies comparing CC, gonadotrophins or aromatase inhibitors in an IUI program reporting on EMT and pregnancy rates in women with unexplained subfertility. We searched MEDLINE, EMBASE and the non-MEDLINE subset of PubMed from inception to 28th June 2016 and cross-checked references of relevant articles. Outcome measures were clinical pregnancy rate and mean pre-ovulatory EMT. We calculated mean differences (MD) with 95% CIs with a fixed effect model, and in case of heterogeneity with an I2 > 50% a random effect model. We performed a meta-regression analysis to determine if stimulating drugs interacted with the estimated effect of EMT. Our search retrieved 1563 articles of which 23 were included, totaling 3846 women. There were 17 RCTs and 6 cohort studies. The average study quality was low and there was considerable to substantial statistical heterogeneity. Seven studies provided data on EMT in relation to pregnancy. There was no evidence of a difference in EMT between women who conceived and women that did not conceive (1525 women, MDrandom: 0.51 mm, 95% CI: -0.05 to 1.07). Women treated with CC had a significantly thinner EMT than women treated with gonadotrophins (two studies, MD: -0.33, 95% CI: -0.64 to -0.01). There was no evidence of a difference in EMT when comparing CC with letrozole (five studies, MDrandom: -0.84, 95% CI: -1.97 to 0.28). The combination of CC plus gonadotrophins resulted in a slightly thinner endometrium than letrozole (nine studies, MDrandom: -0.79, 95% CI: -1.37 to -0.20). Letrozole resulted in a thinner EMT than gonadotrophins (two studies, MDrandom: -1.31, 95% CI: -2.08 to -0.53). The overall quality of the included studies was low to moderate. We found considerable to substantial heterogeneity in the comparisons, hampering firm conclusions. We found no evidence for an association between EMT and pregnancy rates during IUI -OS. As a consequence, canceling IUI cycles because of a thin endometrial lining may negatively affect clinical care. Although we found some evidence for very small differences in EMT when comparing various drugs, we cannot make inferences on their effect on pregnancy chances since these differences may be coincidental. None. N/A.

Biomarkers in adult asthma: a systematic review of 8-isoprostane in exhaled breath condensate

Objectives. We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. Design. A systematic review and meta-analysis of EBC 8-isoprostane. Methods. We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2. Results. We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane levels in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies were appropriate for inclusion in a random effects meta-analysis of mean difference. This found a statistically significant between-groups difference of 22 pg ml−1. Confidence in the result is limited by the small number of studies and by substantial statistical heterogeneity (I2 = 94). Conclusion. The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It is essential to develop a robust and standardised methodology if the use of EBC 8-isoprostane in asthma is to be properly evaluated.

PP030 Socioeconomics Of Cardiac Rehabilitation: A Meta-Analysis

INTRODUCTION:The Guidelines for Rehabilitation in Patients with Cardiovascular Disease recommends convalescent cardiac rehabilitation (CR) as the standard treatment for patients with ST elevation myocardial infarction (STEMI) (class I, evidence level B) (1). However, health economic evaluation of cardiac rehabilitation (CR) is limited.METHODS:This systematic review, meta-analysis study elucidated the cost-effectiveness of CR in the short term. The target population in this study included convalescent and comprehensive CR patients with coronary artery disease (CAD), most with myocardial infarction (MI). We used mortality, life years (LY, expected life years), medical costs, and cost-effectiveness as the evaluation parameters in this analysis. We set medical costs in the analysis associated with testing, diagnosis, and treatment during the observation period related to CR. For cost-effectiveness analysis, we analyzed medical cost per LY. We examined the differences in effects for two comparisons (CR versus Usual Care, UC) using the Risk Ratio (RR) and Standardized Mean Difference (SMD). We assumed the standard deviation (SD) of cost effectiveness in this study by applying the error propagation.RESULTS:We reviewed fifty-nine studies and identified three that matched our selection criteria. The studies had the following characteristics: two randomized clinical trials and one systematic review/meta-analysis; a control that does not include exercise in patients with CAD; an observation period longer than 1 year; adapting medical costs, LY, cost/LY, and mortality as the evaluation index. In total, 129,272 patients were included. Meta-analysis results revealed that the CR arm significantly improved LY (SMD: -.78, 95 percent Confidence Interval (CI): -1.37, -.19) compared with UC. Similar to LY, the CR arm significantly improved the mortality (SMD: .57, 95 percent CI: .22, 1.47) compared with UC arm. Since medical costs showed a high tendency (SMD:.02, 95 percent CI: -.08, .13), cost/LY demonstrated no improvement (SMD: .00; 95 percent CI: -.17, .18). Substantial statistical heterogeneity was observed between the studies with respect to LY and cost/LY.CONCLUSIONS:While sufficient evidence to conclude health economic efficiency is not available at present, these results suggest that CR is not potentially cost-effective in the short term.

