Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study.

Background: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort. Methods: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff's method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS. Results: Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors. Conclusions: Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity.

INTRODUCTION: People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24 months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14 days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE). RESULTS: Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56-0.72) and SGLT-2i (OR 0.62, 95% CI 0.57-0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81-1.05 and OR 0.88, 95% CI 0.76-1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone. CONCLUSION: Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article.

Deprescribing medications among patients with multiple prescribers: A socioecological model.

Deprescribing is the intentional dose reduction or discontinuation of a medication. The development of deprescribing interventions should take into consideration important organizational, interprofessional, and patient-specific barriers that can be further complicated by the presence of multiple prescribers involved in a patient's care. Patients who receive care from an increasing number of prescribers may experience disruptions in the timely transfer of relevant healthcare information, increasing the risk of exposure to drug-drug interactions and other medication-related problems. Furthermore, the fragmentation of healthcare information across health systems can contribute to the refilling of discontinued medications, reducing the effectiveness of deprescribing interventions. Thus, deprescribing interventions must carefully consider the unique characteristics of patients and their prescribers to ensure interventions are successfully implemented. In this special article, an international working group of physicians, pharmacists, nurses, epidemiologists, and researchers from the United States Deprescribing Research Network (USDeN) developed a socioecological model to understand how multiple prescribers may influence the implementation of a deprescribing intervention at the individual, interpersonal, organizational, and societal level. This manuscript also includes a description of the concept of multiple prescribers and outlines a research agenda for future investigations to consider. The information contained in this manuscript should be used as a framework for future deprescribing interventions to carefully consider how multiple prescribers can influence the successful implementation of the service and ensure the intervention is as effective as possible.

Risk of Major Bleeding Associated with Concomitant Direct-Acting Oral Anticoagulant and Clopidogrel Use: A Retrospective Cohort Study.

BACKGROUND AND AIM: Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel. METHODS: We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding. RESULTS: The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.

Risk factors associated with post-acute sequelae of SARS-CoV-2: an N3C and NIH RECOVER study.

BACKGROUND: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). The objective is to identify risk factors associated with PASC/long-COVID diagnosis. METHODS: This was a retrospective case-control study including 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system and COVID index date within ± 45 days of the corresponding case's earliest COVID index date. Measurements of risk factors included demographics, comorbidities, treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. RESULTS: Among 8,325 individuals with PASC, the majority were > 50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30 + days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. CONCLUSIONS: This national study identified important risk factors for PASC diagnosis such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.

Potential drug-drug interactions among U.S. adults treated with nirmatrelvir/ritonavir: A cross-sectional study of the National Covid Cohort Collaborative (N3C).

STUDY OBJECTIVE: To estimate the prevalence of potential moderate to severe drug-drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs. DESIGN: Cross-sectional study. DATA SOURCE: Electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID-19 data resources in the United States. PATIENTS: Outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022. INTERVENTION: Nirmatrelvir/ritonavir. MEASUREMENTS: The outcome is potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir. MAIN RESULTS: Of 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8 ± 17.1 years, 39.5% were male, and 65.8% were non-Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10-year increase, 95% confidence interval [CI] 1.08-1.25), male (OR 1.36, CI 1.09-1.71), smokers (OR 1.38, CI 1.10-1.73), on more co-medications (OR 1.35, CI 1.31-1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05-6.45). CONCLUSIONS: One in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks.

Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with COVID-19: an EHR-based Target Trial Emulation from N3C.

This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing COVID-19 hospitalization rates. From an eligible population of 632,822 COVID-19 patients seen at 33 clinical sites across the United States between December 23, 2021 and December 31, 2022, patients were matched across observed treatment groups, yielding an analytical sample of 410,642 patients. We estimate a 65% reduced odds of hospitalization among Paxlovid-treated patients within a 28-day follow-up period, and this effect did not vary by patient vaccination status. Notably, we observe disparities in Paxlovid treatment, with lower rates among Black and Hispanic or Latino patients, and within socially vulnerable communities. Ours is the largest study of Paxlovid's real-world effectiveness to date, and our primary findings are consistent with previous randomized control trials and real-world studies.

