Statistical Tests For Heterogeneity Research Articles

Malignant Transformation Rate of Oral Submucous Fibrosis: A Systematic Review and Meta-Analysis.

Oral submucous fibrosis (OSF) is a chronic progressive condition affecting the oral cavity, oropharynx and upper third of the oesophagus. It is a potentially malignant disorder. The authors collated and analysed the existing literature to establish the overall malignant transformation rate (MTR). A retrospective analysis of medical and dental scientific literature using online indexed databases was conducted for the period 1956 to 2021. The quality of the enrolled studies was assessed by the Newcastle-Ottawa Scale (NOS). A meta-analysis using a random effects model of a single proportion was performed along with statistical tests for heterogeneity. The overall proportion of malignancy across all studies was 0.06 (95% CI, 0.02–0.10), indicating an overall 6% risk of malignant transformation across all studies and cohorts. Sub-group analyses revealed strong differences in proportion of malignancy according to ethnicity/cohort; Chinese = 0.02 (95% CI 0.01–0.02), Taiwanese = 0.06 (95% CI, 0.03–0.10), Indian = 0.08 (95% CI, 0.03–0.14) and Pakistani = 0.27 (95% CI 0.25–0.29). Overall, the MTR was 6%; however, wide heterogeneity of the included studies was noted. Geographic variations in MTR were noted but were not statistically significant. Further studies are required to analyse the difference between cohort groups.

All-Cause Mortality Outcomes of Usage of Cardiac Contractility Modulation in Patients With Dilated Cardiomyopathy Ineligible for Cardiac Re-Synchronization Therapy: An Updated Meta-Analysis of Randomized Controlled Trials.

IntroductionDilated cardiomyopathy has been associated with remarkably high mortality despite guideline-directed therapy. This study compares the all-cause mortality rate between a cardiac contractility modulation group and a standard therapy group in patients with dilated cardiomyopathy who were monitored via follow-up for 12 weeks or more.Materials and methodsWe conducted a systematic search of Medline (PubMed) and Cochrane Central Register of Controlled Trials for abstracts and fully published studies (from inception to October 2018). We searched for articles comparing cardiac contractility modulation device therapy with standard therapy for patients with dilated cardiomyopathy between September 1, 2018, and October 30, 2018.Only fully published randomized clinical trials comparing all-cause mortality outcomes of device therapy and standard therapy for patients with dilated cardiomyopathy were included in our meta-analysis. A total of 673 studies were identified. Studies that were systematic reviews or meta-analyses, study designs or protocols, trials on other regimens, wherein medical therapy was not compared, or wherein the primary outcome of mortality was not assessed, were excluded.Data were abstracted by two independent reviewers. A random-effect model using the Mantel-Haenszel method calculated the weighted risk ratio (RR). Statistical analyses were performed using Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen). The primary outcome of interest was a comparison of all-cause mortality between the two groups when patients were monitored via follow-up for 12 weeks or more.ResultsFour fully published randomized clinical trials met the inclusion criteria of our analysis. A random-effect model using the Mantel-Haenszel method calculated the weighted RR. Our analysis included a total of 930 patients. The cardiac contractility modulation therapy group showed no significant reduction in all-cause mortality compared to the standard therapy group (RR, 0.63; 95% CI, 0.29-1.35; P = .23). However, the trend was toward device therapy. Tests for statistical heterogeneity did not show any significant heterogeneity (P = .82, I2 = 0%).ConclusionsCardiac contractility modulation device therapy is not associated with significant all-cause mortality reduction in patients with dilated cardiomyopathy. Our meta-analysis underscores the need for a large randomized controlled trial on the efficacy of cardiac contractility modulation in a population with dilated cardiomyopathy who are ineligible for cardiac resynchronization therapy.

