India Hypertension Control Initiative: Blood Pressure Control Using Drug and Dose-Specific Standard Treatment Protocol at Scale in Punjab and Maharashtra, India, 2022.

Background: Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We estimated the effectiveness of various protocol steps to achieve blood pressure (BP) control in public sector health facilities in Punjab and Maharashtra, India, where the India Hypertension Control Initiative (IHCI) was implemented. Methods: We analyzed the records of people enrolled for hypertension treatment and follow-up under IHCI between January 2018 and December 2021 in public sector primary and secondary care facilities across 23 districts from two states. Each state followed a different treatment protocol. We calculated the proportion with controlled BP at each step of the protocol. We also estimated the mean decline in BP pre- and post-treatment. Results: Of 281,209 patients initiated on amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 33,450 individuals who came for the follow-up in Punjab and 125,842 in Maharashtra, 70% and 76% had controlled BP, respectively, at the first step with amlodipine 5 mg. In Punjab, at the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76%-81%) increase was seen in the second step after adding telmisartan 40 mg in Maharashtra. Overall, the mean (SD) systolic blood pressure (SBP) decreased by 16 mmHg from 148 (15) mmHg at the baseline in Punjab. In Maharashtra, the decline in the mean (SD) SBP was about 15 mmHg from the 144 (18) mmHg baseline. Conclusion: Simple drug- and dose-specific protocols helped achieve a high control rate among patients retained in care under program conditions. We recommend treatment protocols starting with a single low-cost drug and escalating with the same or another antihypertensive drug depending on the cost and availability.

Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

South African flag sign to a giant coronary artery aneurysm.

Background: Coronary arteritis leading to aneurysm is one of the unusual presentations of IgG4-related disease. Acute myocardial infarction as a complication of IgG4-related giant coronary artery aneurysm is even rarer. Case summary: We describe the case of a 56-year-old gentleman who presented to our institute with Canadian Cardiovascular Society (CCS) class III angina. His symptoms were persistent even with high-dose antianginal medications. He had an acute coronary syndrome two weeks back for which he was treated conservatively in a peripheral health centre. His 12-lead electrocardiogram at the time of the event was suggestive of high lateral ST-segment elevation myocardial infarction (South African flag sign). His transthoracic echocardiography showed mild left ventricular dysfunction and a large echogenic mass lateral to the left ventricle. Coronary angiography followed by cardiac computed tomography revealed a giant pseudoaneurysm of the proximal and mid-left anterior descending coronary artery. FDG-PET scan showed significant metabolic activity in the aneurysm wall and mediastinal lymph nodes suggesting active inflammation. IgG4-related coronary arteritis was suspected, and the patient underwent aneurysmectomy and coronary artery bypass (CABG) surgery. The histopathology of the resected segment showed diffuse IgG4-secreting plasma cells confirming the diagnosis. Discussion: Atherosclerosis is the most common cause of coronary aneurysms in adults. However, cardiologists should be aware of atypical causes like IgG4-related disease that can even present with acute coronary syndrome. Although multimodality imaging is beneficial during early evaluation, histopathological analysis is the cornerstone for the diagnosis of IgG4-related disease. The management involves both immunosuppressive medication and endovascular or surgical repair.

Improving the availability of antihypertensive drugs in the India Hypertension Control Initiative, India, 2019-2020.

BACKGROUND: Antihypertensive drug supply is sometimes inadequate in public sector health facilities in India. One of the core strategies of the India Hypertension Control Initiative (IHCI) is to improve the availability of antihypertensive drugs in primary and secondary care facilities. We quantified the availability of antihypertensive drugs in 2019-20 and described the practices in supply chain management in 22 districts across four states of India. METHODS: Twenty-two districts from 4 states (Punjab, Madhya Pradesh, Telangana, and Maharashtra) were studied. We described the practices and challenges in supply chain management. We collected data on drug procurement from 2018 to 2020 and drug availability from April 2019 to March 2020. Quantity procured, the proportion of facilities with stockout at the end of each quarter, and availability of drugs in patient days were tabulated. RESULTS: All states selected drug- and dose-specific protocols with Amlodipine as the initial drug and shifted to morbidity-based forecasting. The total number of antihypertensive tablets procured for the 22 districts increased from 16 million in 2017-2018 to 160 million in 2019-2020. The proportion of facilities with Amlodipine stock-out was below 5% during the study period. Amlodipine stock was available for at least 60 patient days from the third quarter of 2019 onward in all districts. CONCLUSIONS: This study demonstrates that including best practices can gradually strengthen the procurement and supply chain for antihypertensives in a low-resource setting. As the program was rapidly growing, there were still gaps in the procurement and distribution system which needed to be addressed to ensure the adequacy of drugs. We recommend that best practices, including choosing a single protocol, basing supply on projected patient load rather than an increment from historical levels, and using simple stock management tools, be replicated in other districts in India to increase and sustain coverage of hypertension treatment.

Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Prevalence and factors associated with tuberculosis infection in India.

BACKGROUND: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. METHODS: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76). CONCLUSION: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

India's tryst with salt: Dandi march to low sodium salts.

Salt plays a critical role in India's past as well as its present, from Dandi March to its role as a vehicle for micronutrient fortification. However, excess salt intake is a risk factor for high blood pressure and cardiovascular diseases (CVDs). Indians consume double the World Health Organization recommended daily salt (<5 g). India has committed to a 30 per cent reduction in sodium intake by 2025. Evidence based strategies for population sodium intake reduction require a moderate reduction in salt in - home cooked foods, packaged foods and outside-home foods. Reducing the sodium content in packaged food includes policy driven interventions such as front-of-package warning labels, food reformulation, marketing restrictions and taxation on high sodium foods. For foods outside of the home, setting standards for foods purchased and served by schemes like mid-day meals can have a moderate impact. For home cooked foods (the major source of sodium), strategies include advocacy for reducing salt intake. In addition to mass media campaigns for awareness generation, substituting regular salt with low sodium salt (LSS) has the potential to reduce salt intake even in the absence of a major shift in consumer behaviour. LSS substitution effectively lowers blood pressure and thus reduces the risk of CVDs. Further research is required on the effect of LSS substitutes on patients with chronic kidney disease. India needs an integrated approach to sodium reduction that uses evidence based strategies and can be implemented sustainably at scale. This will be possible only through scientific research, governmental leadership and a responsive evidence-to-action approach through a multi-stakeholder coalition.

Developing Standard Treatment Workflows-way to universal healthcare in India.

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80-90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC.

Development of prospective hospital-based venous thromboembolism registry across India: a study protocol.

INTRODUCTION: Indian Council of Medical Research (ICMR), New Delhi has established a nationwide registry 'Indian Registry for Venous Thromoembolism Disorder (i-RegVeD)' for real-time analytics of sociodemographic profile of patients, disease patterns, management strategies, treatment choices and outcomes of patients with venous thromboemobolism (VTE). The purpose is to generate evidence on VTE in order to fill the gaps in the knowledge of the disease across various demographic regions. METHODS AND ANALYSIS: This prospective hospital-based registry will be a continuous data collection process on the occurrence and characteristics of VTE from the 16 hospital sites pan India. This process would include obtaining clinical profiles, risk factors, diagnostic tests, treatment and outcome information of patients collected from medical records through an active method of data abstraction and data capture mechanism guided by an online web-based tool. ETHICS AND DISSEMINATION: At centralised programme management unit, the study protocol was approved by the Institutional Ethics Committees (IEC) named ICMR-Central Ethics Committee on Human Research and similarly each of the participating site has obtained the ethical approval by their respective IECs. The results from this study will be disseminated publicly on the study website (https://iregved.icmr.org.in) as well as through scientific meetings and publications.

Complete Revascularization and Angina-Related Health Status in the ISCHEMIA Trial.