Excess deaths from COVID-19 among Medicare beneficiaries with psychiatric diagnoses: Community versus nursing home.

BACKGROUND: Psychiatric illness may pose an additional risk of death for older adults during the COVID-19 pandemic. Older adults in the community versus institutions might be influenced by the pandemic differently. This study examines excess deaths during the COVID-19 pandemic among Medicare beneficiaries with and without psychiatric diagnoses (depression, anxiety, bipolar disorder, and schizophrenia) in the community versus nursing homes. METHODS: This is a retrospective cohort study of a 20% random sample of 15,229,713 fee-for-service Medicare beneficiaries, from January 2019 through December 2021. Unadjusted monthly mortality risks, COVID-19 infection rates, and case-fatality rates after COVID-19 diagnosis were calculated. Excess deaths in 2020, compared to 2019 were estimated from multivariable logistic regressions. RESULTS: Of all included Medicare beneficiaries in 2020 (N = 5,140,619), 28.9% had a psychiatric diagnosis; 1.7% lived in nursing homes. In 2020, there were 246,422 observed deaths, compared to 215,264 expected, representing a 14.5% increase over expected. Patients with psychiatric diagnoses had more excess deaths than those without psychiatric diagnoses (1,107 vs. 403 excess deaths per 100,000 beneficiaries, p < 0.01). The largest increases in mortality risks were observed among patients with schizophrenia (32.4% increase) and bipolar disorder (25.4% increase). The pandemic-associated increase in deaths with psychiatric diagnoses was only found in the community, not in nursing homes. The increased mortality for patients with psychiatric diagnoses was limited to those with medical comorbidities. The increase in mortality for psychiatric diagnoses was associated with higher COVID-19 infection rates (1-year infection rate = 7.9% vs. 4.2% in 2020), rather than excess case fatality. CONCLUSIONS: Excess deaths during the COVID-19 pandemic were disproportionally greater in beneficiaries with psychiatric diagnoses, at least in part due to higher infection rates. Policy interventions should focus on preventing COVID-19 infections and deaths among community-dwelling patients with major psychiatric disorders in addition to those living the nursing homes.

Drug-drug interaction between dexamethasone and direct-acting oral anticoagulants: a nested case-control study in the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE. DESIGN: We used nested case-control study design. SETTING: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA. PARTICIPANTS: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban. RESULTS: McNemar's Χ2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ2=0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18). CONCLUSION: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation.

BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study.

BACKGROUND: While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. METHODS: Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. RESULTS: 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. CONCLUSIONS: There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.

Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries.

OBJECTIVE: To determine the effectiveness of booster vaccinations on the risk of hospitalization with coronavirus disease 2019 (COVID-19) and how it varies by enrollee characteristics and interval from the initial vaccination to receipt of a booster. PATIENTS AND METHODS: This cohort study used 100% Medicare claims from January 1, 2020, through December 31, 2021, and matched 3,940,475 individuals who received boosters to 3,940,475 controls based on week and type of original COVID-19 vaccine and demographic and clinical characteristics. We compared the association of booster vs no booster with COVID-19 hospitalization using Cox proportional hazards regression models controlling for patient characteristics. We also determined the association of time from original vaccine to booster with COVID-19 hospitalization. RESULTS: Over a maximum of 130 days of follow-up, boosted enrollees had 8.20 (95% CI, 7.81 to 8.60) COVID-19 hospitalizations per million days vs 43.70 (95% CI, 42.79 to 44.64) for controls (81% effectiveness). Effectiveness varied by race, prior hospitalizations, and certain comorbidities, for example, leukemia/lymphoma (53% effectiveness), autoimmune disease (73%), and dementia (73%). Boosters received between 6 and 9 months after original vaccination varied between 81% and 85% effectiveness, while boosters received at 5 to 6 months (62%) or less than 5 months (58%) were less effective. CONCLUSION: Boosters are highly effective in the Medicare population. Approximately 69,225 hospitalizations would be prevented by boosters in the 15 million individuals aged 65 years or older currently not boosted in a period similar to the September 2020 through January 2021 period studied. Boosters provided the greatest benefits if they were received between 6 and 9 months following original vaccinations. However, boosters were associated with substantial decreases in COVID-19 hospitalizations in all categories of enrollees.