School-based education programmes for the prevention of unintentional injuries in children and young people.

School-based education programmes for the prevention of unintentional injuries in children and young people.

Diabetes mellitus and long-term mortality of ovarian cancer patients. A systematic review and meta-analysis of 12 cohort studies.

Ovarian cancer (OC) is the sixth most common cancer among women, and its prognosis is not favorable. Diabetes mellitus (DM) is hypothesized to be associated with a higher mortality in ovarian cancer patients, but evidence is inconsistent. Thus, we aim to investigate if DM is associated with the long-term all-cause and long-term cancer-specific mortality in ovarian cancer patients by synthesizing available epidemiologic evidences. We used 4 electronic databases (PubMed, EMBASE, Web of Science, and Scopus) to search for eligible articles. Title/abstract screening, full-text review, data extraction, and quality assessment were performed by reviewers independently. In meta-analysis, studies reporting risk ratio (RR) or hazard ratio that investigated the association between DM and mortality of OC patients were synthesized by a random-effect model. Subgroup and sensitivity analyses were performed by certain stratification or restrictive rules. Publication bias was assessed by funnel plots and Egger test. Statistical heterogeneity was evaluated by the I-squared value and a chi-squared test for the Cochrane Q statistic. Twelve cohort studies involving 14 outcome measures were included. In overall meta-analysis, the synthesized RR for all-cause mortality was 1.44 (95% CI 1.16-1.79) without substantial statistical heterogeneity (PCochrane =.145, I2 =34.1%); the synthesized RR for cancer-specific mortality was 1.44 (95% CI 1.08-1.93) with substantial heterogeneity (PCochrane <.001, I2 =90.1%). No publication bias was observed. Our results suggest DM is associated with a higher all-cause and cancer-specific mortality in ovarian cancer patients. Future studies should be done to examine the association between type 1 DM and ovarian cancer mortality.

Can Aspirin Reduce the Risk of Endometrial Cancer?: A Systematic Review and Meta-analysis of Observational Studies.

Current evidences suggest that nonsteroidal anti-inflammatory drugs can reduce the risk of several types of cancer, including breast, prostate, and colorectal cancer. However, evidences regarding the chemopreventive effect of aspirin to endometrial cancer are inconsistent. Therefore, we aimed to further explore the association. We searched PubMed, EMBASE, Web of Science, and Scopus to identify potentially eligible studies. After title/abstract screening and full-text review, we identified 7 cohort studies and 6 case-control studies. Data extraction and quality assessment were performed independently, and a random-effects model was used for data synthesis. Subgroup analysis was conducted based on obesity, hormone replacement therapy use, and cancer subtype; sensitivity analysis was conducted by pooling risk ratios of the highest dosage or longest duration of use. Dose-response relationship was assessed by a 2-stage linear dose-response model. Statistical heterogeneity was assessed by the I value and a χ test for the Cochrane Q statistic. In overall meta-analysis, the pooled risk ratio was 0.93 (95% confidence interval, 0.88-0.99), and no substantial statistical heterogeneity was observed (I = 0.0%, P = 0.550). In subgroup analysis, a negative association was observed for obese women and type I endometrial cancer. Higher dosage or frequency of aspirin use was significantly associated with a reduced risk, and long-term aspirin use was protective only for obese women. In conclusion, our study suggests that the use of aspirin can reduce the risk of endometrial cancer, particularly for obese women. However, the generalizability of our conclusion should be further studied for premenopausal women and type II endometrial cancer.

Is maternal smoking during pregnancy associated with an increased risk of congenital heart defects among offspring? A systematic review and meta-analysis of observational studies

Objective: To investigate the association between maternal smoking during pregnancy and risk of congenital heart defects (CHDs) among offspring.Methods: PubMed, EMBASE, and Web of Science were searched for eligible studies. The outcomes of interest included risk of any CHD and nine subtypes. We summarized study characteristics and used a random-effects model in meta-analysis, and a two-stage dose–response model was utilized to assess the association between smoking consumption and risk. Statistical heterogeneity was assessed by a chi-squared test of the Cochrane Q statistic and I-squared value. Publication bias was assessed by funnel plots and Egger’s test, and trim and fill method was utilized when publication bias existed.Results: Forty-three observational epidemiologic studies were included. The pooled risk ratio (RR) of any CHD was 1.11 (95% CI: 1.04, 1.18), but it exhibited substantial statistical heterogeneity (p < 0.001, I2 = 69.0%). In sensitivity analysis, we observed significant associations for atrial septal defect (ASD) and marginally significant associations for septal defects (SPD). The two-stage dose–response analysis showed evidence to support that higher levels of tobacco smoke was associated with an increased risk of septal defects, particularly for ASD and VSD (ventricular septal defect).Conclusion: Our study presents evidence to support the cardiovascular teratogenic effect of maternal smoking during pregnancy, and their offspring may suffer from approximately a 10% relative increase in the risk of CHDs on average.

