Sanjeev Sarmukaddam’s research while affiliated with KEM Hospital Research Centre and other places

Introduction An earlier food survey showed dietary potassium deficiency in rheumatoid arthritis (RA). Objective To evaluate an adjunct role of oral potassium to reduce joint pain in RA. Methods 172 consenting eligible symptomatic patients (median duration 6.5 years) on standard care were randomised into an assessor blind, parallel efficacy, controlled, prospective, multiarm single-centre study (80% power, drug trial design) of 16 weeks duration—arm A (potassium-rich vegetarian diet), arm B (arm A plus novel potassium food supplement) and arm C (control, regular diet). Standard efficacy (American College of Rheumatology recommendation) and safety and diet intake (3-day recall) were assessed at monthly intervals (protocol). Standard soft-ware package (SPSS V.20) was used for statistical analysis; analysis of variance), Mann-Whitney statistic and χ ² test.; significant p<0.05, two sided). Study arms were found matched at baseline. Background RA medication remained stable. Preset target for increased potassium intake (India standards) were mostly achieved and participants remained normokalemic. Results 155 patients (90.1%) completed the study and several showed improvement (maximum improved measures in arm B). Potassium intervention was safe and well tolerated. Adverse events were mild; none caused patient withdrawal. On comparison, the mean change in pain visual analogue scale (−2.23, 95% CI −2.99 to −1.48) at week 16 (primary efficacy) from baseline was significantly superior in arm B (per protocol analysis). A high daily potassium intake (5–7.5 g, arm B) was significantly associated with low pain (study completion); OR 2.5 (univariate analysis), likelihood ratio 2.9 (logistic regression). Compliance (intervention), diet record and analysis, RA medication and absence of placebo were potential confounders. Conclusion High oral potassium intake, based on a suitable vegetarian diet and food supplement, reduced joint pain and improved RA. It was a safe adjunct to standard care, Further validation studies are required. Trial registration CTRI/2022/03/040726; Clinical Trial Registry of India.

A Cultural Formulation Interview (CFI) field trial in India, widely reported racist violence in the United States, and casteist and religious communal conflicts in India highlighted inattention to structural issues affecting mental health problems in the Outline for Cultural Formulation (OCF) and the CFI in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Consequently, we revised the OCF as a sociocultural formulation (SCF) to better consider structures of society and culture. We studied and compared clinicians' ratings of SCF case formulations from a constructed assessment instrument (SCF Interview [SCFI]) and the CFI. Socio-cultural formulations from SCFI interviews were rated higher for details of societal structural impact, and overall interrater agreement was better. CFI interviews were rated higher for clinical rapport. Revision of the CFI should enhance consideration of structural issues and incorporate them in SCFs that better integrate assessment process and case formulation content. The need to acknowledge structural sources of mental health problems is clear, and our study indicates how a sociocultural framework may be used for that.

Objective Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. Methods During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. Results The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student’s ‘t test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). Conclusions AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. Trial registration CTRI/2020/06/025557.

Introduction Earlier food surveys showed deficient dietary potassium in rheumatoid arthritis (RA). Objective To evaluate an adjunct role of oral potassium to reduce joint pain in RA Methods 172 consenting and eligible symptomatic patients (median duration 6.5 years) on standard care were randomized into an assessor blind, parallel efficacy, controlled, multi-arm single center study (80% power) of 16 weeks duration-Arm A (potassium rich vegetarian diet), Arm B (Arm A plus novel potassium food supplement) and Arm C (Control, regular diet). Standard efficacy (American College of Rheumatology) and safety, and diet intake (three-day recall) were assessed at monthly intervals (protocol). Standard statistical tests were used; significant p <0.05, two sided). Study arms were well matched at baseline and RA medication remained fairly stable. Patients in Arm A and B met the pre-set target for increased potassium intake (diet analysis, India standards) and remained normokalemic. Diet remained unchanged in Arm C. Results 155 patients (90.1%) completed and several showed improvement (best in Arm B). Potassium intervention was safe and well tolerated. Adverse events were mild; none caused patient withdrawal. On comparison, the mean change in pain visual analogue scale (−2.23, 95% confidence interval −2.99 to −1.48) at week 16 (primary efficacy) from baseline in Arm B was significantly superior as per protocol analysis. A high daily potassium intake (5-7.5 gm, Arm B) was significantly associated with low pain (study completion); Odds Ratio 2.5, Univariate Analysis and Likelihood Ratio 2.9, Logistic Regression. Compliance (intervention), diet record and analysis, RA medication and absence of placebo were potential confounders. Conclusion High oral potassium intake based on a suitable diet and food supplement, reduced joint pain and improved RA. It was a safe adjunct and ought to be considered for standard care in RA. Further validation studies are required. Trial Registration Clinical Trial Registry of India-CTRI/2022/03/040726 KEY MESSAGE What is already known on the topic? Potassium is a vital micronutrient in health, but little is known about its role in RA. Patients suffering from symptomatic RA may consumed potassium deficient diet What this study adds? Increased potassium intake based on a suitable vegetarian diet and a novel food supplement may joint pain and improve RA High oral potassium intake was found safe and well tolerated How this study might affect research, practise or policy/ A high potassium intake based on vegetarian diet and food is a useful adjunct to manage difficult symptomatic RA in clinical practise. The current recommendations/guidelines on potassium intake should be revised