Development and Validation of the Summary Elixhauser Comorbidity Score for Use With ICD-10-CM-Coded Data Among Older Adults.

BACKGROUND: Older adults have many comorbidities contributing to mortality. OBJECTIVE: To develop a summary Elixhauser (S-Elixhauser) comorbidity score to predict 30-day, in-hospital, and 1-year mortality in older adults using the 38 comorbidities operationalized by the Agency for Healthcare Research and Quality (AHRQ). DESIGN: Retrospective cohort study. SETTING: Medicare beneficiaries from 2017 to 2019. PATIENTS: Persons hospitalized in 2018 (n = 899 844) and 3 disease-specific hospitalized cohorts. MEASUREMENTS: Weights were derived for 38 comorbidities to predict 30-day, in-hospital, and 1-year mortality. The S-Elixhauser score was internally validated and calibrated. Individual Elixhauser comorbidity indicators (38 comorbidities), the modified application of the AHRQ-derived Elixhauser summary score, the Charlson comorbidity indicators (17 comorbidities), and the Charlson summary score were externally validated. The c-statistic was used to evaluate discrimination of a comorbidity score model. RESULTS: The S-Elixhauser score was well calibrated and internally validated, with a c-statistic of 0.705 (95% CI, 0.703 to 0.707) in predicting 30-day mortality, 0.654 (CI, 0.651 to 0.657) for in-hospital mortality, and 0.743 (CI, 0.741 to 0.744) for 1-year mortality. In external validation of other comorbidity indices for 30-day mortality, the c-statistic was 0.711 (CI, 0.709 to 0.713) for the individual Elixhauser comorbidity indicators, 0.688 (CI, 0.686 to 0.690) for the AHRQ Elixhauser score, 0.696 (CI, 0.694 to 0.698) for the Charlson comorbidity indicators, and 0.690 (CI, 0.688 to 0.693) for the Charlson summary score. In 3 disease-specific populations, the discrimination of the S-Elixhauser score in predicting 30-day mortality ranged from 0.657 to 0.732. LIMITATION: Validation of the S-Elixhauser comorbidity score and head-to-head comparison with other comorbidity scores in an external population are needed to evaluate comparative performance. CONCLUSION: The S-Elixhauser comorbidity score is well calibrated and internally validated but its advantage over the AHRQ Elixhauser and Charlson summary scores is unclear. PRIMARY FUNDING SOURCE: National Institute on Aging.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

BACKGROUND: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF). METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. RESULTS: Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA2DS2-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA2DS2-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1). CONCLUSIONS: Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Hospitalizations and Mortality From Non-SARS-CoV-2 Causes Among Medicare Beneficiaries at US Hospitals During the SARS-CoV-2 Pandemic.

