Frailty in patients with ovarian cancer and the role of healthcare access, race, and ethnicity.

OBJECTIVE: Ovarian cancer has poor 5-year survival, particularly among non-Hispanic (NH) Black patients. Efforts to identify patients at high-risk of functional limitations and frailty may improve outcomes. In this study, we examined how healthcare access (HCA) and race/ethnicity relate to frailty among patients with ovarian cancer. METHODS: We identified Hispanic, NH Black, and NH White patients diagnosed at ages ≥6 5 years with ovarian cancer between 2009 and 2015 using SEER-Medicare. Log-binomial regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between HCA and race/ethnicity with pre- or post-diagnosis frailty, adjusting for age and comorbidities. RESULTS: A total of 6041 patients with ovarian cancer were included, including 91.8% NH White, 6.6% NH Black, and 1.7% Hispanic. Pre-diagnosis, 14.7% of patients were defined as frail (NH White: 14.3%; NH Black: 17.9%; Hispanic: 20.8%). Post-diagnosis, frailty prevalence increased to 58.8% (NH White: 58.2%; NH Black: 65.2%; Hispanic: 70.2%). No statistically significant associations were observed between race/ethnicity and pre- or post-diagnosis frailty in fully adjusted models. After adjustment for patient characteristics and healthcare accessibility and availability, higher healthcare affordability was associated with a decreased prevalence of pre-diagnosis frailty (PR: 0.91, 95% CI: 0.8 5, 0.98). CONCLUSIONS: Patients with ovarian cancer have a high prevalence of frailty after diagnosis, particularly NH Black and Hispanic patients. Improving healthcare affordability may prevent or help manage frailty in Medicare patients, improve receipt of cancer treatment, and increase cancer survival.

Risk of Atherosclerotic Cardiovascular Disease Hospitalizations after COPD Hospitalization among Older Adults.

BACKGROUND: Meta-analyses have suggested the risk of cardiovascular disease (CVD) events is significantly higher after a chronic obstructive pulmonary disease (COPD) exacerbation. However, many of these studies have included a broad array of CVD events or have been limited to highly selected patient populations potentially not generalizable to the broader population of COPD. METHODS: We assessed the risk of atherosclerotic cardiovascular disease (ASCVD)hospitalizations after COPD hospitalization compared to before COPD hospitalization and identified patient factors associated with ASCVD hospitalizations after COPD hospitalization. This retrospective cohort study used claims data from 920,550 Medicare beneficiaries hospitalized for COPD from 2016-2019 in the US. The primary outcome was risk of a ASCVD hospitalization composite outcome (myocardial infarction, percutaneous coronary intervention, coronary artery by-pass graft surgery, stroke, or transient ischemic attack) in the 30-days and 1 year after-COPD hospitalization relative to the same time period before-COPD hospitalization. Time in the before- and after-COPD hospitalization time periods to a composite ASCVD hospitalization outcome were modeled using an extension of the Cox Proportional-Hazards model, the Anderson-Gill model with adjustment for patient characteristics. Additional analyses evaluated for interactions in subgroups associated with the composite ASCVD hospitalization outcome. RESULTS: Among 920,550 patients in the 30-day and 1-year cohorts, (mean age, 73-74 years) the hazard ratio estimate (HR; 95% CI) for the composite ASCVD hospitalization outcome after-COPD hospitalization vs before-COPD hospitalization for the 30-day cohort was 0.99 (0.93, 1.05; p = 0.67) and for the 1-year cohort was 0.99 (0.97, 1.02; p = 0.53) following adjustment. We observed 3 subgroups that were significantly associated with higher risk for ASCVD hospitalizations 1 year after COPD hospitalization: 76+ years old, women, COPD hospitalization severity. CONCLUSION: Among Medicare beneficiaries hospitalized for COPD, the risk of ASCVD hospitalizations was not significantly increased 30-day or 1-year after COPD-hospitalization relative to before-COPD hospitalization. In sub-group analyses, we identified age 76+ years old, female sex, and COPD hospitalization severity as high risk subgroups with increased risk of ASCVD events 1-year after-COPD hospitalization. Further research is needed to characterize the COPD exacerbation populations at highest ASCVD hospitalization risk.

Misuse of Prescribed and Nonprescribed Substances Among U.S. Cancer Survivors.

