Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.

Attitudes on participation in clinical drug trials: A nationally representative survey of older adults with multimorbidity.

BACKGROUND: Older adults with multimorbidity are under-represented in clinical drug trials. Their inclusion will not increase unless they are willing and able to participate. Data on motivators and barriers to participation in trials of new medications of older adults with multimorbidity are needed. METHODS: Cross-sectional internet and telephone survey of a nationally representative sample of adults ≥65 years with ≥3 chronic conditions (NORC University of Chicago Amerispeak Panel) conducted from March-April, 2023 to determine motivators and barriers to drug trial participation, described graphically and using statistics. RESULTS: Surveyed 1318 (1142 Internet, 176 phone) with mean age 72.3 ± 6.3 (SD), 52% women; race: 83% White, 10% Black or African American, 5% Hispanic or Latino, 1.1% Asian; 4.4 ± 1.9 chronic conditions (of 16 queried), taking 7.5 ± 3.3 medications. Barriers included fear of side effects (48%), taking too many medications (44%), placebo (44%), mobility (33%), bathroom needs (25%), hearing (19%), eyesight (15%), video visits (33%; higher in women, Black or African-American respondents, and those ≥80 years). Sixty-five percent would join all in-person trials, 49% would join all-video trials. Travel >1 h was difficult for 66%, most difficult for women. Trust was a concern in 25% of Black respondents. Caregiving responsibilities or lack of time were not obstacles. Participants were most likely to consider a drug trial for a problem they have (63%) versus prevention (44%) and if invited by a physician (80%) or University healthcare system (58%). Getting better care was ranked very important (79%) followed by helping others (57%). CONCLUSIONS: Major concerns of older patients with multimorbidity about participation in drug trials are potential side effects, taking too many medicines, and video visits. Physicians have the greatest influence on decisions and in-person visits are preferred. Proposed changes in trial design to increase enrollment of under-represented older adults may not align with patient-reported preferences.

Breastfeeding Initiation in People With Hepatitis C Virus Infection in the United States.

OBJECTIVE: To evaluate breastfeeding initiation rates among people living with and without hepatitis C virus (HCV) infection during pregnancy and to identify characteristics associated with breastfeeding initiation. METHODS: We conducted a cross-sectional analysis of individuals who had a live birth in the United States from 2016 to 2021 using the National Center for Health Statistics birth certificate data. We grouped participants by whether they had HCV infection during pregnancy. Using propensity-score matching, we assessed the association between breastfeeding initiation before hospital discharge , defined as neonates receiving any parental breast milk or colostrum, and HCV infection during pregnancy in a logistic regression model. We also assessed factors associated with breastfeeding initiation among those with HCV infection. RESULTS: There were 96,896 reported cases (0.5%) of HCV infection among 19.0 million births that met inclusion criteria during the study period. Using propensity-score matching, we matched 87,761 individuals with HCV infection during pregnancy with 87,761 individuals without HCV infection. People with HCV infection during pregnancy were less likely to initiate breastfeeding compared with those without HCV infection (51.5% vs 64.2%, respectively; odds ratio 0.59, 95% CI, 0.58-0.60, P <.001). Characteristics associated with higher rates of breastfeeding initiation among individuals with HCV infection included a college degree (adjusted odds ratio [aOR] 1.22, 95% CI, 1.21-1.24); self-identified race or ethnicity as Native Hawaiian or Pacific Islander (aOR 1.22, 95% CI, 1.06-1.40), Asian (aOR 1.09, 95% CI, 1.06-1.13), or Hispanic (aOR 1.09, 95% CI, 1.08-1.11); private insurance (aOR 1.07, 95% CI, 1.06-1.08); nulliparity (aOR 1.09, 95% CI, 1.08-1.10), and being married (aOR 1.08, 95% CI, 1.07-1.09). Characteristics associated with not breastfeeding before hospital discharge included receiving no prenatal care (aOR 0.81, 95% CI, 0.79-0.82), smoking during pregnancy (aOR 0.88, 95% CI, 0.88-0.89), and neonatal intensive care unit admission (aOR 0.92, 95% CI, 0.91-0.93). CONCLUSION: Despite leading health organizations' support for people living with HCV infection to breastfeed, our study demonstrates low breastfeeding initiation rates in this population. Our findings highlight the need for tailored breastfeeding support for people with HCV infection and for understanding the additional effects of human immunodeficiency virus (HIV) co-infection, HCV treatment, and concurrent substance use disorders on breastfeeding initiation.