Efficacy of carboplatin-based chemotherapy regimens in patients with bladder cancer in the neoadjuvant setting.

e17001 Background: There is paucity of evidence regarding efficacy of neoadjuvant chemotherapy regimens in bladder cancer patients. Radical cystectomy has been standard of care for patients with T2-T4, N0, M0 bladder cancer. However, recent trials have shown better survival rates in patients who underwent neo-adjuvant chemotherapy. Our meta-analysis is based on the data from non-randomized clinical trials on the efficacy of carboplatin based regimens. Methods: We conducted a systematic search of Medline (Pubmed) and Cochrane (from inception through May, 2018). Only published single arm clinical trials, abstracts of single arm clinical trials and data from one randomized trial on efficacy of neoadjuvant Carboplatin based therapies in patients with bladder cancer were included in our meta-analysis. Total of > 70 studies were identified. Studies which were duplicate, included adjuvant therapy, systematic reviews or meta-analysis, trials not based on neoadjuvant therapy were excluded. A random effect model was used to calculate pooled proportions. Studies based on ITT protocol were analyzed separately as well as studies based on per protocol analysis. Comprehensive Meta-Analysis software version 3.0 was used. Results: The pooled proportion of pCR (pathologic complete response) calculated from trials based on ITT analysis was 0.23 (95% CI 0.19 to 0.28, P= 0.000). Tests for statistical heterogeneity was non-significant heterogeneity p-value = 0.79 (I2 = 0 %). The pooled proportion of pCR calculated from trials based on per-protocol analysis was 0.29 (95% CI 0.19 to 0.42, P= 0.002). Tests for statistical heterogeneity show nonsignificant heterogeneity p-value = 0.95 (I2 = 0 %). The pooled proportion of ORR (objective response rate) calculated from trials based on per-protocol analysis was 0.69 (95% CI 0.57 to 0.78, P= 0.001). Tests for statistical heterogeneity showed heterogeneity p-value = 0.203 (I2 = 37.3). The pooled proportion of cCR (clinical Complete response) calculated from trials based on per-protocol analysis was 0.25 (95% CI 0.18 to 0.34, P= 0.000). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.80 (I2 = 0%). The pooled proportion of cPR (clinical Partial Response) calculated from trials based on per-protocol analysis was 0.47 (95% CI 0.39 to 0.56, P= 0.59). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.93 (I2 = 0%). Conclusions: Carboplatin based chemotherapy has shown significant efficacy in terms of over-all response rate, pathologic complete response and clinical complete response.

PCV4 MEDICAL CANNABIS USE AND RISK OF CARDIOVASCULAR TOXICITY: A TWO-STAGE SYSTEMATIC REVIEW AND META-ANALYSIS

Recent evidence has demonstrated the potential benefits of cannabis in various indications. However, serious cardiovascular (CV) events have been reported with recreational use but little is known about safety issues with medical use. This study aims to investigate the extent of cannabis-associated CV events reported among randomized controlled trials (RCT). A two-stage systematic review (SR) approach was undertaken. First, we searched for SRs of cannabis in PubMed, EMBASE, CENTRAL, and AMED until June 2019. Second, RCTs identified from SRs were included if they were RCT assessing medical cannabis and reporting CV events. The outcomes of interest were all types of CV events. Data were extracted by two independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios and 95% Confidence Intervals (Cis) were calculated using a random-effects model. A total of 142 SRs including 897 RCTs met the first-stage review. In the second stage, 51 studies involving 5,087 patients were included. The median duration of cannabis use was 1.3 weeks (range 0.1 to 46) and 47% of studies excluded patients with underlying cardiovascular diseases. Cannabis use was significantly associated with increased risks of orthostatic hypotension (RR 3.16; 95% CI 2.27 to 4.40; I2 = 2.3%), and hypotension (RR 3.55; 95% CI 1.45 to 8.71; I2 = 31.8%) with a trend of increased risk of tachycardia (RR 2.08; 95% CI 0.90 to 4.81; I2 = 46%). No study reported sudden cardiac arrest, acute coronary syndrome, or heart failure. There is a paucity of evidence of serious CV events among medical cannabis users. This might be due to the low CV risk population or short study duration. This warrants future studies to investigate CV risk among medical cannabis users especially those with CV diseases.

P1662All cause mortality outcomes of various types of stem cell therapies in patients with dilated cardiomyopathy: an updated meta analysis and systematic review

