Qualitative Analysis of the Most Cited Publications from Leading Indian Medical Institutions.

BACKGROUND AND OBJECTIVES: The most important responsibility of physicians is research - advancement of medical knowledge is the core on which the other responsibilities, patient care and research, are based. This study was planned to conduct a qualitative analysis of the major publications from the the country's leading medical institutions. METHODS: We used Scopus to generate a list of total number of publications from the topmost institutions, the number of citations, and citations per article. We calculated the h-index, g-index, i-10 index, and h5-index for these institutions. A more detailed analysis was carried out for the top 20 most cited papers in each of the institutions. Only descriptive statistics were used. RESULTS: Among the top 10 medical institutions included, AIIMS, Delhi and PGIMER, Chandigarh were the top institutes, accounting for more publications and citations than the next eight institutions combined. The other institutions also managed to publish a large number of highly-cited papers. AIIMS was the leading institution when other indices were calculated. Among the most-cited articles, >80% had first/corresponding authors from outside India. A large number papers remained uncited, even after many years of publication. INTERPRETATION AND CONCLUSIONS: Uncited papers could be a result research conducted with the purpose of getting the numbers needed for promotion (NNP). Importance of collaborative research was seen to be an important factor when citations are considered. Even with the huge resource deficit, our institutes managed to publish a decent number of highly cited articles, which can be boosted if funding situation is improved.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial.

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Heart failure in children in tropical regions.

With the ever increasing younger population in tropical countries, the number of children with heart failure is increasing. However, the etiology of heart failure in this region varies considerably from that in the temperate region, with infectious causes leading the list. In this review, we have summarized the important causes of heart failure seen in the pediatric population in tropical regions.

Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction.

The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population.

Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has been shown to play a significant role in neovascularization during inflammation in atherosclerotic plaques, formation of collateral vessels to an area of ischemic myocardium and neovascularization at the edges of a myocardial infarction during its repair. Interleukin-4 (IL-4) has important role in immune cell chemotaxis, formation of endothelial cell adhesion molecules and has numerous anti-inflammatory effects which prevent the complications of atherosclerosis, the primary cause of coronary heart disease (CHD). In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). To analyze polymorphic alleles, ARMS-PCR and RFLP techniques were used. Multiple logistic regression analysis was carried out with statistical software. GG genotype was associated with a decreased risk of development of CHD (OR 0.22, 95% CI 0.12-0.38, P < 0.001). However, A allele showed an increased risk whereas G allele decreased the risk of CHD with diabetes mellitus, hypertension, chronic mental stress and positive familial history of myocardial infarction (MI)/CHD. GG genotype was found to have protective effect with alcohol intake (OR 0.34, 95% CI 0.14-0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04-0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes.

Congestive heart failure in Indians: how do we improve diagnosis & management?

Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients.

Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy.

The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130 consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14 mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted in the sudden cardiac death (SCD) of the proband at the age of 21 years. Further, a DCM causing novel mutation p.Gly377Ser was identified which resulted in the milder phenotype. The present study shows that there is genetic and phenotypic heterogeneity of cardiomyopathies in Indian population. Further, the location and type of mutation in a given sarcomeric gene determines the severity and phenotypic plasticity in cardiomyopathies.

Sildenafil for pulmonary hypertension: need for evidence generation.

BACKGROUND: The present meta-analysis was conducted with the aim of comparing the usefulness of sildenafil for the management of pulmonary hypertension (PH). METHODS: A systematic electronic and manual search was conducted to retrieve all published and unpublished randomized clinical trials of sildenafil in PH. Pertinent data related to various outcomes were extracted. Sildenafil was planned for comparison with placebo, prostacyclin analogs and endothelin receptor antagonists. For continuous data weighted mean difference was used while fixed or random effects models were used for dichotomous data. Revman (Version 4.2) was used for all calculations. RESULTS: Five studies with a total of 190 patients were included in the final analysis. As compared to placebo sildenafil showed a significant improvement in 6-min walk test (68.90 (95% CI 31.14 - 106.65), p = 0.0003), mean pulmonary artery pressure (-13.04 (95% CI - 25.94 to -0.15), p = 0.05), mean cardiac index (0.39 (95% CI 0.24 - 0.54), p < 0.00001), mean Borg dyspnea score (-1.23 (95% CI -1.36 to -1.10), p < 0.00001), mean pulmonary vascular resistance (-171 (95% CI -300 to -30.90), p = 0.02), improvement in functional class (6.48 (95% CI 2.74 - 15.33), p < 0.001) and a nonsignificant change in mean right atrial pressure and clinical worsening. No study satisfied inclusion criteria for comparison with prostacyclin analogs. In comparison with bosentan, sildenafil did not show a significant difference for any of the clinical outcomes of concern. CONCLUSION: In conclusion, sildenafil was shown to produce a significant improvement in functional and clinical outcomes as compared to placebo. There was no significant difference between sildenafil and bosentan for the study outcomes. There is a definite need for conducting adequately powered randomized controlled trials of sildenafil comparing it to placebo and also to other treatments approved for use in PH.

