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Background & objectives: With the availability of a wide range of drugs to treat patients with acute coronary syndrome (ACS), adverse drug reactions (ADRs) have become inevitable in clinical practice. Thorough knowledge of such reactions is essential for the treating physician for optimal treatment and better outcomes. There are many scales to define, measure and assess the ADRs, but there is a dearth of data available on such drug reactions among ACS patients. Hence, this study attempted to analyze the pattern, causality, severity, predictability and preventability of ADRs in ACS patients. All the ADRs reported during the study period were analyzed for causality by the World Health Organization-Uppsala Monitoring Centre (WHO-UMC), Naranjo's and Karch and Lasagna scales; severity by modified Hartwig and Siegel scale; predictability by Rawlins and Thompson criterion and preventability by Schumock and Thornton scale. Methods: A single-centre, record-based analysis for the occurrence of ADRs was done among ACS patients admitted to the department of Cardiology between January and October 2017. Demographic data, comorbid conditions, reported ADRs and ADR assessment details were noted from the hospital case records and ADR monitoring centre (AMC) records. The data were analyzed and presented in a descriptive manner using percentages, mean and standard deviation. The Pearson's chi-squared test was used to ascertain the significance of the association between different groups. Results: Out of 324 patients under evaluation, 67 had developed one or more ADRs. There were 30 different types of ADRs reported, headache being the most common. Among the drugs, heparin was the most common factor, causing 27 per cent of ADRs. Definite causality of a suspected drug causing ADRs was seen in 11.9 (n=8), nine (n=6) and 7.5 (n=5) per cent cases as per WHO-UMC, Naranjo (Naranjo algorithm) and Karch and Lasagna scales, respectively. In the severity of ADRs, the most severe reactions according to the modified Hartwig-Siegel scale (level 4a in our study) were seen in 17.5 (n=12) per cent of patients, and the rest were either level 2 or 3 reactions. Nearly 92.5 (n=62) per cent of reactions were predictable according to the Rawlins and Thompson criterion. Application of the modified Schumock-Thornton scale showed that 22.4 per cent of ACS patients had preventable reactions, and the rest were not preventable. Interpretation & conclusions: The study results suggest that ADRs are relatively common among ACS patients. Most of these can be identified and assessed for causality, severity, predictability and preventability using various available scales. Diligent pharmacovigilance for identifying and assessing ADRs may help manage and mitigate morbidity associated with these in high-risk ACS patients.

Chronic obstructive pulmonary disease (COPD) is known to be associated with cardiovascular disease due to shared risk factors and its impact on the cardiopulmonary vasculature. Speckle-tracking echocardiography (STE) is an effective tool for identifying subclinical, COPD-associated right ventricular (RV) and left ventricular (LV) dysfunction before conventional echocardiography can detect it. A systematic review and meta-analysis of the literature on STE in COPD are presented. A systematic search was conducted of PubMed, Scopus, Cochrane Library, and Science Direct for papers published between 2011 and March 2023, and bias was assessed using the STROBE tool. Eleven studies were included in the two-stage meta-analysis: first among 742 COPD cases, and then a case–control design with 507 COPD cases and 259 healthy controls. Of the 11 studies analyzed, 6 were dedicated to the assessment of RV strain, and 5 studies examined LV global longitudinal strain (GLS). Significant heterogeneity was observed in the STE parameters of COPD patients (I2 = 95%; mean effect size: –17.055 for LV GLS and –19.098 for RV free wall strain; Z = –35.809; P < 0.001) and between COPD patients and controls (I2 = 92%; mean effect size, 2.100; Z = 8.433; P < 0.0001). LV and RV STE parameters were lower in the COPD group than in the healthy control group. The two-dimensional STE parameters correlated with disease severity metrices such as the BODE (body mass index, airflow obstruction, dyspnea, and exercise) index and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, and they predicted mortality, hospitalization rates, and exercise tolerance in COPD patients. STE abnormalities are prevalent in COPD patients and can help identify subclinical LV and RV dysfunction. The presence of STE abnormalities helps in prognostication for COPD patients.

Introduction: Acute coronary syndrome (ACS) caused by coronary atherosclerosis include ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. The relation between psychiatric disorders and coronary artery disease is a complex one which includes the effect of the psychosocial factors on heart and vice versa. Point prevalence studies have been reported, but there is paucity of follow-up studies from India. Materials and Methods: The study is a follow-up evaluation at discharge of 248 consecutive patients presented with ACS at JSS Hospital, Mysuru, Karnataka, over a period of 6 months to assess the psychiatric comorbidities. The patients were assessed on a structured and validated pro forma before discharge, at 3 months, and at 6 months. Screening of psychiatric disorders was done using Mini International Neuropsychiatric Interview PLUS 5.0.0 and assessment of depression was done using Hamilton Depression Rating Scale. ANOVA, Student's t-test, and SPSS 21 were used for statistical analysis. Results: The most common psychiatric comorbidities include major depressive disorder (44%), it persisted at the end of 3 (P < 0.001) and 6 (P < 0.001) months. A spectrum of anxiety disorders including panic disorder (12.10%), dysthymia (3.60%), agoraphobia (2.40%), social phobia (2%), obsessive-compulsive disorder (1.6%), specific phobia (1.2%), and posttraumatic stress disorder (0.8%) in descending order at the end of 6 months were found. Significant reduction in substance use of nicotine (66.1%) and alcohol (56.0%) was reported on follow-up. Conclusion: Depression, anxiety, and substance use occur in patients with ACS which persist on follow-up. Early recognition at discharge and appropriate counseling on follow-up improve the clinical outcomes.

