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.

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.

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.

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.

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.

Effects of life history and reproduction on recruitment time lags in reintroductions of rare plants.

Reintroductions are important components of conservation and recovery programs for rare plant species, but their long-term success rates are poorly understood. Previous reviews of plant reintroductions focused on short-term (e.g., ≤3 years) survival and flowering of founder individuals rather than on benchmarks of intergenerational persistence, such as seedling recruitment. However, short-term metrics may obscure outcomes because the unique demographic properties of reintroductions, including small size and unstable stage structure, could create lags in population growth. We used time-to-event analysis on a database of unusually well-monitored and long-term (4-28 years) reintroductions of 27 rare plant species to test whether life-history traits and population characteristics of reintroductions create time-lagged responses in seedling recruitment (i.e., recruitment time lags [RTLs]), an important benchmark of success and indicator of persistence in reintroduced populations. Recruitment time lags were highly variable among reintroductions, ranging from <1 to 17 years after installation. Recruitment patterns matched predictions from life-history theory with short-lived species (fast species) exhibiting consistently shorter and less variable RTLs than long-lived species (slow species). Long RTLs occurred in long-lived herbs, especially in grasslands, whereas short RTLs occurred in short-lived subtropical woody plants and annual herbs. Across plant life histories, as reproductive adult abundance increased, RTLs decreased. Highly variable RTLs were observed in species with multiple reintroduction events, suggesting local processes are just as important as life-history strategy in determining reintroduction outcomes. Time lags in restoration outcomes highlight the need to scale success benchmarks in reintroduction monitoring programs with plant life-history strategies and the unique demographic properties of restored populations. Drawing conclusions on the long-term success of plant reintroduction programs is premature given that demographic processes in species with slow life-histories take decades to unfold.

Efectos de la Historia de Vida y la Reproducción sobre las Demoras en el Tiempo de Reclutamiento en la Reintroducción de Plantas Raras Resumen Las reintroducciones son componentes importantes de los programas de conservación y recuperación de especies raras de plantas, pero las tasas de éxito a largo plazo cuentan con muy poco entendimiento. Las revisiones previas de las reintroducciones de plantas se han enfocado en la supervivencia a corto plazo (p. ej.: ≤ 3 años) y en el florecimiento de individuos fundadores en lugar de enfocarse en puntos de referencia para la persistencia inter-generacional, como el reclutamiento de plántulas. Sin embargo, las medidas a corto plazo pueden ocultar los resultados ya que las propiedades demográficas únicas de las reintroducciones, incluyendo el menor tamaño y la estructura inestable de estadio, podrían crear demoras en el crecimiento poblacional. Usamos un análisis de tiempo-para-evento en una base de datos de reintroducciones inusualmente bien monitoreadas y de largo plazo (4-28 años) de 27 especies raras de plantas para probar si los atributos de la historia de vida y las características poblacionales de la reintroducción crean respuestas con demoras temporales en el reclutamiento de plántulas (es decir, demoras temporales en el reclutamiento), un punto de referencia importante para el éxito y un indicador de la persistencia en poblaciones reintroducidas. Las demoras temporales de reclutamiento (RTLs, en inglés) fueron muy variables entre las reintroducciones, abarcando desde <1 hasta 17 años después de la instalación. Los patrones de reclutamiento se acoplaron a las predicciones de la teoría de historias de vida, donde las especies de vida corta (especies rápidas) exhibieron RTLs consistentemente más cortas y menos variables que las especies de vida larga (especies lentas). Las RTLs largas ocurrieron en hierbas de vida larga, especialmente en los pastizales, mientras que las RTLs cortas ocurrieron en plantas leñosas subtropicales de vida corta y en hierbas anuales. En todas las historias de vida de las plantas, conforme incrementó la abundancia de adultos reproductivos, las RTLs disminuyeron. Se observaron RTLs altamente variables en las especies con eventos de reintroducción múltiples, lo que sugiere que los procesos locales son igual de importantes que la estrategia de historia de vida para determinar los resultados de las reintroducciones. Las demoras temporales en los resultados de restauración resaltan la necesidad de poner a escala los puntos de referencia de éxito en los programas de monitoreo de reintroducciones que tengan estrategias de historia de vida de las plantas y las propiedades demográficas únicas de las poblaciones restauradas. La obtención de conclusiones sobre el éxito a largo plazo de los programas de reintroducción de plantas es algo prematuro ya que los procesos demográficos de especies con historias de vida lentas tardan décadas en desarrollarse.

The Promise of Selecting Individuals from the Extremes of Exposure in the Analysis of Gene-Physical Activity Interactions.

BACKGROUND: Dichotomization using the lower quartile as cutoff is commonly used for harmonizing heterogeneous physical activity (PA) measures across studies. However, this may create misclassification and hinder discovery of new loci. OBJECTIVES: This study aimed to evaluate the performance of selecting individuals from the extremes of the exposure (SIEE) as an alternative approach to reduce such misclassification. METHOD: For systolic and diastolic blood pressure in the Framingham Heart Study, we performed a genome-wide association study with gene-PA interaction analysis using three PA variables derived by SIEE and two other dichotomization approaches. We compared number of loci detected and overlap with loci found using a quantitative PA variable. In addition, we performed simulation studies to assess bias, false discovery rates (FDR), and power under synergistic/antagonistic genetic effects in exposure groups and in the presence/absence of measurement error. RESULTS: In the empirical analysis, SIEE's performance was neither the best nor the worst. In most simulation scenarios, SIEE was consistently outperformed in terms of FDR and power. Particularly, in a scenario characterized by antagonistic effects and measurement error, SIEE had the least bias and highest power. CONCLUSION: SIEE's promise appears limited to detecting loci with antagonistic effects. Further studies are needed to evaluate SIEE's full advantage.

