Sibling Risk Factor Study in Premature Coronary Artery Disease.

BACKGROUND: Family history of premature coronary artery disease as a risk factor in first degree relatives has been well established by various studies. This study aims at identification and assessment of the presence of risk factors in asymptomatic siblings of patients with documented premature coronary artery disease. Prevalence of Systemic Hypertension in siblings (both male and female) of patients with premature coronary artery disease (males <45yrs, females <55yrs, confirmed by coronary angiography) was analysed. Other risk factor prevalence estimation was also done which included, dyslipidaemia, diabetes mellitus, tobacco use, alcohol intake, obesity, passive smoke exposure, diet and exercise. The study also estimated the percentage of sibling awareness regarding the risk factors for cardiovascular disease. MATERIALS AND METHODS: This was a cross sectional study where all patients (both In and Out patient), visiting Amrita Institute of Medical Sciences, Kochi and diagnosed as having angiographically proven Premature Coronary Artery Disease from December 2014 to June 2016 were identified and risk factor screening was done for both male and female siblings of any age of these patients. Laboratory tests included fasting blood sugar and fasting lipid profile were analysed after sample collection. RESULTS: 47.6% of male siblings and 35.7% of female siblings were found to be hypertensive, 17.3% of the male siblings and 18.7% of the female siblings were found to have abnormal levels of LDL cholesterol, 22.7% of male siblings and female siblings were found to have abnormal fasting plasma sugar levels, 30.5% of male siblings and 20% of male siblings were found to be overweight. 19.1% of male siblings and 21.4% of female siblings were found to be obese. Only 18.1% of male siblings and 5.7% of female siblings performed any kind of exercise on a regular basis. Among male siblings, 21.9% of male siblings were currently using tobacco in some form. Among non-smokers in both sexes, as many as 36% were exposed to some form of passive smoke. Almost half of the male siblings (49.5%) consumed alcohol containing beverages on a regular basis. CONCLUSIONS: Previously undetected risk factors were found to be highly prevalent among the studied siblings. Significant number of siblings were was found to be hypertensive and in addition some had elevated fasting blood sugar levels. Other modifiable risk factors like obesity, alcohol consumption, tobacco use, passive smoking and lack of exercise were also found to be widely prevalent. An important aspect that the study highlighted is the widespread lack of awareness in the study population about risk factors for disease.

White paper on venomous snakebite in India.

Venomous snakebite is one of the leading preventable causes of mortality and morbidity with tremendous socio-economic impact on the family and nation. Venomous snakebite has been relisted as a neglected tropical disease after having been removed off the list in 2013. This paper discusses the various reasons which could be attributed to the high mortality and morbidity due to venomous snakes and also provides recommendations on policy decisions, improvement on the quality of venom and anti-snake venom and in promoting awareness on how to avoid snakebite.

Venomous Snake Bite in India - Why do 50,000 Indians Die Every Year?

Snakebite is an occupational hazard causing considerable morbidity and mortality worldwide, particularly so in tropical countries like India. An estimated 50,000 Indians die due to venomous snakebite every year, seventy percent of whom are males between the ages of 20 to 50 years. Along with the associated morbidity and mortality, snakebite leads to a significant financial burden on the victim, both by way of hospital bills and labour hours lost. Snakebite is also a cause for considerable psychological stress among survivors. Most snakebites are eminently treatable and curable. Given a concerted thrust from all concerned , this menace could surely be curtailed considerably over the next few years.

Comparative functional characterization and in vitro immunological cross-reactivity studies on Daboia russelii and Craspedocephalus malabaricus venom.

BACKGROUND: Snake venom is a complex mixture of organic and inorganic constituents, including proteins and peptides. Several studies showed that antivenom efficacy differs due to intra- and inter-species venom variation. METHODS: In the current study, comparative functional characterization of major enzymatic proteins present in Craspedocephalus malabaricus and Daboia russelii venom was investigated through various in vitro and immunological cross-reactivity assays. RESULTS: The enzymatic assays revealed that hyaluronidase and phospholipase A2 activities were markedly higher in D. russelii. By contrast, fibrinogenolytic, fibrin clotting and L-amino acid oxidase activities were higher in C. malabaricus venom. ELISA results suggested that all the antivenoms had lower binding potential towards C. malabaricus venom. For D. russelii venom, the endpoint titration value was observed at 1:72 900 for all the antivenoms. In the case of C. malabaricus venom, the endpoint titration value was 1:2700, except for Biological E (1:8100). All these results, along with the avidity assays, indicate the strength of venom-antivenom interactions. Similarly, the western blot results suggest that all the antivenoms showed varied efficacies in binding and detecting the venom antigenic epitopes in both species. CONCLUSIONS: The results highlight the need for species-specific antivenom to better manage snakebite victims.

Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA).

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication. METHODS: The intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use. This design will lead to four potential experimental conditions: (i) ASHA-led intervention, (ii) m-health intervention, (iii) ASHA and m-health intervention combination, (iv) standard of care. The cluster randomized trial has been chosen as it randomizes communities instead of individuals, avoiding contamination between participants. Subcenters are a natural subset of the health system, and they will be considered as the cluster/unit. The factorial cluster randomized controlled trial (cRCT) will also incorporate a nested health economic evaluation to assess the cost-effectiveness and return on investment (ROI) of the interventions on medication adherence among patients with CVDs. The sample size has been calculated to be 393 individuals per arm with 4-5 subcenters in each arm. A process evaluation to understand the effect of the intervention in terms of acceptability, adoption (uptake), appropriateness, costs, feasibility, fidelity, penetration (integration of a practice within a specific setting), and sustainability will be done. DISCUSSION: The effect of different types of intervention alone and in combination will be assessed using a cluster randomized design involving 18 subcenter areas. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence. The proposal is aligned to the WHO-NCD aims of improving the availability of the affordable basic technologies and essential medicines, training the health workforce and strengthening the capacity of at the primary care level, to address the control of NCDs. The proposal also helps expand the use of digital technologies to increase health service access and efficacy for NCD treatment and may help reduce cost of treatment. TRIAL REGISTRATION: The trial has been registered with the Clinical Trial Registry of India (CTRI), reference number CTRI/2023/10/059095.

Variations and Associated Factors in Symptom-to-Balloon (STB) Time and Door-to-Balloon (DTB) Time Before and After the COVID-19 Lockdown: A Hospital-Based Cross-Sectional Study.

INTRODUCTION: During the COVID-19 lockdown, India saw a major restriction in the movement of people. Patients with acute myocardial infarction (MI) required early interventions and follow-up of independent predictors like symptom-to-balloon (STB) time and door-to-balloon (DTB) time. This study aimed to determine changes in STB and DTB time before and after the COVID-19 lockdown and its associated risk factors. METHODS: A hospital-based cross-sectional study of 105 patients admitted to the cardiac care units (CCU) of two tertiary care centers in a district of Southern India for six months was conducted to compare the changes in STB and DTB time before and after the COVID-19 lockdown (three months before March 2020 and three months after March 2020), and data was collected from medical records. The data collected was then entered into Microsoft Excel (Microsoft Corporation, Washington, USA), numerically coded, and analyzed using SPSS Statistics version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). The Chi-square and Mann-Whitney U tests assessed the association between the dependent and independent variables. The STB/DTB time (before and after the COVID-19 lockdown) was the dependent variable, while the age, gender, co-morbidities, smoking status, and date of admission of patients (before and after the COVID-19 lockdown) were taken as the independent variables. A p-value of <0.05 was considered statistically significant. The predictor variables were identified using the regression method, where all variables with a significance of <0.2 were taken. RESULTS: The overall mean (±SD) STB time was 408.7 (±307.1) minutes, and the mean (±SD) DTB time was 161.7 (±261.6) minutes. The pre-lockdown mean STB time was 404.6 minutes, and the mean DTB time was 153 minutes, whereas the post-lockdown mean STB and DTB time were higher at 413.3 minutes and 171.6 minutes, respectively. Out of the total 105 patients, 95 (90.5%) had an STB time of ≥120 minutes, and 77 (73.3%) had an ideal DTB time of <90 minutes. There was no statistically significant variation in the STB and DTB time before and after the lockdown. Only the age group >60 years (38 (97.4%)) was found to be statistically significant with an STB time of ≥120 minutes after the lockdown (p-value=0.040), and patients referred from primary and secondary care centers (AOR (95% CI)=4.669 (1.129-19.298)) were found to be an independent factor in reducing DTB time before and after the COVID-19 lockdown. CONCLUSION: The efficiency of the health system, irrespective of the COVID-19 lockdown, was observed; nevertheless, a delay in the overall recognition of symptoms of MI was perceived. The importance of time factors in identifying the symptoms of non-communicable diseases (NCDs), especially MI and stroke, has to be ascertained among the general population.

Personalized allocation of acetylsalicylic acid therapy for secondary prevention of coronary artery disease.

