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Abstract One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

ABSTRACTThe WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at −20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2–8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1.5 mL and LnHRV-2.0 mL) containing buffer and excipients to stabilize the virus against gastric acidity and temperature, were compared with ROTAVAC®. As the immune response of ROTAVAC 5C (LnHRV-2.0 mL) was non-inferior to ROTAVAC®, it was selected for (ii) confirmatory phase, involving 1,302 infants randomized 1:1:1:1 to receive three lots of LnHRV-2.0 mL, or ROTAVAC®. Primary objectives were the evaluation of non-inferiority and lot-to-lot consistency. The secondary objectives were to assess the safety and interference with the concomitant pentavalent vaccine. As it was separately established that buffers are not required for ROTAVAC®, in Study-2, the safety and immunogenicity of ROTAVAC 5D® (with excipients) were compared with ROTAVAC® and lot-to-lot consistency was assessed in another study. All lots elicited consistent immune responses, did not interfere with UIP vaccines, and had reactogenicity similar to ROTAVAC®. ROTAVAC 5C and ROTAVAC 5D® were immunogenic and well tolerated as ROTAVAC®. ROTAVAC 5D® had comparable immunogenicity and safety profiles with ROTAVAC® and can be stored at 2–8°C, leading to WHO pre-qualification.Clinical Trials Registration: Clinical Trials Registry of India (CTRI): CTRI/2015/02/005577CTRI/2016/11/007481 and CTRI/2019/03/017934.

Abstract This is a comprehensive report on immunogenicity of COVAXIN® booster dose against ancestral and Variants of Concern (VOCs) up to 12 months. It is well known that neutralizing antibodies induced by COVID-19 vaccines wane within 6 months of vaccination leading to questions on the effectiveness of two-dose vaccination against breakthrough infections. Therefore, we assessed the persistence of immunogenicity up to 6 months after a two or three-dose with BBV152 and the safety of a booster dose in an ongoing phase 2, double-blind, randomized controlled trial (ClinicalTrials.gov: NCT04471519). We report persistence of humoral and cell mediated immunity up to 12 months of vaccination, despite decline in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, Delta Plus and Omicron) with a slight increase in B cell memory responses. Thus, seronversion rate remain high in boosted recipients compared to non-booster, even after 6 months, post third dose against variants. No serious adverse events observed, except pain at the injection site, itching and redness. Hence, these results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants. Trial registration: Registered with the Clinical Trials Registry (India) No. CTRI/2021/04/032942, dated 19/04/2021 and on Clinicaltrials.gov: NCT04471519.

A typhoid Vi capsular-polysaccharide tetanus toxoid conjugate vaccine (Typbar-TCV®) was recommended by the World Health Organization for use in children >6 months of age. The present post-marketing surveillance study was intended to assess the clinical safety of approximately 11 million doses of TCV sold till 2019 in a diverse age range Indian population. Both active and passive post-marketing surveillance studies were conducted at multiple centers. Active surveillance was performed in two periods, Period-I: February to October 2016, Period-II: April 2017 to October 2018. In Period-II, the Brighton Collaboration Criteria adverse event case definitions were used. Passive surveillance was performed from February 2016 to December 2019 through voluntary reporting by pediatricians across India. During the active surveillance, 1147 adverse events were reported among 4,991 (23.0%) subjects in Period-I, and 596 adverse events among 3898 (21.3%) subjects in Period-II. The most frequent adverse events were fever (9.2% and 12.02%in Periods I and II, respectively), pain at the injection site (8.3% and 7.33%), and swelling (4.0% and 1.93%). No serious adverse events (SAEs) were reported during either Period. Passive surveillance revealed 235 adverse events, including 25 SAEs requiring hospitalization, of which two were due to typhoid fever. All the events mentioned above occurred within one week of vaccination, and all the subjects have recovered from AEs with medications. All reported adverse events resolved with no clinical sequelae. Observations in this study are consistent with the pre-licensure studies with no additional safety signals detected, confirming that Typbar-TCV® is safe. Abbreviations: AE: Adverse event; LMIC: low- and middle-income countries; PMS: Post-marketing surveillance; SAE: Serious adverse event; TCV: Vi-polysaccharide tetanus –toxoid conjugate vaccine (Typbar-TCV®)

