OBJECTIVE:To compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group. METHODS:Using Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation. RESULTS:The event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n = 181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n = 850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62-1.25) and 0.82 (95% CI:0.54-1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66-1.16). Subgroup and sensitivity analyses supported these results. CONCLUSION:5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events.

Acute respiratory failure (ARF) associated with antipsychotic use has been documented through case reports and population-based studies. To assess whether the recent use of antipsychotics is associated with an increased risk of ARF in U.S. Medicare beneficiaries with chronic obstructive pulmonary disease. Case-crossover study conducted among U.S. Fee-for-Service Medicare beneficiaries with chronic obstructive pulmonary disease hospitalized with ARF, from January 1, 2007, through December 31, 2019. Oral antipsychotics. Adjusted odds ratios (aOR) and 95

Background: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vectorbased COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.) are needed to contextualize reports following COVID-19 vaccination. Methods: We estimated annual and monthly IRs of overall TTS, common site TTS, and unusual site TTS for adults aged 18 -64 years in Carelon Research and MarketScan commercial claims (2017 -Oct 2020), CVS Health and Optum commercial claims (2019 -Oct 2020), and adults aged >= 65 years using CMS Medicare claims (2019 -Oct 2020); IRs were stratified by age, sex, and race/ethnicity (CMS Medicare). Results: Across data sources, annual IRs for overall TTS were similar between Jan -Dec 2019 and Jan -Oct 2020. Rates were higher in Medicare (IRs: 370.72 and 365.63 per 100,000 person -years for 2019 and 2020, respectively) than commercial data sources (MarketScan IRs: 24.21 and 24.06 per 100,000 person -years; Optum IRs: 32.60 and 31.29 per 100,000 person -years; Carelon Research IRs: 24.46 and 26.16 per 100,000 person -years; CVS Health IRs: 30.31 and 30.25 per 100,000 person -years). Across years and databases, common site TTS IRs increased with age and were higher among males. Among adults aged >= 65 years, the common site TTS IR was highest among non -Hispanic black adults. Annual unusual site TTS IRs ranged between 2.02 and 3.04 (commercial) and 12.49 (Medicare) per 100,000 person -years for Jan -Dec 2019; IRs ranged between 1.53 and 2.67 (commercial) and 11.57 (Medicare) per 100,000 person -years for Jan -Oct 2020. Unusual site TTS IRs were higher in males and increased with age in commercial data sources; among adults aged >= 65 years, IRs decreased with age and were highest among non -Hispanic American Indian/Alaska native adults. Conclusion: TTS IRs were generally similar across years, higher for males, and increased with age. These rates may contribute to surveillance of post-vaccination TTS.

Purpose: In the United States, the National Death Index (NDI) is the most complete source of death information, while epidemiologic studies with mortality outcomes often rely on U.S. Medicare data for outcome ascertainment. The purpose of this study was to assess the agreement of death information between the Centers for Medicare & Medicaid Services (CMS) Medicare enrolment data and NDI. Methods: Using Medicare and NDI data from 1999 through 2016, we identified Medicare beneficiaries who were reported dead in the CMS Medicare enrolment database (EDB) and Common Medicare Environment (CME), linked these beneficiaries to the NDI using CMS Health Insurance Claim number, and compared death dates between the two data sources. To assess agreement between our data sources, we calculated kappa scores; where a kappa of 1 indicates perfect agreement and a kappa of 0 indicates agreement equivalent to chance. We also examined CMS to NDI linkage and death date matching for stability over time. Results: Of the 36 785 640, Medicare beneficiaries reported dead in CMS enrollment data from 1999 to 2016, 97.5% were linked to the NDI. A kappa score of 0.98 showed a near perfect agreement between NDI and CMS reported deaths. The percentage of linked cases exactly matching on death dates increased from 94.8% in 1999 to 99.4% in 2016. Conclusions: Our findings suggest strong concordance between death dates as recorded by CMS enrollment data and the NDI in the entire Medicare population.

