National Trends in Anticoagulation Therapy for COVID-19 Hospitalized Adults in the United States: Analyses of the National COVID Cohort Collaborative.

BACKGROUND: Anticoagulation (AC) utilization patterns and their predictors among hospitalized coronavirus disease 2019 (COVID-19) patients have not been well described. METHODS: Using the National COVID Cohort Collaborative, we conducted a retrospective cohort study (2020-2022) to assess AC use patterns and identify factors associated with therapeutic AC employing modified Poisson regression. RESULTS: Among 162 842 hospitalized COVID-19 patients, 64% received AC and 24% received therapeutic AC. Therapeutic AC use declined from 32% in 2020 to 12% in 2022, especially after December 2021. Therapeutic AC predictors included age (relative risk [RR], 1.02; 95% confidence interval [CI], 1.02-1.02 per year), male (RR, 1.29; 95% CI, 1.27-1.32), non-Hispanic black (RR, 1.16; 95% CI, 1.13-1.18), obesity (RR, 1.48; 95% CI, 1.43-1.52), increased length of stay (RR, 1.01; 95% CI, 1.01-1.01 per day), and invasive ventilation (RR, 1.64; 95% CI, 1.59-1.69). Vaccination (RR, 0.88; 95% CI, 84-.92) and higher Charlson Comorbidity Index (CCI) (RR, 0.98; 95% CI, .97-.98) were associated with lower therapeutic AC. CONCLUSIONS: Overall, two-thirds of hospitalized COVID-19 patients received any AC and a quarter received therapeutic dosing. Therapeutic AC declined after introduction of the Omicron variant. Predictors of therapeutic AC included demographics, obesity, length of stay, invasive ventilation, CCI, and vaccination, suggesting AC decisions driven by clinical factors including COVID-19 severity, bleeding risks, and comorbidities.

Coronavirus Disease 2019 Severity and Risk of Subsequent Cardiovascular Events.

BACKGROUND: Little is known about the relationship between coronavirus disease 2019 (COVID-19) severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of United States adults. METHODS: Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between 1 April 2020 and 31 May 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 days after COVID-19 diagnosis using inverse probability of treatment-weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only. RESULTS: A total of 1 357 518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [aHR], 1.80 [95% confidence interval {CI}, 1.71-1.89]) or non-ICU hospitalization (aHR, 1.28 [95% CI, 1.24-1.33]). Risk of subsequent hospitalization for CVE was even higher (aHRs, 3.47 [95% CI, 3.20-3.76] for ICU and 1.96 [95% CI, 1.85-2.09] for non-ICU hospitalized vs outpatient only). CONCLUSIONS: COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder COVID-19 who were managed solely in the outpatient setting, even after adjusting for differences between these groups. These findings underscore the continued importance of preventing severe acute respiratory syndrome coronavirus 2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.

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.

The Expert Next Door: Interactions With Friends and Family During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic thrust the field of public health into the spotlight. For many epidemiologists, biostatisticians, and other public health professionals, this caused the professional aspects of our lives to collide with the personal, as friends and family reached out with concerns and questions. Learning how to navigate this space was new for many of us and required refining our communication style depending on context, setting, and audience. Some of us took to social media, utilizing our existing personal accounts to share information after sorting through and summarizing the rapidly emerging literature to keep loved ones safe. However, those in our lives sometimes asked unanswerable questions, or began distancing themselves when we suggested more stringent guidance than they had hoped for, causing additional stress during an already traumatic time. We often had to remind ourselves that we were also individuals experiencing this pandemic and that our time-intensive efforts were meaningful, relevant, and impactful. As this pandemic and other public health crises continue, we encourage members of our discipline to consider how we can best use shared lessons from this period and to recognize that our professional knowledge, when used in our personal lives, can promote, protect, and bolster confidence in public health.

Predictors of new persistent opioid use after benign hysterectomy in the United States.

