Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Population Pharmacokinetics of Hydroxychloroquine Sulfate in Healthcare Workers, Given for Prophylaxis Against Coronavirus Disease 2019 (COVID-19) in India.

Healthcare workers (HCWs) and frontline workers were recommended hydroxychloroquine (HCQ) 400 mg twice a day on day 1, followed by 400 mg once weekly for the next 7 weeks, as prophylaxis against COVID-19. There was limited information on the population pharmacokinetics (popPK) of HCQ in an Indian setting when administered for prophylaxis against COVID-19, and hence this study was proposed. It was a multicentric prospective study conducted at 3 sites in India wherein HCWs who were already on HCQ prophylaxis, who were about to start prophylaxis or who had stopped the prophylaxis for any reason were enrolled. Each participant gave 2 to 6 blood samples at different time points and whole-blood HCQ concentrations were assayed using liquid chromatography with tandem mass spectrometry (LC MS/MS). popPK analysis was performed using PUMAS 1.1.0. A total of N = 338 blood samples from N = 121 participants were included in the popPK analysis. A 2-compartment structural model with linear elimination was able to explain the observed data. Body weight was found to be a significant covariate influencing drug clearance. The final model was assessed using goodness-of-fit plots, a visual predictive check and a bootstrap, all of which confirmed that the model was appropriate. Simulations based on the current regimen showed that trough values were below the half-maximal effective concentration (EC50) of 0.7 µmol against COVID-19. A new weight-based dosage regimen was proposed to maintain the trough concentration above the EC50 threshold.

Prevalence and Predictors of Stress, anxiety, and Depression among Healthcare Workers Managing COVID-19 Pandemic in India: A Nationwide Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused great financial and psychological havoc. Healthcare professionals (HCPs) are among the many groups of people who are in the frontline and facing a risk of direct exposure to the virus. This study aimed to assess the prevalence and predictors of stress, depressive, and anxiety symptoms among HCPs of India. METHODS: It was a cross-sectional, online survey conducted in April 2020 among HCPs who are directly involved in the triage, screening, diagnosing, and treatment of COVID-19 patients and suspects. Stress was estimated using Cohen's perceived stress scale. Depression and anxiety were assessed using the tools Public Health Questionnaire-9 and Generalized Anxiety Disorder-7. Predictors were analyzed using univariate and multivariate binary logistic regression. RESULTS: A total of 433 online responses were obtained, and N = 350 were finally included. The prevalence (95% CI) of HCPs with high-level stress was 3.7% (2.2, 6.2), while the prevalence rates of HCPs with depressive symptoms requiring treatment and anxiety symptoms requiring further evaluation were 11.4% (8.3, 15.2) and 17.7% (13.9, 22.1), respectively. Women had approximately two times the increased odds of developing moderate- or high-level stress, depressive symptoms requiring treatment, and anxiety symptoms requiring further evaluation. Similarly, women staying in a hostel/temporary accommodation had two times the increased odds of developing depression or anxiety symptoms. CONCLUSION: The prevalence of stress, depressive, and anxiety symptoms among HCPs in India during the pandemic is comparable with other countries.