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      Factors associated with unexplained sudden deaths among adults aged 18-45 years in India – A multicentric matched case–control study

      research-article
      1a , 1b , 1a , 1a , 1c , 1c , 1b , 1c , 1c , 12 , 4 , 14 , 15 , 18 , 21 , 22 , 23 , 26 , 32 , 5 , 24 , 36 , 37 , 13 , 42 , 39 , 27 , 31 , 40 , 6 , 41 , 28 , 16 , 44 , 2 , 7 , 38a , 45 , 29 , 19 , 9 , 10 , 46 , 3 , 11 , 47 , 43 , 33 , 8 , 20 , 48 , 34 , 30 , 17 , 35 , 25 , 49 , 1a , 1c , 1c , 1c , 1a , 1a , 1c , 1a , 50 , 50 , 50 , 38b , 1c , Sudden Adult Deaths Study Group *
      The Indian Journal of Medical Research
      Wolters Kluwer - Medknow
      Alcohol, case–control, coronavirus disease 2019, coronavirus disease 2019 vaccination, India, physical activity, smoking, sudden death, young adults

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          Abstract

          Background & objectives:

          In view of anecdotal reports of sudden unexplained deaths in India’s apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case–control study.

          Methods:

          This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI).

          Results:

          Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not.

          Interpretation & conclusions:

          COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

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          Most cited references34

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          A clinical case definition of post-COVID-19 condition by a Delphi consensus

          People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
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            Long-term cardiovascular outcomes of COVID-19

            The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.
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              High-dimensional characterization of post-acute sequalae of COVID-19