Importance: The increased hospital mortality rates from non-SARS-CoV-2 causes during the SARS-CoV-2 pandemic are incompletely characterized. Objective: To describe changes in mortality rates after hospitalization for non-SARS-CoV-2 conditions during the COVID-19 pandemic and how mortality varies by characteristics of the admission and hospital. Design, Setting, and Participants: Retrospective cohort study from January 2019 through September 2021 using 100% of national Medicare claims, including 4626 US hospitals. Participants included 8 448 758 individuals with non-COVID-19 medical admissions with fee-for-service Medicare insurance. Main Outcomes and Measures: Outcome was mortality in the 30 days after admission with adjusted odds generated from a 3-level (admission, hospital, and county) logistic regression model that included diagnosis, demographic variables, comorbidities, hospital characteristics, and hospital prevalence of SARS-CoV-2. Results: There were 8 448 758 non-SARS-CoV-2 medical admissions in 2019 and from April 2020 to September 2021 (mean [SD] age, 73.66 [12.88] years; 52.82% women; 821 569 [11.87%] Black, 438 453 [6.34%] Hispanic, 5 351 956 [77.35%] White, and 307 218 [4.44%] categorized as other). Mortality in the 30 days after admission increased from 9.43% in 2019 to 11.48% from April 1, 2020, to March 31, 2021 (odds ratio [OR], 1.20; 95% CI, 1.19-1.21) in multilevel logistic regression analyses including admission and hospital characteristics. The increase in mortality was maintained throughout the first 18 months of the pandemic and varied by race and ethnicity (OR, 1.27; 95% CI, 1.23-1.30 for Black enrollees; OR, 1.25; 95% CI, 1.23-1.27 for Hispanic enrollees; and OR, 1.18; 95% CI, 1.17-1.19 for White enrollees); Medicaid eligibility (OR, 1.25; 95% CI, 1.24-1.27 for Medicaid eligible vs OR, 1.18; 95% CI, 1.16-1.18 for noneligible); and hospital quality score, measured on a scale of 1 to 5 stars with 1 being the worst and 5 being the best (OR, 1.27; 95% CI, 1.22-1.31 for 1 star vs OR, 1.11; 95% CI, 1.08-1.15 for 5 stars). Greater hospital prevalence of SARS-CoV-2 was associated with greater increases in odds of death from the prepandemic period to the pandemic period; for example, comparing mortality in October through December 2020 with October through December 2019, the OR was 1.44 (95% CI, 1.39-1.49) for hospitals in the top quartile of SARS-CoV-2 admissions vs an OR of 1.19 (95% CI, 1.16-1.22) for admissions to hospitals in the lowest quartile. This association was mostly limited to admissions with high-severity diagnoses. Conclusions and Relevance: The prolonged elevation in mortality rates after hospital admission in 2020 and 2021 for non-SARS-CoV-2 diagnoses contrasts with reports of improvement in hospital mortality during 2020 for SARS-CoV-2. The results of this cohort study suggest that, with the continued impact of SARS-CoV-2, it is important to implement interventions to improve access to high-quality hospital care for those with non-SARS-CoV-2 diseases.

Trends and variation in benzodiazepine use in nursing homes in the USA.

PURPOSE: Because of toxicities, benzodiazepines are not usually recommended in older adults. We therefore sought to describe the trends in benzodiazepine use in long-term care and examine the variation in benzodiazepine use among nursing homes. METHODS: In this retrospective repeated cross-sectional analysis of Medicare Parts A, B, and D claims data linked to the Minimum Data Set from 2013 to 2018, we included long-term residents who stayed in a nursing home for at least one entire quarter of a calendar year in 2013-2018. The outcome was whether residents were prescribed a benzodiazepine drug for at least 30 days during each quarter stay. We use mixed effects logistic regression models to assess the variation in benzodiazepine use among nursing homes, adjusting for patient and nursing home characteristics. RESULTS: The cohort for the time trend analysis included 270,566 unique residents and 1,843,580 quarter stays for 2013-2018. Prescribing rates for short-acting benzodiazepines were stable over 2013-2016, then declined from 12.1% in 2016 to 10.6% in 2018. The rate of long-acting benzodiazepine use remained relatively steady at around 4% over 2013-2018. During 2017-2018, the variation among nursing homes in benzodiazepine use was 7.2% for short-acting vs. 9.3% for long-acting benzodiazepines, after controlling for resident characteristics. CONCLUSION: Prescribing for short-acting benzodiazepines in long-term care declined after 2016, while long-acting benzodiazepine use did not change. The variation in benzodiazepine use among nursing homes is substantial. Identifying factors that explain this variation may help in developing strategies for deprescribing benzodiazepines in nursing home residents.

Real-World Effectiveness of Remdesivir in Adults Hospitalized With Coronavirus Disease 2019 (COVID-19): A Retrospective, Multicenter Comparative Effectiveness Study.

BACKGROUND: There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death. RESULTS: Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls). CONCLUSIONS: These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BACKGROUND: Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals. METHODS: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology. FINDINGS: Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. INTERPRETATION: Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined. FUNDING: None.