Genetic associations with dementia-related proteinopathy: Application of item response theory.

INTRODUCTION: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete. METHODS: We applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aß, tau, α-synuclein, and TDP-43. RESULTS: Final included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aß/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility. DISCUSSION: A novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies. HIGHLIGHTS: Latent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Persistent poverty disparities in incidence and outcomes among oral and pharynx cancer patients.

PURPOSE: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty. METHODS: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality. RESULTS: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty. CONCLUSION: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival.

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.

Evaluating ChatGPT's Accuracy in Providing Screening Mammography Recommendations among Older Women: Artificial Intelligence and Cancer Communication.

Abstract Objective: The U.S. Preventive Services Task Force (USPSTF) recommends biennial screening mammography through age 74. Guidelines vary as to whether or not they recommended mammography screening to women aged 75 and older. This study aims to determine the ability of ChatGPT to provide appropriate recommendations for breast cancer screening in patients aged 75 years and older. Methods: 12 questions and 4 clinical vignettes addressing fundamental concepts about breast cancer screening and prevention in patients aged 75 years and older were created and asked to ChatGPT three consecutive times to generate 3 sets of responses. The responses were graded by a multi-disciplinary panel of experts in the intersection of breast cancer screening and aging . The responses were graded as 'appropriate', 'inappropriate', or 'unreliable' based on the reviewer's clinical judgment, content of the response, and whether the content was consistent across the three responses . Appropriateness was determined through a majority consensus. Results: The responses generated by ChatGPT were appropriate for 11/17 questions (64%). Three questions were graded as inappropriate (18%) and 2 questions were graded as unreliable (12%). A consensus was not reached on one question (6%) and was graded as no consensus. Conclusions: While recognizing the limitations of ChatGPT, it has potential to provide accurate health care information and could be utilized by healthcare professionals to assist in providing recommendations for breast cancer screening in patients age 75 years and older. Physician oversight will be necessary, due to the possibility of ChatGPT to provide inappropriate and unreliable responses, and the importance of accuracy in medicine.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Patient-Provider Discussion About Lung Cancer Screening by Race and Ethnicity: Implications for Equitable Uptake of Lung Cancer Screening.

BACKGROUND: Physician-patient discussions regarding lung cancer screening (LCS) are uncommon and its racial and ethnic disparities are under-investigated. We examined the racial and ethnic disparities in the trends and frequency of LCS discussion among the LCS-eligible United States (US) population. METHODS: We analyzed data from the Health Information National Trends Survey from 2014 to 2020. LCS-eligible individuals were defined as adults aged 55 to 80 years old who have a current or former smoking history. We estimated the trends and frequency of LCS discussions and adjusted the probability of having an LCS discussion by racial and ethnic groups. RESULTS: Among 2136 LCS-eligible participants (representing 22.7 million US adults), 12.9% (95% CI, 10.9%-15%) reported discussing LCS with their providers in the past year. The frequency of LCS discussion was lowest among non-Hispanic White participants (12.3%, 95% CI, 9.9%-14.7%) compared to other racial and ethnic groups (14.1% in Hispanic to 15.3% in non-Hispanic Black). A significant increase over time was only observed among non-Hispanic Black participants (10.1% in 2014 to 22.1% in 2020; P = .05) and non-Hispanic Whites (8.5% in 2014 to 14% in 2020; P = .02). In adjusted analyses, non-Hispanic Black participants (14.6%, 95% CI, 12.3%-16.7%) had a significantly higher probability of LCS discussion than non-Hispanic Whites (12.1%, 95% CI, 11.4%-12.7%). CONCLUSION: Patient-provider LCS discussion was uncommon in the LCS-eligible US population. Non-Hispanic Black individuals were more likely to have LCS discussions than other racial and ethnic groups. There is a need for more research to clarify the discordance between LCS discussions and the actual screening uptake in this population.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults.

INTRODUCTION: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1-2 present), or frail (3-4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. RESULTS: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, ß^ = -0.61, 95% CI: -0.83, -0.38 and ß^ = -0.21, 95% CI: -0.30, -0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. DISCUSSION/CONCLUSION: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.

Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Food insecurity is associated with chronic pain and high-impact chronic pain in the USA.