BACKGROUND: Despite substantial reductions in the past decade, prescription opioids continue to cause widespread morbidity and mortality in the United States. Little is known regarding patterns and predictors of opioid use among women undergoing benign hysterectomy. OBJECTIVE: This study aimed to identify the incidence and predictors of new persistent opioid use after benign hysterectomy among opioid-naïve women from a set of demographic, operative, and opioid prescription characteristics of patients. STUDY DESIGN: In this retrospective cohort study, we identified women undergoing benign hysterectomy from 2011 to 2016 using a validated national insurance claims database (IBM MarketScan Commercial Database). After excluding women with prevalent opioid use (from 365 to 31 days preoperatively), we identified patients who received a perioperative opioid prescription (30 days before to 14 days after hysterectomy) and evaluated them for new persistent opioid use, defined as at least 1 prescription from 15 to 90 days and at least 1 prescription from 91 to 365 days postoperatively. Multivariate logistic regression was used to examine demographic, clinical, operative, and opioid prescription-related factors associated with new persistent use. International Classification of Diseases, Ninth and Tenth Revisions, and Clinical Classification Software codes were used to identify hysterectomies, preoperative pain and psychiatric diagnoses, surgical indications, and surgical complications included as covariates. RESULTS: We identified 114,260 women who underwent benign hysterectomy and were not prevalent opioid users, of which 93,906 (82.2%) received at least 1 perioperative opioid prescription. Of 93,906 women, 4334 (4.6%) developed new persistent opioid use. Logistic regression demonstrated that new persistent use odds is significantly increased by younger age (18-34 years; adjusted odds ratio, 1.97; 95% confidence interval, 1.69-2.30), southern geographic location (adjusted odds ratio, 2.03; 95% confidence interval, 1.79-2.27), preoperative psychiatric and pain disorders (anxiety: adjusted odds ratio, 1.20 [95% confidence interval, 1.09-1.33]; arthritis: adjusted odds ratio, 1.30 [95% confidence interval, 1.21-1.40]), >1 perioperative prescription (adjusted odds ratio, 1.53; 95% confidence interval, 1.24-1.88), mood disorder medication use (adjusted odds ratio, 1.51; 95% confidence interval, 1.40-1.64), tobacco smoking (adjusted odds ratio, 1.65; 95% confidence interval, 1.45-1.89), and surgical complications (adjusted odds ratio, 1.84; 95% confidence interval, 1.69-2.00). Although statistically nonsignificant, total morphine milligram equivalent of ≥300 in the first perioperative prescription increased persistent use likelihood by 9% (95% confidence interval, 1.01-1.17). Dispensing of a first perioperative prescription before the surgery, as opposed to after, increased new persistent use odds by 61% (95% confidence interval, 1.50-1.72). Each additional perioperative day covered by a prescription increased the likelihood of persistent use by 2% (95% confidence interval, 1.02-1.03). In contrast, minimally invasive hysterectomy (laparoscopic: adjusted odds ratio, 0.89 [95% confidence interval, 0.71-0.88]; vaginal: adjusted odds ratio, 0.82 [95% confidence interval, 0.72-0.93]) and a more recent surgery year (2016 vs reference 2011: adjusted odds ratio 0.58; 95% confidence interval, 0.51-0.65) significantly decreased its likelihood. CONCLUSION: New persistent opioid use after hysterectomy was associated with several patient, operative, and opioid prescription-related factors. Considering these factors may be beneficial in counseling patients and shared decision-making about perioperative prescription to decrease the risk of persistent opioid use.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

First Biologic Drug Persistence in Patients With Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis: A Real-World Canadian Physicians' Experience.

METHODS: Data were obtained from persons enrolled in the SpondyloArthritis Research Consortium of Canada registry between 2003 and 2018. Kaplan-Meier curves were constructed from the time of biologic initiation until discontinuation and compared using the log-rank test. Subanalyses were performed according to calendar year and disease activity. Cox proportional hazards models were used to identify factors associated with discontinuation. RESULTS: We identified 385 biologic-naive persons. Overall, the 349 AS participants had longer persistence to their first biologic than the 36 nr-axSpA subjects (p < 0.01). The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index decreased by 2.3 points (95% confidence interval [CI], 1.9-2.7) and 3.2 points (95% CI, 2.6-3.7), respectively, in the first year and were stable thereafter. Adjusting for sex, human leukocyte antigen B27, and smoking status, nr-axSpA patients were more likely to discontinue their biologic than AS patients (hazards ratio, 1.65; 95% CI, 1.03-2.62). CONCLUSIONS: In this real-world study, AS patients had longer persistence to their first biologic compared with nr-axSpA, with disease subtype being the most significant predictor of treatment persistence. Future studies should be targeted at assessing long-term clinical outcome of axSpA in the real-world setting.