BACKGROUND: The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied. OBJECTIVES: Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON. METHODS: Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization. Propensity-weighted modeling was then performed to estimate the treatment effect had CR or ICR been achieved in all INV patients, compared with CON. RESULTS: Anatomic and functional CR were achieved in 43.3% and 57.8% of 1,641 INV patients, respectively. Among revascularized patients, CR was associated with improved Seattle Angina Questionnaire Angina Frequency compared with ICR after adjustment for baseline differences. After modeling CR and ICR in all INV patients, patients with CR and ICR each had greater improvements in health status than CON, with better health status with CR than ICR. The projected benefits of CR were most pronounced in patients with baseline daily/weekly angina and not seen in those with no angina. CONCLUSIONS: Among patients with CCD in ISCHEMIA, health status improved more with CR compared with ICR or CON, particularly in those with frequent angina. Anatomic and functional CR provided comparable improvements in quality of life. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Implementation of drone based delivery of medical supplies in North-East India: experiences, challenges and adopted strategies.

Timely delivery of medical supplies is essential in the healthcare sector, which is hampered by factors such as poor transportation network, traffic and adverse environmental conditions. Alternatively, drone operations can leapfrog the last mile logistic solutions in hard-to-reach terrains. The present paper elucidates the implementation process of drone-based delivery of medical supplies, operational challenges and innovations adopted by scientists in Manipur and Nagaland. Three districts, Bishnupur, Imphal West and Churachandpur from Manipur and two districts, Mokokchung and Tuensang from Nagaland, were selected for the study. Regulatory and ethical approvals and coordination with state health and administrative authorities were accorded. Implementation and operational challenges faced by the research team were recorded elaborately in the field diaries and assessed qualitatively. The experiences encountered by the team for case-to-case based permission and coordination with the central and state aviation authorities, district administration and health authorities were observed. The drone-related technical and logistic challenges were identified as the deployment of suitable drones, payload capacity, time management for operations, and transportation of drones. The officials adopted mitigation strategies to overcome field-based challenges. Drone-based deliveries of medical supplies are proving to be time efficient, however, overcoming operational challenges could provide an effective long-term deployment strategy.

Dealing with infodemic during COVID-19 pandemic: Role of effective health communication in facilitating outbreak response & actions - An ICMR experience.

Objectives: To highlight and assess the impact of intervention tools used by Indian Council of Medical Research (ICMR) against COVID19 associated infodemic in the world's largest democratic country, India. Study design: It is a retrospective cross sectional study. The impact of ICMR's multi-pronged strategy to address the infodemic during pandemic has been assessed through analysis of print media reportage and social media engagements. Methods: The impact of the interventions was assessed using cloud media mappers like MediaCloud and Meltwater using keywords. The data was analysed in terms of reportage, theme of reportage. A sub-section of media reportage (Feb 2020-June 2020) was analysed in details from 4 major dailies to understand the coverage and tonality of media reports. The data on COVID 19 related tweets, posts and uploads were taken from social media platforms of Indian Council of Medical Research (ICMR) particularly twitter, instagram, facebook and youtube and estimate of pre and post pandemic changes in followers or users were collected for analysis. The data was curated and analysed using MS excel. Results: There was a surge of 3800% reportage in media during pandemic as compared to same time frame in pre-pandemic times. A surge of followers on twitter from 26,823 on Feb 2020 (before pandemic) to 3,36,098 at March 2022 (after pandemic) was observed. A drastic increase in monthly followers was observed after start of Pandemic (after Feb 2020) in comparison to before pandemic (Before Feb 2020). Similar trends were observed on other social media platforms of ICMR. Conclusions: The Communications Unit at ICMR geared up with more robust plans and designed several interventions to mitigate the infodemic which helped in evidence based decision making towards outbreak response and action. This highlights the importance of evidence based, crisp, timely and effective communication during the epidemics/pandemics to buid trust and confidence in the community.

The burgeoning cardiovascular disease epidemic in Indians - perspectives on contextual factors and potential solutions.