OBJECTIVE: This study evaluated whether food insecurity (US Adult Food Security Survey) was associated with chronic pain (≥ 3 months) and high-impact chronic pain (i.e. pain that limits work and life) among US adults. DESIGN: Cross-sectional analysis. SETTING: Nationally representative sample of non-institutionalised adults in the USA. PARTICIPANTS: 79 686 adults from the National Health Interview Survey (2019-2021). RESULTS: Marginal, low and very low food security were associated with increased prevalence odds of chronic pain (OR: 1·58 (95 % CI 1·44, 1·72), 2·28 (95 % CI 2·06, 2·52) and 3·37 (95 % CI 3·01, 3·78), respectively) and high-impact chronic pain (OR: 1·28 (95 % CI 1·14, 1·42), 1·55 (95 % CI 1·37, 1·75) and 1·90 (95 % CI 1·65, 2·18), respectively) in a dose-response fashion (P-trend < 0·0001 for both), adjusted for sociodemographic, socio-economic and clinically relevant factors. Participation in Supplemental Nutrition Assistance Program (SNAP) and age modified the association between food insecurity and chronic pain. CONCLUSIONS: These findings illustrate the impact of socio-economic factors on chronic pain and suggest that food insecurity may be a social determinant of chronic pain. Further research is needed to better understand the complex relationship between food insecurity and chronic pain and to identify targets for interventions. Moreover, the consideration of food insecurity in the clinical assessment of pain and pain-related conditions among socio-economically disadvantaged adults may be warranted.

Allostatic load and risk of all-cause, cancer-specific, and cardiovascular mortality in older cancer survivors: an analysis of the National Health and Nutrition Examination Survey 1999-2010.

Background: Allostatic load has been linked to an increased risk of death in various populations. However, to date, there is no research specifically investigating the effect of allostatic load on mortality in older cancer survivors. Aims: To investigate the association between allostatic load (AL) and mortality in older cancer survivors. Method: A total of 1,291 adults aged 60 years or older who survived for ≥1 year since cancer diagnoses were identified from the 1999-2010 National Health and Nutrition Examination Survey. AL was the exposure of interest incorporating 9 clinical measures/biomarkers; one point was added to AL if any of the measures/biomarkers exceeded the normal level. The sum of points was categorized as an ordinal variable to reflect low, moderate, and high AL. Our outcomes of interest were all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. Death was identified by linkage to the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (CI) of mortality by AL category. Results: Overall, 53.6% of participants were male and 78.4% were white. The mean age of study participants at interview was 72.8 years (SD=7.1). A total of 546 participants died during the follow-up (median follow-up time: 8.0 years). Among them, 158 died of cancer and 106 died of cardiovascular events. Results from multivariable Cox proportional hazards models showed that higher ALS was positively associated with higher all-cause mortality (ALS=4-9 vs. ALS =0-1: aHR=1.52, 95% CI =1.17-1.98, p-trend<0.01) and higher cancer-specific mortality (ALS=4-9 vs. ALS =0-1: aHR=1.80, 95% CI =1.12-2.90, p-trend=0.01). The association between ALS and cardiovascular mortality was positive but non-significant (ALS=4-9 vs. ALS =0-1: aHR=1.59, 95% CI =0.86-2.94, p-trend=0.11). Conclusions: Our study suggests that older cancer survivors can have a higher risk of death if they have a high burden of AL.

Association of reproductive risk factors and breast cancer molecular subtypes: a systematic review and meta-analysis.

BACKGROUND: Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. METHODS: Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. RESULTS: A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. CONCLUSION: Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Trends and factors associated with secondhand smoke exposure among US cancer survivors, 2013-2020.

BACKGROUND: Secondhand smoke (SHS) poses a significant public health threat. Cancer survivors are at a greater risk of adverse health outcomes from SHS because of its association with poor prognosis and other downstream clinical events. METHODS: A nationally representative sample of US adults aged 20 years and older was analyzed from the National Health and Nutrition Examination Survey between 2013 and 2020. Data on indoor SHS exposure were reported by 16,778 adults who were not currently smoking (1775 cancer survivors; 15,003 individuals without a cancer history). The weighted prevalence of SHS exposure was estimated and compared across sociodemographic and health-related characteristics. Multivariable logistic regression models were fitted to identify correlates of SHS exposure. RESULTS: Of the 1775 nonsmoking cancer survivors (mean age, 64.9 years; 57.0% female; 84.4% non-Hispanic Whites), 15.8% reported SHS exposure. No significant change in trends of SHS exposure was observed during the study period. The prevalence of SHS exposure was higher in cancer survivors who were younger, racial minorities, and had a household income below 130% of the federal poverty level. After adjustment for multiple correlates, age below 40 years, low income, smoking history, and diagnosis within 2 years were associated with SHS exposure. Cancer survivors were most likely to report that SHS exposure occurred at home or in a car. CONCLUSIONS: The prevalence of SHS exposure among cancer survivors remained steady in the past decade. However, disparities exist in SHS exposure among cancer survivors across sociodemographic characteristics and smoking status. Smoking cessation programs should be promoted among caregivers and families of cancer survivors.