Abstract Background Dilated Cardiomyopathy (ischemic and non-ischemic) has been associated with very high mortality despite maximal medical and device therapy. Recently, several clinical trials involving different types of stem cells for the management of dilated cardiomyopathy have shown significant improvement in cardiac function, however, these studies were not powered to calculate mortality benefit. A previous meta analysis included 17 randomized controlled trials, however, there has been new randomized trials published since last meta analysis, hence the need for an updated meta analysis. Purpose Comparison of all cause mortality rate between stem cell therapy group and standard therapy group in patients with Dilated Cardiomyopathy followed for 12 months or more. Methods We conducted a systematic search of Medline (Pubmed) and Cochrane Central Register of Controlled Trials for abstracts and fully published studies (from inception through April, 2018) comparing various types of stem cell therapies with standard of therapy for patients with dilated cardiomyopathy (ischemic and non-ischemic). Study selection Only fully published randomized clinical trials and abstracts of randomized trials comparing all cause mortality outcomes of various types of stem cell therapies and standard therapy for patient with dilated cardiomyopathy (ischemic and non-ischemic) followed over a period of 12 or more months were included in our meta-analysis. Total of 1392 studies were identified. Studies which were duplicate, non-randomized, included pediatric population, systematic reviews or meta-analysis, study designs or protocols, trials including gene therapy or had follow up of patients for less than 12 months were excluded. Data extraction and Synthesis: Data were abstracted by two independent reviewers. Using Mantel-Haenszal method, a random effect model was used to calculate weighted Risk ratio (RR). RevMan 5.3 was used for statistical analyses. Results Twenty eight fully published randomized clinical trials and one abstract of randomized controlled trial met inclusion criteria of our analysis. Using Mantel-Haenszel method, a random effect model was used to calculate the weighted risk ratios. Our analysis included a total of 1662 patients. Stem cell therapy group showed significant reduction in mortality compared to standard therapy group (risk ratio [RR], 0.68; 95% confidence interval, 0.53–0.87) Fig 1. Tests for statistical heterogeneity did not show any significant heterogeneity p-value = 0.80 (I2 = 0%). Limitations of our study include selection, attrition and performance biases in the included studies. Fig 2 shows distribution of the included studies. Conclusion Stem cell therapy is associated with significant mortality reduction in patients with dilated cardiomyopathy (ischemic and non-ischemic). Our meta-analysis underscores the importance of conducting large randomized clinical trial to assess the mortality outcomes of stem cell therapy.

Integrated models of care for diabetes and hypertension in low- and middle-income countries (LMICs)\xa0: Protocol for a systematic review

BackgroundIn low- and middle-income countries (LMICs), the burden of non-communicable diseases (NCDs) is growing against an existing burden of other diseases such as HIV/AIDS. Integrated models of care can help address the rising burden of multi-morbidity. Although integration of care can occur at various levels and has been defined in numerous ways, our aim is to assess the effects of integration of service delivery at primary healthcare level in LMICs.MethodsWe will consider randomised controlled trials (RCTs), cluster RCTs, non-randomised trials, controlled before-after studies and interrupted time series that examine integrated models of care among people with multi-morbidities, of which diabetes or hypertension is one, living in LMICs. We will compare fully integrated models of care to stand-alone care, partially integrated models of care to stand-alone care and fully integrated models to partially integrated models of care. Primary outcomes include all-cause mortality, disease-specific morbidity, HbA1c, systolic blood pressure and cholesterol levels. Secondary outcomes include access to care, retention in care, adherence, continuity of care, quality of care and cost of care. We will conduct a comprehensive search in the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Control Trials, LILACS, Africa-Wide Information, CINAHL and Web of Science. In addition, we will search trial registries, relevant conference abstracts and check references lists of included studies. Selection of studies, data extraction and assessment of risk of bias will be performed independently by two review authors. We will resolve discrepancies through discussion with a third author. We will contact study authors in case of missing data. If included studies are sufficiently homogenous, we will pool results in a meta-analysis. Clinical heterogeneity related to the population, intervention, outcomes and context will be documented in table format and explored through subgroup analysis. We will assess χ2and I2 tests for statistical heterogeneity. We will use GRADE to make judgements about the certainty of evidence and present findings in a summary of findings table.DiscussionIn light of limited evidence on the provision of comprehensive care for diabetes and hypertension, and its comorbidity in LMCIs, we believe that the findings of this systematic review will provide a synthesis of evidence on effective models of integrated care for diabetes and hypertension and their comorbidities at primary healthcare level. This will enable policy-makers to device policies and programs that are evidence informed.Systematic review registrationPROSPERO CRD42018099314.

PROTOCOL: Mass deworming for improving health and cognition of children in endemic helminth areas: a systematic review and individual participant data network meta-analysis.

PROTOCOL: Mass deworming for improving health and cognition of children in endemic helminth areas: a systematic review and individual participant data network meta-analysis.