Linking wood traits to vital rates in tropical rainforest trees: Insights from comparing sapling and adult wood.

PREMISE OF THE STUDY: Wood density is the top predictor of growth and mortality rates (vital rates) but with modest explanatory power at best. Stronger links to vital rates are expected if wood density is decomposed into its anatomical properties at sapling and adult stages, since saplings and adults differ in wood traits and vital rates. We examined whether anatomical determinants of wood density and strength of the relationship between wood traits and vital rates shift between saplings and adults. METHODS: Using wood segments from near pith (sapling) and near bark (adult) for 20 tree species (three adults each) from Barro Colorado Island, Panama, we quantified wood traits. Vital rates for saplings and adults were obtained from an earlier study. KEY RESULTS: Anatomical predictors of wood density were similar for sapling and adult wood, with wood density variation largely explained by fiber lumen area and fiber wall fraction. In sapling wood only, growth rates decreased with fiber wall fraction and increased with fiber lumen area, while mortality rates increased with vessel area but decreased with fiber wall fraction and vessel density. CONCLUSIONS: Wood traits of sapling trees provide functional insight into the growth-mortality tradeoff. Sapling wood with relatively large fiber lumen area and wide vessels, enabling faster hydraulic transport but less mechanical strength, is associated with fast growth and high mortality. Sapling wood with relatively more fiber wall and many narrow vessels, enabling greater mechanical strength but slower hydraulic transport, is associated with slow growth and low mortality.

Selective logging: do rates of forest turnover in stems, species composition and functional traits decrease with time since disturbance? - A 45 year perspective.

Selective logging, the targeted harvesting of timber trees in a single cutting cycle, is globally rising in extent and intensity. Short-term impacts of selective logging on tropical forests have been widely investigated, but long-term effects on temporal dynamics of forest structure and composition are largely unknown. Understanding these long-term dynamics will help determine whether tropical forests are resilient to selective logging and inform choices between competing demands of anthropogenic use versus conservation of tropical forests. Forest dynamics can be studied within the framework of succession theory, which predicts that temporal turnover rates should decline with time since disturbance. Here, we investigated the temporal dynamics of a tropical forest in Kibale National Park, Uganda over 45 years following selective logging. We estimated turnover rates in stems, species composition, and functional traits (wood density and diameter at breast height), using observations from four censuses in 1989, 1999, 2006, and 2013, of stems ≥ 10 cm diameter within 17 unlogged and 9 logged 200 × 10 m vegetation plots. We used null models to account for interdependencies among turnover rates in stems, species composition, and functional traits. We tested predictions that turnover rates should be higher and decrease with increasing time since the selective logging event in logged forest, but should be less temporally variable in unlogged forest. Overall, we found higher turnover rates in logged forest for all three attributes, but turnover rates did not decline through time in logged forest and was not less temporally variable in unlogged forest. These results indicate that successional models that assume recovery to pre-disturbance conditions are inadequate for predicting the effects of selective logging on the dynamics of the tropical forest in Kibale. Selective logging resulted in persistently higher turnover rates, which may compromise the carbon storage capacity of Kibale's forest. Selective logging effects may also interact with effects from other global trends, potentially causing major long-term shifts in the dynamics of tropical forests. Similar studies in tropical forests elsewhere will help determine the generality of these conclusions. Ultimately, the view that selective logging is a benign approach to the management of tropical forests should be reconsidered in the light of studies of the effects of this practice on long-term forest dynamics.

Radial variation in wood specific gravity of tropical tree species differing in growth-mortality strategies.

UNLABELLED: • PREMISE OF THE STUDY: Wood specific gravity (WSG) mediates an interspecific trade-off between growth and mortality and is a key measure for estimating carbon stocks. Most studies use species mean values to represent WSG, despite variation at different levels of biological organization. We examined sources of variation in WSG across four nested scales (segments within cores, cores within trees, trees within species, and species), compared the pattern of radial variation in WSG among species differing in growth strategies, and investigated the effect of WSG radial variation on aboveground biomass estimates.• METHODS: We took two perpendicular cores from six individuals each of 20 tropical tree species representing a broad range of mean WSGs and growth-mortality strategies in a lowland tropical moist forest in Panama. Cores were divided into 1-cm segments, and WSG was determined for each segment.• KEY RESULTS: The bulk of the total variance in WSG was dominated by interspecies variation (88%), whereas variation due to measurement error, segments within cores, and cores within trees (8%) was minimal. Radial variation in WSG, defined as change in WSG with increasing distance from the pith, was significant in 17 of the 20 species and included significant monotonic increases in 6 species and nonmonotonic patterns in 11 species. Radial variation in WSG resulted in a small but significant bias in aboveground biomass estimates.• CONCLUSIONS: Radial variation in WSG is related to a species' growth strategy and, though minimal compared with interspecific variation in WSG, can cause a downward bias when not incorporated into aboveground biomass estimates.

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.

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.

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.

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.

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.

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.

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.

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.