Diagnostic Errors in Hospitalized Adults Who Died or Were Transferred to Intensive Care.

Importance: Diagnostic errors contribute to patient harm, though few data exist to describe their prevalence or underlying causes among medical inpatients. Objective: To determine the prevalence, underlying cause, and harms of diagnostic errors among hospitalized adults transferred to an intensive care unit (ICU) or who died. Design, Setting, and Participants: Retrospective cohort study conducted at 29 academic medical centers in the US in a random sample of adults hospitalized with general medical conditions and who were transferred to an ICU, died, or both from January 1 to December 31, 2019. Each record was reviewed by 2 trained clinicians to determine whether a diagnostic error occurred (ie, missed or delayed diagnosis), identify diagnostic process faults, and classify harms. Multivariable models estimated association between process faults and diagnostic error. Opportunity for diagnostic error reduction associated with each fault was estimated using the adjusted proportion attributable fraction (aPAF). Data analysis was performed from April through September 2023. Main Outcomes and Measures: Whether or not a diagnostic error took place, the frequency of underlying causes of errors, and harms associated with those errors. Results: Of 2428 patient records at 29 hospitals that underwent review (mean [SD] patient age, 63.9 [17.0] years; 1107 [45.6%] female and 1321 male individuals [54.4%]), 550 patients (23.0%; 95% CI, 20.9%-25.3%) had experienced a diagnostic error. Errors were judged to have contributed to temporary harm, permanent harm, or death in 436 patients (17.8%; 95% CI, 15.9%-19.8%); among the 1863 patients who died, diagnostic error was judged to have contributed to death in 121 (6.6%; 95% CI, 5.3%-8.2%). In multivariable models examining process faults associated with any diagnostic error, patient assessment problems (aPAF, 21.4%; 95% CI, 16.4%-26.4%) and problems with test ordering and interpretation (aPAF, 19.9%; 95% CI, 14.7%-25.1%) had the highest opportunity to reduce diagnostic errors; similar ranking was seen in multivariable models examining harmful diagnostic errors. Conclusions and Relevance: In this cohort study, diagnostic errors in hospitalized adults who died or were transferred to the ICU were common and associated with patient harm. Problems with choosing and interpreting tests and the processes involved with clinician assessment are high-priority areas for improvement efforts.

Measuring Implicit Bias in ICU Notes Using Word-Embedding Neural Network Models.

BACKGROUND: Language in nonmedical datasets is known to transmit human-like biases when used in natural language processing (NLP) algorithms that can reinforce disparities. It is unclear if NLP algorithms of medical notes could lead to similar transmissions of biases. RESEARCH QUESTION: Can we identify implicit bias in clinical notes, and are biases stable across time and geography? STUDY DESIGN AND METHODS: To determine whether different racial and ethnic descriptors are similar contextually to stigmatizing language in ICU notes and whether these relationships are stable across time and geography, we identified notes on critically ill adults admitted to the University of California, San Francisco (UCSF), from 2012 through 2022 and to Beth Israel Deaconess Hospital (BIDMC) from 2001 through 2012. Because word meaning is derived largely from context, we trained unsupervised word-embedding algorithms to measure the similarity (cosine similarity) quantitatively of the context between a racial or ethnic descriptor (eg, African-American) and a stigmatizing target word (eg, noncooperative) or group of words (violence, passivity, noncompliance, nonadherence). RESULTS: In UCSF notes, Black descriptors were less likely to be similar contextually to violent words compared with White descriptors. Contrastingly, in BIDMC notes, Black descriptors were more likely to be similar contextually to violent words compared with White descriptors. The UCSF dataset also showed that Black descriptors were more similar contextually to passivity and noncompliance words compared with Latinx descriptors. INTERPRETATION: Implicit bias is identifiable in ICU notes. Racial and ethnic group descriptors carry different contextual relationships to stigmatizing words, depending on when and where notes were written. Because NLP models seem able to transmit implicit bias from training data, use of NLP algorithms in clinical prediction could reinforce disparities. Active debiasing strategies may be necessary to achieve algorithmic fairness when using language models in clinical research.