Abstract Background The stillbirth rate is an indicator of quality of care during pregnancy and delivery. Good quality care is supported by a functional heath system. The objective of this study was to explore the risk factors for stillbirths, particularly those related to a health system. Methods This case-control study was conducted in two districts of Bihar, India. Information on cases (stillbirths) were obtained from facilities as reported by Health Management Information System; controls were consecutive live births from the same population as cases. Data were collected from 400 cases and 800 controls. The risk factors were compared using a hierarchical approach and expressed as odds ratio, attributable fractions and population attributable fractions. Results Of all the factors studied, 22 risk factors were independently associated with stillbirths. Health system-related factors were: administration of two or more doses of oxytocics to augment labour before reaching the facilities (OR 1.6; 95% CI 1.2–2.1), any complications during labour (OR 2.3;1.7–3.1), >30 min to reach a facility from home (OR 1.4;1.05–1.8), >10 min to attend to the pregnant woman after reaching the facility (OR 2.8;1.7–4.5). In the final regression model, modifiable health system-related risk factors included: >10 min taken to attend to women after they reach the facilities (AOR 3.6; 95% CI 2.5–5.1), untreated hypertension during pregnancy (AOR 2.9; 95% CI 1.5–5.6) and presence of any complication during labour, warranting treatment (AOR 1.7; 95% CI 1.2–2.4). Among mothers who reported complications during labour, time taken to reach the facility was significantly different between stillbirths and live births (2nd delay; 33.5 min v/s 25 min; p 30 min to reach the facility 0.48 (95% CI 0.31–0.60) and institution of management 10 min after reaching the facility 0.68 (95% CI 0.58–0.75). Reaching a facility within 30 min, initiation of management within 10 min of reaching the facility and timely management of complications during labour could have prevented 17%, 37% and 20% of stillbirths respectively. Conclusion A pro-active health system with accessible, timely and quality obstetric services can prevent a considerable proportion of stillbirths in low and middle income countries.

Background: Several programmatic and logistic issues affect the overall performance of Accredited Social Health Activists (ASHAs). Bihar Government provided bicycles to ASHAs in West Champaran district for increasing coverage of services by improving their mobility. Objective: To assess the use of bicycles by ASHAs and it's effect on service delivery. It also captures the perspectives of ASHAs in terms of its utilization for performing tasks. Methods: A community-based quasi-experimental study was undertaken during March-May 2016. Proportion of newborn babies visited within 24 h of birth was the primary outcome. Data were collected from two intervention blocks (West Champaran district) and a control block from the neighboring East Champaran district. A total of 323 (177 from intervention blocks and 146 from control block) mothers having children

Background: Quality of care at the facilities during childbirth remains a major concern. Improved quality could have the greatest dividend in saving maternal and newborn lives. Objective: The objective of this study was to implement quality assurance measures in the labor rooms of select public health facilities in two districts of Bihar. Methods: The labor room quality assurance intervention was implemented in two districts, Gaya and Purnea in Bihar. Health facilities having >200 deliveries/month were assessed using labor room quality assurance checklist developed by the Ministry of Health and Family Welfare. The critical gaps affecting service delivery were identified, and a list of priority actions for quality improvement was developed. An intervention model was rolled out in consultation with the district authorities focusing on the building blocks of the health system. The interventions were implemented from August 2014 to March 2016 in selected facilities after which an assessment was conducted. Results: Initial assessment of labor room was conducted in 24 facilities. After 2 years of intervention, there was a definite improvement in quality assurance scores in most facilities. The infection control scores increased by 20 points in Gaya (from 40 to 59.9) and 10 points in Purnea (from 57.6 to 67.1). The highest gain in scores was observed in quality management component in Gaya (from 6.2 to 58.2). The model attempted to incorporate all the elements of the health system to ensure scalability and sustainability. Conclusion: It is possible to have an implementable quality assurance mechanism within public health system with sustained efforts and commitment.