Background: A single-daily dose of 75 mg of acetylsalicylic acid inhibits 100% of thromboxane-B2 synthesis within 30-60 min. Thromboxane-B2 synthesis then recovers slowly as new platelets are released from the bone marrow. Normally, only 10% of the platelets are replaced daily by new platelets entering circulation. Hence, 24 h after a dose of acetylsalicylic acid, thromboxane-B2 synthesis is still suppressed by more than 90%. Hence, there is an adequate anti-platelet effect even after 24 h of acetylsalicylic acid intake. However, some patients treated with once-daily acetylsalicylic acid may have an incomplete 24-h suppression of thromboxane-B2 synthesis due to increased platelet turnover. The response could be improved in such patients by twice-daily acetylsalicylic acid administration. This study aimed to identify such a group of patients who would benefit from a twice-daily dose of acetylsalicylic acid. Materials and methods: Serum thromboxane-B2 levels were measured in 79 patients with coronary artery disease receiving 75 mg of acetylsalicylic acid for secondary prophylaxis. Serum levels of thromboxane-B2 were measured after 4 and 24 h of acetylsalicylic acid intake. Patients were then classified into three groups: steady suppression group (serum thromboxane B2 is adequately suppressed at 4 and 24 h), i.e., adequate response to acetylsalicylic acid; fast recovery group (more than 10% rise in serum thromboxane-B2 levels at 24-h when compared to at 4-h) and non-responders (serum thromboxane-B2 levels of >3,100 pg/ml after 4 h of acetylsalicylic acid intake). Patients in the fast recovery group were given twice-daily acetylsalicylic acid and thromboxane-B2 levels were re-measured. Results: A total of 20 patients (24.3%) had steady suppression of thromboxane-B2 and 11 patients (13.9%) belonged to the fast recovery group, i.e., thromboxane-B2 levels were adequately suppressed at 4 h but had recovered by more than 10% at 24 h; which was adequately suppressed by twice-daily acetylsalicylic acid (p 0.004). A total of 48 patients (60.8%) were non-responders. Conclusion: Twice-daily acetylsalicylic acid may be beneficial if serum thromboxane-B2 levels at 4 h are <3,100 and >3,100 pg/ml at 24 h. If thromboxane-B2 levels at 4 and 24 h is <3100 pg/ml but if there is a >10% rise in serum thromboxane B2 at 24 h as compared to that at 4 h, then twice-daily acetylsalicylic acid should be considered. However, if thromboxane-B2 at 4 and 24 h is >3,100 pg/ml consider switching over to a P2Y12 inhibitor.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) of carotid arteries and non-alcoholic fatty liver disease (NAFLD): An analytical cross-sectional study from a teaching hospital, Kerala, South India.

Introduction: Evidence related to carotid artery F-fluorodeoxyglucose-positron emission tomography (FDG -PET) and non-alcoholic fatty liver disease (NAFLD) is limited from a low-resource setting. The present study aims to examine the association between FDG-PET uptakes by the carotid arteries in patients having different grades of NAFLD. Materials and Methods: An analytical cross-sectional study was done in a tertiary care center in South India for 1 year. Sonographically confirmed NAFLD patients of the age group 18 years and above were consecutively enrolled for the study after getting informed consent. Anthropometric measurements, ultrasonography for identifying the grades of fatty liver and FDG-PET were performed in the study participants. The data for the study were collected by the research personnel and entered in Microsoft Excel. The data were analyzed in the IBM SPSS version 20.0 software. Results: A total of 24 patients were in the final analysis. The mean age of patients in this study was 56.79 (11.26) years. Among the 24 patients, 95.83% (n = 23) were males. The mean FDG-PET uptake in the carotids was 1.75 (0.42) units. The FDG uptake was higher in the moderate NAFLD group (1.46 [0.40] v/s 2.04 [0.14]) and the difference was statistically significant with P < 0.001. The FDG uptake between the coronary artery disease (CAD) with NAFLD and non CAD with NAFLD groups was not statistically significant (1.60 [0.46] v/s 1.86 [0.36], P = 0.17). The FDG uptake in CAD patients with mild and moderate NAFLD had no statistical significance between the two groups (1.43 [0.45] v/s 2.00 [0.00], P= 0.06). Conclusion: The findings of this study showed increased uptake of FDG-PET in carotids in subjects with moderate fatty liver when compared with those with mild fatty liver.

Hypocholesterolaemia as a prognostic factor in venomous snakebite: a retrospective study from a single centre in Kerala, India.