Association Between Chronic Use of Immunosuppresive Drugs and Clinical Outcomes From Coronavirus Disease 2019 (COVID-19) Hospitalization: A Retrospective Cohort Study in a Large US Health System.

BACKGROUND: It is unclear whether chronic use of immunosuppressive drugs worsens or improves the severity of coronavirus disease 2019 (COVID-19), with plausible mechanisms for both. METHODS: Retrospective cohort study in 2121 consecutive adults with acute inpatient hospital admission between 4 March and 29 August 2020 with confirmed or suspected COVID-19 in a large academic health system, with adjustment for confounding with propensity score-derived stabilized inverse probability of treatment weights. Chronic immunosuppression was defined as prescriptions for immunosuppressive drugs current at the time of admission. Outcomes included mechanical ventilation, in-hospital mortality, and length of stay. RESULTS: There were 2121 patients admitted with laboratory-confirmed (1967, 93%) or suspected (154, 7%) COVID-19 during the study period, with a median age of 55 years (interquartile range, 40-67). Of these, 108 (5%) were classified as immunosuppressed before COVID-19, primarily with prednisone (>7.5 mg/day), tacrolimus, or mycophenolate mofetil. Among the entire cohort, 311 (15%) received mechanical ventilation; the median (interquartile range) length of stay was 5.2 (2.5-10.6) days, and 1927 (91%) survived to discharge. After adjustment, there were no significant differences in the risk of mechanical ventilation (hazard ratio [HR], .79; 95% confidence interval [CI], .46-1.35), in-hospital mortality (HR, .66; 95% CI, .28-1.55), or length of stay (HR, 1.16; 95% CI, .92-1.47) among individuals with immunosuppression and counterparts. CONCLUSIONS: Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.

Comparative risk of serious infections among real-world users of biologics for psoriasis or psoriatic arthritis.

OBJECTIVE: To examine whether initiation of interleukin (IL)-17, IL-12/23 or tumour necrosis factor (TNF) inhibitor is associated with an increased risk of serious infection among real-world psoriasis (PsO) or psoriatic arthritis (PsA) patients. METHODS: We assembled a retrospective cohort of commercially insured adults in the USA diagnosed with PsO or PsA between 2015 and 2018. Exposure was dispensation for IL-17 (ixekizumab or secukinumab), IL-12/23 (ustekinumab) or TNF (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab). The outcome was infection requiring hospitalisation after biologic initiation. Incidence rates (IRs) per 100 person-years were computed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusted for inverse probability of treatment-weighted propensity scores. RESULTS: A total of 11 560 new treatment episodes were included. Overall, 190 serious infections (2% of treatment episodes) were identified in 9264 person-years of follow-up. Class-specific IRs were similar among IL-17 and TNF, yet significantly lower for IL-12/23. After adjustment for propensity scores, there was no increased risk with IL-17 compared with either TNF (HR=0.89, 95% CI 0.48 to 1.66) or IL-12/23 (HR=1.12, 95% CI 0.62 to 2.03). By contrast, IL-23/23 were associated with a lower risk of infections than TNF (HR=0.59, 95% CI 0.39 to 0.90). CONCLUSIONS: Relative to TNF and IL-17, IL-12/23 inhibitors were associated with a reduced risk of serious infection in biologic-naïve patients with PsO or PsA. In biologic-experienced individuals, there was no difference in infection risk across TNF, IL-17 or IL-12/23 inhibitors.

Persons diagnosed with COVID-19 in England in the Clinical Practice Research Datalink (CPRD): a cohort description.

OBJECTIVE: To create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England. DESIGN: Retrospective cohort study. SETTING: Electronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England. PARTICIPANTS: 2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022. MAIN OUTCOME MEASURES: Age, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 'COVID-19'). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination). RESULTS: Compared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65-84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score. CONCLUSIONS: CPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.

Using a data-driven approach to define post-COVID conditions in US electronic health record data.