Comparison of Adenoma Detection Rate (ADR) in Split Dose versus Day Before Colonoscopy Preparation: A Systemic Review and Meta-Analysis

Introduction: Split dose preparation (SDP) has been shown to have a superior bowel cleansing effect compared day before preparation (DBP) for screening colonoscopy in previous trials. Most of these studies reported bowel cleanliness as primary outcome. Compared to assessment of bowel cleansing which inherently has certain degree of subjective component, adenoma detection rate (ADR) is more objective and relevant parameter when it comes to colonoscopy for cancer screening. Unlike bowel cleanliness, increased ADR has been directly linked to colon cancer survival rate[1]. A recent study estimated that higher adenoma detection rate is inversely related to Colon Cancer mortality[2]. A previously done meta-analysis which compared ADR as a secondary outcome of interest included two trials and did not show a statistically significant difference between the two preparation methods[3]. In the light of new available evidence, we wanted to compare ADR between the two groups. Methods: On May 17,2017 we conducted a systematic search of Medline, EMBASE, Web of Science Collection databases and the Cochrane Central Register of Controlled Trials for abstracts and fully published studies comparing day before versus split dose colonoscopy regimens. Both fully published randomized clinical trials and abstracts of unpublished trials were included in our meta-analysis. Studies which were non-randomized, included pediatric population or compared different preparation regimens in two groups were excluded. The primary outcome of interest was comparison of adenoma detection rate (ADR) between the two groups. Secondary outcome of interest was advanced adenoma detection rate between split dose and day before preparation. Using Mantel-Haenszal method, a fixed effect model was used to calculate weighted odds ratio (OR). Duval and Tweedie's trim and fill test was used to detect any publication bias. RevMan 5.3 and CMA version 3.0 was used for statistical analyses. Results: Five fully published randomized clinical trials and one abstract of randomized trial met inclusion criteria of our analysis. Using Mantel-Haenszel method, a fixed effect model was used to calculate the weighted effect size. Our analysis included a total of 2033 patients. Split dose preparation showed significantly higher adenoma detection rate (ADR) compared to day before group (odds ratio [OR], 1.58; 95% confidence interval, 1.32- 1.90). Tests for statistical heterogeneity did not show any significant heterogeneity P-value=0.52 (I2=0 %). After adjustment for publication bias using Trim and Fill test, our analysis showed adjusted OR of 1.56; 95% confidence interval, 1.30-1.88. In secondary analysis, split dose preparation had significantly higher advanced adenoma detection rate compared to day before preparation (OR 1.46; 95% confidence interval, 1.14-1.89). Conclusion: Based on our meta-analysis, split dose colonoscopy preparation has significantly higher adenoma detection rate (ADR) compared to traditional day before preparation.Figure: Forrest Plot of Adenoma Detection Rate (ADR) in Split Dose Vs Day Before Colonoscopy Preparation.Figure: Funnel Plot of Adenoma Detection Rate (ADR) in Split Dose Vs Day Before Colonoscopy Preparation.

Accuracy of high b-value diffusion-weighted MRI for prostate cancer detection: a meta-analysis.

Background The diagnostic accuracy of diffusion-weighted imaging (DWI) to detect prostate cancer is well-established. DWI provides visual as well as quantitative means of detecting tumor, the apparent diffusion coefficient (ADC). Recently higher b-values have been used to improve DWI's diagnostic performance. Purpose To determine the diagnostic performance of high b-value DWI at detecting prostate cancer and whether quantifying ADC improves accuracy. Material and Methods A comprehensive literature search of published and unpublished databases was performed. Eligible studies had histopathologically proven prostate cancer, DWI sequences using b-values ≥ 1000 s/mm2, less than ten patients, and data for creating a 2 × 2 table. Study quality was assessed with QUADAS-2 (Quality Assessment of diagnostic Accuracy Studies). Sensitivity and specificity were calculated and tests for statistical heterogeneity and threshold effect performed. Results were plotted on a summary receiver operating characteristic curve (sROC) and the area under the curve (AUC) determined the diagnostic performance of high b-value DWI. Results Ten studies met eligibility criteria with 13 subsets of data available for analysis, including 522 patients. Pooled sensitivity and specificity were 0.59 (95% confidence interval [CI], 0.57-0.61) and 0.92 (95% CI, 0.91-0.92), respectively, and the sROC AUC was 0.92. Subgroup analysis showed a statistically significant ( P = 0.03) improvement in accuracy when using tumor visual assessment rather than ADC. Conclusion High b-value DWI gives good diagnostic performance for prostate cancer detection and visual assessment of tumor diffusion is significantly more accurate than ROI measurements of ADC.