Postoperative thrombotic events following major surgery in patients with a history of COVID-19: a retrospective cohort analysis of commercially insured beneficiaries in the USA.

PURPOSE: We sought to evaluate the synergistic risk of postoperative thrombosis in patients with a history of COVID-19 who undergo major surgery. Major surgery and SARS-CoV-2 infection are independently associated with an increased risk of thrombosis, but the magnitude of additional risk beyond surgery conferred by a COVID-19 history on the development of perioperative thrombotic events has not been clearly elucidated in the literature. METHODS: We conducted a retrospective cohort study among commercially insured adults in the USA from March 2020 to June 2021 using the Optum Labs Data Warehouse (OLDW), a longitudinal, real-world data asset containing deidentified administrative claims and electronic health records. We compared patients with prior COVID-19 who underwent surgery with control individuals who underwent surgery without a COVID-19 history and with control individuals who did not undergo surgery with and without a COVID-19 history. We assessed the interaction of surgery and previous COVID-19 on perioperative thrombotic events (venous thromboembolism and major adverse cardiovascular events) within 90 days using multivariable logistic regression and interaction analysis. RESULTS: Two million and two-hundred thousand eligible patients were identified from the OLDW. Patients in the surgical cohorts were older and more medically complex than nonsurgical population controls. After adjusting for confounders, only surgical exposure-not COVID-19 history-remained associated with perioperative thrombotic events (adjusted odds ratio [aOR], 4.07; 95% confidence interval [CI], 3.81 to 4.36). The multiplicative interaction term (aOR, 1.25; 95% CI, 0.96 to 1.61) and the synergy index (0.76; 95% CI, 0.56 to 1.04) suggest minimal effect modification of prior COVID-19 on surgery with regards to overall thrombotic risk. CONCLUSIONS: We found no evidence of synergistic thrombotic risk from previous COVID-19 in patients who underwent selected major surgery relative to the baseline thrombotic risk from surgery alone.

RéSUMé: OBJECTIF: Nous avons cherché à évaluer le risque synergique de thrombose postopératoire chez les patient·es ayant des antécédents de COVID-19 qui bénéficient d'une intervention chirurgicale majeure. La chirurgie majeure et l'infection par le SRAS-CoV-2 sont indépendamment associées à un risque accru de thrombose, mais l'ampleur du risque supplémentaire d'apparition de complications thrombotiques périopératoires, au-delà de la chirurgie et conféré par des antécédents de COVID-19, n'a pas été clairement élucidée dans la littérature. MéTHODE: Nous avons mené une étude de cohorte rétrospective auprès d'adultes assuré·es commercialement aux États-Unis de mars 2020 à juin 2021 à l'aide de la base de données Optum Labs Data Warehouse (OLDW), un actif de données longitudinales du monde réel contenant des requêtes administratives anonymisées et des dossiers de santé électroniques. Nous avons comparé les patient·es ayant déjà souffert de COVID-19 et ayant bénéficié d'une intervention chirurgicale avec des personnes témoins ayant bénéficié d'une intervention chirurgicale sans antécédents de COVID-19 et avec des personnes témoins n'ayant pas bénéficié de chirurgie, avec et sans antécédents de COVID-19. Nous avons évalué l'interaction de la chirurgie et des antécédents de COVID-19 avec les complications thrombotiques périopératoires (thromboembolie veineuse et événements cardiovasculaires indésirables majeurs) dans les 90 jours à l'aide d'une régression logistique multivariée et d'une analyse des interactions. RéSULTATS: Deux millions deux cent mille personnes admissibles ont été identifiées à partir du registre OLDW. Les patient·es des cohortes chirurgicales étaient plus âgé·es et présentaient une plus grande complexité médicale que les personnes témoins de la population non chirurgicale. Après ajustement pour tenir compte des facteurs de confusion, seule l'exposition chirurgicale ­ et non les antécédents de COVID-19 ­ est restée associée aux complications thrombotiques périopératoires (rapport de cotes ajusté [RCa], 4,07; intervalle de confiance [IC] à 95 %, 3,81 à 4,36). Le terme d'interaction multiplicative (RCa, 1,25; IC 95 %, 0,96 à 1,61) et l'indice de synergie (0,76; IC 95 %, 0,56 à 1,04) suggèrent une modification minimale de l'effet d'un diagnostic antérieur de COVID-19 sur la chirurgie en matière de risque thrombotique global. CONCLUSION: Nous n'avons trouvé aucune preuve de risque thrombotique synergique lié à une COVID-19 antérieure chez les patient·es ayant bénéficié d'une intervention chirurgicale par rapport au risque thrombotique de base lié à la chirurgie seule.