The present United States and European treatment guidelines recommend that antihypertensive therapy be initiated with a combination of agents from different classes to facilitate the achievement of control of blood pressure (BP). This prospective, randomized, open-label study was conducted at 3 tertiary hospitals in India to evaluate the effects of combination therapy with an angiotensin receptor blocker and a calcium antagonist on office BP and central hemodynamic parameters in patients with untreated hypertension or uncontrolled BP (>130/>80 mm Hg) during treatment with antihypertensive monotherapy. Patients were randomized to treatment with telmisartan 40 mg/day + amlodipine 5 mg/day or telmisartan 40 mg/day + cilnidipine 10 mg/day. Change from baseline to 8 weeks of treatment was assessed for seated office BP, ambulatory BP monitoring, and seated central hemodynamics (central BP, aortic augmentation index, central aortic augmentation pressure, and pulse wave velocity). A total of 94 of 96 enrolled patients completed the study. From baseline to 8 weeks a significant decrease was observed in both telmisartan + amlodipine and telmisartan + cilnidipine groups for mean BP (148.0 ± 12.80 to 124.0 ± 10.4 and 144.5 ± 10.2 to 123.0 ± 10.0 mm Hg, respectively; both p <0.001); in only telmisartan + amlodipine group for mean central aortic systolic and diastolic BP (131.1 ± 19.1 to 119.7 ± 14.9 mm Hg [p <0.001] and 93.3 ± 12.0 to 89.2 ± 14.6 mm Hg [p = 0.0008], respectively) and for central aortic pulse wave velocity (7.6 ± 1.4 to 7.2 ± 1.3 m/s, p = 0.0011); in only telmisartan + cilnidipine group for aortic augmentation index (27.5 ± 14.6 to 22.3 ± 12.2; p = 0.0178). Heart rate was unchanged in both treatment groups. Combination therapy with an angiotensin receptor blocker and a calcium antagonist effectively reduced BP to below the new <130/80 mm Hg target and had favorable effects on central hemodynamics.

Purpose: To analyze the risk factors and comorbidities among the young Indian adults with hypertension. Patients and Methods: This was a retrospective, multicentric real-world study which included patients diagnosed with and receiving treatment for hypertension. Data were collected from the medical records of clinics/hospitals across 623 study sites in India. Patients of either sex and aged 18-15 years were included. Demographic details (age, sex, anthropometric measurement), medical and family history, sedentary lifestyle, smoking status and alcohol consumption data were extracted. Descriptive and comparative analysis (Mann-Whitney U and chi-squared test) was done. Results: Out of 15,006 young patients diagnosed with hypertension (men=63.6%), 65.7% belonged to the age group of >35-15 years. The median body mass index was 27.0 kg/[m.sup.2]. Patients diagnosed with only hypertension were 29.1% while other predominant comorbidities with hypertension were diabetes mellitus (42.4%) and dyslipidemia (7.8%). Hypertension with diabetes mellitus were prevalent in the age group of >35-15 years (43.8%). More than half of the patients with hypertension (n=7656) had a sedentary lifestyle. Overall, 35.6%, 47.3%, and 56.7% of the patients were alcoholic, smokers (present and former), and had a family history of hypertension, respectively. Conclusion: The results showed that among the young population, hypertension was common in the age group of >35-45 years and diabetes mellitus and dyslipidemia were common comorbidities. Family history, sedentary lifestyle, smoking, alcohol consumption, and body mass index may also contribute to hypertension. Keywords: diabetes mellitus, dyslipidemia, prevalence, young population

To analyze the risk factors and comorbidities among the young Indian adults with hypertension. This was a retrospective, multicentric real-world study which included patients diagnosed with and receiving treatment for hypertension. Data were collected from the medical records of clinics/hospitals across 623 study sites in India. Patients of either sex and aged 18-45 years were included. Demographic details (age, sex, anthropometric measurement), medical and family history, sedentary lifestyle, smoking status and alcohol consumption data were extracted. Descriptive and comparative analysis (Mann-Whitney and chi-squared test) was done. Out of 15,006 young patients diagnosed with hypertension (men=63.6%), 65.7% belonged to the age group of >35-45 years. The median body mass index was 27.0 kg/m . Patients diagnosed with only hypertension were 29.1% while other predominant comorbidities with hypertension were diabetes mellitus (42.4%) and dyslipidemia (7.8%). Hypertension with diabetes mellitus were prevalent in the age group of >35-45 years (43.8%). More than half of the patients with hypertension (n=7656) had a sedentary lifestyle. Overall, 35.6%, 47.3%, and 56.7% of the patients were alcoholic, smokers (present and former), and had a family history of hypertension, respectively. The results showed that among the young population, hypertension was common in the age group of >35-45 years and diabetes mellitus and dyslipidemia were common comorbidities. Family history, sedentary lifestyle, smoking, alcohol consumption, and body mass index may also contribute to hypertension.

