Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial.

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown. Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo. Design, Setting, and Participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022. Participants were randomized 3:1 to SII-NVX-CoV2373 or placebo and monitored for 179 days. The participants, study team, and laboratory staff were blinded. This was a multicenter study conducted across 10 tertiary care hospitals in India. Exclusion criteria included previous COVID-19 infection or vaccination, immunocompromised condition, and immunosuppressive medications. Interventions: Two doses of 0.5-mL SII-NVX-CoV2373 or placebo were administered intramuscularly on days 1 and 22. Main Outcomes and Measures: Primary outcomes were geometric mean titer ratio of both anti-spike (anti-S) IgG and neutralizing antibodies (NAbs) between both pediatric age groups to that of adults on day 36. Noninferiority was concluded if the lower bound of 95% CI of this ratio was greater than 0.67 for each age group. Both the antibodies were assessed for the index strain and for selected variants at various time points. Solicited adverse events (AEs) were recorded for 7 days after each vaccination, unsolicited AEs were recorded for 35 days, and serious AEs and AEs of special interest were recorded for 179 days. Results: A total of 460 children in each age cohort were randomized to receive vaccine or placebo. The mean (SD) age was 6.7 (2.7) years in the child cohort and 14.3 (1.6) years in the adolescent cohort; 231 participants (50.2%) in the child cohort and 218 in the adolescent cohort (47.4%) were female. Both anti-S IgG and NAb titers were markedly higher in the SII-NVX-CoV2373 group than in the placebo group on both day 36 and day 180. The geometric mean titer ratios compared to those in adults were 1.20 (95% CI, 1.08-1.34) and 1.52 (95% CI, 1.38-1.67) for anti-S IgG in adolescents and children, respectively; while for NAbs, they were 1.33 (95% CI, 1.17-1.50) and 1.93 (95% CI, 1.70-2.18) in adolescents and children, respectively, indicating noninferiority. SII-NVX-CoV2373 also showed immune responses against variants studied. Injection site reactions, fever, headache, malaise, and fatigue were common solicited AEs. There were no AEs of special interest and no causally related serious AEs. Conclusions and Relevance: SII-NVX-CoV2373 was safe and well tolerated in children and adolescents in this study. The vaccine was highly immunogenic and may be used in pediatric vaccination against COVID-19. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2021/02/031554.

Community health volunteer for blood pressure control in rural people with stroke in India: Pilot randomised trial.

OBJECTIVE: To test the hypothesis that an Accredited social health activist (ASHA), a community health volunteer in a task-sharing model can help in sustained control of systolic blood pressure (BP) in rural people with Stroke and hypertension at 6 months follow up. METHODS: In this randomized trial two rural areas (Pakhowal and Sidhwan bet) with 70 and 94 villages respectively were screened for people with stroke and hypertension. They were assigned to either ASHA-assisted BP control in addition to standard-of-care (Pakhowal-intervention Group) or standard-of-care alone (Sidhwan bet- Control Group). Assessors blinded to intervention conducted the baseline and 6 months follow-up visits to measure risk factors in both the rural areas. RESULTS: A total of 140 people with stroke with mean age of 63.7 ± 11.5 years and 44.3% females were randomised. The baseline systolic BP was higher in the intervention group (n = 65,173.5 ± 22.9 mmHg) compared to the control group (n = 75,163 ± 18.7 mmHg, p = 0.004). The follow-up systolic BP was lower in the intervention group compared to the control group 145 ± 17.2 mmHg and 166.6 ± 25.7 mmHg respectively (p < 0.0001). According to the intention-to-treat analysis a total of 69.2% of patients in the intervention group achieved systolic BP control compared to 18.9% in the control group patients (OR 9, 95% CI 3.9-20.3; p < 0.0001). CONCLUSION: Task sharing with ASHA a community health volunteer can improve BP control in rural people with stroke and hypertension. They can also help in the adoption of healthy behaviour. CLINICAL TRIAL REGISTRATION NUMBER: ctri.nic.in, CTRI/2018/09/015709.

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.

Transient Ischemic Attack (TIA) Incidence with Geographic Information Systems (GIS) Mapping for Stroke Prevention Interventions.