BACKGROUND: Studies have suggested a association between serum cholesterol values and severity of envenoming. The objective of the study was to correlate the serum cholesterol levels with severity of envenoming in victims of snakebite, across snake species in our patient population. METHODS: Retrospective secondary data analysis of health records of a cohort of snakebite victims treated at Little Flower Hospital, Angamaly, Kerala during June 2006-January 2008 was performed. The cholesterol values were assessed in 205 consecutive patients admitted with snakebite envenoming, within 24 h of admission and 10 h of overnight fasting. Lipid fractions were estimated from fasting serum through the standard CHOD-PAP method on a Hitachi analyzer. The cholesterol level was compared between victims with mild and serious envenoming to assess the proportion among each category with a low cholesterol (defined as ≤150 mg/dl as per institutional criteria). In addition, low cholesterol as a marker of severity was compared with other laboratory parameters suggesting severe envenoming such as low fibrinogen, low platelet count, neutrophilia, elevated creatinine, d-dimer, hepatic transaminases and albuminuria. RESULTS: Of the 146 victims with serious degree of snakebite envenoming 116 (79%) had low cholesterol values ≤150 mg%, while 30 (21%) had values >150 mg%. Of the patients with low cholesterol, 116 (78%) had serious envenoming, while 22% had mild envenoming. By contrast, 30 patients (21%) had values >150 mg%. The risk of moderate-severe envenoming with low cholesterol was 2.7 times (170%) that of victims with normal or high cholesterol on admission. CONCLUSIONS: A low cholesterol on admission in victims of snake envenoming suggested a more severe degree of envenoming and likelihood of complications.

ICMR task force project- survey of the incidence, mortality, morbidity and socio-economic burden of snakebite in India: A study protocol.

BACKGROUND: Snakebite is possibly the most neglected of the NTDs (Neglected Tropical Diseases). Half of the global deaths due to venomous snakebites, estimated at 100,000 per year, occur in India. The only representative data on snakebite available from India is the mortality data from the RGI-MDS study (Registrar General of India- 1 Million Death Study) and another study on mortality from the state of Bihar. Incidence data on snakebite is available for 2 districts of the state of West Bengal only. Hospital-based data on snakebite admissions and use of ASV are gross underestimates as most snakebite victims in rural India depend more on alternate treatment methods which do not get represented in National registries. The proposed study is a multi-centric study to determine the incidence, morbidity, mortality and economic burden of snakebites in India covering all 5 geographical zones of the country. PROTOCOL: A community level surveillance for snakebite covering 31 districts in 13 states of India in order to obtain annual incidence of snakebites from the community. Frontline health workers will be trained to gather information on new cases of snakebite over the study period of 1-year, from "wards "(smallest administrative subunit of a village or town) that they represent in the study districts. Dedicated field officers would collect data on snakebites, victim characteristics, outcomes, utilization of health facilities on a questionnaire sheet designed for this purpose. The study duration is for 18 months from April 2022 to October 2023. DISCUSSION: The study would be the first of its kind in India looking prospectively at the incidence of snakebite covering 13 states in 5 zones of India and a population of 84 million. Our study covers 6.12% of the total population of the country as compared to the incidence study conducted in Sri Lanka which covered 1% of the total population.

Effectiveness of a community-based education and peer support led by women's self-help groups in improving the control of hypertension in urban slums of Kerala, India: a cluster randomised controlled pragmatic trial.

BACKGROUND: With less than 20% of people with hypertension achieving their target blood pressure (BP) goals, uncontrolled hypertension remains a major public health problem in India. We conducted a study to assess the effectiveness of a community-based education and peer support programme led by women's self-help group (SHG) members in reducing the mean systolic BP among people with hypertension in urban slums of Kochi city, Kerala, India. METHODS: A cluster randomised controlled pragmatic trial was conducted where 20 slums were randomised to either the intervention or the control arms. In each slum, participants who had elevated BP (>140/90) or were on antihypertensive medications were recruited. The intervention was delivered through women's SHG members (1 per 20-30 households) who provided (1) assistance in daily hypertension management, (2) social and emotional support to encourage healthy behaviours and (3) referral to the primary healthcare system. Those in the control arm received standard of care. The primary outcome was change in mean systolic BP (SBP) after 6 months. RESULTS: A total of 1952 participants were recruited-968 in the intervention arm and 984 in the control arm. Mean SBP was reduced by 6.26 mm Hg (SE 0.69) in the intervention arm compared with 2.16 mm Hg (SE 0.70) in the control arm; the net difference being 4.09 (95% CI 2.15 to 4.09), p<0.001. CONCLUSION: This women's SHG members led community intervention was effective in reducing SBP among people with hypertension compared with those who received usual care, over 6 months in urban slums of Kerala, India. TRIAL REGISTRATION NUMBER: CTRI/2019/12/022252.