The unexpected and catastrophic cardiovascular effects of psychotropic drugs are well described albeit uncommon. The list of drugs which have been associated with prolonging QT interval and hence potentially causing Torsades de pointes is exhaustive. The insight into the plausible mechanisms are largely unclear. However, the practical implications of anticipating and recognizing QT prolongation cannot be overemphasized.

There is increasing evidence supporting the additional utility of nonlinear techniques such as chaos analysis of heart rate (HR) time series as indictors of prognosis in cardiac patients. Prolongation of rate-corrected QT interval, QTc, is strongly associated with sudden cardiac death. Recent studies of beat-to-beat QT interval variability (QTV) have shown that an increase in QTV is associated with increased sympathetic activity. QTvi, a QT variability index (QT variance corrected for mean QT divided by HR variance corrected for mean HR), is also a predictor of sudden cardiac death. We studied the utility of a measure of chaos, the Largest Lyapunov Exponent (LLE) of beat-to-beat HR and QT time series at baseline and after treatment in patients with congestive heart failure (CHF). We compared beat-to-beat HR and QT interval data in 23 patients with CHF and 19 age-matched normal controls. The ECG data were acquired in lead II configuration at a sampling rate of 1000 Hz. CHF patients had a significantly lower LLE of HR and a significantly higher LLE of QT time series than did normal controls. Clinical improvement in a subgroup of these patients was associated with a decrease in QT-LLE and a decrease in LLEqthr (LLE-QT/LLE-HR). These results demonstrate a decreased chaos of HR and increased chaos of QT time series in patients with CHF suggesting decreased cardiac vagal and increased sympathetic function in patients with CHF. Nonlinear measures may prove to be of additional utility to linear measures as surrogate end points to evaluate treatment effect in these patients.

The role of RORγ as a transcription factor for Th17 cell differentiation and thereby regulation of IL-17 levels is well known. Increased RORγ expression along with IL-17A levels was observed in animal models, immune cells and BAL fluid of COPD patients. Increased IL-17A levels in severe COPD patients are positively correlated with decreased lung functions and increased severity symptoms and emphysema, supporting an urgency to develop novel therapies modulating IL-17 or RORγ for COPD treatment. We identified a potent RORγ inhibitor, PCCR-1 using hit to lead identification followed by extensive lead optimization by structure–activity relationship. PCCR-1 resulted in RORγ inhibition with a high degree of specificity in a biochemical assay, with > 300-fold selectivity over other isoforms of ROR. Our data suggest promising potency for IL-17A inhibition in human and canine PBMCs and mouse splenocytes with no significant impact on Th1 and Th2 cytokines. In vivo, PCCR-1 exhibited significant efficacy in the acute CS model with dose-dependent inhibition of the PD biomarkers that correlated well with the drug concentration in lung and BAL fluid, demonstrating an acceptable safety profile. This inhibitor effectively inhibited IL-17A release in whole blood and BALf samples from COPD patients. Overall, we identified a selective inhibitor of RORγ to pursue further development of novel scaffolds for COPD treatment.

Fibroblasts embedded in a 3D matrix microenvironment can remodel the matrix to regulate cell adhesion and function. Collagen hydrogels are a useful in vitro system to study cell–matrix interactions in a 3D microenvironment. While major matrix reorganizations are easily recognizable, subtle changes in response to environmental or biochemical cues are challenging to discern in 3D hydrogels. Three-dimensional collagen gels at 1.0 mg/ml vs 1.5 mg/ml were labelled with DQ-collagen and imaged by confocal reflectance microscopy to evaluate these small changes. An image analysis pipeline was developed, hydrogel area and number of cross-sections analysed were optimized, and fibrillar collagen properties (number of branches, number of junctions, and average branch length) were quantified. While no significant changes were seen in fibrillar collagen organization between 1.0 mg/ml and 1.5 mg/ml collagen hydrogels, embedded mouse fibroblasts caused a significant increase in collagen branching and organization. Using the phalloidin-labelled cells, this change was quantitated in immediate proximity of the cell. A distinct increase in branch and junction numbers was observed, significantly altered by small changes in collagen concentration (1.0 mg/ml vs 1.5 mg/ml). Together, this analysis gives a quantitative evaluation of how cells respond to and modify their immediate microenvironment in a 3D collagen hydrogel.