BACKGROUND: Substance misuse is common among cancer survivors and can negatively impact cancer outcomes. METHODS: We conducted a cross-sectional study using National Survey on Drug Use and Health data for 2015 to 2020. We included adult respondents with a history of solid tumor cancer. We calculated the weighted prevalence and corresponding SEs (both expressed as percentages) of substance (alcohol, opioid, sedative, stimulant, other) misuse for respondents with any history of solid tumor cancer and, in secondary analyses, respondents diagnosed with cancer in the prior 12 months. RESULTS: The study included 6,101 respondents with any history of cancer, 1,437 diagnosed in the prior 12 months. Alcohol was the most commonly misused substance. The average prevalence of alcohol misuse was 14.4% (SE 0.60%) across cancer types; it was markedly more common among people with a history or cervical (24.2% [3.0%]) or head and neck cancer (27.4% [7.1%]). The next most common form of substance misuse was opioid misuse (average prevalence: 2.7% [0.25%]). As with alcohol misuse, the prevalence of opioid misuse was higher among those with a lifetime history of cervical cancer (5% [1%]) or head and neck cancer (5% [3%]). Results were generally consistent among cancer survivors diagnosed in the prior 12 months. CONCLUSIONS: There is a clear opportunity to address substance misuse-particularly alcohol misuse-among cancer survivors. Such efforts should focus on populations with a high prevalence of substance misuse (e.g., cervical and head and neck cancer survivors) and have strong potential to improve cancer-specific and overall health outcomes.

Trends and factors associated with receipt of human papillomavirus (HPV) vaccine in private, public, and alternative settings in the United States.

BACKGROUND: One of the goals of the President's Cancer Panel was to maximize access to human papillomavirus (HPV) vaccination through expansion of alternative settings for receiving the vaccine, such as in public health settings, schools, and pharmacies. METHODS: In a cross-sectional analysis, we utilized the National Immunization Survey-Teen data from 2014 to 2020 (n = 74,645) to describe trends and factors associated with HPV vaccine uptake in private, public, and alternative settings. We calculated annual percent change (APC) between 2014 and 2020, estimating rate of HPV vaccine uptake across settings. Using multinomial logistic regression, we estimated the odds of receipt of HPV vaccine in public health settings and other alternative settings compared to private healthcare settings, adjusting for sociodemographic covariates. RESULTS: We found a 5 % annual increase in the use of private facilities between 2014-2018 (APC = 5.3; 95 % CI 3.4, 7.1), and almost 7 % between 2018-2020 (APC = 6.7; 95 % CI 1.4, 12.3). Adjusted multinomial logistic regression analyses found that odds of receiving vaccinations at a public facility vs. a private facility increased almost two times for adolescents living below poverty (aOR = 1.82, 95 % CI: 1.60, 2.08) compared to above poverty. Additionally, adolescents without physician recommendations had lower odds of receiving vaccines at public versus private facilities (aOR = 1.75, 95 % CI: 1.44, 2.12). Finally, odds of receiving HPV vaccines at public facilities vs. private facilities decreased by 33 % for White adolescents (aOR = 0.67, 95 % CI: 0.57, 0.78) versus Black adolescents. CONCLUSIONS: Sociodemographic factors such as race, and socioeconomic factors such as poverty level, and receipt of physician HPV recommendations are associated with receiving the vaccine at private settings vs. public health facilities and alternative settings. This information is important in strengthening alternative settings for HPV vaccine uptake to increase access to the vaccine among disadvantaged individuals.

ACO leakage among gynecologic cancer patients: Incidence, predictors, and impact on annual Medicare expenditure.

OBJECTIVE: To examine patterns of Accountable Care Organizations (ACO) leakage, the receipt of healthcare by ACO-assigned patients from institutions outside assigned ACO network, among patients with gynecologic cancer. ACO leakage was estimated as rates of patients seeking care external to their ACO assignment. Factors associated with ACO leakage were identified and cost differences within the first year of cancer diagnosis described. METHODS: Medicare 5% data (2013-2017) was used to quantify rates of leakage among gynecologic cancer patients with stable ACO assignment. Crude and multivariable adjusted risk ratios of ACO leakage risk factors were estimated using log-binomial regression models. Overall and cancer-specific spending differences by ACO leakage status were compared using Wilcoxon rank-sum test. RESULTS: Overall incidence of ACO leakage was 28.1% with highest leakage for outpatient care and uterine cancer patients. ACO leakage risk was 56% higher among Black relative to White patients, and 77% more for those in higher relative to lowest quintiles of median household income. Leakage decreased by 3% and 8% with each unit increase in ACO size and number of subspecialists, respectively. Healthcare costs were 19.5% higher for leakage patients. CONCLUSIONS: ACO leakage rates among gynecologic cancer patients was overall modest, with some regional and temporal variation, higher leakage for certain subgroups and substantially higher Medicare spending in inpatient and outpatient settings for patients with ACO leakage. These findings identify targets for further investigations and strategies to encourage oncologists to participate in ACOs and prevent increased health care costs associated with use of non-ACO providers.

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1ß, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

Health Care Access Dimensions and Racial Disparities in End-of-Life Care Quality among Patients with Ovarian Cancer.