In a successful transition from youth to adulthood, individuals pass through a sequence of roles involving school, work, and family formation that culminate in their becoming self-sufficient adults. However, some “disconnected” youth spend extended periods of time outside of any role that constitutes an element of the pathway towards adult independence. Assisting these youth requires a systematic understanding of what “disconnection” means, how many disconnected youth there are, who these youth are, and how the scale of the problem has evolved over time. Using the National Longitudinal Surveys of Youth for 1997 and 1979, we address these issues by creating concrete definitions of “disconnection spells” using rich data on youths’ enrollment, work, and personal histories. We estimate a multi-state duration model to account for right censoring and to understand differences across salient sub-groups. Our estimates imply that in the early 2000s, almost 19% and 25% of young men and young women, respectively, experienced a disconnection spell by age 23 using our basic definition. These rates are substantially higher for certain sub-groups defined by race/ethnicity, parental education, and government aid receipt, rising as high as 30+% by age 23. Approximately 60% of youth with a disconnection spell have it last longer than a year, and close to 10% have it last longer than 4 years. However, once reconnected, a majority of youth go at least three years without a re-disconnection spell. Patterns of initial disconnection changed markedly from the 1980s to the 2000s, as young women saw a 12 percentage point decline over time. Moreover, the Black-White gap in disconnection has fallen for women, but increased for men. Our profile of disconnection experiences provides a starting point for government agencies aiming to understand where, how, and with whom to intervene to prevent lengthy disconnection spells.

BACKGROUND:Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations. AIMS:To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death. METHODS:Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization. RESULTS:We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). CONCLUSIONS:Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.

Importance:The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. Objective:To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. Design, Setting, and Participants:This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. Exposures:Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. Main Outcomes and Measures:Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). Results:At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. Conclusions and Relevance:The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

Objective: To characterize the development and performance of a cataract surgery episode-based cost measure for the Medicare Quality Payment Program.Design: Claims-based analysis.Participants: Medicare clinicians with cataract surgery claims between June 1, 2016, and May 31, 2017.Methods: We limited the analysis to claims with procedure code 66984 (routine cataract surgery), excluding cases with relevant ocular comorbidities. We divided episodes into subgroups by surgery location (Ambulatory Surgery Center [ASC] or Hospital Outpatient Department [HOPD]) and laterality (bilateral when surgeries were within 30 days apart). For the episode-based cost measure, we calculated costs occurring between 60 days before surgery and 90 days after surgery, limited to services identified by an expert committee as related to cataract surgery and under the influence of the cataract surgeon. We attributed costs to the clinician submitting the cataract surgery claim, categorized costs into clinical themes, and calculated episode cost distribution, reliability in detecting clinician-dependent cost variation, and costs with versus without complications. We compared episode-based cost scores with hypothetical "nonselective" cost scores (total Medicare beneficiary costs between 60 days before surgery and 90 days after surgery).Main Outcome Measures: Episode costs with and without complications, clinician-dependent variation (proportion of total cost variance), and proportion of costs from cataract surgery-related clinical themes.Results: We identified 583 356 cataract surgery episodes attributed to 10 790 clinicians and 8189 with > 10 episodes during the measurement period. Most surgeries were performed in an ASC (71%) and unilateral (66%). The mean episode cost was $2876. The HOPD surgeries had higher costs; geography and episodes per clinician did not substantially affect costs. The proportion of cost variation from clinician-dependent factors was higher in episode-based compared with nonselective cost measures (94% vs. 39%), and cataract surgery-related clinical themes represented a higher proportion of total costs for episode-based measures. Episodes with complications had higher costs than episodes without complications ($3738 vs. $2276).Conclusions: The cataract surgery episode-based cost measure performs better than a comparable nonselective measure based on cost distribution, clinician-dependent variance, association with cataract surgery-related clinical themes, and quality alignment (higher costs in episodes with complications). Cost mea-sure maintenance and refinement will be important to maintain clinical validity and reliability.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology Science 2023;3:100315 Published by Elsevier on behalf of the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Background Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. Methods We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. Findings Four outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. Interpretation This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

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 (COVID19), 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, 0.911.07) (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. Published by Elsevier Inc. center dot The American Journal of Medicine (2023) 136:1018-1025

