Risk of Severe COVID-19 in Prevalent Users of Alpha-1 Adrenergic Receptor Antagonists: A National Case-Control Study of Medicare Beneficiaries.

BACKGROUND: Alpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure. METHODS: We performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: There were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18). CONCLUSIONS: Prevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19.

Evaluation of optic neuritis following human papillomavirus vaccination.

To assess the relationship between human papillomavirus (HPV) vaccination and occurrence of optic neuritis (ON) and to evaluate a claims-based algorithm for identification of ON. Females of 9-26 year olds in the HealthCore's Integrated Research Database (HIRDSM) with and without claims evidence of HPV vaccination between 2007 and 2012 were included in this study. Potential ON cases were identified using the claims-based algorithm, positive predictive value (PPV) was determined using medical chart review. For the claims analysis, two study designs, a self-controlled temporal scan statistic and a retrospective matched cohort analysis, were used. ON was defined based on an algorithm developed using diagnosis and procedure codes from the medical claims. The PPV for ON cases using charts that had enough information for reviewers to make a determination was 62.5% (95% CI: 49.5%-74.3%). With the self-controlled temporal scan statistic, the primary analysis restricting on recommended vaccination schedule timing showed an increased risk of potential ON after second dose (RR = 3.39; p = 0.03), this finding was not confirmed for any of the additional analyses performed for individual or combined doses. With the cohort design, there was no increased risk of potential ON following vaccination in either individual or combined dose analyses. The risk of potential ON was higher among participants with a history of prior autoimmune diseases. In conclusion, identifying confirmed ON cases through administrative claims data proved challenging. The claims-based analysis in this study did not provide evidence for an association of ON with HPV vaccination.

Posttransfusion purpura occurrence and potential risk factors among the inpatient US elderly, as recorded in large Medicare databases during 2011 through 2012.

BACKGROUND: Posttransfusion purpura (PTP) is a serious transfusion complication resulting in sudden thrombocytopenia with bleeding. The study's objective was to assess PTP occurrence and potential risk factors among the inpatient US elderly, ages 65 and older, during 2011 through 2012. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare databases for calendar years 2011 and 2012. Transfusions of blood and blood components were identified by recorded ICD-9-CM procedure codes and revenue center codes, and PTP was ascertained via ICD-9-CM diagnosis code. Our study evaluated PTP rates (per 100,000 inpatient transfusion stays) among elderly Medicare beneficiaries, overall and by age, sex, race, number of units, and blood components transfused. Multivariate regression analyses were used to assess potential risk factors. RESULTS: Among 4,336,338 inpatient transfusion stays for elderly beneficiaries during the study period, 78 had a PTP diagnosis code recorded, an overall rate of 1.8 per 100,000 stays. PTP occurrence varied by the blood components, units transfused, and other characteristics. Significantly higher odds of PTP were found for platelet (PLT)-containing transfusions, with greater number of units transfused, as well as for elderly with histories of cardiac arrhythmias (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.43-4.93), coagulopathy (OR, 1.79; 95% CI, 1.01-3.21), leukemia (OR, 2.37; 95% CI, 1.07-5.26), transplant (OR, 2.68; 95% CI, 1.41-5.09), and other conditions. CONCLUSION: Our population-based study suggests a substantially higher PTP risk with PLT-containing transfusions. The study also suggests increased PTP risk with greater number of units transfused as well as the importance of underlying health conditions and prior recipient alloimmunization for PTP occurrence among the elderly.

Early mortality after aortic valve replacement with mechanical prosthetic vs bioprosthetic valves among Medicare beneficiaries: a population-based cohort study.

IMPORTANCE: Early mortality for patients who undergo aortic valve replacement (AVR) may differ between mechanical and biological prosthetic (hereinafter referred to as bioprosthetic) valves. Clinical trials may have difficulty addressing this issue owing to limited sample sizes and low mortality rates. OBJECTIVE: To compare early mortality after AVR between the recipients of mechanical and bioprosthetic aortic valves. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of patients 65 years or older in the Medicare databases who underwent AVR from July 1, 2006, through December 31, 2011. In the mixed-effects models adjusting for physician and hospital random effects, we estimated odds ratios (OR) of early mortality to compare mechanical vs bioprosthetic valves. EXPOSURES: Mechanical or bioprostheticaortic valve replacement. MAIN OUTCOMES AND MEASURES: Early mortality was measured as death on the date of surgery, death within 1 to 30 or 31 to 365 days after the date of surgery, death within 30 days after the date of hospital discharge, and operative mortality (death within 30 days after surgery or at discharge, whichever is longer). RESULTS: Of the 66 453 Medicare beneficiaries who met inclusion criteria, 19 190 (28.88%) received a mechanical valve and 47 263 (71.12%) received a bioprosthetic valve. The risk for death on the date of surgery was 60% higher for recipients of mechanical valves than recipients of bioprosthetic valves (OR, 1.61 [95% CI, 1.27-2.04; P < .001]; risk ratio [RR], 1.60). The risk difference decreased to 16% during the 30 days after the date of surgery (OR, 1.18 [95% CI, 1.09-1.28; P < .001]; RR, 1.16). We found no differences within 31 to 365 days after the date of surgery and within the 30 days after discharge. The risk for operative mortality was 19% higher for recipients of mechanical compared with bioprosthetic valves (OR, 1.21 [95% CI, 1.13-1.30; P < .001]; RR, 1.19). The number needed to treat with mechanical valves to observe 1 additional death on the surgery date was 290; to observe 1 additional death within 30 days of surgery, 121. Consistent findings were observed in subgroup analyses of patients who underwent concurrent AVR and coronary artery bypass graft, but not in the subgroup undergoing isolated AVR. CONCLUSIONS AND RELEVANCE: In this cohort analysis of Medicare beneficiaries, use of mechanical aortic valves was associated with a higher risk for death on the date of surgery and within the 30 days after surgery compared with bioprosthetic aortic valves among patients who underwent concurrent AVR and coronary artery bypass graft but not isolated AVR.