Traumatic Fracture of Pacemaker Lead by Suture Transfixation to Pectoral Muscle.

We report acute lead fracture during pacemaker implantation. Suturing the lead without the sleeve might damage the lead. To avoid this result, we suggest tying knots tightly, but not too vigorously.

Clinical safety profile of ticagrelor compared to clopidogrel in 1208 patients: Real world evidence.

INTRODUCTION: Dual antiplatelet treatment is recommended by current clinical practice guidelines for patients undergoing PCI. The PLATO trial showed superiority of ticagrelor to clopidogrel in reducing the rate of death from vascular causes, myocardial infarction and stroke without increase in the rate of overall major bleeding in ACS patients. However, real world evidence in Indian patients is limited. The objective of this study is to compare safety profile of ticagrelor with clopidogrel in real world settings. METHODOLOGY: In this single centered retrospective observational study, a total of 1208 serial patient records undergoing PCI (ACS and stable angina patients as well) treated with Ticagrelor or Clopidogrel were collected and analyzed to look into in hospital outcomes. We excluded the patient's data that were incomplete. RESULTS: In total of 1208 patients, 604 patients received ticagrelor and similarly 604 patient received clopidogrel. No significant differences in the rates of major life threatening bleeding and any major bleeding were observed between ticagrelor and clopidogrel group (0.2% (n = 1) vs. 0.7% (n = 4), p = 0.18 and 2.8% (n = 17) vs. 3% (n = 18), p = 0.86 respectively). There was increase in minor bleeding rate with ticagrelor compared to clopidogrel (21.4% & 13.6%, p = 0.00). CONCLUSION: In the real world settings, patients undergoing PCI treated with ticagrelor showed similar safety profile compared to clopidogrel but with increase in minor bleeding rate. The observed results were in alignment with PLATO clinical trial.

Carotid intima-medial thickness as a marker of disease activity in Takayasu's arteritis.

BACKGROUND: Assessment of disease activity in patients with Takayasu's arteritis (TA) is difficult due to absence of definitive tests. Presence of carotid intima-medial thickening has been suggested as a possible marker of inflammation and disease activity. METHODS: We evaluated common carotid artery carotid intima-medial thickness (CCA-IMT) in 56 common carotid arteries (CCAs) in 28 healthy controls and 74 CCAs in 37 patients of TA. We correlated these findings with the presence of activity as assessed by the National Institutes of Health (NIH) criteria. RESULTS: CCA-IMT was increased (>0.8 mm) in 59% of the patients with TA. In patients with disease activity, the CCA-IMT was more than in those without activity (1.5+/-0.16 vs. 0.9+/-0.2 mm, P<0.005). This is presumably because of ongoing inflammation causing abnormal thickening. Even among patients without active disease, CCA-IMT was more than in controls (0.9+/-0.2 vs. 0.6+/-0.1 mm, P<0.05) possibly due to a milder degree of inflammation or healing with fibrosis. All patients with angiographic carotid obstruction had increased CCA-IMT irrespective of whether they were active or not. However, in patients with angiographically normal carotid arteries, CCA-IMT was increased only among the patients who were active (1.4+/-0.2 vs. 0.7+/-0.04, P<0.05). Abnormal CCA-IMT as marker of disease activity had a sensitivity of 82% and specificity of 60%. On excluding patients with increased CCA-IMT who had angiographic carotid stenosis (because the increase in CCA-IMT cannot be attributed entirely to activity alone in these patients), the specificity increased to 70%. CONCLUSION: Increased CCA-IMT is a reliable marker of active disease, especially in the absence of angiographically visible carotid disease.

Association between subclinical inflammation & fasting insulin in urban young adult north Indian males.