Negativity and Positivity in the ICU: Exploratory Development of Automated Sentiment Capture in the Electronic Health Record.

OBJECTIVES: To develop proof-of-concept algorithms using alternative approaches to capture provider sentiment in ICU notes. DESIGN: Retrospective observational cohort study. SETTING: The Multiparameter Intelligent Monitoring of Intensive Care III (MIMIC-III) and the University of California, San Francisco (UCSF) deidentified notes databases. PATIENTS: Adult (≥18 yr old) patients admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: We developed two sentiment models: 1) a keywords-based approach using a consensus-based clinical sentiment lexicon comprised of 72 positive and 103 negative phrases, including negations and 2) a Decoding-enhanced Bidirectional Encoder Representations from Transformers with disentangled attention-v3-based deep learning model (keywords-independent) trained on clinical sentiment labels. We applied the models to 198,944 notes across 52,997 ICU admissions in the MIMIC-III database. Analyses were replicated on an external sample of patients admitted to a UCSF ICU from 2018 to 2019. We also labeled sentiment in 1,493 note fragments and compared the predictive accuracy of our tools to three popular sentiment classifiers. Clinical sentiment terms were found in 99% of patient visits across 88% of notes. Our two sentiment tools were substantially more predictive (Spearman correlations of 0.62-0.84, p values < 0.00001) of labeled sentiment compared with general language algorithms (0.28-0.46). CONCLUSION: Our exploratory healthcare-specific sentiment models can more accurately detect positivity and negativity in clinical notes compared with general sentiment tools not designed for clinical usage.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Changes in Bone Density in Carriers of BRCA1 and BRCA2 Pathogenic Variants After Salpingo-Oophorectomy.

