Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.

CKD is the Major Cause of Death in Uddanam: A Population-Representative Study Using Smart Verbal Autopsy.

Introduction: Uddanam is an agricultural area with a high burden of chronic kidney disease of unknown etiology (CKDu). Despite reports of many deaths due to CKD in the lay press, the exact contribution of CKD to deaths remains uncertain because most deaths occur outside medical care. Methods: We used SmartVA automated verbal autopsy tool to ascertain the cause-specific mortality fractions among a 2419 subject-strong general population cohort of adult subjects in Uddanam between 2018 and 2022. Verbal autopsy interviews were conducted twice with the family members of the deceased. Results: A total of 133 deaths were recorded, giving a crude death rate of 5.5%, 10 times higher than that recorded in national surveys. CKD was responsible for 45% of all deaths, followed by ischemic heart disease (15%) and respiratory disease (6%). Conclusion: This study confirms CKD as the leading cause of mortality in this high CKD burden area and provides crucial data for public health decision-making and resource allocation.

Patterns of multimorbidity among a community-based cohort in rural India.

Background: Multimorbidity estimates are expected to increase in India primarily due to the population aging. However, there is a lack of research estimating the burden of multimorbidity in the Indian context using a validated tool. We estimated the prevalence and determinants of multimorbidity amongst the adult population of the rural Uddanam region, Andhra Pradesh. Methods: This community-based cross-sectional study was conducted as a part of an ongoing research program. Multistage cluster sampling technique was used to select 2419 adult participants from 40 clusters. Multimorbidity was assessed using Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC) tool, collecting information on 13 chronic diseases. Patient Health Questionnaire (PHQ-12) was used to screen for depression. Multiple logistic regression was conducted to identify the strongest determinants of multimorbidity. Results: Of the 2419 participants, 2289 completed the MAQ-PC tool. Mean age (standard deviation) of participants was 48.1 (13.1) years. The overall prevalence of multimorbidity was 58.5% (95% CI 56.5-60.6); with 30.7%, 15.6%, and 12.2% reporting two, three, and four chronic conditions, respectively. Acid peptic disease-musculoskeletal disease (44%) and acid peptic disease-musculoskeletal disease-hypertension (14.9%) were the most common dyad and triad. Among metabolic diseases, diabetes-hypertension (28.3%) and diabetes-hypertension-chronic kidney disease (7.6%) were the most common dyad and triad, respectively. Advancing age, female gender, and being obese were the strongest determinates of the presence of multimorbidity. Depression was highly prevalent among the study population, and participants with higher PHQ-12 score had 3.7 (2.5-5.4) greater odds of having multimorbidity. Conclusions: Our findings suggest that six of 10 adults in rural India are affected with multimorbidity. We report a higher prevalence of multimorbidity as compared with other studies conducted in India. We also identified vulnerable groups which would guide policy makers in developing holistic care packages for individuals with multimorbidity.

A Systematic Study of the Prevalence and Risk Factors of CKD in Uddanam, India.

INTRODUCTION: Despite reports of a high prevalence of chronic kidney disease (CKD) from the coastal Uddanam region of Andhra Pradesh, India, there are no accurate data on the distribution of kidney function abnormalities and CKD risk factors in this region. METHODS: A total of 2419 participants were recruited through multistage cluster random sampling from 67 villages. Serum creatinine and urine protein creatinine ratio were measured using validated methodologies. All abnormal estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio values were reconfirmed after 3 months. A range of sociodemographic factors were evaluated for their association with CKD using Poisson regression. RESULTS: Of 2402 eligible subjects (mean ± SD age, 45.67 ± 13.29 years; 51% female), 506 (21.07%) had CKD (mean ± SD age, 51.79 ± 13.12 years; 41.3% female). A total of 246 (10.24%) had eGFR <60 ml/min/1.73 m2, whereas 371 (15.45%) had an elevated urine protein creatinine ratio (>0.15 g/g). The poststratified estimates, adjusted for age and sex distribution of the region for CKD prevalence, are 18.7% (range, 16.4%-21.0%) overall and 21.3% (range, 18.2%-24.4% ) and 16.2% (range, 13.7%-18.8%) in men and women, respectively. Older age, male sex, tobacco use, hypertension, and family history of CKD were independently associated with CKD. Compared with those with higher eGFR, those with eGFR <60 ml/min/1.73m2 were older, were more likely to be uneducated, manual laborers/farmers, or tobacco users, and were more likely to have hypertension, a family history of CKD, a diagnosis of heart disease, and a lower body mass index. Among those with low eGFR, there was no difference between those with urine protein creatinine ratio <0.15 or >0.15, except a lower frequency of males in the former. CONCLUSION: We confirmed the high prevalence of CKD in the adult population of Uddanam. The cause was not apparent in a majority. Subjects with a low eGFR with or without elevated proteinuria were phenotypically distinct from those with proteinuria and preserved eGFR. Our data suggest the need to apply a population-based approach to screening and prevention and studies to understand the causes of CKD in this region.

Qualitative enquiry on irregular intake of antihypertensive medications to inform a model of care to improve blood pressure control.

Background: A large proportion of people with hypertension do not take medications regularly. There is little understanding of this complex behaviour in India.Methods: A descriptive qualitative study was conducted in two districts of Andhra Pradesh, India, to explore the reasons for irregular intake of anti-hypertensive drugs from patient's and health care provider's (HCP) perspectives. In-depth interviews and focus group discussions were carried out among HCPs and patients with irregular drug intake.Results: The major themes that emerged were: (i) patient's perception of immediate relief and poor awareness about the disease, (ii) patient's misconceptions about the drug and fear of life long medications, (iii) busy schedule and forgetfulness, (iv) health system factors such as lack of patient counselling, high cost of care and non-availability of medicines, and (v) lack of peer/family/social support and social stigma.Conclusion: Better patient education and counselling services and active engagement of family members and peers are needed to improve medication adherence. The NPCDCS program should implement mechanisms to assess and monitor adherence to medications in chronic diseases particularly for hypertension.Impact: Currently there is no strategy to ensure medication adherence in India. The results of the study will be utilized in developing a community model of care to improve the level of adherence and better control of blood pressure.KEYWORDS: hypertension; medication adherence; compliance; qualitative study.

