Rationalizing the Use of COVID-19 Questionable Efficacy Drugs in a Low Middle-income Country: A Hospital Tocilizumab Committee Experience.

BACKGROUND: Only corticosteroids have confirmed mortality benefits in coronavirus disease of 2019 (COVID-19). Rational use of costlier drugs with questionable benefits poses a great concern to hospital pharmacies in low middle-income countriesAim: The present study aimed to assess the rational utilization of hospital supply tocilizumab and understand its clinical benefits in hospitalized COVID-19 pneumonia patientsMethods: The Hospital Tocilizumab Committee (HTC) decision support system framework was developed to make patients eligible or ineligible for tocilizumab procurement from the hospital pharmacy. A total of 33 consecutive patients receiving tocilizumab were analyzed retrospectively in the 3-month study period. The records of the inpatient stay of the patients were observed for pulse, blood pressure, respiratory rate (RR), oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) laboratory work-up, hospital stay duration, and mortality benefit, if any. Patients were analyzed as "died," "survived," and "composite" subgroupsResults: The study observed death as a final outcome in 48% of patients. The study observed a significant effect of tocilizumab on C-reactive protein (CRP) (p = 0.02) and ferritin (p = 0.018) levels on a 10-day follow-up when all patients were analyzed together. Rising and declining trends of RR and FiO2 were observed among the "died" (RR, p = 0.02; FiO2, p = 0.03) and survived (RR, p = 0.03; FiO2, p = 0.05) subgroups. The second dose of tocilizumab was received by 88% of survivors as against 50% of patients who died (p = 0.04)Conclusion: Hospital Tocilizumab Committee (HTC) was successfully established to continue the assessment of the costlier drug with uncertain treatment benefits. A repeat dose of tocilizumab may provide a mortality benefit in Asian Indians.

Comparison of master two-step exercise stress test versus six-min walk test in patients tested positive for SARS-CoV-2.

Background and Aim: There has been a lack of uniformity on how to triage coronavirus disease 2019 (COVID-19) patients visiting the emergency units of hospitals. Triage tools are themselves spreading the pandemic in hospital areas. The present study compared a master two-step (M2ST) exercise stress test versus a 6-min walk test (6MWT) in COVID-19-positive patients visiting the emergency unit of a hospital. Materials and Methods: Thirty-nine patients underwent 6MWT followed by M2ST, while another set of 38 patients underwent M2ST followed by 6MWT in this randomized, crossover, open-label, and noninferiority study. The exercise tests assessed the change from baseline in SpO2, heart rate (HR), respiratory rate, blood pressure, exertion, and dyspnea on the modified-Borg scale. Results: Noninferiority was established for SpO2 (P < 0.05), systolic blood pressure (SBP; P < 0.001), and diastolic blood pressure (DBP; P < 0.05), but not for HR (P = 0.3) and respiratory rate (P = 0.6). The difference between the pretest and posttest (delta change) values for the parameters SpO2, respiratory rate, HR, SBP, and DBP correlated significantly (P < 0.001) with Pearson correlation coefficient (r = 0.764, 0.783, 0.473, 0.838, and 0.783, respectively). The delta change values of modified-Borg scale for dyspnea (P = 0.291) and exertion (P = 0.208) were statistically insignificant between the two exercise tests. However, the correlation between the tests was statistically significant (P < 0.001). Conclusion: M2ST, a timesaving, cost-effective, and easy to perform exercise stress test, has been identified as a reliable alternative for 6MWT.

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034). Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Total synthesis of remdesivir.

Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield.

System for administering and monitoring hydroxychloroquine prophylaxis for COVID-19 in accordance with a national advisory: preliminary experience of a tertiary care institute in India.

BACKGROUND: Hydroxychloroquine (HCQ) was one of the earliest drugs to be recommended for tackling the COVID-19 threat leading to its widespread usage. We provide preliminary findings of the system, established in a tertiary care academic center for the administration of HCQ prophylaxis to healthcare workers (HCW) based on Indian Council of Medical Research (ICMR) advisory. METHODS: A dedicated clinical pharmacology and internal medicine team screened for contraindications, administered informed consent, maintained compliance and monitored for adverse events. RESULTS: Among the 194 HCWs screened for ruling out contraindications for prophylaxis, 9 were excluded and 185 were initiated on HCQ. A total of 55 adverse events were seen in 38 (20.5%) HCWs out of which 70.9%, 29.1% were mild and moderate & none were severe. Before the completion of therapy, a total of 23 participants discontinued. Change in QTc interval on day 2 was 5 (IQR: -3.75, 11) ms and the end of week 1 was 15 ms (IQR: 2, 18). Out of the 5 HCW who turned positive for COVID-19, 2 were on HCQ. CONCLUSION: HCQ prophylaxis was found to be safe and well tolerated in HCW when administered after appropriate screening and with monitoring for adverse events.