A comparison of clinical outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India.

THE PROBLEM CONSIDERED: This multi-centric study analyzed data of COVID-19 patients and compared differences in symptomatology, management, and outcomes between vaccinated and vaccine-naive patients. METHODS: All COVID-19 positive individuals treated as an in-or out-patient from the 1stMarch to 15th May 2021 in four selected study sites were considered for the study. Treatment details, symptoms, and clinical course were obtained from hospital records. Chi-square was used to test the association of socio-demographic and treatment variables with the vaccination status and binary logistic regression were used to obtain the odds ratio with a 95% confidence interval. RESULTS: The analysis was of 1446 patients after exclusion of 156 with missing data of which males were 57.3% and females 42.7%. 346 were vaccinated; 189 received one dose and 157 both doses. Hospitalization was more in vaccinated (38.2% vs 27.4%); ICU admissions were less in vaccinated (3.5% vs 7.1%). More vaccinated were symptomatic (OR = 1.5); half less likely to be on non-invasive ventilation (OR = 0.5) while vaccine naive patients had 4.21 times the risk of death. CONCLUSION: Severe infection, duration of hospital stays, need for ventilation and death were significantly less among vaccinated when compared with vaccine naive patients.

Estimating epidemiological and economic burden and community derived disability weights for snake bite in Kerala: a study protocol.

Background: In India, geographical variation, lack of data and underreporting on cases and deaths due to snakebite makes it difficult to estimate socio-economic burden of snakebites. Previous studies measuring economic burden of snakebite in low-and-middle-income countries (LMICs) using different approaches have been conducted, but none so far in India. The proposed study aims to provide evidence on disability weights, epidemiological and economic burden due to snakebites in Kerala state, India. Protocol: A cross-sectional community based study for estimating epidemiological and economic burden of snakebite, recruiting victims of snakebite occurring over a nine month period prior to start and over the three month period of the study, across Ernakulam district, Kerala state, India. For the community derived disability weights, 60 adult patients admitted and treated at Amrita Institute of Medical Sciences, Kochi or Little Flower Hospital, Angamaly would be interviewed. The sample size to determine the mortality rate is calculated at 108,458 persons in Ernakulam.The study will measure annual incidence, mortality, treatment cost of snakebites along with community-derived disability weights for snakebites. Standard methods for analysis and reporting of mortality, morbidity, years of lives lost, years lived with disability, disability weights, and costs of treatment will be calculated and presented. The study will be started in March 2021 and is expected to be completed by June 2021. Discussion: This protocol is the first published for estimating epidemiological, economic burden and community derived disability weights for snakebites in India. Besides, the Global Burden of Disease has not attached a particular disability weight to snakebite and this would be an attempt to do so.The protocol has been developed using guidelines for both cross-sectional studies and  for conducting community derived disability weights. The evidence generated will contribute to knowledge regarding epidemiology, economic burden and community-derived disability weights for snakebites in India and other LMICs.

Capillary leak syndrome in Daboia russelii bite-a complication associated with poor outcome.

Background: Capillary leak syndrome (CLS) has been previously observed as a complication of Daboia russelii bite but not clearly defined or studied in length. This observational case-control study evaluates the mortality along with associated clinical and laboratory features. Methods: Twenty-five patients who developed CLS were compared with 25 patients without CLS following Daboia russelii (Russell's viper) bite. Results: Development of CLS is associated with a significantly high risk of mortality; 11 (44%) patients with CLS died compared with 1 (4%) control (odds ratio 18.8 [95% confidence interval 2.2 to 161.99], p=0.002). Disease-defining manifestations included myalgia (22 [88%]), thirst (20 [80%]), parotid swelling (15 [60%]), conjunctival chemosis (19 [76%]) and hypotension (22 [88%]), which were unobserved in controls. Although several clinical and laboratory parameters were found to be predictive for development of CLS in univariate analysis, none of them had independent predictive value in multivariate analysis. Similarly, development of parotid swelling was the only factor with independent predictive value for mortality in multivariate analysis. Even though the number of vials of snake antivenom used is more in CLS, it seems unlikely to improve the mortality in CLS. Conclusions: This study proves that CLS is a well-defined complication of Russell's viper bite with high mortality but with clear predictors for the development of CLS and mortality.