This study investigated the association between health care access (HCA) dimensions and racial disparities in end-of-life (EOL) care quality among non-Hispanic Black (NHB), non-Hispanic White (NHW), and Hispanic patients with ovarian cancer. This retrospective cohort study used the Surveillance, Epidemiology, and End Results-linked Medicare data for women diagnosed with ovarian cancer from 2008 to 2015, ages 65 years and older. Health care affordability, accessibility, and availability measures were assessed at the census tract or regional levels, and associations between these measures and quality of EOL care were examined using multivariable-adjusted regression models, as appropriate. The final sample included 4,646 women [mean age (SD), 77.5 (7.0) years]; 87.4% NHW, 6.9% NHB, and 5.7% Hispanic. In the multivariable-adjusted models, affordability was associated with a decreased risk of intensive care unit stay [adjusted relative risk (aRR) 0.90, 95% confidence interval (CI): 0.83-0.98] and in-hospital death (aRR 0.91, 95% CI: 0.84-0.98). After adjustment for HCA dimensions, NHB patients had lower-quality EOL care compared with NHW patients, defined as: increased risk of hospitalization in the last 30 days of life (aRR 1.16, 95% CI: 1.03-1.30), no hospice care (aRR 1.23, 95% CI: 1.04-1.44), in-hospital death (aRR 1.27, 95% CI: 1.03-1.57), and higher counts of poor-quality EOL care outcomes (count ratio:1.19, 95% CI: 1.04-1.36). HCA dimensions were strong predictors of EOL care quality; however, racial disparities persisted, suggesting that additional drivers of these disparities remain to be identified. SIGNIFICANCE: Among patients with ovarian cancer, Black patients had lower-quality EOL care, even after adjusting for three structural barriers to HCA, namely affordability, availability, and accessibility. This suggests an important need to investigate the roles of yet unexplored barriers to HCA such as accommodation and acceptability, as drivers of poor-quality EOL care among Black patients with ovarian cancer.

Substance Use Disorders Among US Adult Cancer Survivors.

Importance: Some individuals are predisposed to cancer based on their substance use history, and others may use substances to manage cancer-related symptoms. Yet the intersection of substance use disorder (SUD) and cancer is understudied. Because SUD may affect and be affected by cancer care, it is important to identify cancer populations with a high prevalence of SUD, with the goal of guiding attention and resources toward groups and settings where interventions may be needed. Objective: To describe the cancer type-specific prevalence of SUD among adult cancer survivors. Design, Setting, and Participants: This cross-sectional study used data from the annually administered National Survey on Drug Use and Health (NSDUH) for 2015 through 2020 to identify adults with a history of solid tumor cancer. Substance use disorder was defined as meeting at least 1 of 4 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for abuse or at least 3 of 6 criteria for dependence. Main Outcomes and Measures: Per NSDUH guidelines, we made adjustments to analysis weights by dividing weights provided in the pooled NSDUH data sets by the number of years of combined data (eg, 6 for 2015-2020). The weighted prevalence and corresponding SEs (both expressed as percentages) of active SUD (ie, within the past 12 months) were calculated for respondents with any lifetime history of cancer and, in secondary analyses, respondents diagnosed with cancer within 12 months prior to taking the survey. Data were analyzed from July 2022 to June 2023. Results: This study included data from 6101 adult cancer survivors (56.91% were aged 65 years or older and 61.63% were female). Among lifetime cancer survivors, the prevalence of active SUD was 3.83% (SE, 0.32%). Substance use disorder was most prevalent in survivors of head and neck cancer (including mouth, tongue, lip, throat, and pharyngeal cancers; 9.36% [SE, 2.47%]), esophageal and gastric cancer (9.42% [SE, 5.51%]), cervical cancer (6.24% [SE, 1.41%]), and melanoma (6.20% [SE, 1.34%]). Alcohol use disorder was the most common SUD (2.78% [SE, 0.26%]) overall and in survivors of head and neck cancer, cervical cancer, and melanoma. In survivors of esophageal and gastric cancers, cannabis use disorder was the most prevalent SUD (9.42% [SE, 5.51%]). Among respondents diagnosed with cancer in the past 12 months, the overall prevalence of active SUD was similar to that in the lifetime cancer survivor cohort (3.81% [SE, 0.74%]). However, active SUD prevalence was higher in head and neck (18.73% [SE, 10.56%]) and cervical cancer survivors (15.70% [SE, 5.35%]). The distribution of specific SUDs was different compared with that in the lifetime cancer survivor cohort. For example, in recently diagnosed head and neck cancer survivors, sedative use disorder was the most common SUD (9.81% [SE, 9.17%]). Conclusions and Relevance: Findings of this study suggest that SUD prevalence is higher among survivors of certain types of cancer; this information could be used to identify cancer survivors who may benefit from integrated cancer and SUD care. Future efforts to understand and address the needs of adult cancer survivors with comorbid SUD should prioritize cancer populations in which SUD prevalence is high.

