Treatment Outcome with High versus low-to-moderate Dosing of Corticosteroids in Early vis-a-vis Late-onset Hypoxic Cases of COVID-19: A Multicentric Retrospective Cohort Study.

Background: Corticosteroid dosing in COVID-19 cases associated with early-onset and late-onset hypoxia have not been separately explored. Methods: In this retrospective cohort study, we divided hypoxic COVID-19 cases into groups based on timing of initiation of corticosteroids relative to onset of symptoms; Group A (≤6th day), Group B (7th-9th day) and Group C (≥10th day), each group being sub-grouped into high and low-to-moderate dose corticosteroid recipients. Cox regression with propensity scoring was used to compare 28-day mortality between high and low-to-moderate dose recipients separately in Group A, Group B, Group C. Results: Among 505 patients included, propensity score matched Cox regression showed greater risk of all-cause mortality among high dose recipients in Group A [HR= 7.35, 95%CI 3.36-16.11, p-value<0·01, N=114] and Group B [HR=3.17, 95%CI 1.65-6.07, p-value<0·01, N=251]. In Group C, mortality was lowest [12.8% (18/140)] with no significant difference between sub-groups [HR=2.52, 95%CI 0.22-29.15, p-value=0.459, N=140]. Kruskal-Wallis Test between Group A, Group B and Group C for six pre-defined exposure variables showed significant differences for Neutrophil:Lymphocyte Ratio (NLR). Conclusion: When steroids were initiated early (owing to an earlier onset of hypoxic symptoms), a high dose of corticosteroid was associated with greater overall 28-day mortality compared to a low-to-moderate dose. NLR, a marker for individual immune response, varied between treatment groups.

Information adequacy of medicine package inserts in India: A critical evaluation.

OBJECTIVES: Package inserts (PIs) are used by physicians and other health-care providers as ready source of approved prescribing information. In India, they are subject to statutory regulations that specify the information to be provided under various headings. Uniformity of PIs with optimal level of information is desirable, the absence of which may lead to medication errors. This observational study aimed to evaluate the information adequacy and accuracy of PIs available in the Indian market. MATERIALS AND METHODS: PIs of drugs marketed in India, and approved by United States Food and Drug Administration, were collected from various retail pharmacies through purposive sampling. The adequacy and accuracy of the information in each PI were evaluated with the help of a 25-item checklist prepared as per stipulations mentioned in statutory guidelines. Each required item of information was scored 1 if present and appropriate or 0 if absent or deemed incomplete or inaccurate. A total information adequacy score (IAS), with maximum value 25, was thereby calculated. RESULTS: From the total 135 PIs analyzed, the median IAS was 17 (interquartile range 15-19). Deficiencies were observed under important headings. For example, "references" were mentioned in only 6.67% and "date of last updating" in only 19.26% of PIs. Other notable shortcomings were in "disposal" (not mentioned in 92.59%), "effects on ability to drive and use machines" (76.30%), "pharmaceutical incompatibilities" (66.67%), "shelf life" (62.96%), "excipients" (60.00%), and "overdose" (17.78%) information. Information on "generic name," "composition," and "indications" were however provided by all (100%) PIs. CONCLUSIONS: The information provided by PIs in India being inadequate, may not be able to serve as a reliable source of information.

A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole.

A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but with different molecules of fluoroquinolone (ciprofloxacin or ofloxacin) and nitroimidazole (tinidazole or ornidazole). He could not however avoid the rash. This time the patient presented with multiple, round-to-oval, well-defined, hyperpigmented cutaneous patches of different dimensions, all over the body. He appeared to have run out of options and therefore consulted us seeking advice on how he should treat himself next time he suffered from diarrhea. Causality assessment by Naranjo's algorithm revealed a definite relationship between the cutaneous adverse reaction and the offending drug. He was counselled regarding medication in general and advised, in particular, to avoid the tendency to self-treat any future episode of diarrhea.