Gastrointestinal prophylaxis for COVID-19: an illustration of severe bias arising from inappropriate comparators in observational studies.

OBJECTIVES: We aimed to use setting-appropriate comparisons to estimate the effects of different gastrointestinal (GI) prophylaxis pharmacotherapies for patients hospitalized with COVID-19 and setting-inappropriate comparisons to illustrate how improper design choices could result in biased results. STUDY DESIGN AND SETTING: We identified 3,804 hospitalized patients aged ≥ 18 years with COVID-19 from March to November 2020. We compared the effects of different gastroprotective agents on clinical improvement of COVID-19, as measured by a published severity scale. We used propensity score-based fine-stratification for confounding adjustment. Based on guidelines, we prespecified comparisons between agents with clinical equipoise and inappropriate comparisons of users vs. nonusers of GI prophylaxis in the intensive care unit (ICU). RESULTS: No benefit was detected when comparing oral famotidine to omeprazole in patients treated in the general ward or ICUs. We also found no associations when comparing intravenous famotidine to intravenous pantoprazole. For inappropriate comparisons of users vs. nonusers in the ICU, the probability of improvement was reduced by 32%-45% in famotidine users and 21%-48% in omeprazole or pantoprazole users. CONCLUSION: We found no evidence that GI prophylaxis improved outcomes for patients hospitalized with COVID-19 in setting-appropriate comparisons. An improper comparator choice can lead to spurious associations in critically ill patients.

Ambulatory Fluoroquinolone Use in the United States, 2015-2019.

BACKGROUND: Frequently used fluoroquinolones have been subject to increasing safety concerns and regulatory alerts. This study characterized ambulatory fluoroquinolone utilization in the United States and evaluated the impact of 2016 Food and Drug Administration (FDA) safety advisories on its use. METHODS: We used IQVIA's National Disease and Therapeutic Index to quantify adult outpatient fluoroquinolone use ("treatment visits"). Descriptive statistics and segmented regression were used to report trends and quantify the varied use before and after FDA's 2016 alerts. RESULTS: Between 2015 to 2019, fluoroquinolone use decreased by 26.7% (18.7 million treatment visits in 2015 to 13.7 million treatment visits in 2019). Annual use declined by 44%, 24%, and 24% for respiratory, urogenital, and gastrointestinal conditions, respectively; and by 66% among providers ≤44 years old vs negligible decline among those ≥65 years old. Before 2016 FDA advisories, there were approximately 4.8 million fluoroquinolone treatment visits/quarter, which had a statistically significant immediate drop by 641035 visits (95% confidence interval [CI], -937368 to -344702; P=.000) after FDA's 2016 advisories. A statistically significant difference of approximately 45000 visits/quarter (95% CI, -85956 to -3122; P=.036) was observed after the advisories. CONCLUSIONS: Large reductions in ambulatory fluoroquinolone use in the United States have coincided with increasing evidence of safety concerns and FDA advisories. However, fluoroquinolone use varies significantly based on patient and provider characteristics, suggesting heterogeneous effects of emerging risks on clinical practice.

Impact of Adherence, Patient Perception, and Knowledge to Statin Therapy - A Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Cardiovascular diseases and its risk factors, such as diabetes and hyperlipidemia, are common in Indian population. Statin utilization is high across the country and it is important to assess the adherence because it plays an important role in treatment outcome. Statin adherence is not studied well in India. This study aims at measuring the adherence, perception, and knowledge of individuals on statin therapy. STUDY DESIGN: Cross-sectional observational study on 130 consented individuals visiting a tertiary care teaching hospital. Study was conducted for a duration of 9 months. METHODS AND MATERIALS: After obtaining approval from the institutional ethics committee the study subjects were assessed for knowledge, perception, and adherence to statin therapy using a systematically developed interview questionnaire. RESULTS: Good adherence was seen in 42.30% patients. Higher proportions of females were reported to have good adherence. Good adherence was observed in patients with a history of coronary heart disease and atorvastatin as monotherapy (P = 0.0029) and fixed dose combination (P = 0.0012), whereas lipid reduction was found directly related to type of adherence. Lack of knowledge, cost, re-fill issues, and adverse effects were some of the barriers identified. INTERPRETATION AND CONCLUSION: Knowledge and patient perception plays a very important role in determining the adherence to statin therapy. A history of coronary heart disease, choice of statin, and cost of therapy are the contributing factors to adherence. Patient counselling and improving the cost-effectiveness of statin therapy can be considered as interventional strategies to overcome adherence issues.

Azathioprine-Induced Pancytopenia and Septic Complications: A Probable Cause of Death.

Azathioprine, an immunosuppressant which is widely used in the management of the autoimmune neuromuscular disorder. Myasthenia gravis is known to cause myelotoxicity. A 55-year-old male recently diagnosed with myasthenia gravis and chronic kidney disease was put on azathioprine (100 mg/d) along with pyridostigmine and prednisolone. When the treatment was initiated, the hematological reports revealed normal levels of blood count. However, approximately within 3 weeks of continuing the prescribed drugs, the patient was readmitted for complaints of loose watery stools, weakness, and giddiness. Clinical investigations revealed severe pancytopenia, suspecting to be related to azathioprine. The suspected drug (azathioprine) was withdrawn, and the management for pancytopenia was initiated. However, on the second day of hospitalization, the patient underwent cardiac arrest and septic shock which lead to death. Adverse drug reaction assessment revealed a plausible and causal relationship of azathioprine with pancytopenia and other adverse effects seen in this patient.