Does the addition of biologic agents to chemotherapy in patients with unresectable colorectal cancer metastases result in a higher proportion of patients undergoing resection? A systematic review and meta-analysis.

690 Background: The likelihood of converting unresectable metastatic colorectal cancer (CRC) to operable disease with systemic therapy is unknown. The purpose of this study was to determine the proportion of patients with unresectable CRC metastases that become resectable on combination systemic therapy, and whether biologic agents (antiantiogenics, anti-EGFR and multitargeted agents) improve the rate of resection (primary outcome). Methods: We searched Medline, Embase, CENTRAL and PubMed for randomized controlled trials comparing chemotherapy and biologics (intervention) vs. combination chemotherapy alone (control) in patients with unresectable CRC metastases. Study selection, data abstraction, risk of bias and quality of the evidence assessment were carried out in duplicate. Secondary outcomes included overall survival (OS) and progression free survival (PFS). Risk of bias was assessed using the Cochrane tool. Statistical heterogeneity was calculated using chi-squared and I2. Clinical heterogeneity was explored via subgroup analyses. The quality of the evidence was assessed using GRADE. Protocol was published in PROSPERO. Results: Of 7954 abstracts retrieved, 12 studies were analyzed and 8 reported the primary outcome, with 2604 intervention and 2661 control patients. The proportion of patients resected was higher in the intervention group, Relative Risk 1.36, 95% confidence interval (CI) 1.08-1.69, p = 0.008. The absolute risk of undergoing resection was 48 per 1000 (control); compared to 65 per 1000 (intervention). There was no difference in OS, Hazard Ratio (HR) 0.91, 95% CI 0.82-1.01. PFS was better in the intervention group (HR 0.83, 95% CI 0.74-0.92). Overall the risk of bias for the included studies was low. Statistical test for heterogeneity was low (I2 was 0%, p = 0.72). There was significant clinical heterogeneity, which was not explained with subgroup analyses. The quality of the evidence (GRADE) was moderate. Conclusions: The addition of biologic agents to systemic chemotherapy in patients with unresectable CRC metastasis improves resectability and PFS but not OS.

Betahistine for symptoms of vertigo.

Vertigo is a symptom in which individuals experience a false sensation of movement. This type of dizziness is thought to originate in the inner ear labyrinth or its neural connections. It is a commonly experienced symptom and can cause significant problems with carrying out normal activities. Betahistine is a drug that may work by improving blood flow to the inner ear. This review examines whether betahistine is more effective than a placebo at treating symptoms of vertigo from different causes. To assess the effects of betahistine in patients with symptoms of vertigo from different causes. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. We also contacted manufacturers and researchers in the field. The date of the search was 21 September 2015. We included randomised controlled trials of betahistine versus placebo in patients of any age with vertigo from any neurotological diagnosis in any settings. We used the standard methodological procedures expected by Cochrane. Our primary outcome was the proportion of patients with reduction in vertigo symptoms (considering together the intensity, frequency and duration those symptoms). We included 17 studies, with a total of 1025 participants; 12 studies were published (567 patients) and five were unpublished (458 patients). Sixteen studies including 953 people compared betahistine with placebo. All studies with analysable data lasted three months or less. The majority were at high risk of bias, but in some the risk of bias was unclear. One study, at high risk of bias, included 72 people with benign paroxysmal positional vertigo (BPPV) and compared betahistine with placebo; all patients also had particle repositioning manoeuvres. The studies varied considerably in terms of types of participants, their diagnoses, the dose of betahistine and the length of time it was taken for, the study methods and the way any improvement in vertigo symptoms was measured. Using the GRADE system, we judged the quality of evidence overall to be low for two outcomes (proportion of patients with improvement and proportion with adverse events).Pooled data showed that the proportion of patients reporting an overall reduction in their vertigo symptoms was higher in the group treated with betahistine than the placebo group: risk ratio (RR) 1.30, 95% confidence interval (CI) 1.05 to 1.60; 606 participants; 11 studies). This result should be interpreted with caution as the test for statistical heterogeneity as measured by the I(2) value was high.Adverse effects (mostly gastrointestinal symptoms and headache) were common but medically serious events in the study were rare and isolated: there was no difference in the frequency of adverse effects between the betahistine and placebo groups, where the rates were 16% and 15% respectively (weighted values, RR 1.03, 95% CI 0.76 to 1.40; 819 participants; 12 studies).Sixteen per cent of patients from both the betahistine and the placebo groups withdrew (dropped out) from the studies (RR 0.96, 95% CI 0.65 to 1.42; 481 participants; eight studies).Three studies looked at objective vestibular function tests as an outcome; the numbers of participants were small, techniques of measurement very diverse and reporting details sparse, so analysis of this outcome was inconclusive.We looked for information on generic quality of life and falls, but none of the studies reported on these outcomes. Low quality evidence suggests that in patients suffering from vertigo from different causes there may be a positive effect of betahistine in terms of reduction in vertigo symptoms. Betahistine is generally well tolerated with a low risk of adverse events. Future research into the management of vertigo symptoms needs to use more rigorous methodology and include outcomes that matter to patients and their families.