OBJECTIVE: To evaluate the effect of risk-reducing salpingo-oophorectomy (RRSO) on change in bone mineral density (BMD) in women aged 34-50 years with pathogenic variants in BRCA1 or BRCA2 ( BRCA1 /2). METHODS: The PROSper (Prospective Research of Outcomes after Salpingo-oophorectomy) study is a prospective cohort of women aged 34-50 years with BRCA1 or two germline pathogenic variants that compares health outcomes after RRSO to a non-RRSO control group with ovarian conservation. Women aged 34-50 years, who were planning either RRSO or ovarian conservation, were enrolled for 3 years of follow-up. Spine and total hip BMD were measured by dual-energy X-ray absorptiometry (DXA) scans obtained at baseline before RRSO or at the time of enrollment for the non-RRSO group, and then at 1 and 3 years of study follow-up. Differences in BMD between the RRSO and non-RRSO groups, as well as the association between hormone use and BMD, were determined by using mixed effects multivariable linear regression models. RESULTS: Of 100 PROSper participants, 91 obtained DXA scans (RRSO group: 40; non-RRSO group: 51). Overall, total spine, and hip BMD decreased significantly from baseline to 12 months after RRSO (estimated percent change -3.78%, 95% CI -6.13% to -1.43% for total spine; -2.96%, 95% CI -4.79% to -1.14% for total hip) and at 36 months (estimated percent change -5.71%, 95% CI -8.64% to -2.77% for total spine; -5.19%, 95% CI -7.50% to -2.87% for total hip. In contrast, total spine and hip BMD were not significantly different from baseline for the non-RRSO group. The differences in mean percent change in BMD from baseline between the RRSO and non-RRSO groups were statistically significant at both 12 and 36 months for spine BMD (12-month difference -4.49%, 95% CI -7.67% to -1.31%; 36-month difference -7.06%, 95% CI -11.01% to -3.11%) and at 36 months for total hip BMD (12-month difference -1.83%, 95% CI -4.23% to 0.56%; 36-month difference -5.14%, 95% CI -8.11% to -2.16%). Across the study periods, hormone use was associated with significantly less bone loss at both the spine and hip within the RRSO group compared with no hormone use ( P <.001 at both 12 months and 36 months) but did not completely prevent bone loss (estimated percent change from baseline at 36 months -2.79%, 95% CI -5.08% to -0.51% for total spine BMD; -3.93%, 95% CI -7.27% to -0.59% for total hip BMD). CONCLUSION: Women with pathogenic variants in BRCA1 /2 who undergo RRSO before the age of 50 years have greater bone loss after surgery that is clinically significant when compared with those who retain their ovaries. Hormone use mitigates, but does not eliminate, bone loss after RRSO. These results suggest that women who undergo RRSO may benefit from routine screening for BMD changes to identify opportunities for prevention and treatment of bone loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01948609.

Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression.

INTRODUCTION: Sarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk stratification tools for important clinical outcomes in sarcoidosis, such as progressive lung disease. This study will address two clinical practice needs: (1) development of a risk calculator that provides an estimate of the likelihood of pulmonary progression in sarcoidosis patients during the follow-up period and (2) determine the optimal interval for serial clinical monitoring (eg, 6, 12, 18 months) using these risk prediction tools. METHODS AND ANALYSIS: The Risk Indicators of Sarcoidosis Evolution-Unified Protocol study is a National Institutes of Health-sponsored, longitudinal observational study of adults with pulmonary sarcoidosis who will be enrolled at five US tertiary care centres. Participants will be evaluated at approximately 6-month intervals for up to 60 months with collection of lung function, blood samples and clinical data. The target sample size is 557 and the primary objective is to determine which clinical features measured during a routine clinic visit carry the most prognostic information for predicting clinical progression of pulmonary sarcoidosis over the follow-up period. The primary outcome measure will be quantified by a clinically meaningful change in forced vital capacity, forced expiratory volume in 1 s or diffusing capacity of the lung for carbon monoxide. The secondary objective is to determine if blood biomarkers measured during a routine clinic visit can improve the risk assessment modelling for progression of pulmonary sarcoidosis over the follow-up period. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Boards at each centre and the reliance Institutional Review Board overseeing the study (WCG, Protocol #20222400). Participants will provide informed consent prior to enrolment. Results will be disseminated via publication in a relevant peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05567133.

The past, present, and future of opioid prescribing: Perioperative opioid use in gynecologic oncology patients after laparotomy at a single institution from 2012 to 2021.