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Introduction: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELDTM) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. Methods and Analysis: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks.

Objectives: Comparative study of Ashwagandha (Withania somnifera; WS) and hydroxychloroquine (HCQ) for chemoprophylaxis against COVID-19 in actively engaged high-risk health-care workers. Design: Randomized, multicentric, open label, active control, two arm parallel efficacy study of 16 weeks. Sample size was based on pre-set 15% non-inferiority margin to HCQ for prophylaxis against COVID-19 with 80% power and alpha < 0.05. Participants: 400 health-care workers from three sites who were asymptomatic and tested negative for a quantitative Reverse Transcription Polymerase Chain Reaction test (RT-PCR) for COVID-19 and SARS-CoV-2 antibodies (IgG) were randomized in a 1:1 ratio. Participants observed physical protection measures as per the national policy. All incident confirmed COVID-19 were withdrawn.Interventions: Two tablets of 250 mg standardized aqueous extract of WS, twice daily after meal or HCQ 800 mg loading followed by 400 mg weekly for 16 weeks as per the national guidelines. Main outcome measures: The primary efficacy measure was “failure of prophylaxis” as confirmed by RT-PCR at any time during the study. Both intention-to-treat (ITT) and per-protocol (PP) efficacy analyses were performed.Results: 95 participants in the Ashwagandha (WS) arm and 101 participants in the HCQ arm completed the study. Both groups were well matched at the baseline. 91 participants from the Ashwagandha arm and 84 from the HCQ arm were withdrawn because they received the COVID-19 vaccination. Four participants (2%; 95% CI 2.8 to 3.9%) in the Ashwagandha and 5 (2.5%; 95% CI 5.4 to 8%) in the HCQ arm developed confirmed COVID-19. This was within the prefixed non-inferiority margin and the 95% CI of the absolute risk reduction (ARR) was -2.9 to 3.8% intention to treat (ITT) and -5.9 to 7.5% per protocol (PP). The 95% CI of ARR for the total COVID-19 cases was -2.8 to 11.9% ITT and -5.7 to 20.3% PP. Several health measures, particularly anxiety and stress, improved significantly in the Ashwagandha arm. Seven out of 117 in the Ashwagandha and 59 out of 178 in the HCQ groups were reported to be possible drug-related adverse events (AE); there were significantly less gut-related AE in the Ashwagandha group. AE were mostly mild and did not cause withdrawal. All incident COVID-19 cases recovered without complications. Conclusions: Ashwagandha was non-inferior to HCQ in the chemoprophylaxis against COVID-19 in high risk health-care workers. It was significantly safer, well tolerated and improved quality of life measures. Ashwagandha as COVID-19 prophylaxis seems appropriate in high-risk populations. Trial registration: The Clinical Trials Registry India Number CTRI/2020/08/027163 dated August 14, 2020.

Introduction The government of India has rolled out COVID-19 vaccine program for individuals who are 18 years of age and above and priority is being given to the elderly, and individuals with morbidity. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD) is most widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Ashwagandha and its potential as vaccine adjuvant. We plan to study co-administration of Ashwagandha with COVISHIELD vaccine on safety, immunogenicity and protection. Methods and analysis We designed a prospective, randomized, double blind, parallel group, placebo controlled, two arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. In addition to the two dose schedule of COVISHIELD vaccine as per national guidelines, participants will be administered 8gm Ashwagandha or placebo tablets respectively per day. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. Adverse event following immunization will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. Ethics and dissemination Ethical approval was obtained through the Central and institutional Ethics Committees. Participant recruitment is expected to commence by August 2021. Results will be presented in conferences and published in preprint followed by peer-reviewed medical journals. Registration details Clinical Trial Registry India (CTRI) Registration Number: CTRI/2021/06/034496. Date of Registration June 30, 2021.