Factors Associated With Receipt of Molecular Testing and its Impact on Time to Initial Systemic Therapy in Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: Despite recommendations for molecular testing irrespective of patient characteristics, differences exist in receipt of molecular testing for oncogenic drivers amongst metastatic non-small cell lung cancer (mNSCLC) patients. Exploration into these differences and their effects on treatment is needed to identify opportunities for improvement. PATIENTS AND METHODS: We conducted a retrospective cohort study of adult patients diagnosed with mNSCLC between 2011 and 2018 using PCORnet's Rapid Cycle Research Project dataset (n = 3600). Log-binomial, Cox proportional hazards (PH), and time-varying Cox regression models were used to ascertain whether molecular testing was received, and time from diagnosis to molecular testing and/or initial systemic treatment in the context of patient age, sex, race/ethnicity, and multiple comorbidities status. RESULTS: The majority of patients in this cohort were ≤ 65 years of age (median [25th, 75th]: 64 [57, 71]), male (54.3%), non-Hispanic white individuals (81.6%), with > 2 comorbidities in addition to mNSCLC (54.1%). About half the cohort received molecular testing (49.9%). Patients who received molecular testing had a 59% higher probability of initial systemic treatment than patients who were yet to receive testing. Multiple comorbidity status was positively associated with receipt of molecular testing (RR, 1.27; 95% CI 1.08, 1.49). CONCLUSION: Receipt of molecular testing in academic centers was associated with earlier initiation of systemic treatment. This finding underscores the need to increase molecular testing rates amongst mNSCLC patients during a clinically relevant period. Further studies to validate these findings in community centers are warranted.

Association of Human Papillomavirus Status With Suicide Risk Among Patients With Head and Neck Cancer.

Importance: Human papillomavirus (HPV) is strongly associated with head and neck cancer, and HPV status is considered a prognostic factor. Being a sexually transmitted infection, HPV-related cancers may have greater risk of stigma and psychological distress; however, the potential association of HPV-positive status with psychosocial outcomes, such as suicide, is understudied in head and neck cancer. Objective: To investigate the association between HPV tumor status and suicide risk among patients with head and neck cancer. Design, Setting, and Participants: This population-based retrospective cohort study included adult patients with clinically confirmed cases of head and neck cancer based on HPV tumor status from the Surveillance, Epidemiology, and End Results database from January 1, 2000, to December 31, 2018. Data analysis was conducted from February 1 to July 22, 2022. Main Outcomes and Measures: The outcome of interest was death by suicide. Primary measure was HPV status of tumor site, dichotomized as positive or negative. Covariates included age, race, ethnicity, marital status, cancer stage at presentation, treatment modality, and type of residence. Cumulative risk of suicide among patients with HPV-positive and HPV-negative head and neck cancer was assessed using Fine and Gray competing risk models. Results: Of 60 361 participants, the mean (SD) age was 61.2 (13.65) years, and 17 036 (28.2%) were women; there were 347 (0.6%) American Indian, 4369 (7.2%) Asian, 5226 (8.7%) Black, 414 (0.7%) Native Hawaiian or Other Pacific Islander, and 49 187 (81.5%) White individuals. A competing risk analysis showed a significant difference in the cumulative incidence of suicide between HPV-positive cancers (5-year suicide-specific mortality, 0.43%; 95% CI, 0.33%-0.55%) and HPV-negative cancers (5-year suicide-specific mortality, 0.24%; 95% CI, 0.19%-0.29%). Tumor status that was HPV positive was associated with increased suicide risk in the unadjusted model (hazard ratio [HR], 1.76; 95% CI, 1.28-2.40), but not the fully adjusted model (adjusted HR, 1.18; 95% CI, 0.79-1.79). Among people with oropharyngeal cancer only, HPV status was associated with increased suicide risk, but the width of the confidence interval prevented definitive conclusion (adjusted HR, 1.61; 95% CI 0.88-2.94). Conclusions and Relevance: The results of this cohort study suggest that patients with HPV-positive head and neck cancer have similar risk of suicide as patients with HPV-negative cancer, despite differences in overall prognosis. Early mental health interventions may be associated with reduced suicide risk in all patients with head and neck cancer and should be assessed in future work.