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles.

For the last few decades urinary human chorionic gonadotrophin (uhCG) has been used to trigger final oocyte maturation in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Recombinant technology has allowed the production of two drugs, recombinant human chorionic gonadotrophin (rhCG) and recombinant luteinising hormone (rLH), that can be used for the same purpose, to mimic the endogenous luteinising hormone (LH) surge. This allows commercial manufacturers to adjust production according to market requirements and to remove all urinary contaminants, facilitating the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, it is necessary to compare the effectiveness of the recombinant drugs to the currently used urinary human chorionic gonadotrophin (uhCG). To assess the effects of subcutaneous rhCG and high dose rLH versus uhCG for inducing final oocyte maturation in subfertile women undergoing IVF and ICSI cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE (1946 to April 2015), EMBASE (1980 to April 2015) and PsycINFO (1806 to April 2015) as well as trial registers at ClinicalTrials.gov on 13 May 2015 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal on 14 May 2015. Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. We included randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normogonadotropic women. Two authors independently performed assessment for inclusion or exclusion, quality assessment and data extraction. We discussed any discrepancies in the presence of a third author to reach a consensus. The primary review outcomes were ongoing pregnancy/live birth and incidence of ovarian hyperstimulation syndrome (OHSS). Clinical pregnancy, miscarriage rate, number of oocytes retrieved and adverse events were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) and assessed statistical heterogeneity using the I(2) statistic. We evaluated the overall quality of the evidence for the main comparisons using GRADE methods. We included 18 RCTs involving 2952 participants; 15 compared rhCG with uhCG, and 3 compared rhLH with uhCG. The evidence for different comparisons ranged from very low to high quality: limitations were poor reporting of study methods and imprecision. Pharmaceutical companies funded 9 of the 18 studies, and 5 studies did not clearly report funding source. Ongoing pregnancy/live birthThere was no conclusive evidence of a difference between rhCG and uhCG (OR 1.15, 95% CI 0.89 to 1.49; 7 RCTs, N = 1136, I(2) = 0%, moderate quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.51 to 1.78, 2 RCTs, N = 289, I(2) = 0%, very low quality evidence) for ongoing pregnancy/live birth rates. OHSS There was no evidence of a difference between rhCG and uhCG in the incidence of OHSS: moderate to severe OHSS (OR 1.76, 95% CI 0.37 to 8.45; 3 RCTs, N = 417, I(2) = 0%, low quality evidence), moderate OHSS (OR 0.78, 95% CI 0.27 to 2.27; 1 RCT, N = 243, I(2) = 0%, low quality evidence), mild to moderate OHSS (OR 1.00, 95% CI 0.42 to 2.38; 2 RCTs, N = 320, I(2) = 0%, low quality evidence) or undefined OHSS (OR 1.18, 95% CI 0.50 to 2.78; 3 RCTs, N = 495, I(2) = 0%, low quality evidence). Likewise, there was no evidence of a difference between rhLH and uhCG in OHSS rates for moderate OHSS (OR 0.82, 95% CI 0.39 to 1.69, 2 RCTs, N = 280, I(2) = 5%, very low quality evidence). Other adverse events There was no evidence of a difference in miscarriage rates between rhCG and uhCG (OR 0.72, 95% CI 0.41 to 1.25; 8 RCTs, N = 1196, I(2) = 0%, low quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.38 to 2.40; 2 RCTs, N = 289, I(2) = 0%, very low quality evidence). For other adverse effects (most commonly injection-site reactions) rhCG was associated with a lower number of adverse events than uhCG (OR 0.52, 95% CI 0.35 to 0.76; 5 RCTS, N = 561; I(2) = 67%, moderate quality evidence). However, when we used a random-effects model due to substantial statistical heterogeneity, there was no evidence of a difference between the groups (OR 0.56, 95% CI 0.27 to 1.13). Only one study comparing rLH and uhCG reported other adverse events, and it was impossible to draw conclusions. We conclude that there is no evidence of a difference between rhCG or rhLH and uhCG for live birth or ongoing pregnancy rates or rates of OHSS.