BACKGROUND:Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life-saving/health-preserving therapy. The study describes US IG utilization patterns from 2009 to 2019.STUDY DESIGN AND METHODS:Using IBM MarketScan commercial and Medicare claims data, we examined four metrics overall and by condition-specific categories during 2009-2019: (1) IG administrations per 100,000 person-years, (2) IG recipients per 100,000 enrollees, (3) average annual administrations per recipient, and (4) average annual dose per recipient.RESULTS:In the commercial and Medicare populations respectively: IG administrations per 100,000 person-years increased by 120% (213-470) and 144% (692-1693); IG recipients per 100,000 enrollees grew by 71% (24-42) and 102% (89-179); average annual administrations per recipient rose by 28% (8-10) and 19% (8-9); and average annual dose (grams) per recipient increased by 29% (384-497) and 34% (317-426). IG administrations associated with immunodeficiency (per 100,000 person-years) increased by 154% (from 127 to 321) and 176% (from 365 to 1007). Autoimmune and neurologic conditions were associated with higher annual average administrations and dose than other conditions.DISCUSSION:IG use increased, coinciding with a growth in the IG recipient population in the United States. Several conditions contributed to the trend, with the largest increase observed among immunodeficient individuals. Future investigations should assess changes in the demand for IVIG by disease state or indication and consider treatment effectiveness.