OBJECTIVE: To create a data-driven definition of post-COVID conditions (PCC) by directly measure changes in symptomatology before and after a first COVID episode. MATERIALS AND METHODS: Retrospective cohort study using Optum® de-identified Electronic Health Record (EHR) dataset from the United States of persons of any age April 2020-September 2021. For each person with COVID (ICD-10-CM U07.1 "COVID-19" or positive test result), we selected up to 3 comparators. The final COVID symptom score was computed as the sum of new diagnoses weighted by each diagnosis' ratio of incidence in COVID group relative to comparator group. For the subset of COVID cases diagnosed in September 2021, we compared the incidence of PCC using our data-driven definition with ICD-10-CM code U09.9 "Post-COVID Conditions", first available in the US October 2021. RESULTS: The final cohort contained 588,611 people with COVID, with mean age of 48 years and 38% male. Our definition identified 20% of persons developed PCC in follow-up. PCC incidence increased with age: (7.8% of persons aged 0-17, 17.3% aged 18-64, and 33.3% aged 65+) and did not change over time (20.0% among persons diagnosed with COVID in 2020 versus 20.3% in 2021). For cases diagnosed in September 2021, our definition identified 19.0% with PCC in follow-up as compared to 2.9% with U09.9 code in follow-up. CONCLUSION: Symptom and U09.9 code-based definitions alone captured different populations. Maximal capture may consider a combined approach, particularly before the availability and routine utilization of specific ICD-10 codes and with the lack consensus-based definitions on the syndrome.

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.

Health Care Resource Utilization and Costs Associated With COVID-19 Among Pediatrics Managed in the Community or Hospital Setting in England: A Population-based Cohort Study.

BACKGROUND: Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial health care resource burden. This study aimed to describe health care resource utilization (HCRU) and costs associated with COVID-19 in pediatrics 1-17 years old in England. METHODS: A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care secondary care data. HCRU and associated costs to the National Health Service were stratified by age, risk of severe COVID-19 and immunocompromised status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). RESULTS: This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those 1-4 years of age (face-to-face: 4.3%; telephone: 6.0%) compared with those 5-11 (2.0%; 2.1%) and 12-17 years of age (2.2%; 2.5%). In the hospitalized cohort, mean (SD) length of stay was longer [5.0 (5.8) days] among those 12-17 years old (n = 24) than those 1-4 [n = 15; 1.8 (0.9) days] and 5-11 years old [n = 21; 2.8 (2.1) days]. CONCLUSIONS: Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those 12-17 years old. Our results may help optimize the management and resource allocation of COVID-19 in this population.

Economic burden of COVID-19 for employers and employees in the United States.

OBJECTIVE: Describe the economic burden of COVID-19 on employers and employees in the United States (US). METHODS: A targeted literature review was conducted to evaluate the impact of COVID-19 on US-based employers and employees in terms of healthcare resource utilization (HCRU), medical costs, and costs associated with work-loss. Searches were conducted in MEDLINE, Embase, and EconLit using a combination of disease terms, populations, and outcomes to identify articles published from January 2021 to November 4, 2022. As data from the employer perspective were lacking, additional literature related to influenza were included to contextualize the impact of COVID-19, as it shifts into an endemic state, within the existing respiratory illness landscape. RESULTS: A total of 41 articles were included in the literature review. Employer and employee perspectives were not well represented in the literature, and very few articles overlapped on any given outcome. HCRU, costs, and work impairment vary by community transmission levels, industry type, population demographics, telework ability, mitigation implementation measures, and company policies. Work-loss among COVID-19 cases were higher among the unvaccinated and in the week following diagnosis and for some, these continued for 6 months. HCRU is increased in those with COVID-19 and COVID-19-related HCRU can also continue for 6 months. CONCLUSIONS: COVID-19 continues to be a considerable burden to employers. The majority of COVID-19 cases impact working age adults. HCRU is mainly driven by outpatient visits, while direct costs are driven by hospitalization. Productivity loss is higher for unvaccinated individuals. An increased focus to support mitigation measures may minimize hospitalizations and work-loss. A data-driven approach to implementation of workplace policies, targeted communications, and access to timely and appropriate therapies for prevention and treatment may reduce health-related work-loss and associated cost burden.

In January 2020, the US government declared COVID-19 a public health emergency. This lasted until May 2023. To fight this health emergency, the US government provided free testing, vaccination, and treatment. Although the US government has declared the emergency over, COVID-19 continues to infect people. For people with private health insurance, costs associated with COVID-19 patient healthcare have now been transferred from the government to employers. In this study, we collected information from published scientific articles about the costs of COVID-19 for employers and workers in the US. We found that people who were not vaccinated against COVID-19 required more medical care and cost more than people who were vaccinated. In some cases, this trend lasted for as long as 6 months. This was mostly because of workers missing work, not working effectively while sick, and needing to be hospitalized. People who could work from home, whose companies had policies to prevent infections, and who took steps to avoid getting infected needed less medical care and missed work less often. This information may be used to help develop policies, communications, and guidance to prevent COVID-19 and limit its impact on employers and workers.