OBJECTIVES: GIS mapping as a public health tool has been increasingly applied to chronic disease control. While evaluating TIA incidence from an existing regional stroke registry in Ludhiana city, India, we aim to apply the innovative concept of regional TIA GIS mapping for planning targeted stroke prevention interventions. METHODS: TIA patient data was obtained from hospitals, scan centers and general practitioners from March 2010 to March 2013 using WHO-Stroke STEPS based surveillance as part of establishing a population-based stroke registry in Ludhiana city. From this registry, patients with TIA (diagnosed by MRI image-based stroke rule-out, or clinically) were chosen and data analyzed. RESULTS: A total of 138 TIA patients were included in the final analysis. The annual TIA incidence rate for Ludhiana city was 7.13/100,000 (95% confidence interval: 5.52 to 8.74) for 2012-2013. Mean age was 58.5 ± 13.9 years (range: 22-88 years) and 87 (63%) were men. Majority of the TIA cases had anterior circulation TIAs. Hypertension (87.4%) was the most common risk factor. Using Geographic Information System (GIS) mapping, high TIA incidence was seen in central, western, and southern parts and clustering of TIA cumulative incidence was seen in the central part of Ludhiana city. CONCLUSION: Incidence rate of TIA was lower than that expected from a low- and middle-income country (LMIC). TIA GIS mapping, looking at regional localization, can be a novel option for developing targeted, cost-effective stroke prevention programs.

Rural Stroke Surveillance and Establishment of Acute Stroke Care Pathway Using Frontline Health Workers in Rural Northwest India: The Ludhiana Experience.

BACKGROUND AND PURPOSE: The role of community health workers (CHWs) in stroke surveillance and in establishing the stroke care pathway has not been studied. The aim of the study was to evaluate the feasibility of using CHWs in the public health system to identify stroke patients for population-based stroke registration and to study the establishment of acute stroke care pathway in rural areas of Ludhiana, Punjab, Northwest India. METHODS: Two rural blocks in Ludhiana district, comprising 164 villages and a population of 259,778, were selected. Phase-1 (feasibility study) was from August to November 2016 and phase-2 from December 2016 to November 2018. All first-ever stroke cases in adults (aged ≥18 years) were included. The accredited social health activists (ASHAs) were trained to identify stroke patients in the community, who were later evaluated by a neurologist. Stroke characteristics were recorded, and the outcome was assessed at 6 months using modified Rankin scale (0-2, good outcome). FINDINGS: During phase-2, 359 first-ever stroke patients and 102 stroke mimics were identified. The age-standardized incidence rate was 218.5/100,000 and 197∙6/100,000 for each year. Half (52.4%) of the patients reached health-care facilities within 4.5 h, yet none of them received thrombolysis. Very few patients (1.9%) utilized free government 108 ambulance service to reach a health-care facility. Out of 359 stroke cases, the majority (306, 85.23%) were reported by ASHAs and 14.77% were reported by other sources. Brain imaging was available in 127 (35.4%) patients, and 100 (78.7%) had ischemic stroke. The most common risk factor was hypertension (320, 89%) and drug abuse (154, 42.9%). At 6 months, 168 (64%) patients had a good outcome. CONCLUSION: ASHAs were able to identify stroke patients in the villages. Despite high numbers of patients reaching health-care facilities within a window period, the hospitals were unable to provide acute stroke treatment like thrombolysis. The health-care system needs to be strengthened to improve stroke care.

Multicomponent Short-Term Training of ASHAs for Stroke Risk Factor Management in Rural India.

Background Stroke is one of the leading causes of disability-adjusted life years and may be the leading cause of death in rural regions in India. We aim to train the ASHAs (Accredited Social Health activist) for nonpharmacological management of risk factors for secondary stroke prevention in rural India. We tested the hypothesis that focused, multicomponent, short-term training on secondary prevention of stroke enhances the knowledge of ASHAs about risk factor management. Objectives To test the hypothesis that focused, multicomponent, short-term training on secondary prevention of stroke enhances the knowledge of ASHAs about risk factor management. Materials and Methods This study is part of the ASSIST trial (Training ASHA to Assist in Secondary Stroke Prevention in Rural Population). The study design is quasi-experimental (pretest and posttest). Culturally appropriate and pragmatic training material was developed by the study team. Three focused group training sessions were conducted in Sidhwan Bet and Pakhowal blocks of Ludhiana district, Punjab. Results A total of 274 ASHAs from 164 villages with mean ± SD age of 39.5 ± 7.6 years participated in the three training sessions. The perceived knowledge of stroke risk factors and blood pressure assessment was 67.5 ± 18.3% and 84.4 ± 16.7%, respectively. The objective baseline knowledge about stroke prevention and management among ASHAs was lower 58.7 ± 19.7% compared with perceived knowledge ( p = 0.04). This increased to 82.5 ± 16.36% ( p < 0.001) after the mop-up training after a mean of 191 days. More than 30% increment was seen in knowledge about the stroke symptoms (35.9%, p < 0.001), avoiding opium after stroke for treatment (39.5%, p < 0.001), causes of stroke (53.3%, p < 0.001), modifiable risk factors for stroke (45.4%, p < 0.001), and lifestyle modifications for stroke prevention (42.1%, p < 0.001). Conclusions Focused group training can help enhance the knowledge of ASHAs about stroke prevention and management. ASHAs are also able to retain this complex multicomponent knowledge over a 6-month period. ASHA may be able to partake in reducing the secondary stroke burden in rural India.