SESSION TITLE: COPD Assessment Tools and ComorbiditiesSESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/17/2022 12:15 pm - 1:15 pmPURPOSE: Background: Case reports and observational studies describe severe respiratory events associated with antipsychotic use.Purpose: To determine whether antipsychotic use is associated with an increased risk of acute respiratory failure (ARF) requiring invasive mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD).METHODS: We conducted a case-crossover study among US Medicare Fee-for-Service beneficiaries with COPD diagnosed with ARF requiring invasive mechanical ventilation between January 2007 and December 2019. We excluded beneficiaries with prior ARF, active cancer treatment, select conditions that may cause ARF, use of antipsychotics as anti-emetics or by a non-oral route, and those hospitalized or residing in a skilled nursing facility (Part A) during the case and/or control periods. We ascertained antipsychotic exposure in the case and control windows, defined as -1 to -14 and -75 to -88 days prior to admission, respectively. We used conditional logistic regression adjusted for use of select CNS depressants, oral corticosteroids, COPD medications, presence of delirium, and ARF background rate to calculate adjusted odd ratios (aORs) of ARF with use of antipsychotics in the case period compared to the control period. To assess effect modification, we performed analyses in subgroups defined by age, sex, race, dementia, heart failure, home oxygen use, frailty score, reason for entering Medicare, and nursing home residence.RESULTS: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the risk window and 1,728 only during the control window. The aOR of antipsychotic use within 14 days before ARF was 1.13 (1.06, 1.20). Risk was not increased in patients below age 75 years (aOR 18-49 years: 1.01 [0.85, 1.20]; 50-64 years: 1.03 [0.93, 1.15]; 65-74 years: 1.12 [0.98, 1.28]), but was increased in patients ages 75-84 years (aOR: 1.37 [1.17, 1.60]) and 85+ years (aOR: 1.50 [1.20, 1.89]). The risk of ARF with antipsychotic use was also increased in patients residing in nursing homes and with high frailty scores.CONCLUSIONS: Recent antipsychotic use by older Medicare beneficiaries with COPD was associated with increased risk of ARF. Ongoing efforts include evaluating the interaction of age with other relevant covariates, as well in certain subgroups, and addressing potential concerns of violation of intermittent use and exposure time-trend assumptions and persistent user bias. This abstract reflects the views of the authors and should not be construed to represent FDA’s views or policies.CLINICAL IMPLICATIONS: Recent antipsychotic use may increase the risk of acute respiratory failure requiring intubation and mechanical ventilation in older patients with COPD.DISCLOSURES: No relevant relationships Added 04/01/2022 by Armen Avagyan, value=SalaryRemoved 04/01/2022 by Armen AvagyanSpouse has direct stock ownership relationship with Abbvie Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=DividendsSpouse has direct ownership of stock relationship with Bristol Myers Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=DividendsSpouse has direct ownership of stock relationship with Johnson & Johnson Please note: 2013-present Added 04/12/2022 by Amy Brehm, value=DividendsNo relevant relationships by David GrahamNo relevant relationships by Jeff KelmanNo relevant relationships by Hyeseung LeeNo relevant relationships by Kira LeishearNo relevant relationships by anchi loNo relevant relationships by Thomas MaCurdyNo relevant relationships by Andrew MosholderNo relevant relationships by Silvia Perez-VilarNo relevant relationships Added 03/30/2022 by Elizabeth Smith, value=SalaryRemoved 03/30/2022 by Elizabeth SmithNo relevant relationships by Marc StoneNo relevant relationships by Michael WerneckeNo relevant relationships by yueqin zhao SESSION TITLE: COPD Assessment Tools and Comorbidities SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Background: Case reports and observational studies describe severe respiratory events associated with antipsychotic use. Purpose: To determine whether antipsychotic use is associated with an increased risk of acute respiratory failure (ARF) requiring invasive mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD). METHODS: We conducted a case-crossover study among US Medicare Fee-for-Service beneficiaries with COPD diagnosed with ARF requiring invasive mechanical ventilation between January 2007 and December 2019. We excluded beneficiaries with prior ARF, active cancer treatment, select conditions that may cause ARF, use of antipsychotics as anti-emetics or by a non-oral route, and those hospitalized or residing in a skilled nursing facility (Part A) during the case and/or control periods. We ascertained antipsychotic exposure in the case and control windows, defined as -1 to -14 and -75 to -88 days prior to admission, respectively. We used conditional logistic regression adjusted for use of select CNS depressants, oral corticosteroids, COPD medications, presence of delirium, and ARF background rate to calculate adjusted odd ratios (aORs) of ARF with use of antipsychotics in the case period compared to the control period. To assess effect modification, we performed analyses in subgroups defined by age, sex, race, dementia, heart failure, home oxygen use, frailty score, reason for entering Medicare, and nursing home residence. RESULTS: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the risk window and 1,728 only during the control window. The aOR of antipsychotic use within 14 days before ARF was 1.13 (1.06, 1.20). Risk was not increased in patients below age 75 years (aOR 18-49 years: 1.01 [0.85, 1.20]; 50-64 years: 1.03 [0.93, 1.15]; 65-74 years: 1.12 [0.98, 1.28]), but was increased in patients ages 75-84 years (aOR: 1.37 [1.17, 1.60]) and 85+ years (aOR: 1.50 [1.20, 1.89]). The risk of ARF with antipsychotic use was also increased in patients residing in nursing homes and with high frailty scores. CONCLUSIONS: Recent antipsychotic use by older Medicare beneficiaries with COPD was associated with increased risk of ARF. Ongoing efforts include evaluating the interaction of age with other relevant covariates, as well in certain subgroups, and addressing potential concerns of violation of intermittent use and exposure time-trend assumptions and persistent user bias. This abstract reflects the views of the authors and should not be construed to represent FDA’s views or policies. CLINICAL IMPLICATIONS: Recent antipsychotic use may increase the risk of acute respiratory failure requiring intubation and mechanical ventilation in older patients with COPD. DISCLOSURES: No relevant relationships Added 04/01/2022 by Armen Avagyan, value=Salary Removed 04/01/2022 by Armen Avagyan Spouse has direct stock ownership relationship with Abbvie Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=Dividends Spouse has direct ownership of stock relationship with Bristol Myers Please note: 1980-present Added 04/13/2022 by Amy Brehm, value=Dividends Spouse has direct ownership of stock relationship with Johnson & Johnson Please note: 2013-present Added 04/12/2022 by Amy Brehm, value=Dividends No relevant relationships by David Graham No relevant relationships by Jeff Kelman No relevant relationships by Hyeseung Lee No relevant relationships by Kira Leishear No relevant relationships by anchi lo No relevant relationships by Thomas MaCurdy No relevant relationships by Andrew Mosholder No relevant relationships by Silvia Perez-Vilar No relevant relationships Added 03/30/2022 by Elizabeth Smith, value=Salary Removed 03/30/2022 by Elizabeth Smith No relevant relationships by Marc Stone No relevant relationships by Michael Wernecke No relevant relationships by yueqin zhao

