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Nitric oxide (NO . ) is critical for functionality of endothelial colony forming cells (ECFCs). Dimerization of endothelial nitric oxide synthase (eNOS) is must to produce NO . and tetrahydrobiopterin (BH4) plays a crucial role in stabilizing this state. We investigated BH4 level in ECFCs and its effect on ECFCs functionality in CAD patients. Intracellular biopterin levels and ECFCs functionality in terms of cell viability, adhesion, proliferation, in vitro wound healing and angiogenesis were assessed. Guanosine Triphosphate Cyclohydrolase-1 (GTPCH-1) expression was studied in ECFCs. Serum total reactive oxygen/nitrogen species was measured and effect of nitrosative stress on ECFC’s biopterins level and functionality were evaluated by treating with 3-morpholino sydnonimine (SIN-1). BH4 level was significantly lower in ECFCs from CAD patients. Cell proliferation, wound closure reflecting cellular migration as well as in vitro angiogenesis were impaired in ECFCs from CAD patients. Wound healing capacity and angiogenesis were positively correlated with ECFC’s BH4. A negative effect of nitrosative stress on biopterins level and cell functionality was observed in SIN-1 treated ECFCs. ECFCs from CAD exhibited impaired functionality and lower BH4 level. Association of BH4 with wound healing capacity and angiogenesis suggest its role in maintaining ECFC’s functionality. Oxidative stress may be a determinant of intracellular biopterin levels.

ObjectiveTo investigate gender discrimination in access to healthcare and its relationship with the patient’s age and distance from the healthcare facility.Design and settingAn observational study based on outpatient data from a large referral public hospital in Delhi, India.ParticipantsConfirmed clinical appointments.Primary and secondary outcome measuresEstimates from the logistic regression are used to compute sex ratios (male/female) of patient visits with respect to distance from the hospital and age. Missing female patients for each state—a measure of the extent of gender discrimination—is computed as the difference in the actual number of female patients who came from each state and the number of female patients that should have visited the hospital had male and female patients come in the same proportion as the sex ratio of the overall population from the 2011 census.ResultsOf 2377028 outpatient visits, excluding obstetrics and gynaecology patients, the overall sex ratio was 1.69 male to one female visit. Sex ratios, adjusted for age and hospital department, increased with distance. The ratio was 1.41 for Delhi, where the facility is located; 1.70 for Haryana, an adjoining state; 1.98 for Uttar Pradesh, a state further away; and 2.37 for Bihar, the state furthest from Delhi. The sex ratios had a U-shaped relationship with age: 1.93 for 0–18 years, 2.01 for 19–30 years, and 1.75 for 60 years or over compared with 1.43 and 1.40 for the age groups 31–44 and 45–59 years, respectively. We estimate there were 402 722 missing female outpatient visits from these four states, which is 49% of the total female outpatient visits for these four states.ConclusionWe found gender discrimination in access to healthcare, which was worse for female patients who were in the younger and older age groups, and for those who lived at increasing distances from the hospital.

Background & objectives: Impaired high density lipoprotein (HDL) functionality has been shown to be associated with cardiovascular disease risk. The study was aimed to identify the alterations in HDL function [antioxidative activity (AOA)] and subfraction distribution between acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) individuals and analysing the accuracy of HDL parameters to discriminate between the groups. Methods: HDL subfraction distribution analysis was performed in 200 coronary artery disease patients (ACS and SCAD) and 60 control individuals using dextran sulphate, heparin and manganese chloride precipitation method. In terms of HDL function, AOA was evaluated by dihydrorhodamine-based fluorescent cell-free assay and paraoxonase (PON1) enzyme paraoxonase and arylesterase activity. Results: We found that higher AOA [odds ratio (95% confidence interval {CI})]: 0.09 (0.02-0.44), P<0.01 for SCAD; 0.008 (0.001-0.07), P<0.001 for ACS and higher PON1 activity [0.22 (0.8-0.59), P<0.01 for SCAD; 0.16 (0.06-0.4), P<0.001 for ACS] were associated with a lower odds of developing coronary artery disease (CAD). AOA of apoB-depleted serum was significantly correlated with HDL2-C/HDL3-C (HDL-cholesterol) ratio in controls (r=−0.31, P=0.01) and ACS (r=−0.18, P=0.04). It was observed that AOA and HDL subfraction distribution together could discriminate between the two groups of CAD with an accuracy of 72.8 per cent (P=0.004). Interpretation & conclusions: Impaired AOA and altered subfraction distribution of HDL may be responsible for its diminished anti-athero protective activity and can discriminate between the two groups of CAD individuals.

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.