Manual perineal support at the time of childbirth: a systematic review and meta-analysis.

Genital tract trauma is common with vaginal births and is associated with significant morbidity, particularly with obstetric anal sphincter injuries (OASIS). Debate continues regarding the effectiveness of perineal support during childbirth in reducing the risk of trauma. This review aimed to assess the effect of routine 'hands on'/manual perineal support (MPS) during childbirth, versus ad hoc/no perineal support ('hands off/poised'), on the risk and degree of perineal trauma. This review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007058). We searched the CENTRAL, Embase, Medline, CINAHL, and OVIDs midwifery and infant care databases (from inception to December 2014). Published randomised controlled trials (RCTs) and non-randomised studies (NRSs) evaluating any 'hands on' perineal support technique during childbirth. Two reviewers independently assessed trials for inclusion, data extraction, and methodological quality. Discrepancies were resolved by discussion with a third reviewer. We included five RCTs and seven NRSs in the review. Meta-analysis of RCTs did not demonstrate a statistically significant protective effect of MPS on the risk of OASIS (three studies, 6647 women; relative risk, RR 1.03; 95% confidence interval, 95% CI 0.32-3.36; statistical test for heterogeneity I(2) = 71%). Meta-analysis of NRSs showed a significant reduction in the risk of OASIS with MPS (three studies, 74,744 women; RR 0.45; 95% CI 0.40-0.50; I(2) = 32%). Current evidence is insufficient to drive change in practice. An adequately powered randomised trial with an efficient design to evaluate the complex interventions adopted as part of MPS policies, ensuring controlled childbirth, is urgently needed.

Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women.

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2-)], Luminal B (HER2+), HER2 subtype, basal-like phenotype (BP) and five-negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend , 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend , 0.002), Luminal B (HER2-) (ptrend , 0.02), Luminal B (HER2+) (ptrend , 0.06), and also for the HER2 subtype (ptrend , 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.

Analyzing 395,793 samples shows significant association between rs999737 polymorphism and breast cancer.

Large-scale genome-wide association studies (GWAS) have been conducted and reported the association between rs999737 polymorphism at 14q24.1 (RAD51L1) and breast cancer risk. Following studies investigated rs999737 polymorphism in European and Asian populations. However, some of these studies reported weak and no significant association. Here, we reevaluated this association using large-scale samples from previous 11 studies (n=395,793; 162,261 cases and 233,532 controls) from the PubMed database. We evaluated the genetic heterogeneity among the selected studies. The pooled odds ratio (OR) is calculated by the fixed effect model. All statistical tests for heterogeneity and meta-analysis were computed using R package. We did not identify significant heterogeneity among the included studies using the allele model (P=0.1314 and I (2)=33.4 %). We observed significant association between rs999737 and breast cancer using the allele model (P=2.47E - 35, OR=0.92, 95 % confidence interval (CI) 0.91-0.93). Our analysis further supports previous findings that the rs999737 polymorphism contributes to breast cancer susceptibility. We believe that our finding will be very useful for future genetic studies in breast cancer.