              The acute clinical manifestations of COVID-19 have been well characterized1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J Med Res
                IJMR
                Indian J Med Res
                The Indian Journal of Medical Research
                Wolters Kluwer - Medknow (India )
                0971-5916
                0975-9174
                October 2023
                25 September 2023
                : 158
                : 4
                : 351-362
                Affiliations
                [1a ] Division of Online Courses, Chennai, Tamil Nadu, India
                [1b ] ICMR School of Public Health, Chennai, Tamil Nadu, India
                [1c ] Division of Epidemiology and Biostatistics, ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India
                [2 ] Department of Community Medicine, Government Medical College, Omandurar Government Estate, Chennai, Tamil Nadu, India
                [3 ] Department of Cardiology, Sri Ramachandra Institute of Higher Education & Research, Chennai, Tamil Nadu, India
                [4 ] Department of Community Medicine, Kanyakumari Government Medical College, Kanyakumari, Tamil Nadu, India
                [5 ] Department of Emergency Medicine, Christian Medical College & Hospital, Vellore, Tamil Nadu, India
                [6 ] Department of Community Medicine, Government Medical College, Virudhunagar, Tamil Nadu, India
                [7 ] Department of Community Medicine, KMCH Institute of Health Sciences & Research, Coimbatore, Tamil Nadu, India
                [8 ] Department of Community Medicine, PSG Institute of Medical Sciences & Research, Coimbatore, Tamil Nadu, India
                [9 ] Department of Community Medicine, Tirunelveli Medical College & Hospital, Tirunelveli, Tamil Nadu, India
                [10 ] Department of Cardiology, Velammal Medical College Hospital & Research Institute, Madurai, Tamil Nadu, India
                [11 ] Institute of Community Medicine, Madurai Medical College, Madurai, Tamil Nadu, India
                [12 ] Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India
                [13 ] Department of Internal Medicine, Medanta, Gurugram, Haryana, India
                [14 ] Department of General Surgery, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
                [15 ] Infectious Disease Department, Institute of Post-Graduate Medical Education & Research, West Bengal, India
                [16 ] Department of Respiratory Medicine, College of Medicine & Sagore Dutta Hospital, West Bengal, India
                [17 ] Department of Geriatric Medicine, Medical College Kolkata, West Bengal, India
                [18 ] Department of Community Medicine, Government Medical College, Jalgaon, India
                [19 ] Department of Community Medicine, Dr. Vasantrao Pawar Medical College, Hospital & Research Center, Nashik, India
                [20 ] Department of Medicine, Dnyandeo Yashwantrao Patil Medical College, Pune, Maharashtra, India
                [21 ] Department of Community and Family Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
                [22 ] Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India
                [23 ] SPH and Community Medicine, All India Institute of Medical Sciences, Jodhpur, India
                [24 ] Department of Medicine, Sardar Patel Medical College, Bikaner, India
                [25 ] Department of Community Medicine, Mahatma Gandhi Medical College & Hospital, Jaipur, Rajasthan, India
                [26 ] Department of Emergency Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
                [27 ] Department of Community Medicine, Manipal Academy of Higher Education, Manipal, India
                [28 ] Department of Community Medicine, Adichunchanagiri Institute of Medical Sciences, Balagangadharanatha Nagara, Mandya, India
                [29 ] Department of Community Medicine, SDM College of Medical Science & Hospital, Dharwad, India
                [30 ] Department of Community Medicine, Bidar Institute of Medical Sciences, Bidar, India
                [31 ] Department of Community Medicine, Kasturba Medical College, Mangalore, Karnataka, India
                [32 ] Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
                [33 ] Department of Respiratory Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India
                [34 ] Department of Medicine, Government Institute of Medical Sciences, Noida, India
                [35 ] Department of Emergency, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
                [36 ] Department of Community & Family Medicine, All India Institute of Medical Sciences, Bathinda, Punjab, India
                [37 ] Department of Emergency and Critical Care Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India
                [38a ] Department of Emergency Medicine & Trauma, Jawaharlal Institute of Post Graduate Medical Education & Research, Puducherry, India
                [38b ] Department of Medical Gastroenterology, Jawaharlal Institute of Post Graduate Medical Education & Research, Puducherry, India
                [39 ] Department of Community Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
                [40 ] Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences, Shillong, Meghalaya, India
                [41 ] Department of Community Medicine, GMERS Medical College, Vadodara, India
                [42 ] Department of General Medicine, Smt. NHL Municipal Medical College, Ahmedabad, India
                [43 ] Department of Respiratory Medicine, SBKS MI&RC, Sumandeep Vidyapeeth, Pipariya, Vadodara, India
                [44 ] Department of Community Medicine, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Maharashtra, India
                [45 ] Department of Community Medicine, Gauhati Medical College, Guwahati, Assam, India
                [46 ] Department of PSM/Community Medicine, Shaheed Nirmal Mahato Medical College, Dhanbad, Jharkhand, India
                [47 ] Department of Trauma & Emergency (Division of Cardiology), All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
                [48 ] Department of Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
                [49 ] Department of Community Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir
                [50 ] Clinical Studies & Trials Unit, Indian Council of Medical Research, New Delhi, India
                [* ] Sudden Adult Deaths Study Group (In alphabetical order of State): Anjan Jyoti Talukdhar, Raj Prathim Das, Pranab Jyoti Bhattacharyya, Pankaj Jyoti Barman, Partha Pratim Das, Gauhati Medical College, Guwahati, Assam; P.V.M. Lakshmi, Naveen Panday, Ashok Kumar Pannu, Debaprasad Dhibar, Post Graduate Institute of Medical Education and Research, Chandigarh; Pankaj Kumar Kanauje, Satyajit Singh, Sabah Siddiqui, Nitin Bhajandas Borkar, Kalleshwar IT, AIIMS, Raipur, Chhattisgarh; Mayur Adalja, Sandip Shah Varsha Godbole, Rikin Raj, GMERS Medical College, Vadodara; Nehal Shah, Nilay Suthar, Hemang Purohit, Bhargav Patel, Rutika Pathkjee, Smt NHL Municipal Medical College, Ahmedabad; Niraj Pandit, Siddharth Shah, Bhavesh Patel, Anuja Agrawal, SBKS Medical College & Research Centre Sumandeep Vidyapeeth, Vadodara, Gujarat; Deepak Jain, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak; Manish Bansal, Vikas Deswal, Pooja Sharma, Medanta, Gurugram, Haryana; Farhana Siraj, Aamir Rashid, Anjum Bashir Fazili, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir; Pradip Kumar Bhattacharya, Hirendra Birua, Manoj Kumar Prasad, Shashi Bhushan Singh, Rajendra Institute of Medical Sciences, Ranchi; Umendra Kumar Ojha, Ravi Ranjan Jha, Shaheed Nirmal Mahato Medical College, Dhanbad, Jharkhand; Manuja LM, Raghavendra S.K, Vijay Hugar, Radha R, Adichunchanagiri Institute of Medical Sciences, Balagangadharanatha Nagara, Mandya; Pallavi Kesari, Sunil Tapse, Ambrish Avate, Prasanna Kumar, Bidar Institute of Medical Sciences, Bidar; Bhaskaran Unnikrishnan, Rekha T, Basavaprabhu A, Mithun Rao, Kasturba Medical College, Mangalore; Prithvishree Ravindra, Chythra R.Rao, Jayaraj Mymbilly Balakrishnan,Vikram Palimar, Kasturba Medical College, Manipal; Ashwini S, Bhavana Hiremath, Rajnikanth Malapur, SDM College of Medical Science and Hospital, Dharwad, Karnataka; Ankur Joshi, Manoj Nagar, Atul S. Keche, Mahadev Meena, AIIMS, Bhopal, Madhya Pradesh; Arjun Lal Kakrani, Shubhangi Kanitkar, Srikanth Tripathy, Savita Mahajan, Dnyandeo Yashwantrao Patil Medical College, Pune; Akshada Shinde, Sunil Patil, Dr.Vasantrao Pawar Medical College Hospital & Research Center, Nashik; Vijay Gaikwad, Ganesh Lokhande, Astha Ganeriwal, Ramesh Wasnik, Government Medical College, Jalgaon; Ashwini Kalantri, Dhiraj Bhandari, Preetam Salunkhe, Abhishek Raut, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Maharashtra; Star Pala, K.G. Lynrah, Nari Lyngdoh, Rajani Thabah, Manish Kapoor, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya; Sadananda Barik, Chitta Ranjan Mohanty, Sonu Hangma Subba, Satyabrata Guru, AIIMS, Bhubaneswar, Odisha; Manu Ayyan, Sitanshu Sekhar Kar, Nanda Kishore Maroju, Jawaharlal Institute of Post Graduate Medical Education & Research, Puducherry; Naveen Kumar, Roselin Mohandas, Charulatha Tamilselvan, Saranya Rajaram, Pondicherry Institute of Medical Sciences, Puducherry; Ankita Kankaria, Moonis Mirza, Preeti Singh Dhoat, Jaspreet Shergill, AIIMS, Bathinda, Punjab; Manoj Kumar Gupta, Akhil Dhanesh Goel, Amit Kumar Rohila, Durga Shankar Meena AIIMS, Jodhpur, Archana Paliwal, Niti Gahlot, Nikita Sharma, Harkesh Kumar, Mahatma Gandhi Medical College and Hospital, Jaipur; Dinesh Choudhary, Shyam Lal Meena, Dinesh Bhambhu, Jigyasa Gupta, Sardar Patel Medical College, Bikaner, Rajasthan; Priya G, Sonia Samuel, Bagyalakshmi S., Sathish Kumar T., Christian Medical College, Vellore; Aazmi Mohamed, G Rathna Kumar, A. Rajesh, V. Rajendran, Tirunelveli Medical College & Hospital, Tirunelveli, Soorya M.,Sridevi P.N., A.Karthika, K.Santha Sheela Kumari, Government Medical College, Virudhunagar, K.Sathish Kumar, Pavithra Gnanavel, Dasarathan Ramesh, Aravind Gunasekaran, Government Medical College Omandurar Government Estate, Chennai; R. Kaverikannan, Madhumitha Manohar, P. Sofia, R. Abishek, Kanyakumari Government Medical College, Kanyakumari; Jeevithan Shanmugam, Mohan Kumar, Aparnavi Periyasamy, Dhilipan Kumar, KMCH Institute of Health Sciences and Research, Coimbatore; Selvarani G, Thirukumaran Ramasamy, SureshN., Kannan Muthuraman Alagappan, Madurai Medical College, Madurai; Mathavasami Vijayageetha, Sudha Ramalingam, Petchiappan Velammal, Yamini Subramani, PSG Institute of Medical Sciences and Research, Coimbatore; Lakshmi Marappa, Viswanathan Pandurangan, Muralidharan T.R., M.Rajkumar, Sri Ramachandra Institute of Higher Education and Research, Chennai, Senthil Murugan Ramasamy, Bodhare Trupti, Bharath Rajh, Duvuru Amareswar Reddy, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu; Rashmi Upadhyay, Anurag Srivastava, Rakesh Gupta, Government Institute of Medical Sciences, Noida; Ranjan Bhattnagar, Manaswi Chaubey, Soumik Ghosh, Nilesh Kumar, Institute of Medical Sciences, Banaras Hindu University, Varanasi; Mohammad Azharuddin, Nafees A. Khan, Mohammad Aslam, Asad Mahmood, Jawaharlal Nehru Medical College, Aligarh; R.K.Singh, Priyank Yadav, Aditya Kapoor, Om Prakash Sanjeev, Shyam Sundar, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; Prasan Kumar Panda, Mukesh Bairwa, Mahendera Singh Gehlot, Pooja Bhadoria, AIIMS, Rishikesh, Uttarakhand; Arup Chakravorty, Sarmistha Chakravorty, Medical College, Kolkata; Arindam Ray, Aparup Dhua, Amitava Pal, Priyanka Ghosh, College of Medicine and Sagore Dutta Hospital, Kolkata, Yogiraj Roy, Sinjita Dutta, Subhro Samujjal Basu, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India.
                Author notes
                For correspondence: Dr Manoj Vasant Murhekar, ICMR-National Institute of Epidemiology, Chennai 600 077, Tamil Nadu, India e-mail: mmurhekar@ 123456nieicmr.org.in
                Article
                IJMR-158-351
                10.4103/ijmr.ijmr_2105_23
                10793826
                37988028
                dbec6b84-5d8d-4ee7-9d13-ed8e5a90b1b4
                Copyright: © 2023 Indian Journal of Medical Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 30 October 2023
                Categories
                Programme: Original Article

                Medicine
                alcohol,case–control,coronavirus disease 2019,coronavirus disease 2019 vaccination,india,physical activity,smoking,sudden death,young adults

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