Objective Myocardial iron overload (MIO) in thalassemia major (TM) may cause subclinical left ventricular (LV) dysfunction which manifests with abnormal strain parameters before a decrease in ejection fraction (EF). Early detection of MIO using cardiovascular magnetic resonance (CMR)-T2* is vital. Our aim was to assess if CMR feature-tracking (FT) strain correlates with T2*, and whether it can identify early contractile dysfunction in patients with MIO but normal EF. Methods One hundred and four consecutive TM patients with LVEF > 55% on echocardiography were prospectively enrolled. Those fulfilling the inclusion criteria underwent CMR, with T2* being the gold standard for detecting MIO. Group 1 included patients without significant MIO (T2* > 20 ms) and group 2 with significant MIO (T2* < 20 ms). Results Eighty-six patients (mean age, 17.32 years, 59 males) underwent CMR. There were 68 (79.1%) patients in group 1 and 18 (20.9%) in group 2. Fourteen patients (16.3%) had mild-moderate MIO, and four (4.6%) had severe MIO. Patients in group 2 had significantly lower global radial strain (GRS). Global longitudinal strain (GLS) and global circumferential strain (GCS) did not correlate with T2*. T1 mapping values were significantly lower in patients with T2* < 10 ms than those with T2* of 10–20 ms; however, FT-strain values were not significantly different between these two groups. Conclusion CMR-derived GRS, but not GLS and GCS, correlated with CMR T2*. GRS is significantly decreased in TM patients with MIO and normal EF when compared with those without. FT-strain may be a useful adjunct to CMR T2* and maybe an early marker of myocardial dysfunction in TM. Key Points • A global radial strain of < 29.3 derived from cardiac MRI could predict significant myocardial iron overload in patients with thalassemia, with a sensitivity of 76.5% and specificity of 66.7%. • Patients with any myocardial iron overload have significantly lower GRS, compared to those without, suggesting the ability of CMR strain to identify subtle myocardial contractile disturbances. • T1 and T2 mapping values are significantly lower in those with severe myocardial iron than those with mild-moderate iron, suggesting a potential role of T1 and T2 mapping in grading myocardial iron.

The goal of the global congestive heart failure (G-CHF) registry is to collect comparative international data on heart failure characteristics, management, and outcomes and to better understand the determinants that impact the clinical course of heart failure. G-CHF is a multicenter, prospective cohort study of adult patients with a new or prior clinical diagnosis of heart failure. We have enrolled 23,047 participants from 257 centers in 40 countries from 8 major geographic regions of the world, with recruitment ongoing. Approximately 4,000 participants will also participate in substudies to assess frailty, comorbidity, diet, barriers to care, biomarkers, and planned detailed echocardiographic analyses. Follow-up is planned for a period of 5 years. The primary outcome is cause-specific mortality. Key secondary outcomes include hospitalizations, quality of life, and major cardiovascular and noncardiovascular outcomes. A total of 31.9% of participants were enrolled as inpatients. Thus far, mean age of the cohort at baseline is 63.1 years, and 60.8% are male. Participants most commonly have heart failure with reduced ejection fraction (53.6%) followed by preserved ejection fraction (24.2%) and midrange ejection fraction (20.6%). The most common causes of heart failure are ischemic (37.8%) followed by hypertensive (20.0%), idiopathic (15.1%), and valvular disease (8.8%). G-CHF will provide a greater understanding of the characteristics of the global heart failure population, variations in its management, clinical outcomes, and what continues to impact morbidity and mortality in this high-risk population.

Background Internship is a phase of training wherein medical graduates acquire the skills and competencies required to function independently. It has been reported that interns lack confidence in performing common procedures, as these skills are often learnt through self-learning or performing without supervision. This type of learning endangers patient safety and fails to instil the required confidence in the student. Training in skills laboratories provide opportunity to learn clinical skills in a safe environment. However, skills laboratories are resource-intensive, and there is limited information on different training approaches, such as blended learning, and how the trainees perceive their usefulness. Hence, we conducted this pilot study to assess the perceived usefulness of a blended learning approach for skills training among medical interns. Methods This mixed methods study was conducted in the skills laboratory of an apex medical institute in India, among 42 interns posted for the Interns Skill-based Clinical Induction Program (ISCIP). In this training, a blended learning approach was adopted, which comprised of two components - an online e-learning module, followed by a hands-on training session. The trainees were asked to complete a feedback form and grade different components of the online session, and hands-on session on a five-item Likert-based scale. The scores were expressed as the mean (SD) of a maximum possible score of 5 for each of the components. In order to gain insight of the perceived usefulness of skills training among learners, focused group discussions (FGDs) were conducted. Results The mean (SD) score for perceived importance ranged from 5 (0) to 4.9 (0.2) for various skills. The proportion of interns who felt confident in performing the skill after the training was 88.1% for IV cannulation to 97.6% handwashing, and gloving and gowning. The findings of the qualitative component revealed that interns found the training to be useful and interesting. It was perceived to be more ethical, uniform, well-structured, and provided an opportunity to practice a skill repeatedly. Conclusions The blended learning approach was perceived to be useful among the medical interns. Further research may be conducted in other medical institutes to assess the effectiveness of skills training. Clinical trial registration number Not applicable, as the study is not a trial.