The use of erythropoiesis-stimulating agents (ESAs) for treatment of chemotherapy-induced anemia (CIA) has been linked to potential negative health effects. Additionally, research has identified disparities in ESA utilization for CIA treatment. This study examines (1) health disparities in ESA use and (2) whether reimbursement (Medicare National Coverage Determination [NCD]) or regulatory (Risk Evaluation and Mitigation Strategy [REMS]) policies impacted disparities. In a retrospective cohort study (2006–2018) among 1,747,889 patients with cancer in the United States receiving myelosuppressive chemotherapy at age ≥ 65 years, differences in ESA use for CIA were estimated using generalized estimating equation models, adjusting for policy periods, demographic characteristics, and clinical factors extracted from Medicare claims data. After controlling for covariates, ESA use was higher among Black, female, and urban patients in all policy periods, but these disparities decreased significantly following the NCD. The gap continued to close through the REMS period. Disparities in ESA use across geographic regions were modest, and ESA use disparities across socioeconomic characteristics (area deprivation index or dual Medicare/Medicaid eligibility) were not observed. Being female, Black, or an urban resident was associated with higher ESA use for CIA in older patients with cancer. Both NCD and REMS implementation helped reduce disparities. REMS release was not observed to contribute to racial, sex, and rural–urban disparities in ESA use for CIA.

Background: Active monitoring of safety outcomes following COVID-19 vaccination is critical to under-stand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure tri-als. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals. Methods: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively. We conducted biweekly or monthly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. Findings: Among 17 outcomes evaluated, 15 did not meet the threshold for statistical signal in any of the three databases. Myocarditis/pericarditis met the statistical threshold for a signal following BNT162b2 in two of three databases (RRs: 1.83-2.47). Anaphylaxis met the statistical threshold for a signal in all three databases following BNT162b2 vaccination (RRs: 4.48-10.86) and mRNA-1273 vaccination (RRs: 7.64- 12.40). Discussion: Consistent with published literature, our near-real time monitoring of 17 adverse outcomes following COVID-19 vaccinations identified signals for myocarditis/pericarditis and anaphylaxis follow-ing mRNA COVID-19 vaccinations. The method is intended for early detection of safety signals, and results do not imply a causal effect. Results of this study should be interpreted in the context of the meth-od's utility and limitations, and the validity of detected signals must be evaluated in fully adjusted epi-demiologic studies. Published by Elsevier Ltd.

OBJECTIVE Pimavanserin, a serotonin 5-HT2 antagonist, is indicated for treatment of hallucinations and delusions associated with Parkinson's disease psychosis. In premarketing trials in patients with Parkinson's disease psychosis, 11% of patients died during open-label pimavanserin treatment. Antipsychotics, which are used off-label in Parkinson's disease psychosis, increase mortality in dementia patients. The authors compared mortality with pimavanserin and atypical antipsychotics in a large database. METHODS This was a retrospective new-user cohort study of Medicare beneficiaries with Parkinson's disease initiating pimavanserin (N=3,227) or atypical antipsychotics (N=18,442) from April 2016 to March 2019. All-cause mortality hazard ratios and 95% confidence intervals were estimated for pimavanserin compared with atypical antipsychotics, using segmented proportional hazards regression over 1-180 and 181+ days of treatment. Potential confounding was addressed through inverse probability of treatment weighting (IPTW). RESULTS Pimavanserin users had a mean age of approximately 78 years, and 45% were female. Before IPTW, some comorbidities were more prevalent in atypical antipsychotic users; after IPTW, comorbidities were well balanced between groups. In the first 180 days of treatment, mortality was approximately 35% lower with pimavanserin than with atypical antipsychotics (hazard ratio=0.65, 95% CI=0.53, 0.79), with approximately one excess death per 30 atypical antipsychotic-treated patients; however, during treatment beyond 180 days, there was no additional mortality advantage with pimavanserin (hazard ratio=1.05, 95% CI=0.82, 1.33). Pimavanserin showed no mortality advantage in nursing home patients. CONCLUSIONS Pimavanserin use was associated with lower mortality than atypical antipsychotic use during the first 180 days of treatment, but only in community-dwelling patients, not nursing home residents.