Appropriateness of Hysterectomy as Treatment for Benign Gynecological Conditions.

Objective: To assess the appropriateness of hysterectomies performed at a large tertiary health system using the 1997 RAND appropriateness classification system and an updated algorithm. Design: We abstracted structured and unstructured data from electronic medical records on patient demographics, primary indication(s) for hysterectomy, diagnosis codes associated with the hysterectomy, previous treatments, and laboratory results. Subjects: Patients aged 18-44 years. Exposure: Receipt of hysterectomy for benign and nonobstetric conditions from October 2014 to December 2017. Main Outcome Measures: Using these data, we provided a RAND-based (dichotomous: inappropriate/appropriate) and Wright-based (3-level: inappropriate/ambiguous/appropriate) appropriateness rating and characterized missing information patterns associated with inappropriate ratings. Results: We analyzed 1,829 hysterectomies across 30 nonmutually exclusive primary indications for surgery. Nearly a third (32.8%) of surgeries had only one primary indication for surgery. Using the RAND-based classifier, 31.3% of hysterectomies were rated as appropriate and 68.7% as inappropriate. Using the Wright-based algorithm, 58.1% of hysterectomies were rated as appropriate, 15.7% as ambiguous, and 26.2% as inappropriate. Missing information on diagnostic procedures was the most common characteristic related to both RAND-based (46.1%) and Wright-based (51.2%) inappropriate ratings. Conclusions: The 1997 RAND classification lacked guidance for several contemporary indications, including gender-affirming care. RAND also has an outdated requirement for diagnostic surgeries such as laparoscopies, which have decreased in practice as diagnostic imaging has improved. Sensitivity analyses suggest that inappropriate surgeries cannot all be attributed to bias from missing electronic medical record data. Accurately documenting care delivery for benign gynecological conditions is key to ensuring quality and equity in gynecological care.

Quantifying the Time to Administer Outpatient Parenteral Antimicrobial Therapy: A Missed Opportunity to Compensate for the Value of Infectious Diseases.

Outpatient parenteral antimicrobial therapy (OPAT) relies on substantial uncompensated provider time. In this study of a large academic OPAT program, the median amount of unbilled OPAT management time was 27 minutes per week, per OPAT course. These data should inform benchmarks in pursuing novel payment approaches for OPAT.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

The Perceived Usability of Virtual Visits Among Black Adults' Receiving Oncology Care: A Qualitative Analysis.

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.

Incidence of new outpatient long-acting reversible contraceptive insertions among a commercially insured, US population from 2010 to 2020.

Objectives: Characterize new use of long-acting reversible contraceptives (LARCs), highly effective contraceptive methods, in a broad population over time. Study Design: We constructed a retrospective cohort of commercially insured individuals aged 15 to 54 years from 2010 to 2020 and estimated monthly incidence of new LARC insertions. Results: The monthly standardized incidence increased from 6.0 insertions per 10,000 individuals in January 2010 to 14.1 in December 2020, with a dip in insertions after March 2020. Hormonal intrauterine devices were consistently the most inserted LARC; implants were increasingly favored over time. Conclusions: LARCs are increasingly popular forms of contraception among commercially insured individuals. Implications: Given the increasing popularity, ensuring access to LARCs is critical.

Vaccine patterns among patients diagnosed with Guillain-Barré Syndrome and matched counterparts in a Medicare supplemental population, 2000-2020.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study.

PURPOSE: Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. METHODS: We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. RESULTS: Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. CONCLUSIONS: Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.

Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Disparate statin prescribing following hospital discharge for stroke or transient ischemic attack: Findings from COMPASS.

BACKGROUND: Published guidelines recommend high-intensity statins following an ischemic stroke or transient ischemic attack (TIA). The authors examined the potential for disparate patterns of statin prescribing in a cluster randomized trial of transitional care following acute stroke or TIA. METHODS: Medications taken before hospitalization and statins prescribed at discharge among stroke and TIA patients at 27 participating hospitals were examined. Any statin and intensive statin prescribed at discharge were compared by age (<65, 65-75, >75 years), racial category (White vs. Black), sex (male vs. female), and rurality (urban vs. non-urban) using logistic mixed models. RESULTS: Among 3211 patients (mean age 67 years; 47% female; 29% Black), 90% and 55%, respectively, were prescribed any statin or intensive statin therapy at discharge. White (vs. Black) patients (0.71, 0.51-0.98) less commonly received any statin prescription, while stroke (vs. TIA) patients (1.90, 1.38-2.62) and those residing in urban areas (1.66, 1.07-2.55) more commonly received any statin prescription. Among those prescribed a statin, only 42% of White and 51% of Black patients >75 years. were prescribed an intensive statin; the OR for intensive statin prescribing was 0.44 for patients >75 years and was similar in a subgroup not on a statin previously. CONCLUSION/RELEVANCE: Following stroke or TIA, statin prescribing remains lower in White patients, in those with TIA, and in those in non-urban areas. Intensive statin prescribing remains limited, particularly in patients >75 years. These data may inform efforts to improve guideline concordant prescribing for post-stroke patients.

Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Methodologic challenges and lessons learned through conducting a hospital-based Salmonella Javiana case-control study.

OBJECTIVE: Determine the food(s) most likely contaminated by Salmonella Javiana associated with a salmonellosis outbreak involving 2 hospitals in North Carolina that were within 50 miles of each other in November 2021. METHODS: A 2:1 matched case-control study was conducted. Food histories were obtained from hospital food orders and potential confounder covariates were collected from patient medical records. Attack rates and conditional logistic regression odds ratios (OR) were estimated at the 80% confidence interval (CI) for each food exposure and salmonellosis. RESULTS: There were 21 cases and 42 controls included. Fruit cups had the strongest association with salmonellosis (matched and adjusted OR = 7.9 80% CI: 2.7, 23.6). Hospital-specific ORs varied for several food items, but attack rates analyses provided additional evidence that fruit cups were a likely common source. CONCLUSION: Our analyses implicated fruit cups in an outbreak of salmonellosis in 2 hospitals. Other methodologic challenges included selection of controls among sick patients, heterogeneity of food exposures, reliance on food orders rather than foods consumed, and retention of food history records. Understanding and anticipating these challenges through changes to policies and operational procedures is critical for conducting efficient and effective case-control studies in the hospital setting.

Inverse Probability Weighting to Estimate Exposure Effects on the Burden of Recurrent Outcomes in the Presence of Competing Events.

Recurrent events-outcomes that an individual can experience repeatedly over the course of follow-up-are common in epidemiologic and health services research. Studies involving recurrent events often focus on time to first occurrence or on event rates, which assume constant hazards over time. In this paper, we contextualize recurrent event parameters of interest using counterfactual theory in a causal inference framework and describe an approach for estimating a target parameter referred to as the mean cumulative count. This approach leverages inverse probability weights to control measured confounding with an existing (and underutilized) nonparametric estimator of recurrent event burden first proposed by Dong et al. in 2015. We use simulations to demonstrate the unbiased estimation of the mean cumulative count using the weighted Dong-Yasui estimator in a variety of scenarios. The weighted Dong-Yasui estimator for the mean cumulative count allows researchers to use observational data to flexibly estimate and contrast the expected number of cumulative events experienced per individual by a given time point under different exposure regimens. We provide code to ease application of this method.

Impact of COVID-related policies on gunshot wound assault hospitalizations in the United States: a statewide time series analysis.

BACKGROUND: The CDC recently reported that firearm homicide rates in the United States increased in 2020, particularly among Black/African American individuals and men 25-44 years old. It is unclear whether firearm hospitalizations also increased, and more importantly, what impact the COVID-19 pandemic and COVID-related policies had. Using the North Carolina Trauma Registry, a statewide registry of trauma admissions to eighteen North Carolina hospitals, we calculated weekly GSW hospitalization rates from 1/2019 to 12/2020, overall and stratified by race-ethnicity, age, and sex. Interrupted time-series design and segmented linear regression were used to estimate changes in weekly hospitalization rates over time after (1) U.S. declaration of a public health emergency; (2) statewide Stay-at-Home order; (3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and (4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Non-GSW assault hospitalizations were used as a control to assess whether trends were observed across all assault hospitalizations or if effects were specific to gun violence. FINDINGS: Overall, 47.3% (n = 3223) of assault hospitalizations were GSW. Among GSW hospitalizations, median age was 27 years old (interquartile range [IQR] 21-25), 86.2% were male, and 49.5% occurred after the U.S. declared a public health emergency. After the Stay-at-Home order was implemented, weekly GSW hospitalization rates began increasing substantially among Black/African American residents (weekly trend change = 0.775, 95% CI = 0.254 to 1.296), peaking at an average 15.6 hospitalizations per 1,000,000 residents. Weekly hospitalization rates declined after restrictions were lifted but remained elevated compared to pre-COVID levels in this group (average weekly rate 10.6 per 1,000,000 at the end of 2020 vs. 8.9 per 1,000,000 pre-pandemic). The Stay-at-Home order was also associated with increasing GSW hospitalization rates among males 25-44 years old (weekly trend change = 1.202, 95% CI = 0.631 to 1.773); rates also remained elevated among 25-44-year-old males after restrictions were lifted in 2020 (average weekly rate 10.1 vs. 7.9 per 1,000,000). Non-GSW hospitalization rates were relatively stable in 2020. CONCLUSIONS: The COVID-19 pandemic and statewide Stay-at-Home orders appeared to have placed Black/African American residents and men ages 25-44 at higher risk for GSW hospitalizations, exacerbating pre-existing disparities. Persistent gun violence disparities must be addressed.

Effect of Stay-at-Home orders and other COVID-related policies on trauma hospitalization rates and disparities in the USA: a statewide time-series analysis.