BACKGROUND & OBJECTIVES: Elevated levels of c-reactive protein (CRP) are known to be associated with insulin resistance and metabolic syndrome in adults. A substantial prevalence of hyperinsulinaemia and elevated CRP levels have been shown in Indian young adults. We therefore studied the association of serum high-sensitivity C-reactive protein (hs-CRP) with fasting insulin and insulin resistance in urban adolescent and young adult males in north India. METHODS: In this cross-sectional study 324 healthy males, 14-25 yr of age were selected randomly and their clinical and anthropometric profile [body mass index (BMI), waist and hip circumferences, waist-to-hip circumference ratio (W-HR), and skinfold thickness at four sites], percentage of body fat (%BF) and biochemical (fasting blood glucose, lipoprotein profile, fasting insulin and hs-CRP) parameters were recorded. Insulin resistance was assessed by the homeostasis model of assessment (HOMA-IR). RESULTS: Fasting insulin and hs-CRP levels correlated significantly with BMI, waist circumference, and triceps and subscapular skinfold thickness. Fasting insulin also correlated with %BF, and hs- CRP correlated with W-HR. No correlation was observed between hs-CRP and fasting insulin levels or insulin resistance. In multiple logistic regression analysis different independent risk factors for hyperinsulinaemia and elevated hs-CRP levels were observed; hypercholesterolaemia, overweight and high subscapular skinfold thickness for the former, and high triceps skinfold thickness for the latter. INTERPRETATION & CONCLUSION: Lack of correlation between hs-CRP and surrogate markers of insulin resistance and different risk factors for each, in young Indian males are unique observations of our study. Further studies on a larger sample of both genders need to be done to confirm these findings.

Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.

This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients.

Low-density lipoprotein cholesterol estimation by a new formula in Indian population.

BACKGROUND: Estimation of low-density lipoprotein cholesterol is crucial in the management of ischemic heart disease patients. Low-density lipoprotein cholesterol is routinely calculated in laboratories world over by applying Friedewald formula for logistic reasons. We derived a new formula based on multiple regression approach. METHODS: Lipid profiles were done on blood samples of 2008 patients. In initial 1000 patients, low-density lipoprotein cholesterol was estimated by a direct method and also by Friedewald formula. By applying linear regression methods on the data of direct estimation method, a new formula was obtained and the accuracy of this new formula was validated in the next 1008 patients. RESULTS: The mean low-density lipoprotein cholesterol was 116+/-41.5 mg/dl (3.02+/-1.08 mmol/l) measured by direct low-density lipoprotein cholesterol assay and that calculated by Friedewald formula was 119+/-46 mg/dl (3.09+/-1.2 mmol/l) for the initial 1000 patients. Low-density lipoprotein cholesterol measured by direct low-density lipoprotein cholesterol assay and calculated from Friedewald formula showed good correlation (r = 0.88), however, there was minimal overestimation by the Friedewald formula. The correlation improved between direct low-density lipoprotein cholesterol and calculated low-density lipoprotein cholesterol after excluding the patients with triglycerides more than 350 mg/dl (r = 0.92). The mean low-density lipoprotein cholesterol measured by the direct assay and by new formula in the next 1008 patients was 117+/-40 mg/dl (3.04+/-1.04 mmol/l) and 113.7+/-37 mg/dl (2.96+/-0.96 mmol/l), respectively with very good correlation (r = 0.97) between them. CONCLUSIONS: The new formula derived from multiple linear regression analysis appears to be more accurate than Friedewald formula in Indian population.

Screening for pre-clinical hypertrophic cardiomyopathy by tissue Doppler imaging.

BACKGROUND: Hypertrophic cardiomyopathy is an autosomal dominant inherited disorder. On a routine clinical basis, genetic analysis is both time consuming and impractical at present. Thus, use of tissue Doppler imaging as a surrogate for genetic screening is an attractive option. METHODS AND RESULTS: Fifty-five first-degree relatives of 15 patients with hypertrophic cardiomyopathy were screened. Of them, two were found to have hypertrophic cardiomyopathy and were included in Group 1, which hence had 17 patients with overt hypertrophic cardiomyopathy. Group 2 had 53 family members who did not manifest any overt echocardiographic abnormality. Twenty healthy volunteers comprised Group 3. Doppler tissue myocardial longitudinal velocities were measured in systole and early diastole and with atrial contraction at the medial mitral annulus, lateral mitral annulus, mid lateral wall and mid interventricular septum. The tissue Doppler characteristics were analyzed for the presence of abnormalities suggestive of subclinical myocardial involvement. Myocardial velocities were highest in the normal control group and lowest in the hypertrophic cardiomyopathy group. The velocities of the relatives without overt hypertrophy were intermediate in range. Of the 53 relatives screened, nine (17%) subjects showed tissue Doppler abnormality in the systolic and early diastolic velocities at the medial and lateral mitral annulus suggestive of a possibility of pre-clinical hypertrophic cardiomyopathy and a carrier state for a hypertrophic cardiomyopathy. Twenty-two of the 53 screened members had a mean early diastolic velocity less than 13.5 cm/s, among this group 9 had an ejection fraction more than 68%. These findings suggest that at least 16.7% of the screened population may carry beta-myosin heavy chain mutation. CONCLUSIONS: Screening for hypertrophic cardiomyopathy is feasible and tissue Doppler imaging is a sensitive and easy means to detect subclinical myocardial involvement in apparently normal family members without overt hypertrophy.