Mineral trioxide aggregate versus formocresol pulpotomy: a systematic review and meta-analysis of randomized clinical trials

This study systematically reviewed randomized clinical trials (RCTs) investigating the effectiveness of primary molar pulpotomies with mineral trioxide aggregate (MTA) and formocresol. The study also aimed to assess the possible association of reported prognostic factors on the success rate and relative risk using meta-regression analysis. A comprehensive literature search using Medline, EMBASE, and Cochrane Central databases up to March 2013 was conducted. After scoring and data extraction of qualified trials (n = 19, representing 1,585 patients), meta-analyses were performed using Mantel-Haenszel model and inverse variance-weighted method. The results revealed that MTA is more effective than formocresol in primary molars pulpotomy, resulting in a lower failure rate with a relative risk of 0.26 (CI, 0.13-0.49), 0.37 (CI, 0.19-0.70), and 0.41 (CI, 0.25-0.68) for 6-, 12-, and 24-month follow-ups (test for statistical heterogeneity: p = 0.99, p = 0.98, and p = 0.23), respectively. Compared to amalgam restoration, success rate was significantly greater with SS crown (P < 0.05); however, no evidence for association between other reported prognostic factors such as selection of first/second molar, upper/lower jaw, gender, and various follow-up times with treatment success was observed. Based on the quality, homogeneity, and sufficient number of included RCTs, primary molar pulpotomy with MTA can produce a higher success rate in comparison with formocresol. When compared with formocresol, MTA pulpotomy is superior in treating primary molars.

Occupational exposure to methylene chloride and risk of cancer: a meta-analysis

We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied. We summarized data from five cohort studies and 13 case-control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin's lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of heterogeneity among the studies (I (2) = 26.9 %, p = 0.205). We found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia that have shown weak effects should be investigated further.

Belimumab: a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis

ObjectivesTo undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies.MethodsWe searched eight electronic...

Looking for new strategies to combat an old foe

Looking for new strategies to combat an old foe

Important steps for a reliable meta-analysis

1 Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, the WHO-coordinated Global Rotavirus Surveillance Network. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12: 136–41. 2 Egger M, Smith GD. Bias in location and selection of studies. BMJ 1998; 316: 61–66. 3 Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007; 36: 666–76. 4 Rucker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I in assessing heterogeneity may mislead. BMC Med Res Methodol 2008; 8: 79. 5 Thompson SG. Why sources of heterogeneity in meta-analysis should be investigated. BMJ 1994; 309: 1351–55. Quality assessment is a principal part of all systematic reviews and meta-analyses, but most reported meta-analyses do not include such an assessment, or do not report the method of assessment. We would be interested to know if Tate and colleagues did a quality assessment and the method they used for critical appraisal. How the investigators reached agreement about study selection and the κ coeffi cient should also have been reported. An important question is which heterogeneity test was done: Q2, I2, or τ2? τ2 is most useful when the number of studies in the analysis is low, because it is not dependent on this variable. However, the statistical test of heterogeneity should not be the only determinant for data interpretation in meta-analyses—selection of patients and diff erent baseline diseases should also be considered when determining heterogeneity sources. Tate and colleagues did not show the number of included studies in forest plots for each country; such plots would have enabled them to chose an appropriate heterogeneity test. Funnel plots assessing publication bias should also have been included. An additional funnel plot for language bias should also be Important steps for a reliable meta-analysis

Neurokinin-1 Receptor Antagonists for Chemotherapy-Induced Nausea and Vomiting: A Systematic Review

The addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention. We systematically searched the MEDLINE, EMBASE, and CENTRAL databases, and meeting proceedings for randomized controlled trials (RCTs) that evaluated NK1R antagonists plus standard antiemetic therapy for CINV prevention. Complete response (CR) to therapy was defined as the absence of emesis and the absence of rescue therapy. The endpoints were defined as CR in the overall phase (during the first 120 hours of chemotherapy), CR in the acute phase (first 24 hours), and the delayed phase (24-120 hours) after chemotherapy, nausea, and toxicity. Subgroup analyses evaluated the type of NK1R antagonist used, the emetogenic potential of the chemotherapy regimen, and prolonged use of 5-HT3 (serotonin) receptor antagonists, a class of standard antiemetic agents. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates and publication bias were two-sided. Seventeen trials (8740 patients) were included in this analysis. NK1R antagonists increased the CR rate in the overall phase from 54% to 72% (OR = 0.51, 95% CI = 0.46 to 0.57, P < .001). CR and nausea were improved in all phases and subgroups. The expected side effects from NK1R antagonists did not statistically significantly differ from previous reports; however, this analysis suggests that the incidence of severe infection increased from 2% to 6% in the NK1R antagonist group (three RCTs with a total of 1480 patients; OR = 3.10; 95% CI = 1.69 to 5.67, P < .001). NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.