Continuum of care for non-communicable diseases during COVID-19 pandemic in rural India: A mixed methods study.

BACKGROUND: COVID-19 pandemic has resulted in disruption to routine health services delivery as strict lockdowns were implemented in India and health workforce redeployed for COVID-19 focused responses. We assess the perceptions about COVID-19, the impact of the lockdown on access to health services and continuum of care for Non-communicable diseases (NCDs) among a cohort of adults in rural India. METHODOLOGY: Since 2018, we have been following up a cohort of persons with non-communicable diseases in a high NCD burden region in Srikakulam District of Andhra Pradesh under the STOP CKDu study. We conducted this mixed methods study, administered through a structured telephonic questionnaire and interview to determine the awareness, perceptions and their compliance to ongoing treatment schedules. RESULTS: Overall, 68% of the participants exhibited adequate knowledge of symptoms of COVID-19, while 43% were not aware of the mode of transmission of the virus. In all, 822 (36.1%) participants reported at least one NCD condition. Among them, 115 (14%) missed their follow-up visit, 110 (13.4%) reported facing challenges in medication procurement and 11.6% either developed new complaints or experienced worsening of pre-existing symptoms. A total of 233 (28.5%) used a telemedicine facility and took telephonic advice from (private) physicians. As the access to medicines was restricted due to the lockdown, majority of the respondents were depending on rural medical practitioners (RMPs) for the procurement of medication. CONCLUSION: Our finding implies the need for the future guidelines on adaptation of telehealth approaches within health systems to maintain the continuum of care, digital health tools to facilitate the patient's appointments including virtual follow-up visits for those with NCDs coupled with regular engagement by frontline healthcare workers at the local levels, evidence informed public health messaging taking into consideration the social and behavioural aspect and uninterrupted essential primary healthcare services.

Study to Test and Operationalize Preventive Approaches for CKD of Undetermined Etiology in Andhra Pradesh, India.

INTRODUCTION: High prevalence of chronic kidney disease (CKD) not associated with known risk factors has been reported from coastal districts of Andhra Pradesh. The Study to Test and Operationalize Preventive Approaches for Chronic Kidney Disease of Undetermined Etiology in Andhra Pradesh (STOP CKDu AP) aims to ascertain the burden (prevalence and incidence) of CKD, the risk factor profile, and the community perceptions about the disease in the Uddanam area of Andhra Pradesh. METHODS: Study participants will be sampled from the Uddanam area using multistage cluster random sampling. Information will be collected on the demographic profile, occupational history, and presence of conventional as well as nonconventional risk factors. Glomerular filtration rate (GFR) will be estimated using the Chronic Kidney Disease Epidemiology Collaboration equation, and proteinuria will be measured. All abnormal values will be confirmed by repeat testing after 3 months. Cases of CKD not associated with identified etiologies will be identified. Biospecimens will be stored to explore future hypotheses. The entire cohort will be followed up every 6 months to determine the incidence of CKD and to identify risk factors for decline in kidney function. Qualitative studies will be performed to understand the community perceptions and expectations with respect to the interventions. IMPLICATIONS: CKD is an important public health challenge in low- and middle-income countries. This study will establish the prevalence and determine the incidence of CKD not associated with known risk factors in a reported high-burden region, and will provide insights to help design targeted health systems responses. The findings will contribute to the policy development to tackle CKD in the region and will permit international comparisons with other regions with similar high prevalence.

Are people at high risk for diabetes visiting health facility for confirmation of diagnosis? A population-based study from rural India.

BACKGROUND: India is witnessing a rising burden of type 2 diabetes mellitus. India's National Programme for Prevention and Control of Diabetes, Cancer, Cardiovascular diseases and Stroke recommends population-based screening and referral to primary health centre for diagnosis confirmation and treatment initiation. However, little is known about uptake of confirmatory tests among screen positives. OBJECTIVE: To estimate the uptake of confirmatory tests and identify the reasons for not undergoing confirmation by those at high risk for developing diabetes. METHODS: We analysed data collected under project UDAY, a comprehensive diabetes and hypertension prevention and management programme, being implemented in rural Andhra Pradesh, India. Under UDAY, population-based screening for diabetes was carried out by project health workers using a diabetes risk score and capillary blood glucose test. Participants at high risk for diabetes were asked to undergo confirmatory tests. On follow-up visit, health workers assessed if the participant had undergone confirmation and ask for reasons if not so. RESULTS: Of the 35,475 eligible adults screened between April 2015 and August 2016, 10,960 (31%) were determined to be at high risk. Among those at high risk, 9670 (88%) were followed up, and of those, only 616 (6%) underwent confirmation. Of those who underwent confirmation, 'lack of symptoms of diabetes warranting visit to health facility' (52%) and 'being at high risk was not necessary enough to visit' (41%) were the most commonly reported reasons for non-confirmation. Inconvenient facility time (4.4%), no nearby facility (3.2%), un-affordability (2.2%) and long waiting time (1.6%) were the common health system-related factors that affected the uptake of the confirmatory test. CONCLUSION: Confirmation of diabetes was abysmally low in the study population. Low uptake of the confirmatory test might be due to low 'risk perception'. The uptake can be increased by improving the population risk perception through individual and/or community-focused risk communication interventions.