Transition to surgery after pessary among female Medicare beneficiaries with pelvic organ prolapse.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year. OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery. STUDY DESIGN: The Medicare 5% Limited Data Set was queried from 2011 to 2016 for women aged ≥65 years with a diagnosis of prolapse who underwent pessary fitting. Cases with at least 3 years of follow-up in the Medicare Data Set were followed longitudinally for the primary outcome of surgery for prolapse. The cumulative incidence of prolapse surgery following index pessary fitting was calculated. Characteristics of women who underwent surgery and those who did not were compared using time-varying Cox regression analysis. RESULTS: Among 2032 women fitted with a pessary, 608 underwent surgery within 7 years. The median time to surgery was 496 days (interquartile range, 187-1089 days). The cumulative incidence of prolapse surgery was 12.2% at 1 year and 30.9% at 7 years. After adjusting for covariates, factors significantly associated with the transition to surgery included previous prolapse surgery (adjusted hazard ratio, 1.50; 1.09-2.07) and a diagnosis of urinary incontinence at the time of pessary fitting (adjusted hazard ratio, 1.20; 0.62-0.99). Factors associated with a lower hazard of surgery included age (adjusted hazard ratio, 0.96 per year; 95% confidence interval, 0.95-0.97), dual Medicare/Medicaid eligibility (adjusted hazard ratio, 0.75; 95% confidence interval, 0.56-1.00), and pessary fitting by a nongynecologist (adjusted hazard ratio, 0.78; 95% confidence interval, 0.62-0.99). CONCLUSION: In this population of Medicare beneficiaries, within 7 years of pessary fitting, almost one-third of women aged >65 years underwent surgery for prolapse. These results add to our current understanding of the demographics of pessary use in an older population and may aid in counseling older patients presenting for treatment of symptomatic pelvic organ prolapse.

Initial Thoracic Endovascular Aortic Repair vs Medical Therapy for Acute Uncomplicated Type B Aortic Dissection.

Importance: Thoracic endovascular aortic repair (TEVAR) has increasingly been used for uncomplicated type B aortic dissection (uTBAD) despite limited supporting data. Objective: To assess whether initial TEVAR following uTBAD is associated with reduced mortality or morbidity compared with medical therapy alone. Design, Setting, and Participants: This cohort study included Centers for Medicare & Medicaid Services inpatient claims data for adults aged 65 years or older with index admissions for acute uTBAD from January 1, 2011, to December 31, 2018, with follow-up available through December 31, 2019. Exposures: Initial TEVAR was defined as TEVAR within 30 days of admission for acute uTBAD. Main Outcomes and Measures: Outcomes included all-cause mortality, cardiovascular hospitalizations, aorta-related and repeated aorta-related hospitalizations, and aortic interventions associated with initial TEVAR vs medical therapy. Propensity score inverse probability weighting was used. Results: Of 7105 patients with eligible index admissions for acute uTBAD, 1140 (16.0%) underwent initial TEVAR (623 [54.6%] female; median age, 74 years [IQR, 68-80 years]) and 5965 (84.0%) did not undergo TEVAR (3344 [56.1%] female; median age, 76 years [IQR, 69-83 years]). Receipt of TEVAR was associated with region (vs South; Midwest: adjusted odds ratio [aOR], 0.66 [95% CI, 0.53-0.81]; P < .001; Northeast: aOR, 0.63 [95% CI, 0.50-0.79]; P < .001), Medicaid dual eligibility (aOR, 0.76; 95% CI, 0.63-0.91; P = .003), hypertension (aOR, 1.26; 95% CI, 1.03-1.54; P = .03), peripheral vascular disease (aOR, 1.24; 95% CI, 1.02-1.49; P = .03), and year of admission (2012, 2013, 2014, and 2015 were associated with greater odds of TEVAR compared with 2011). After inverse probability weighting, mortality was similar for the 2 strategies up to 5 years (hazard ratio [HR], 0.95; 95% CI, 0.85-1.06), as were aorta-related hospitalizations (HR, 1.12; 95% CI, 0.99-1.27), aortic interventions (HR, 1.01; 95% CI, 0.84-1.20), and cardiovascular hospitalizations (HR, 1.05; 95% CI, 0.93-1.20). In a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality over a period of 1 year (adjusted HR [aHR], 0.86; 95% CI, 0.75-0.99; P = .03), 2 years (aHR, 0.85; 95% CI, 0.75-0.96; P = .008), and 5 years (aHR, 0.87; 95% CI, 0.80-0.96; P = .004). Conclusions and Relevance: In this study, 16.0% of patients underwent initial TEVAR within 30 days of uTBAD, and receipt of initial TEVAR was associated with hypertension, peripheral vascular disease, region, Medicaid dual eligibility, and year of admission. Initial TEVAR was not associated with improved mortality or reduced hospitalizations or aortic interventions over a period of 5 years, but in a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality. These findings, along with cost-effectiveness and quality of life, should be assessed in a prospective trial in the US population.

Risk of Atherosclerotic Cardiovascular Disease Hospitalizations after COPD Hospitalization among Older Adults.