Cardiovascular diseases (CVD) are the leading cause of death and disability in India. The CVD epidemic in Indians is characterized by a higher relative risk burden, an earlier age of onset, higher case fatality and higher premature deaths. For decades, researchers have been trying to understand the reason for this increased burden and propensity of CVD among Indians. It can partly be explained by population-level changes and the remaining by increased inherent biological risk. While increased biological risk can be attributed to phenotypic changes caused by early life influences, six major transitions can be considered largely responsible for the population-level changes in India-epidemiological, demographic, nutritional, environmental, social-cultural and economic. Although conventional risk factors explain substantial population attributable risk, the thresholds at which these risk factors operate are different among Indians compared with other populations. Therefore, alternate explanations for these ecological differences have been sought and multiple hypotheses have been proposed over the years. Prenatal factors that include maternal and paternal influences on the offspring, and postnatal factors, ranging from birth through childhood, adolescence and young adulthood, as well as inter-generational influences have been explored using the life course approach to chronic disease. In addition to this, recent research has illustrated the importance of the role of inherent biological differences in lipid metabolism, glucose metabolism, inflammatory states, genetic predispositions and epigenetic influences for the increased risk. A multifaceted and holistic approach to CVD prevention that takes into consideration population-level as well as biological risk factors would be needed to control the burgeoning CVD epidemic among Indians.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Evaluation of a Hospitalized Pediatric COVID-19 Cohort from Indian National Clinical Registry of COVID-19.

OBJECTIVE: To evaluate the factors associated with mortality of a multicentric cohort of hospitalized COVID-19 patients, 0-18 y old, from 42 centers across India. METHODS: The National Clinical Registry for COVID-19 (NCRC) is an on-going prospective data collection platform enrolling COVID-19 patients diagnosed by real-time PCR or rapid antigen test. The data are collected in prestructured e-capture forms. The sociodemographic, clinical, laboratory, and hospital outcome data from 1st September 2020 to 20th February 2022 were analyzed. RESULTS: Of the 1244 enrolled hospitalized COVID-19 patients aged 0-18 y, 98 and 124 were infants and neonates, respectively. Only 68.6% children were symptomatic at admission, with fever being the most common symptom. Diarrhea, rash, and neurological symptoms were also noted. At least 1 comorbidity was present in 260 (21%) children. The in-hospital mortality rate was 6.2% (n = 67), the highest in infants (12.5%). Altered sensorium (aOR: 6.8, CI: 1.9, 24.6), WHO ordinal scale ≥ 4 at admission (aOR: 19.6, CI: 8.0, 47.8), and malignancy (aOR: 8.9, 95% CI: 2.4, 32.3) were associated with higher odds of death. Malnutrition did not affect the outcome. Mortality rates were similar across the three waves of the pandemic, though a significant shift towards the under-five group was observed in the third wave. CONCLUSION: This multicentric cohort of admitted Indian children showed that the COVID-19 was milder in children than adults, and the pattern was consistent across all waves of the pandemic.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.

The India Hypertension Control Initiative-early outcomes in 26 districts across five states of India, 2018-2020.

Hypertension is the leading single preventable risk factor for cardiovascular disease. The India Hypertension Control Initiative (IHCI) project was designed to improve hypertension control in public sector clinics. The project was launched in 2018-2019 in 26 districts across five states: Punjab (5), Madhya Pradesh (3), Kerala (4), Maharashtra (4), and Telangana (10), with five core strategies: standard treatment protocol, reliable supply of free antihypertensive drugs, team-based care, patient-centered care, and an information system to track individual patient treatment and blood pressure control. All states implemented simple treatment protocols with three drugs: a long-acting dihydropyridine calcium channel blocker (amlodipine), angiotensin receptor blocker (telmisartan), and thiazide or a thiazide-like diuretic (hydrochlorothiazide or chlorthalidone). Medication supplies were adequate to support at least one month of treatment. Overall, 570,365 hypertensives were enrolled in 2018-2019; 11% did not have follow-up visits in the most recent 12 months. Clinic-level blood pressure control averaged 43% (range 22-79%) by Jan-March, 2020. The proportion of the estimated people with hypertension who had it controlled and documented in public clinics increased three-fold, albeit from very low levels (1.4-5.0%). The IHCI demonstrated the feasibility of implementing protocol-based hypertension treatment and control supported by a reliable drug supply and accurate information systems at scale in Indian primary health care facilities. Lessons from the IHCI's initial phase will inform plans to improve screening in health care facilities, increase retention in care, and ensure a sustained supply of drugs as part of a nationwide hypertension control program.