Noninterventional studies in the COVID-19 era: methodological considerations for study design and analysis.

The global COVID-19 pandemic has generated enormous morbidity and mortality, as well as large health system disruptions including changes in use of prescription medications, outpatient encounters, emergency department admissions, and hospitalizations. These pandemic-related disruptions are reflected in real-world data derived from electronic medical records, administrative claims, disease or medication registries, and mobile devices. We discuss how pandemic-related disruptions in healthcare utilization may impact the conduct of noninterventional studies designed to characterize the utilization and estimate the effects of medical interventions on health-related outcomes. Using hypothetical studies, we highlight consequences that the pandemic may have on study design elements including participant selection and ascertainment of exposures, outcomes, and covariates. We discuss the implications of these pandemic-related disruptions on possible threats to external validity (participant selection) and internal validity (for example, confounding, selection bias, missing data bias). These concerns may be amplified in populations disproportionately impacted by COVID-19, such as racial/ethnic minorities, rural residents, or people experiencing poverty. We propose a general framework for researchers to carefully consider during the design and analysis of noninterventional studies that use real-world data from the COVID-19 era.

Identifying Minimal and Meaningful Change in a Patient-Reported Outcomes Measurement Information System for Rheumatoid Arthritis: Use of Multiple Methods and Perspectives.

OBJECTIVE: Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. Our objective was to use different methods and perspectives to evaluate the responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms (SFs) and to identify minimal and meaningful score changes. METHODS: Adults with RA who were enrolled in a multisite prospective observational cohort completed PROMIS physical function, pain interference, fatigue, and participation in social roles/activities SFs, the PROMIS 29-item form (PROMIS-29), and pain and patient global assessment, and rated change in specific symptoms and RA (a little versus lot better or worse) at the second visit. Physicians recorded joint counts, physician global assessment, and change in RA at visit 2. We compared mean score differences for minimal and meaningful improvement/worsening using patient and physician change ratings and distribution-based methods, and we visually inspected empirical cumulative distribution function curves by change categories. RESULTS: The 348 adults were mostly female (81%) with longstanding RA. Using patient ratings, generally 1-3-point differences were observed for minimal change and 3-7 points for meaningful change. Larger differences were observed with patient versus physician ratings and for symptom-specific versus RA change. Mean differences were similar among SF versions. Prespecified hypotheses about change in PROMIS physical function, pain interference, fatigue, and participation and legacy scales were supported. CONCLUSION: PROMIS SFs and the PROMIS-29 profiles are responsive to change and generally distinguish between minimal and meaningful improvement and worsening in key RA domains. These data add to a growing body of evidence demonstrating the robust psychometric properties of PROMIS and supporting its use in RA care, research, and decision-making.

A Bridge Too Far? Real-World Practice Patterns of Early Glucocorticoid Use in the Canadian Early Arthritis Cohort.

OBJECTIVE: To describe patterns of glucocorticoid use in a large real-world cohort with early rheumatoid arthritis (RA) and assess the impact on disease activity and treatment. METHODS: Data are from adults with new RA (≤1 year) recruited to the Canadian Early Arthritis Cohort (CATCH) and are stratified on the basis of whether a person was prescribed oral glucocorticoids within 3 months of study entry. Disease activity was compared over 24 months. Mixed-effects logistic regression was used for adjusted odds ratios (aORs) of escalation to biologics separately for 12 and 24 months, with random effects terms to account for prescribing patterns clustering by study site. RESULTS: Among 1891 persons, 30% received oral steroids. Users were older, were less often employed, and had shorter disease duration and higher disease activity. Disease activity improved over time, with early glucocorticoid users starting at higher levels of disease activity. Participants with early oral glucocorticoids were more likely to be on a biologic at 12 months (aOR = 2.4; 95% confidence interval [CI], 1.5-3.7) and 24 months (aOR = 1.9; 95% CI, 1.3-3.0). Despite Canadian clinical practice guidelines to limit corticosteroid use to short-term or 'bridge' therapy, 30% of patients who used oral glucocorticoids still used them 2 years later. CONCLUSION: Early steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics.

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.

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.

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.