BACKGROUND: Meta-analyses have suggested the risk of atherosclerotic cardiovascular disease (ASCVD) events is significantly higher after a chronic obstructive pulmonary disease (COPD) exacerbation. However, these studies have been limited to highly selected patient populations potentially not generalizable to the broader population of COPD. METHODS: We assessed the risk of ASCVD hospitalizations after COPD hospitalization compared to before COPD hospitalization and identified patient factors associated with ASCVD hospitalizations after COPD hospitalization. This retrospective cohort study used claims data from 920,550 Medicare beneficiaries hospitalized for COPD from 2016-2019 in the US. The primary outcome was risk of a ASCVD hospitalization composite outcome (myocardial infarction, percutaneous coronary intervention, coronary artery by-pass graft surgery, stroke, or transient ischemic attack) in the 1 year after-COPD hospitalization relative to the 1 year before-COPD hospitalization. Time from discharge to a composite ASCVD hospitalization outcome was modeled using an extension of the Cox Proportional-Hazards model, the Anderson-Gill model with adjustment for patient characteristics. Additional analyses evaluated for interactions in subgroups and risk factors associated with the composite ASCVD hospitalization outcome. RESULTS: Among 920,550 patients (mean age, 73 years) the hazard ratio estimate (HR; 95% CI) for the composite ASCVD hospitalization outcome after-COPD hospitalization vs before-COPD hospitalization was 0.99 (0.97, 1.02; p = 0.53) following adjustment. We observed 3 subgroups that were significantly associated with higher risk for ASCVD hospitalizations after COPD hospitalization: 76+ years old, women, COPD hospitalization severity. Among the 19 characteristics evaluated, 10 were significantly associated with higher risk of CVD events 1 year after COPD hospitalization with hyperlipidemia (2.78; 2.67, 2.90) and history of cardiovascular disease (1.77; 1.72 1.83) associated with the greatest risk. CONCLUSION: Among Medicare beneficiaries hospitalized for COPD, the risk of ASCVD hospitalizations was not significantly increased after COPD-hospitalization relative to before-COPD hospitalization. Although, we identified age 76+ years old, female sex, and COPD hospitalization severity as high risk subgroups and 10 risk factors associated with increased risk of ASCVD events after-COPD hospitalization. Further research is needed to characterize the COPD exacerbation populations at highest ASCVD hospitalization risk.

Factors Related to Biologic Adherence and Outcomes Among Moderate-to-Severe Asthma Patients.

BACKGROUND: Adherence barriers to asthma biologics may not be uniform across administration settings for patients with moderate-to-severe asthma. OBJECTIVE: To examine differences in asthma biologic adherence and associated factors, as well as association with a 1-year all-cause emergency department (ED) visit, across administration settings. METHODS: A retrospective study of biologic naïve moderate-to-severe asthma patients with initial biologic therapy between January 1, 2016, and April 30, 2020, in the Optum Clinformatics Data Mart was performed. Three administration settings were identified: Clinic-only (outpatient office/infusion center), Home (self-administration), and Hybrid setting (mixture of clinic and self-administration). Asthma biologic adherence was the proportion of observed over expected biologic dose administrations received within 6 months from initial therapy. Factors associated with adherence were identified by administration setting, using Poisson regression analyses. A relationship between a 1-year all-cause ED visit and adherence was assessed for each administration setting using Cox regression analyses. RESULTS: The study cohort was 3932 patients. Biologics adherence was 0.75 [0.5, 1] in Clinic setting, the most common administration setting, and 0.83 [0.5, 1] in both Home and Hybrid settings. Specialist access was consistently associated with better biologic adherence, whereas Black race, Hispanic ethnicity, lower education, Medicare only insurance, and higher patient out-of-pocket cost were associated with worse biologic adherence in some settings. In the Hybrid setting, hazard for a 1-year all-cause ED visit decreased with biologic adherence. CONCLUSIONS: Asthma biologic adherence varied by administration setting. Efforts to improve asthma biologic adherence should consider promoting self-administration when beneficial, improving prior specialist access, and targeting patients with higher risk of suboptimal adherence particularly Black and Hispanic patients.

Differential Outcomes Among Survivors of Head and Neck Cancer Belonging to Racial and Ethnic Minority Groups.

