Safety and efficacy of Siddha management as adjuvant care for COVID-19 patients admitted in a tertiary care hospital - An open-label, proof-of-concept Randomized Controlled Trial.

Background: COVID-19 resulted in loss of human lives owing to respiratory failure caused by dysregulated immune system. Though many treatments are evaluated, the most appropriate is yet to be established. Objective: To determine the safety and efficacy of Siddha add-on therapy in COVID -19 in terms of accelerated recovery, reduced hospital stay & mortality and follow up assessment of post discharge status until 90 days as compared to the Standard Care management. Methods: In a randomized, controlled, single-center, open-label trial conducted on 200 hospitalized COVID-19 patients, they were allocated equally to be treated with add-on Siddha regimen with Standard care or only Standard care. Standard care was in accordance to the Government norms. Recovery was defined as amelioration of symptoms, viral clearance and attaining SpO2 > 94% in room air indicating the derived score of zero on WHO clinical progression scale. The primary and secondary end points were accelerated recovery (≤ 7 days) and mortality comparison between the groups respectively. Also, disease duration, length of hospital stays and laboratory parameters were assessed for safety and efficacy. Patients were followed through for 90 days after admission. Results: In this study the accelerated recovery was 59.0% and 27.0% in treatment and control groups (ITT analyses) (p < 0.001) respectively and Odds for it were four times higher in the treatment group (OR: 3.9; 95% CI: 1.9, 8.0). The estimated median time for recovery in the treatment group was 7 days (95% CI: 6.0, 8.0; p=0.003) and 10 days (95% CI: 8.7, 11.3) in control. Hazard ratio for death in control was 2.3 times that of treatment group. No adverse reactions or alarming laboratory values were observed in response to intervention. In Severe COVID treatment group (n=80), mortality was 15.0% and 39.5% in control (n=81). The COVID stage progression was 65% less in test group. Mortality during treatment and 90 days follow up in Severe COVID patients were 12 (15%) and 35 (43.2%) in treatment and control groups respectively. Conclusion: The selected Siddha regimen when co-administered with Standard of Care have demonstrated that they can synergistically act to improve oxygenation status of patients, enhance the recovery rate from COVID-19 and reduce the mortality better when compared to administration of only Standard of Care. Clinical Trial Registry of India: CTRI/2020/06/025768 Registered on: 09/06/2020.

Safety and immunogenicity of the Rotavac and Rotasiil rotavirus vaccines administered in an interchangeable dosing schedule among healthy Indian infants: a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial.