Often a single blood pressure (BP) measurement is used to diagnose and manage hypertension in busy clinics. However, repeated BP measurements have been shown to be more representative of the true BP status of the individual. Improper measurement of office BP can lead to inaccurate classification, overestimation of a patient’s true BP, unnecessary treatment, and misinterpretation of the true prevalence of hypertension. There is no consensus among major guidelines on the number of recommended measurements at a single visit or the method of arriving at final clinic BP reading. The participants of the National Family Health Survey (NFHS-4), a nationwide survey conducted in India from 2015 to 2016, were used for the analysis. The prevalence and median difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for single as well as combinations of two or more readings were calculated. Cross-tabulation was used to assess classification of individuals based on first BP reading compared with the mean of two or more BP measurements. There was a 63% higher prevalence of hypertension when only the first reading was considered for diagnosis in comparison to the mean of the second and third readings. A decrease of 3.6 mmHg and 2.4 mm Hg in mean SBP and DBP, respectively, was observed when the mean of the second and third readings was compared to the first reading. In those who are identified to have grade 1 or higher categories of hypertension, we recommend three BP measurements, with the mean of the second and third measurements being the clinic BP.

Survival outcomes of patients with heart failure (HF) based on their disease etiology are not well described. Here, we provide one-year mortality outcomes of 10850 patients with HF (mean age = 59.9 years, 31% women) in India. Ischemic heart disease (71.9%), dilated cardiomyopathy (17.3), rheumatic heart disease (5.4), non-rheumatic valvular heart disease (1.9), hypertrophic cardiomyopathy (0.8), congenital heart disease (0.7), peri-partum cardiomyopathy (0.5), restrictive cardiomyopathy (0.4), and infective endocarditis (0.1) were the main disease etiologies. Mortality rate per 100-person years of follow-up varied from 13.8 (95% CI: 6.2–30.7) in peri-partum cardiomyopathy to 92.9 (46.5–185.9) in infective endocarditis. Compared to ischemic heart disease, the mortality was two to five times higher in rheumatic heart disease (HR = 2.0; 95% CI: 1.6–2.4), congenital heart disease (2.9; 1.9–4.2), and infective endocarditis (4.8; 2.4–9.8). The wide variations in mortality rate in HF patients may bring possible clinical applicability of risk stratification. The NHFR is India’s first nationally representative heart failure (HF) registry. Here the authors studied the survival outcomes of 10,850 HF patients and found wide variations in mortality rates based on HF etiologies.

Impaired high-density lipoprotein (HDL) functions are associated with development of coronary artery disease. In this study, we explored the quantitative differences in HDL (i.e. HDL proteome and fatty acid profile of HDL phospholipids) underlying the functional deficits associated with acute coronary syndrome (ACS). The relationship between HDL function and composition was assessed in 65 consecutive ACS patients and 40 healthy controls. Cholesterol efflux capacity (CEC) of HDL and lecithin cholesterol acyl transferase (LCAT) activity were significantly lower in patients with ACS compared to controls. In HDL proteome analysis, HDL isolated from ACS individuals was enriched in apolipoprotein C2 (inhibitor of LCAT), apolipoprotein C4 and serum amyloid A proteins and was deficient in apolipoprotein A-I and A-II. The fatty acid profile of HDL phospholipids analyzed using gas chromatography showed significantly lower percentages of stearic acid (17.4 ± 2.4 vs 15.8 ± 2.8, p = 0.004) and omega-3 fatty acids [eicosapentaenoic acid (1.0 (0.6–1.4) vs 0.7 (0.4–1.0), p = 0.009) and docosahexaenoic acid (1.5 ± 0.7 vs 1.3 ± 0.5, p = 0.03)] in ACS patients compared to controls. Lower percentages of these fatty acids in HDL were associated with higher odds of developing ACS. Our results suggest that distinct phospholipid fatty acid profiles found in HDL from ACS patients could be one of the contributing factors to the deranged HDL functions in these patients apart from the protein content and the inflammatory conditions.