BACKGROUND: To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home order and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. METHODS: We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations for 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly rates of assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalizations between January 1, 2019, and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalization rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and sex. Changes in hospitalization rates were assessed after 1) USA declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). RESULTS: There were 70,478 trauma hospitalizations in North Carolina, 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but substantial increases were only observed among Black/African American residents (weekly trend change = 1.147, 95% CI = 0.634 to 1.662) and 18-44-year-old males (weekly trend change = 1.708, 95% CI = 0.870 to 2.545). After major restrictions were lifted, assault rates decreased but remained elevated compared to pre-COVID levels. Unintentional non-MVC injury hospitalizations decreased after the USA declared a public health emergency, especially among women ≥ 65 years old (weekly trend change = -4.010, 95% CI = -6.166 to -1.855), but returned to pre-pandemic levels within several months. CONCLUSIONS: Statewide Stay-at-Home orders placed Black/African American residents at higher risk of assault hospitalizations, exacerbating pre-existing disparities. Males 18-44 years old were also at higher risk of assault hospitalization. Fear of COVID-19 may have led to decreases in unintentional non-MVC hospitalization rates, particularly among older females. Policy makers must anticipate policy-related harms that may disproportionately affect already disadvantaged communities and develop mitigation approaches.

Predicting Risk of Multidrug-Resistant Enterobacterales Infections Among People With HIV.

Background: Medically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors. Methods: We performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the Southeastern United States from 2000 to 2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach. Results: Among 4734 study participants, MDR-E was isolated from 1.6% (95% CI, 1.2%-2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm3 (PR, 4.0; 95% CI, 2.3-7.4), history of an AIDS-defining clinical condition (PR, 3.7; 95% CI, 2.3-6.2), and hospital admission in the prior 12 months (PR, 5.0; 95% CI, 3.2-7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm3, and current CD4 cell count 201-500 cells/mm3. Female gender was the most important demographic predictor. Conclusions: PWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protect against antimicrobial-resistant bacterial infections.

Postoperative Use of Biologics was Less Common among Patients with Crohn's Disease With Emergent/Urgent Versus Elective Intestinal Resection.

Background & Aims: Given the risk of intestinal resection for Crohn's disease, postoperative treatment may be informed by several risk factors, including resection type. We compared postoperative treatment strategies for Crohn's disease between emergent/urgent versus elective resection. Methods: We identified patients with intestinal resection for Crohn's disease between 2002-2018 using the MarketScan databases. We classified emergent/urgent resections as those occurring after emergency department admission or after the second day of admission. We estimated adjusted risk differences for the association between resection type (emergent/urgent versus elective) and 6-month postoperative medication strategy (biologic monotherapy, biologic combination therapy with an immunomodulator, immunomodulator monotherapy, other non-biologic medication for Crohn's [5-aminosalicylates, antibiotics, corticosteroids], or no medications for Crohn's). Results: During 6 months after resection among 4,187 patients, 23% received biologic monotherapy, 6% received combination therapy, 16% received immunomodulator monotherapy, and 36% received other non-biologics. Compared to elective resection, emergent/urgent resection was associated with more common use of "other non-biologic" medications (risk difference 6.4%; 95% confidence interval [CI] 2.8%, 10.0%), but less common use of biologic monotherapy (risk difference -3.2%; 95% CI -6.2%, -0.1%) and no medications (risk difference -3.6%; 95% CI -6.6%, -0.6%). Conclusions: Although patients with emergent/urgent resection may benefit from more aggressive postoperative therapy, there was evidence that emergent/urgent resection was more associated than elective resection with postoperative use of non-biologics for Crohn's disease. Future studies of treatment patterns and comparative effectiveness of postoperative treatment strategies for Crohn's patients should consider these differences between resection types, which may be important drivers of longer-term outcomes.

Effect of Stay-at-Home Orders and Other COVID-Related Policies on Trauma Hospitalization Rates and Disparities in the United States: A Statewide Time-Series Analysis.

Background: To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. Methods: We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations to 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalization rates between January 1, 2019 and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalizations rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and gender. Hospitalization rates were compared after 1) U.S. declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Results: There were 70,478 trauma hospitalizations in North Carolina from 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but only among Black/African American residents (incidence rate difference [IRD]=7.9; other racial/ethnic groups' IRDs ranged 0.9 to 1.7) and 18-44 year-old males (IRD=11.9; other sex/age groups' IRDs ranged -0.5 to 3.6). After major restrictions were lifted, assault rates returned to pre-COVID levels. Unintentional injury hospitalizations decreased after the public health emergency, especially among older adults, but returned to 2019 levels within several months. Conclusions: Statewide Stay-at-Home orders put Black/African American residents at higher risk for assault hospitalizations, exacerbating pre-existing disparities. Fear of COVID-19 may have also led to decreases in unintentional non-MVC hospitalization rates, particularly among older adults. Policy makers must anticipate possible negative effects and develop approaches for mitigating harms that may disproportionately affect already disadvantaged communities.

Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). OBJECTIVE: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. METHODS: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. RESULTS: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. CONCLUSIONS: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.