BACKGROUND: Rotavirus is the leading cause of severe dehydrating gastroenteritis among children younger than 5 years in low-income and middle-income countries. Two vaccines-Rotavac and Rotasiil-are used in routine immunisation in India. The safety and immunogenicity of these vaccines administered in a mixed regimen is not documented. We therefore aimed to compare the safety and seroresponse of recipients of a mixed regimen versus a single regimen. METHODS: We did a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial at two sites in India. We recruited healthy infants aged 6-8 weeks. Infants with systemic disorders, weight-for-height Z scores of less than minus three SDs, or a history of persistent diarrhoea were excluded. Eligible infants were randomly allocated to six groups in equal numbers to receive either the single vaccine regimen (ie, Rotavac-Rotavac-Rotavac [group 1] or Rotasiil-Rotasiil-Rotasiil [group 2]) or the mixed vaccine regimen (ie, Rotavac-Rotasiil-Rotavac [group 3], Rotasiil-Rotavac-Rotasiil [group 4], Rotavac-Rotasiil-Rotasiil [group 5], or Rotasiil-Rotavac-Rotavac [group 6]). Randomisation was done using an online software by site in blocks of at least 12. The primary outcome was seroresponse to rotavirus vaccine, measured using rotavirus-specific serum IgA antibodies 4 weeks after the third dose. The seroresponse rates were compared between recipients of the four mixed vaccine regimens (consisting of various combinations of Rotavac and Rotasiil) with recipients of the single vaccine regimens (consisting of Rotavac or Rotasiil only for all three doses). The non-inferiority margin was set at 10%. Safety follow-ups were done for the duration of study participation. This trial was registered with the Clinical Trials Registry India, number CTRI/2018/08/015317. FINDINGS: Between March 25, 2019, and Jan 15, 2020, a total of 1979 eligible infants were randomly assigned to receive a single vaccine regimen (n=659; 329 in group 1 and 330 in group 2) or a mixed vaccine regimen (n=1320; 329 each in groups 3 and 4, and 331 each in groups 5 and 6). All eligible participants received the first dose, 1925 (97·3%) of 1979 received the second dose, and 1894 (95·7%) received all three doses of vaccine. 1852 (93·6%) of 1979 participants completed the follow-up. The immunogenicity analysis consisted of 1839 infants (1238 [67·3%] in the mixed vaccine regimen and 601 [32·7%] in the single vaccine regimen; 13 samples were insufficient in quantity) who completed vaccination and provided post-vaccination sera. The seroresponse rate in the mixed vaccine regimen group (33·5% [95% CI 30·9-36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1-33·4]); the seroresponse rate difference was 3·9% (95% CI -0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4-93·0) in the single vaccine regimen group and 91·1% (89·5-92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study. INTERPRETATION: Rotavac and Rotasiil can be safely used in an interchangeable manner for routine immunisation since the seroresponse was non-inferior in the mixed vaccine regimen compared with the single vaccine regimen. These results allow for flexibility in administering the vaccines, helping to overcome vaccine shortages and supply chain issues, and targeting migrant populations easily. FUNDING: Ministry of Health and Family Welfare, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Fitting HIV Prevalence 1981 Onwards for Three Indian States Using the Goals Model and the Estimation and Projection Package.

Models are designed to provide evidence for strategic program planning by examining the impact of different interventions on projected HIV incidence. We employed the Goals Model to fit the HIV epidemic curves in Andhra Pradesh, Maharashtra and Tamil Nadu states of India where HIV epidemic is considered to have matured and in a declining phase. Input data in the Goals Model consisted of demographic, epidemiological, transmission-related and risk group wise behavioral parameters. The HIV prevalence curves generated in the Goals Model for each risk group in the three states were compared with the epidemic curves generated by the Estimation and Projection Package (EPP) that the national program is routinely using. In all the three states, the HIV prevalence trends for high-risk populations simulated by the Goals Model matched well with those derived using state-level HIV surveillance data in the EPP. However, trends for the low- and medium-risk populations differed between the two models. This highlights the need to generate more representative and robust data in these sub-populations and consider some structural changes in the modeling equation and parameters in the Goals Model to effectively use it to assess the impact of future strategies of HIV control in various sub-populations in India at the sub-national level.

A single weighting approach to analyze respondent-driven sampling data.

BACKGROUND AND OBJECTIVES: Respondent-driven sampling (RDS) is widely used to sample hidden populations and RDS data are analyzed using specially designed RDS analysis tool (RDSAT). RDSAT estimates parameters such as proportions. Analysis with RDSAT requires separate weight assignment for individual variables even in a single individual; hence, regression analysis is a problem. RDS-analyst is another advanced software that can perform three methods of estimates, namely, successive sampling method, RDS I and RDS II. All of these are in the process of refinement and need special skill to perform analysis. We propose a simple approach to analyze RDS data for comprehensive statistical analysis using any standard statistical software. METHODS: We proposed an approach (RDS-MOD - respondent driven sampling-modified) that determines a single normalized weight (similar to RDS II of Volz-Heckathorn) for each participant. This approach converts the RDS data into clustered data to account the pre-existing relationship between recruits and the recruiters. Further, Taylor's linearization method was proposed for calculating confidence intervals for the estimates. Generalized estimating equation approach was used for regression analysis and parameter estimates of different software were compared. RESULTS: The parameter estimates such as proportions obtained by our approach were matched with those from currently available special software for RDS data. INTERPRETATION & CONCLUSIONS: The proposed weight was comparable to different weights generated by RDSAT. The estimates were comparable to that by RDS II approach. RDS-MOD provided an efficient and easy-to-use method of estimation and regression accounting inter-individual recruits' dependence.