Importance: Approximately 1 in 5 new patients with head and neck cancer (HNC) in the US belong to racial and ethnic minority groups, but their survival rates are worse than White individuals. However, because most studies compare Black vs White patients, little is known about survival differences among members of racial and ethnic minority groups. Objective: To describe differential survival and identify nonclinical factors associated with stage of presentation among patients with HNC belonging to racial and ethnic minority groups. Design, Setting, and Participants: This population-based retrospective cohort study used data from the 2007 to 2016 Surveillance, Epidemiology, and End Results (SEER) database and included non-Hispanic Black, Asian Pacific Islander, American Indian/Alaska Native, and Hispanic patients with HNC. The data were analyzed from December 2020 to May 2021. Main Outcomes and Measures: Outcomes were time to event measures: (HNC-specific and all-cause mortality) and stage of presentation. Covariates included nonclinical (age at diagnosis, sex, race and ethnicity, insurance status, marital status, and a composite socioeconomic status [SES]) and clinical factors (stage, cancer site, chemotherapy, radiation, and surgery). A Cox regression model was used to adjust associations of covariates with the hazard of all-cause death, and a Fine and Gray competing risks proportional hazards model was used to estimate associations of covariates with the hazard of HNC-specific death. A proportional log odds ordinal logistic regression identified which nonclinical factors were associated with stage of presentation. Results: There were 21 966 patients with HNC included in the study (mean [SD] age, 56.02 [11.16] years; 6072 women [27.6%]; 9229 [42.0%] non-Hispanic Black, 6893 [31.4%] Hispanic, 5342 [24.3%] Asian/Pacific Islander, and 502 [2.3%] American Indian/Alaska Native individuals). Black patients had highest proportion with very low SES (3482 [37.7%]) and the lowest crude 5-year overall survival (46%). After adjusting for covariates, Hispanic individuals had an 11% lower subdistribution hazard ratio (sdHR) of HNC-specific mortality (sdHR, 0.89; 95% CI, 0.83-0.95), 15% lower risk for Asian/Pacific Islander individuals (sdHR, 0.85; 95% CI, 0.78-0.93), and a trending lower risk for American Indian/Alaska Native individuals (sdHR, 0.85; 95% CI, 0.71-1.01), compared with non-Hispanic Black individuals. Race, sex, insurance, marital status, and SES were consistently associated with all-cause mortality, HNC-specific mortality, and stage of presentation, with non-Hispanic Black individuals faring worse compared with individuals of other racial and ethnic minority groups. Conclusions and Relevance: In this cohort study that included only patients with HNC who were members of racial and ethnic minority groups, Black patients had significantly worse outcomes that were not completely explained by stage of presentation. There may be unexplored multilevel factors that are associated with social determinants of health and disparities in HNC outcomes.

Vaginal Complications after Cystectomy: Results from a Medicare Sample.

PURPOSE: Cystectomy with a vaginal-sparing approach may be associated with unique complications specific to the female population. The objective of this study was to estimate the incidence of vaginal complications (defined to include vaginal prolapse, vaginal fistula, dyspareunia and vaginal cuff dehiscence/evisceration) after cystectomy and to determine risk factors for these complications. MATERIALS AND METHODS: Women 65 years or older undergoing cystectomy for any indication were identified by procedural codes in the Medicare Limited Data Set 5% sample from January 1, 2011 to December 31, 2017. Patients experiencing a vaginal complication after cystectomy were compared to those who did not. Demographic and biological factors that could increase likelihood of complications were identified and time to development of complications determined. Cumulative incidence was calculated using cumulative incidence function. Multivariable cause-specific Cox proportional hazards model assessed risk factors for vaginal complications. RESULTS: In all, 481 women undergoing cystectomy were identified during the study period, and 37.2% were younger than 70 years old. The majority (378, 79%) had bladder cancer, and 401 (83.4%) underwent an incontinent conduit or catheterizable channel diversion. Within 2 years of cystectomy, 93 patients (19.5%) had 1 or more complications on record. Vaginal cuff dehiscence had the highest cumulative incidence, occurring in 49 patients (10.2%). Over the entire study period (2011-2017), 102 women (21.2%) were diagnosed with a vaginal complication, and 27 (5.6%) received an intervention. CONCLUSIONS: Among women who undergo cystectomy, vaginal complications occur at rates higher than expected with over 20% of women experiencing a complication and over a quarter of those diagnosed undergoing intervention.

Nonsurgical Risk Factors Associated With Pharyngocutaneous Fistula in Patients Who Have Undergone Laryngectomy.

Importance: Pharyngocutaneous fistula (PCF) is a serious complication after total laryngectomy. Despite the well-described clinical risk factors for PCF and its association with poor quality of life, there is a paucity of data on the nonclinical factors that may be associated with this complication. Objective: To determine whether nonclinical risk factors (eg, age, sex, race and ethnicity) are associated with an increased risk of developing a PCF after total laryngectomy, and whether or not the method of reconstruction explains any differences found. Design, Setting, and Participants: This retrospective multicenter cohort study used data from a nationally validated, risk-adjusted, outcomes-based, surgical quality improvement database (the National Surgical Quality Improvement Program) to examine outcomes in patients who underwent a total laryngectomy from 2005 to 2018. The database was queried from January 1, 2005, to December 31, 2018; data analyses were performed from September 1, 2020, to March 31, 2021. Main Outcomes and Measures: The primary outcome was development of a PCF within 30 days of a total laryngectomy. Patient characteristics, including age, sex, race and ethnicity, comorbidities, and mode of reconstruction, were analyzed. Results: A cohort of 1573 adult patients (median age [IQR], 63 [56-71] years; 1280 [81.4%] men; 293 [18.6%] women; 1001 [63.6%] non-Hispanic White individuals) had undergone a total laryngectomy during the study period and were included in the analyses. The overall rate of PCF formation was 4.3% (68 of 1573 patients). Hispanic patients had the highest rate (9.5%; 9 of 95 patients) of PCF formation, which was more than twice the rate among non-Hispanic White patients (3.8%; 38 of 1001) and non-Hispanic Black patients (4.7%; 11 of 236). After adjusting for clinical and other covariates, women were 1.9 times more likely to develop a PCF compared with men (adjusted odds ratio, 1.90; 95% CI, 1.08-3.35). We also found that the odds of developing a PCF were 3-fold higher among Hispanic patients compared with non-Hispanic White patients (adjusted odds ratio, 2.96; 95% CI, 1.36-6.47). The type of reconstruction did not differ across age or race and ethnicity after controlling for clinical risk factors. Conclusions and Relevance: This multicenter cohort study found that 2 nonclinical risk factors-Hispanic ethnicity and female sex-were associated with an increased risk of PCF formation. Knowledge of these risk factors should be included in patient-physician decision-making as well as future interventions to decrease the rate of PCF formation after laryngectomy.