Objective: To describe the evolution of perioperative opioid management in gynecologic oncology patients after open surgeries and determine current opioid over-prescription rates. Methods: Part one of this two-part study was a retrospective chart review of adult patients who underwent laparotomy by a gynecologic oncologist from July 1, 2012 to June 30, 2021, comparing changes in clinical characteristics, pain management and discharge opioid prescription sizes between fiscal year 2012 (FY2012) and 2020 (FY2020). In part two, we prospectively surveyed patients after laparotomy in 2021 to determine opioid use after hospital discharge. Results: 1187 patients were included in the chart review. Demographic and surgical characteristics remained stable from FY2012 to FY2020 with differences notable for increased rates of interval cytoreductive surgeries for advanced ovarian cancer and decreased rates of full lymph node dissection. Median inpatient opioid use decreased by 62 % from FY2012 to FY2020. Median discharge opioid prescription size was 675 oral morphine equivalents (OME) per patient in FY2012 and decreased by 77.7 % to 150 OME in FY2020. Of 95 surveyed patients in 2021, median self-reported opioid use after discharge was 22.5 OME. Patients had an excess of opioids equivalent to 1331 doses of 5-milligram oxycodone tablets per 100 patients. Conclusion: Inpatient opioid use in our gynecologic oncology open surgical patients and post-discharge opioid prescription size significantly decreased over the last decade. Despite this progress, our current prescribing patterns continue to significantly overestimate patients' actual opioid use after hospital discharge. Individualized point of care tools are needed to determine an appropriate opioid prescription size.

High Risk of Substance Use Disorder-Related Outcomes in Veterans Released from Correctional Facilities in Mid to Late Life.

BACKGROUND: Veterans Affairs (VA) is likely to encounter a growing number of veterans returning to the community in mid to late life following incarceration (i.e., experiencing reentry). Yet, rates of negative health outcomes due to substance use disorders (SUDs) in this population are unknown. OBJECTIVE: To determine risk of and risk factors for SUD-related emergency department visits and inpatient hospitalizations (ED/IPH) and overdose death among older reentry veterans compared with never-incarcerated veterans. DESIGN: Retrospective cohort study using national VA and Medicare healthcare systems data. PARTICIPANTS: Veterans age ≥50, incarcerated for ≤5 consecutive years, and released between October 1, 2010, and September 30, 2017 (N = 18,803), were propensity score-matched 1:5 with never-incarcerated veterans (N = 94,015) on demographic characteristics, reason for Medicare eligibility, and SUD history. MAIN MEASURES: SUD-related ED/IPH (overall and substance-specific) were obtained from in-/outpatient VA health services and CMS data within the year following release date/index date (through September 30, 2018). Overdose death within 1 year was identified using the National Mortality Data Repository. Fine-Gray proportional hazards regression compared risk of SUD-related ED/IPH and overdose death between the two groups. RESULTS: The number of SUD-related ED/IPHs and overdose deaths was 2470 (13.1%) and 72 (0.38%) in the reentry sample versus 4402 (4.7%) and 198 (0.21%) in the never-incarcerated sample, respectively. Mid-to-late-life reentry was associated with higher risk of any SUD-related ED/IPH (13,136.2 vs. 2252.8 per 100,000/year; adjusted hazard ratio [AHR] = 2.19; 95% confidence interval [CI] = 2.08, 2.30) and overdose death (382.9 vs. 210.6 per 100,000/year; AHR = 2.24, 95% CI = 1.63, 3.08). CONCLUSIONS: Older reentry veterans have more than double the risk of experiencing SUD-related ED/IPH (overall and substance-specific) and overdose death, even after accounting for SUD history and other likely confounders. These findings highlight the vulnerability of this population. Improved knowledge regarding SUD-related negative health outcomes may help to tailor VA reentry programming.

A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy.

OBJECTIVES: The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies. METHODS: A systematic review and meta-analysis was performed to assess cfDNA accuracy for prenatal detection of 45,X, 47,XXY, 47,XXX and 47,XYY. Inclusion was restricted to studies published between January 2010 and December 2021 reporting both cfDNA and confirmatory diagnostic test results. RESULTS: For 45,X, the sensitivity was 98.8% (95%CI 94.6%-100%), specificity 99.4% (95%CI 98.7%-99.9%) and positive predictive value (PPV) 14.5% (95%CI 7.0%-43.8%). For 47,XXY, the sensitivity was 100% (95%CI 99.6%-100%), specificity 100% (95%CI 99.9%-100%) and PPV 97.7% (95%CI 78.6%-100%). For 47,XXX, the sensitivity was 100% (95%CI 96.9%-100%), specificity 99.9% (95%CI 99.7%-100%) and PPV 61.6% (95%CI 37.6%-95.4%). For 47,XYY, the sensitivity was 100% (95%CI 91.3%-100%), specificity 100% (95% CI 100%-100%) and PPV 100% (95%CI 76.5%-100%). All four SCAs had estimated negative predictive values (NPV) exceeding 99.99%, though false negatives were reported. CONCLUSIONS: This analysis suggests that cfDNA is a reliable screening test for SCA, though both false negatives and false positives were reported. These estimates of test performance are derived from pregnancies at high pretest risk for aneuploidy, limiting the generalisability to average risk pregnancies.