Transfusion-related acute lung injury and potential risk factors among the inpatient US elderly as recorded in Medicare claims data, during 2007 through 2011.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication leading to pulmonary edema and respiratory failure. This study's objective was to assess TRALI occurrence and potential risk factors among inpatient US elderly Medicare beneficiaries, ages 65 and older, during 2007 through 2011. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare administrative databases. Transfusions were identified by recorded procedure and revenue center codes. TRALI was ascertained via ICD-9-CM diagnosis code. The study evaluated TRALI rates among the inpatient elderly overall and by calendar year, age, sex, race, blood components, and units transfused. Logistic regression analyses were used to assess potential risk factors. RESULTS: Of 11,378,264 inpatient transfusion stays for elderly Medicare beneficiaries, 2556 had a recorded TRALI diagnosis code, an overall rate of 22.46 per 100,000 stays. TRALI rates were higher for platelet (PLT)- and plasma-containing transfusions and increased by year and number of units transfused (p < 0.0001). Significantly higher odds of TRALI were also found for persons ages 65 to 79 years versus more than 79 years (OR, 1.19; 95% confidence interval CI, 1.09-1.29), females versus males (OR, 1.26; 95% CI, 1.16-1.38), white versus nonwhite (OR, 1.43; 95% CI, 1.27-1.66), and with 6-month histories of postinflammatory pulmonary fibrosis (OR, 1.89; 95% CI, 1.52-2.20), tobacco use (OR, 1.16; 95% CI, 1.00-1.26), and other diseases. CONCLUSION: Our study among the elderly suggests TRALI to be a severe event and identifies a substantially increased TRALI occurrence with greater number of units and with PLT- or plasma-containing transfusions. The study also suggests importance of underlying health conditions, prior recipient alloimmunization, and nonimmune mechanism in TRALI development among the elderly.

Incidence of endophthalmitis after corneal transplant or cataract surgery in a medicare population.

OBJECTIVE: To estimate the incidence of infectious endophthalmitis after corneal transplant or cataract surgery, to evaluate the trend of endophthalmitis during the study period, and to assess demographic risk factors for endophthalmitis after surgeries. DESIGN: A retrospective population-based cohort study. PARTICIPANTS AND CONTROLS: Study cohorts were derived from the Medicare claims databases, 2006 to 2011. Patients were continuously enrolled in Medicare Part A, Part B, and Part D. Patients undergoing corneal transplant or cataract surgery were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. METHODS: Endophthalmitis was defined in 3 different ways: (1) using ICD-9-CM codes (sensitive definition), (2) combining ICD-9-CM codes with Current Procedural Terminology, Fourth Edition (CPT-4) codes (specific definition), or (3) combining ICD-9-CM codes with antifungal prescriptions for endophthalmitis caused by fungal infection. Demographic risk factors for endophthalmitis were examined using multivariate Cox models. MAIN OUTCOME MEASURES: Incidence rates of endophthalmitis were calculated and compared for each definition of endophthalmitis at 6-week and 6-month intervals after corneal transplant or cataract surgery. RESULTS: The infectious endophthalmitis incidence rates ranged from 0.11% to 1.05% in the corneal transplant cohort, 0.06% to 0.20% in the cataract surgery cohort, and 0.16% to 0.68% in the concurrent surgery cohort, depending on the definition and time interval after surgery. Compared with the cataract surgery cohort, the corneal transplant cohort had a higher adjusted hazard ratio (HR) of endophthalmitis within the 6-week postoperative interval (HR, 2.744; 95% confidence interval [CI], 1.544-4.880 in the sensitive definition and HR, 2.792; 95% CI, 1.146-6.802 in the specific definition) and within the 6-month postoperative interval (HR, 4.607; 95% CI, 3.144-6.752 for the sensitive definition and HR, 4.385; 95% CI, 2.245-8.566 for the specific definition). CONCLUSIONS: It is possible to monitor the trend of infectious endophthalmitis after corneal transplant or cataract surgery through examining Medicare claims databases as long as a consistent definition of endophthalmitis is used. The annual incidence of endophthalmitis was stable over time during the study period for both corneal transplant and cataract surgery procedures; however, there was a wider year-to-year variation for the corneal transplant cohort.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine.

CONTEXT: In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years. OBJECTIVE: To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV. DESIGN, SETTING, AND PARTICIPANTS: Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting. MAIN OUTCOME MEASURES: Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates. RESULTS: VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barré syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods. CONCLUSIONS: Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system.