Background: A functional newborn care corner (NBCC) is critical to provide immediate care to newborns including resuscitation, warmth, and initial care to sick newborns. NBCC provides an acceptable environment for all infants at birth, and it is mandatory for all delivery points at all levels in the health system including operation theaters. Objective: The objective of this study was to find the status of availability of NBCCs and service provision in selected public health facilities of Bihar. Methods: A total of 57 NBCCs, having high delivery load (>100 deliveries/month), across 25 high-priority districts in Bihar, were selected purposively in consultation with the State Health Society, Bihar, for the assessment. These facilities were assessed for the availability and/or functioning of infrastructure, equipment maintenance, human resource, supply of drugs and consumables, adherence to protocols, and record keeping. Results: Only 22.8% of the NBCCs were found to be fully functional, majority (68.4%) were partially functional, and 9% were nonfunctional. Thirty-seven (64.9%) NBCCs were located inside the labor room premises. Approximately, one-third of the neonates delivered were kept in NBCCs. Equipment though available lacked the provision of annual maintenance contract. Essential drugs such as adrenaline (24.6%) and Vitamin K injection (42.1%) were not available in many facilities. Only 6.2% of the newborns had low birth weight, indicating underreporting. Majority of the health-care staff available were trained but possessed poor skills. Data recording and reporting was also suboptimal. Conclusion: The network of NBCCs needs to be strengthened across the state and linked with higher facilities to achieve the desired reduction in neonatal morbidity and mortality.

Purpose: In response to the evolving COVID-19 pandemic, many universities have transitioned to online instruction. With learning promising to be online, at least in part, for the near future, instructors may be thinking of providing online collaborative learning opportunities to their students who are increasingly isolated from their peers because of social distancing guidelines. This paper aims to provide design recommendations for online collaborative project-based learning exercises based on this research in a software engineering course at the university level. Design/methodology/approach: Through joint work between learning scientists, course instructors and software engineering practitioners, instructional design best practices of alignment between the context of the learners, the learning objectives, the task and the assessment are actualized in the design of collaborative programming projects for supporting learning. The design, first segments a short real-time collaborative exercise into tasks, each with a problem-solving phase where students participate in collaborative programming, and a reflection phase for reflecting on what they learned in the task. Within these phases, a role-assignment paradigm scaffolds collaboration by assigning groups of four students to four complementary roles that rotate after each task. Findings: By aligning each task with granular learning objectives, significant pre- to post-test learning from the exercise as well as each task is observed. Originality/value: The roles used in the paradigm discourage divide-and-conquer tendencies often associated with collaborative projects. By requiring students to discuss conflicting ideas to arrive at a consensus implementation, their ideas are made explicit, thus providing opportunities for clarifying misconceptions through discussion and learning from the collaboration.

Aim: The present aim of the study is to study cardiac dysfunction in chronic liver disease using 2D Echo cardiography and tissue Doppler Imaging. Methodology: This was a hospital-based cross-sectional descriptive study conducted over 16 months (between March 2021 and June 2022) among patients seeking medical attention at Narayana Medical College & Hospital, Nellore. Results: A total of 100 cirrhosis patients were recruited. The average age was 46.6±11.13 years (Range 23 to 80 years). 80% patients were males. Most of the male patients (30 patients) were in 41 to 50 years age group but most female patients (7 patients) were less than 40 years in age group. Alcohol was the most common etiology (69%). Abdominal distention due to ascites (59 patients) was the most common clinical presentation and eleven among them had spontaneous bacterial peritonitis. 53 patients were found to have some echocardiographic abnormalities at the time of assessment. All 53 patients had diastolic dysfunction. However, only 18 patients had an ejection fraction less than 55%, indicating significant LV dysfunction. 8% of patients had RV Systolic dysfunction, and 8% of patients had pulmonary arterial hypertension. Based on the complications developed by the patients, 53.19% of hepatic encephalopathy, 72.73% of SBP, 50% of cases with GI Bleeding and HRS had Echo changes. Likewise, 21.15% of cases with esophageal varices and 10% of cases with PHG & GAVE had Echo changes respectively. Conclusion: The study concluded that to assess the cardiac dysfunction in chronic liver disease patients, it is preferable to do 2D Echo-Tissue Doppler Imaging rather than a conventional Colour Doppler study. [ABSTRACT FROM AUTHOR]

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively. [ABSTRACT FROM AUTHOR]