High risk of complications after a "low risk" procedure: A national study of nursing home residents and older adults undergoing haemorrhoid surgery.

AIM: To evaluate 30-day complications and 1-year mortality for older adults undergoing haemorrhoid surgery. METHOD: This retrospective cohort study evaluated older adults (age 66+) undergoing haemorrhoid surgery using Medicare claims and the minimum data set (MDS). Long-stay nursing home residents were identified, and propensity score matched to community-dwelling older adults. Generalized estimating equation models were created to determine the adjusted relative risk of 30-day complications, length of stay (LOS), and 1-year mortality. Among nursing home residents, functional and cognitive status were evaluated using the MDS-activities of daily living (ADL) score and the Brief Instrument of Mental Status. Faecal continence status was evaluated among a subset of nursing home residents. RESULTS: A total of 3664 subjects underwent haemorrhoid surgery and were included in the analyses. Nursing home residents were at significantly higher risk for 30-day complications (52.3% vs. 32.9%, aRR 1.6 [95% CI: 1.5-1.7], p < 0.001), and 1-year mortality (24.9% vs. 16.1%, aRR 1.6 [95% CI: 1.3-1.8], p < 0.001). Functional and mental status showed an inflection point of decline around the time of the procedure, which did not recover to the baseline trajectory in the following year. Additionally, a subset of nursing home residents demonstrated worsening faecal incontinence. CONCLUSION: This study demonstrated high rates of 30-day complications and 1-year mortality among all older adults (yet significantly worse among nursing home residents). Ultimately, primary care providers and surgeons should carefully weigh the potential harms of haemorrhoid surgery in older adults living in a nursing home.

Impact of persistent pain on function, cognition, and well-being of older adults.

BACKGROUND: We sought to determine the population-level associations between persistent pain and subsequent changes in physical function, cognitive function, and well-being, outcomes important to older adults. METHODS: We used data from National Health Aging Trends Study (NHATS) of community-dwelling Medicare beneficiaries age 65+ from 2011 to 2019. We defined "persistent pain" as being bothered by pain in the last month in both the 2011and 2012 interviews and "intermittent" pain including those reporting bothersome pain in one interview only. We used competing risks regression to estimate the association between persistent pain and the development of clinically meaningful declines in physical function, cognitive function, and well-being, adjusting for age, sex, race, education, and marital status at baseline. RESULTS: Of the 5589 eligible NHATS participants, 38.7% reported persistent pain and 27.8% reported intermittent pain. Over one-third described pain in five or more sites. Over the subsequent 7 years, participants with persistent pain were more likely to experience declines in physical function (64% persistent pain, 59% intermittent pain, 57% no bothersome pain; aHR 1.14, 95% CI 1.05-1.23) and well-being (48% persistent pain, 45% intermittent pain, 44% no bothersome pain; aHR 1.11, 95% CI 1.01-1.21), but were not more likely to experience cognitive decline (25% persistent pain, 24% intermittent pain, 23% no bothersome pain; aHR 1.02, 95% CI 0.90-1.16). CONCLUSIONS: Persistent pain is common in older adults and occurs in multiple body sites. Persistent pain contributes to meaningful declines in physical function and well-being over 7 years and warrants proactive interventions to mitigate pain.

Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis.

Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. In this study, a series of 11 uterine IMTs, 5 of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and additionally subjected to capture-based next-generation sequencing with or without whole-transcriptome RNA sequencing. In the 6 IMTs without aggressive behavior, ALK fusions were the sole pathogenic alteration. In contrast, all 5 aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. We combined our series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk stratification score assigning 1 point each for: age above 45 years, size≥5 cm,≥4 mitotic figures per 10 high-power field, and infiltrative borders. No tumors with 0 points had an aggressive outcome, while 21% of tumors with 1 to 2 points and all tumors with ≥3 points had aggressive outcomes. We propose a 2-step classification model that first uses the clinicopathologic risk stratification score to identify low-risk and high-risk tumors, and recommend molecular testing to further classify intermediate-risk tumors.

Patterns of Peripartum Depression and Anxiety During the Pre-Vaccine COVID-19 Pandemic.

Background: Pregnant people are vulnerable to new or worsening mental health conditions. This study aims to describe prevalence and course of symptomatic depression and anxiety in pregnancy during the pre-vaccine COVID-19 pandemic. Methods: This is a prospective cohort study of pregnant individuals with known or suspected COVID-19. Participants completed Edinburgh Postnatal Depression Scale (EPDS) and Generalized-Anxiety Disorder-7 (GAD-7) questionnaires at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum. Prevalence of symptomatic depression and anxiety at each visit was described. Univariable logistic regression analysis was used to determine the association between demographic and clinical factors and symptomatic depression or anxiety. Results: 317 participantswere included. The prevalence of antepartum depression was 14.6%, 10.3%, and 20.6% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. The rate of anxiety was 15.1%, 10.0%, and 17.3% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. A prior history of depression and/or anxiety (p's<0.03), as well as higher EPDS and GAD-7 scores at enrollment (p's<0.04) associated with depression and anxiety throughout pregnancy and the postpartum period. Quarantining during pregnancy was associated with symptomatic anxiety at 34weeks gestational age in univariate (P=0.027) analyses. COVID-19 diagnosis and hospitalization were not associated with depression or anxiety. Conclusions: Depression and anxiety were prevalent throughout pregnancy and the postpartum period, particularly in those with prior depression and/or anxiety and who quarantined. Strategies that target social isolation may mitigate potential adverse consequences for pregnant people, and continued vigilance in recognition of depression and anxiety in pregnancy should be considered.

Prolonged use of newly prescribed gabapentin after surgery.

BACKGROUND: Surgeons have made substantial efforts to decrease postoperative opioid prescribing, largely because it can lead to prolonged use. These efforts include adoption of non-opioid pain medication including gabapentin. Like opioids, gabapentin use may be prolonged, increasing the risk of altered mental status and even overdose and death when taken concurrently with opioids. However, little is known about postoperative prolonged use of gabapentin in older adults. METHODS: We merged a 20% sample of Medicare Carrier, MedPAR and Outpatient Files with Part D for 2013-2018. We included patients >65 years old without prior gabapentinoid use who underwent common non-cataract surgical procedures. We defined new postoperative gabapentin as fills for 7 days before surgery until 7 days after discharge. We excluded patients whose discharge disposition was hospice or death. The primary outcome was prolonged use of gabapentin, defined as a fill>90 days after discharge. To identify risk factors for prolonged use, we constructed logistic regression models, adjusted for procedure and patient characteristics, length of stay, disposition location, and care complexity. RESULTS: Overall, 17,970 patients (3% of all eligible patients) had a new prescription for gabapentin after surgery. Of these, the mean age was 73 years old and 62% were female. The most common procedures were total knee (45%) and total hip (21%) replacements. Prolonged use occurred in 22%. Those with prolonged use were more likely to be women (64% vs. 61%), be non-White (14% vs. 12%), have concurrent prolonged opioid use (44% vs. 18%), and have undergone emergency surgery (8% vs. 4%). On multivariable analysis, being female, having a higher Charlson comorbidity score, having an opioid prescription at discharge and at >90 days and having a higher care complexity were associated with prolonged use of gabapentin. CONCLUSIONS: More than one-fifth of older adults prescribed gabapentin postoperatively filled a prescription >90 days after discharge, especially among patients with more comorbidities and concurrent prolonged opioid use, increasing the risk of adverse drug events and polypharmacy.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.