Manya Prasad

Culprit vessel versus immediate complete revascularization in patients with ST-segment myocardial infarction—a systematic review

BACKGROUND Guidelines suggest percutaneous intervention (PCI) of only the culprit artery in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, recent randomized controlled trials (RCTs) suggest benefit to performing PCI of other stenotic vessels at the same time as culprit vessel PCI. METHODS We conducted a systematic review with complete case meta-analysis and sensitivity analyses. Data sources included MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and CINAHL from 1946 to March 2014; MEDLINE and EMBASE from March 2014 to March 2015; and scanning of literature for new studies until August 2015. All RCTs comparing multivessel versus culprit-only PCI in patients with STEMI were eligible. The primary outcomes of interest were recurrent myocardial infarction (MI), recurrent revascularization, and mortality. We combined data from trials to estimate the pooled risk ratio (RR) and associated 95% CIs using random-effects models. RESULTS Five RCTs including 1,606 patients of whom 1,568 had complete data proved eligible. Multivessel revascularization was associated with decreased risk of repeat revascularization (RR 0.36, 95% CI 0.27-0.49, risk difference 9.7% over 2 years) and recurrent nonfatal MI (RR 0.58, 95% CI 0.36-0.93, risk difference 1.8% over 2 years), without increase in mortality (RR 0.82, 95% CI 0.53-1.26) or other adverse events. CONCLUSIONS Pooled data provide moderate-certainty evidence that performance of multivessel PCI will provide an appreciable reduction in nonfatal MI and high-certainty evidence that it will reduce need for repeat revascularization. Patients are likely to place a high value on these benefits.

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis

Abstract Objective: Studies on association between methylenetetrahydrofolate reductase gene (MTHFR) C677T gene polymorphism and ischemic stroke have shown conflicting results. We have conducted a meta-analysis to determine the precise association of the C677T polymorphism of MTHFR gene with risk of ischemic stroke. Materials and methods: We searched electronic databases Medline, EMBASE, and Google Scholar (last search dated till August 2014). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from random or fixed-effects models were calculated. The methodological quality of included studies was determined by the quality assessment scale. Results: Thirty eight case–control studies fulfilled our inclusion criteria comprising 6310 patients and 8297 controls. The significant associations between MTHFR C677T genetic polymorphism and risk of ischemic stroke were observed in dominant (OR, 1·09; 95% CI, 1·06–1·12, P-value < 0·001) and recessive (OR, 1·31; 95% CI, 1·19–1·44, P-value < 0·001) inheritance models. In an Asian population, significant association between the MTHFR polymorphism and ischemic stroke was observed (dominant model: OR 1·36, 95% CI 1·23–1·49 and under recessive model OR, 1·29; 95% CI, 1·15–1·45). In the Caucasian population borderline, non-significant association was observed under dominant model of inheritance (OR, 1·05; 95% CI, 0·99–1·10) but significant association was observed under the recessive model of inheritance (OR, 1·33; 95% CI, 1·13–1·58). Conclusion: The present study results suggest that MTHFR C677T genetic polymorphism is a probable risk of ischemic stroke.

Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population

Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case–control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case–control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12–3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.

Low Socioeconomic Status Is an Independent Risk Factor for Ischemic Stroke: A Case-Control Study in North Indian Population

Background: Stroke is a multifactorial disease and is influenced by complex environmental interactions. The contribution of various risk factors to the burden of stroke worldwide is not well known, particularly in developing countries. The present case-control study is aimed at exploring the association between a low socioeconomic status and the risk of ischemic stroke among the North Indian population. Methods: The study design was a hospital-based, case-control study. Age- and sex-matched controls were included. The demographic characteristics and risk factor variables were documented by means of a personal interview through a standardized case record form. The household asset index for determining the socioeconomic status (HAISS) was used for the assessment of the socioeconomic status of the population. HAISS was validated with the widely used Kuppuswamy scale for measurement of socioeconomic status. The multivariable logistic regression model was used to estimate the odds ratio associated with stroke. Results: In all, 224 ischemic stroke patients and 224 controls were recruited between February 2009 and February 2012. The mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The low economic status was independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.8; 95% CI 1.2-6.3). Conclusion: Our findings suggest that there is a significant association between a low socioeconomic status and the risk of ischemic stroke risk in North Indian population. Well-designed studies embedded with long-term prospective cohorts are required for confirming the results.