A Comparison of Insulin Pen Devices and Disposable Plastic Syringes - Simplicity, Safety, Convenience and Cost Differences.

Context: Managing diabetes efficiently demands a simple, safe, convenient and economical therapy. This study was done to understand the simplicity, safety, convenience and cost effectiveness of using pen versus syringe devices in patients on long-term insulin therapy. Design: This prospective observational study was conducted at the endocrine outpatient department of a universityaffiliated teaching hospital in North India. The investigator interviewed patients using a self-made questionnaire after obtaining consent; patients were scored based on their answers. A high score represented a poor response. A total of 90 completed questionnaires (45 from each group) were obtained. Results: Mean simplicity, safety and convenience score among the pen users was 5.31 ± 0.51, 5.4 ± 0.89 and 4.13 ± 1.04 respectively, as compared to 9.78 ± 1.43, 8.09 ± 2.02 and 8.67 ± 0.56 in syringe users respectively. The difference in these scores was statistically significant (p=0.0001). All patients felt that treatment using pen device was costlier when compared to using syringes, with pen users spending Rs1,756 per month on their insulin therapy, as compared to syringe users, who spent Rs590 per month. Among insulin pen users, 22.2% had optimal glycated haemoglobin levels (6-7.5%) as compared to 2.2% among syringe users, and this difference was statistically significant (p=0.007). Conclusions: An insulin pen is simple, safe and convenient to use, and may provide better glycaemic control. Treatment with a pen device is costlier, which may be due to the higher use of analogue insulin among pen users.

Stroke profile and outcome between urban and rural regions of Northwest India: Data from Ludhiana population-based stroke registry.

INTRODUCTION: The objective of this study is to compare the clinical profile, risk factors, type and outcome of stroke patients in urban and rural areas of Punjab, India. METHODS: The primary data source was from the Ludhiana urban population-based stroke registry. The data of first-ever stroke patients with age ≥18 years were collected using WHO stepwise approach from all hospitals, general practitioners, physiotherapy and scan centres between 26 March 2011 and 25 March 2013. RESULTS: A total of 4989 patients were included and out of 4989 patients, 3469 (69%) were from urban areas. Haemorrhagic stroke was seen more in rural as compared to urban regions (urban 1104 (32%) versus rural 552 (36%); p = 0.01). There were significant differences seen in stroke risk factors; hypertension (urban 1923 (84%) versus rural 926 (89%); p = 0.001) and hyperlipidaemia (urban 397 (18%) versus rural 234 (23%); p = 0.001) between two groups. In the multivariable analysis the rural patients were more likely to be younger (age < 40 years) (OR: 1.82; 95% CI: 1.24-2.68; p = 0.002), Sikhs (OR: 2.57; 95% CI: 1.26-5.22; p = 0.009), farmers (OR: 9.41; 95% CI: 5.36-16.50; p < 0.001), housewives (OR: 2.71; 95% CI: 1.45-5.06; p = 0.002), and consumed alcohol (OR: 1.57; 95% CI: 1.19-2.06; p = 0.001) as compared to urban patients. In addition, use of imaging was higher in rural patients (OR: 1.99; 95% CI: 1.06-3.74; p = 0.03) as compared to urban patients. DISCUSSION AND CONCLUSION: In this large cohort of patients, rural and urban differences were seen in risk factors and type of stroke. Stroke prevention strategies need to take into consideration these factors including regional sociocultural practices.

Incidence, short-term outcome, and spatial distribution of stroke patients in Ludhiana, India.