National trends in repair for type B aortic dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) first gained in popularity for repair of type B aortic dissections (TBADs) in the early 2000's. We aimed to describe patients undergoing open repair, TEVAR, and no repair and analyze factors associated with repair within 14 days of presentation in the contemporary era. METHODS: We used the MarketScan database to find patients with TBAD between 2014 and 2017. To assess factors associated with early repair, univariable, and multivariable log-binomial regression were used. RESULTS: There were 2613 patients admitted with TBAD between 2014 and 2017 across the United States, of whom 38.4% underwent repair within 14 days of admission (25.3% open repair and 13.1% TEVAR). The incidence of repair within 14 days decreased over the study period (43% of the study cohort in 2014 to 26.4% in 2017) primarily due to a decrease in open repairs from 30.8% of patients in 2014 to 12.5% in 2017. In multivariable analysis, older age, Middle Atlantic location, diabetes mellitus, insulin use, antiplatelet use, and more recent year were associated with lower likelihood of early repair; male sex, peripheral vascular disease, and the presence of extremity ischemia, rupture, shock, and acidosis were associated with higher likelihood of repair. CONCLUSIONS: Overall, repair of TBAD within 14 days of presentation declined from 2014 to 2017, with a steady rate of TEVAR but declining rate of open repairs. Further investigation into provider- and hospital-specific factors as they relate to likelihood of repair is needed.

Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures.

Although multiple lifestyle exposures simultaneously impact blood pressure (BP) and cardiovascular health, most analysis so far has considered each single lifestyle exposure (e.g., smoking) at a time. Here, we exploit gene-multiple lifestyle exposure interactions to find novel BP loci. For each of 6,254 Framingham Heart Study participants, we computed lifestyle risk score (LRS) value by aggregating the risk of four lifestyle exposures (smoking, alcohol, education, and physical activity) on BP. Using the LRS, we performed genome-wide gene-environment interaction analysis in systolic and diastolic BP using the joint 2 degree of freedom (DF) and 1 DF interaction tests. We identified one genome-wide significant (p < 5 × 10-8 ) and 11 suggestive (p < 1 × 10-6 ) loci. Gene-environment analysis using single lifestyle exposures identified only one of the 12 loci. Nine of the 12 BP loci detected were novel. Loci detected by the LRS were located within or nearby genes with biologically plausible roles in the pathophysiology of hypertension, including KALRN, VIPR2, SNX1, and DAPK2. Our results suggest that simultaneous consideration of multiple lifestyle exposures in gene-environment interaction analysis can identify additional loci missed by single lifestyle approaches.

Accurate forest projections require long-term wood decay experiments because plant trait effects change through time.

Whether global change will drive changing forests from net carbon (C) sinks to sources relates to how quickly deadwood decomposes. Because complete wood mineralization takes years, most experiments focus on how traits, environments and decomposer communities interact as wood decay begins. Few experiments last long enough to test whether drivers change with decay rates through time, with unknown consequences for scaling short-term results up to long-term forest ecosystem projections. Using a 7 year experiment that captured complete mineralization among 21 temperate tree species, we demonstrate that trait effects fade with advancing decay. However, wood density and vessel diameter, which may influence permeability, control how decay rates change through time. Denser wood loses mass more slowly at first but more quickly with advancing decay, which resolves ambiguity about the after-life consequences of this key plant functional trait by demonstrating that its effect on decay depends on experiment duration and sampling frequency. Only long-term data and a time-varying model yielded accurate predictions of both mass loss in a concurrent experiment and naturally recruited deadwood structure in a 32-year-old forest plot. Given the importance of forests in the carbon cycle, and the pivotal role for wood decay, accurate ecosystem projections are critical and they require experiments that go beyond enumerating potential mechanisms by identifying the temporal scale for their effects.