Association between Beta Adrenergic Receptor Polymorphism and Ischemic Stroke: A Meta-Analysis

Background and Purpose The purpose of this meta-analysis was to determine the precise association between beta-2 adrenergic receptor (β2AR) polymorphism and Ischemic stroke. Methods Published case control studies on association between β2AR and ischemic stroke were searched from electronic databases. Pooled Odds ratio and 95% Confidence interval were calculated by using software RevMan version 5.2. Results A total of three studies involving 1,642 cases and 1,673 controls, which were published from 2007 to 2014, were subjected to meta-analysis for allelic association and 518 cases and 510 controls for genotypic association. Pooled analysis of two studies for genotypic association suggested that subjects carrying Gln27Glu polymorphism of β2AR had an increased risk for Ischemic stroke under recessive model (OR 2.09; 95% CI; 1.20 to 3.64) and under dominant model (OR 1.47; 95% CI 1.14 to 1.90). Pooled analysis of three studies for allelic association showed a significantly higher Glu27 allele of β2AR in the patients with ischemic stroke (OR 1.58; 95% CI; 1.38 to 1.81). Conclusions The present meta-analysis suggests that Gln27Glu polymorphism of β2AR gene is associated with increased risk for ischemic stroke.

Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review

Bone marrow mononuclear cell (BM‐MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM‐MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM‐MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta‐analysis. We included non‐randomized open‐label, single‐arm and non‐randomized comparative studies or randomized controlled trials (RCTs) if BM‐MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non‐randomized comparative trials and four single‐arm open‐label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta‐analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16–0.43) who were exposed to BM‐MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM‐MNCs was 20% (95% CI 0.12–0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM‐MNC therapy is safe up to 1 year post‐intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well‐designed randomized controlled trials are required to provide more information on the efficacy of BM‐MNC transplantation in patients with IS.

Genetics of ischemic stroke: An Indian scenario.

Stroke, a heterogeneous multifactorial disorder, is known to be a major cause of death and adult disability within both the developed and developing countries. Approximately 85% of stroke cases are ischemic, whereas the remaining 15% are hemorrhagic. It is caused by multiple genetic factors, environmental factors, and interactions among these factors. Several candidate genes have been found to be associated with ischemic stroke. The most extensively studied genes include those involved in hemostasis, inflammation, nitric oxide production, homocysteine and lipid metabolism, and rennin-angiotensin-aldosterone system. Combined linkage/association studies have demonstrated that genes encoding phosphodiesterase 4D (PDE4D) and arachidonate 5-lipoxygenase-activating protein (ALOX5AP) confer risk for stroke. Even though there is substantial evidence for the genetic basis of stroke as provided by the epidemiological data from twin- and family-based studies, the contribution of genetic factors identified till now is either not enough or very less to explain the entire spectrum of encountered phenomena associated with ischemic stroke. Till date, no genome-wide association studies (GWAS) have been carried out in India. We aim to extensively review the studies on candidate genes that may have potential applications in the early diagnosis, prevention, and treatment of ischemic stroke in the Indian population. This article further emphasizes the role of GWAS in ischemic stroke and the need for an extensive GWAS in the Indian population.

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis

Importance Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit. Objective To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life. Data Sources For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016. Study Selection Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies. Data Extraction and Synthesis We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions. Main Outcome and Measure The association between PFS duration and HRQoL. Results Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, −0.27 to 0.52); for physical HRQoL (n = 20 trials) it was −0.20 (95% CI, −0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, −0.05 to 1.60). Conclusions and Relevance We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

Nominations for B. K. Bachhawat Memorial Life Time Achievement Award & KT Shetty Memorial Oration of Indian Academy of Neurosciences

Singh, Dean, Indian Academy of Neurosciences and Director, Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi – 110 054, E-Mail director@dipas.drdo.in and a copy of the same to Dr. Vinay K. Khanna, Secretary HQ and Principal Scientist, CSIR – Indian Institute of Toxicology Research, MG Marg, Lucknow – 226 001, E-Mail vkkhanna1@gmail. com positively by July 31, 2016. Nominations received after the last date will be considered next year. Nominations for B. K. Bachhawat Memorial Life Time Achievement Award and KT Shetty Memorial Oration for 2016 and 2017 are invited. The nominee must be a Fellow/Life Member of the Indian Academy of Neurosciences. He/She should have at least 10 years standing in the area of Neurosciences. The contributions in Neuroscience in India will be judged by i. Research publications ii. Awards iii. Contributions to growth of Neuroscience in India. Nominations alongwith complete Bio-data and supporting documents should be sent to Dr. Shashi Bala Published online: July 7, 2016