OBJECTIVE: To estimate the incidence, short-term outcome, and spatial distribution of stroke patients and to evaluate the completeness of case ascertainment in Ludhiana. METHODS: This population-based prospective cohort study was conducted in Ludhiana, Punjab, Northwest India. All first-ever stroke patients (≥18 years) were included between March 2010 and March 2013 using WHO Stepwise Approach Surveillance methodology from the city. Stroke patient data were obtained from hospitals, scan centers, and general practitioners, and details of deaths from the Municipal Corporation. RESULTS: Out of 7,199 stroke patients recruited, 3,441 were included in final analysis. The mean age was 59 ± 15 years. The annual incidence rate was 140/100,000 (95% confidence interval [CI] 133-147) and age-adjusted incidence rate was 130/100,000 (95% CI 123-137). The annual incidence rate for stroke in the young (18-49 years) was 46/100,000 (95% CI 41-51). The case fatality at 28 days was 22%. Patients above 60 years of age (p = 0.03) and patients who were managed in public hospitals had poor survival (p = 0.01). Hot spots for cumulative incidence were seen in central and southern parts of the city, and hot spots for poor outcome were seen in the outskirts of the city. CONCLUSIONS: The incidence rates are similar to other studies from India. Stroke patient survival is poor in public hospitals. The finding of spatial analysis is of public health significance for stroke prevention and strengthening of stroke services.

Pattern of Inpatient Dermatology Consultations in a Tertiary Care Centre from Northern India.

INTRODUCTION: The importance of dermatology inpatient consultation is of significant importance yet is not well documented. AIM: To retrospectively analyse the spectrum of dermatology inpatient consultations from the various departments and to document the most commonly occurring dermatological disorders from each speciality. MATERIALS AND METHODS: This study was done in an 800 bedded premier teaching hospital in Ludhiana, Punjab, North Western India. It was an audit of inpatient referrals to the dermatology department from January 2014 to August 2014. We analysed the spectrum of dermatological disorders in relation to the various specialities, demographic profile and age groups. STATISTICAL ANALYSIS: The data was entered in Microsoft Excel and analysed using SPSS Version 21. Descriptive statistics, frequency and proportions were used. RESULTS: Of the 559 in-patients, 60% were males. The majority of the patients belonged to age group 51-60 years (25.9%). The departments most commonly requesting for dermatology consultations were Medicine (27.7%), Neurology (9.7%), Cardiology (8.8%), Urology (7%), Haematology (6.4%), Nephrology (6.1%), Intensive Care Unit (ICU) (5.4%), General Surgery (5.2%), Orthopaedics (5%), Gynaecology and Neurosurgery (2.9%) and Paediatrics (2.7%). The commonest dermatological diagnoses for which consultations were sought were eczematous dermatitis (12.9%), superficial dermatophytosis (12.3%), drug reactions (8.9%) and viral skin infections (8.5%). CONCLUSION: Dermatology consultations offer a significant role in diagnosis and management of the in-patients from various clinical speciality departments. There is a significant need of inter-departmental dermatology consultations which help to decrease morbidity and improve the quality of the patient's hospital stay. Knowledge about the pattern of dermatoses in the inpatients can help the primary clinician to recognize when to seek dermatology consultation on a priority basis.

Kite flying: ancient tradition or death trap?

BACKGROUND: Kite flying has been popular in India since ancient times, especially during harvest festivals of Lohri, Basant and Makar Sankranti. It often takes form of a competitive sport and in recent times has been associated with multiple, sometimes fatal injuries. This prognostic study was conducted to try and understand the epidemiology and factors associated with kite flying injuries in the state of Punjab, India. METHODS: Case reports of patients who presented to the ED with trauma as a result of kite flying were reviewed. The study included patients reporting to the Christian Medical College, Ludhiana, between January 2005 and January 2010. Details of the type and mode of injury, and outcomes were recorded. RESULTS: The highest incidence of injuries occurred during months of the kite flying festivals. The most common mode of injury was fall from heights, associated with traumatic brain injury. The mortality rate in this series was 6.25%. CONCLUSIONS: This study highlights the importance of kite flying injuries as a common mode of injury in children and adolescents. It is an easily preventable mode of injury with simple safety regulations and possibly stronger legislation.

Pediatric foreign body aspiration: How much does our community know?

AIMS: Foreign body aspiration (FBA) is one of the main causes of accidental death in childhood. This study was designed to evaluate the level of awareness of FBA and its resultant dangers in the community. MATERIALS AND METHODS: Sixty-three primary caregivers were interviewed about their awareness of FBA, its attendant dangers, preventive measures taken, and how will they take care of a child in the event of a FBA according to an agreed protocol. RESULTS: Awareness levels about FBA were abysmally low in the population that was studied. Twenty-five percentage of the study population had not heard about this condition, and 46% could not recognize a FBA if it happened. Also, 76% of the study group did not know about the attendant dangers of this condition. CONCLUSIONS: There is a dire need to spread awareness about both prevention and treatment of this morbid condition. Health care professionals need to increase their efforts to spread more knowledge in the community about FBA.