Clinician and patient perspectives on screening mammography among women age 75 and older: A pilot study of a novel decision aid.

Objective: Supporting patient-clinician communication is key to implementing tailored, risk-based screening for older adults. Objectives of this multiphase mixed methods study were to identify factors that primary care clinicians consider influential when making screening mammography recommendations for women ≥ 75 years, develop a patient decision aid that incorporates these factors, and gather feasibility and acceptability from the patients' perspective. Methods: Clinicians from a Mid-Atlantic practice network completed online surveys. Women in the same network completed surveys before and after receiving a tailored booklet that included information about the benefits and harms of screening for women ≥ 75 years, a breast cancer risk-estimate, and a question prompt list to support patient-clinician communication. Results: Clinicians (N = 21) were primarily women [57.1%] and practiced family medicine [81.0%]. They cited patients' age ≥ 75 years [95.4%], comorbidity [86.4%], functional status [77.3%], cancer family history [63.6%], U.S. Preventive Services Task Force guidelines [81.8%] and new research [77.3%] as factors influencing their recommendations. Fourteen women completed baseline surveys and received personalized decision aids (Mean age = 79.1 years). Eleven completed the post-intervention survey. All were satisfied with the booklet length, 81.8% found the booklet easy to understand and 72.7% helpful in decision-making Perceived lifetime breast cancer risk decreased significantly from pre- to post-intervention (p = 0.02). Conclusions: Results suggest this decision aid, which incorporates key decisional factors from the clinician's perspective, is feasible and acceptable to patients. Innovation: A tailored decision aid booklet is innovative as it provides information on personalized risk and potential benefits and harms to older women considering screening.

Socioeconomic disparities in immunotherapy use among advanced-stage non-small cell lung cancer patients: analysis of the National Cancer Database.

Socioeconomic and racial disparities exist in access to care among patients with non-small cell lung cancer (NSCLC) in the United States. Immunotherapy is a widely established treatment modality for patients with advanced-stage NSCLC (aNSCLC). We examined associations of area-level socioeconomic status with receipt of immunotherapy for aNSCLC patients by race/ethnicity and cancer facility type (academic and non-academic). We used the National Cancer Database (2015-2016), and included patients aged 40-89 years who were diagnosed with stage III-IV NSCLC. Area-level income was defined as the median household income in the patient's zip code, and area-level education was defined as the proportion of adults aged ≥ 25 years in the patient's zip code without a high school degree. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) using multi-level multivariable logistic regression. Among 100,298 aNSCLC patients, lower area-level education and income were associated with lower odds of immunotherapy treatment (education: aOR 0.71; 95% CI 0.65, 0.76 and income: aOR 0.71; 95% CI 0.66, 0.77). These associations persisted for NH-White patients. However, among NH-Black patients, we only observed an association with lower education (aOR 0.74; 95% CI 0.57, 0.97). Across all cancer facility types, lower education and income were associated with lower immunotherapy receipt among NH-White patients. However, among NH-Black patients, this association only persisted with education for patients treated at non-academic facilities (aOR 0.70; 95% CI 0.49, 0.99). In conclusion, aNSCLC patients residing in areas of lower educational and economic wealth were less likely to receive immunotherapy.

Survival Differences by Comorbidity Burden among Patients with Stage I/II Non-Small-Cell Lung Cancer after Thoracoscopic Resection.

We sought to compare overall survival (OS) by comorbidity burden among patients with stage I/II non-small cell lung cancer (NSCLC) who received thoracoscopic resection. Utilizing data from the National Cancer Database, we conducted a survival analysis among patients aged 50+ with stage I/II NSCLC who received thoracoscopic resection between 2010 and 2017. The comorbidity burden was measured by the Charlson comorbidity index (CCI, 0, 1, 2+). Multivariable Cox proportional hazard models were used to compare overall survival relative to the CCI (CCI of 0 as the referent). Subgroup analyses were conducted considering sex, age groups, days from diagnosis to surgery, facility type, laterality, and type of surgery. For this study, 61,760 patients were included, with a mean age of 69.1 years (SD: 8.5). Notably, 51.2% had a CCI of 0, 31.8% had a CCI of 1, and 17.0% had a CCI of 2+. Most participants were non-Hispanic White (87.5%), and 56.9% were female. We found that an increase in the CCI was associated with a higher risk of all-cause mortality (CCI 1 vs. 0 aHR: 1.24, 95% CI: 1.20-1.28; CCI 2+ vs. 0 aHR: 1.51, 95% CI: 1.45-1.57; p-trend < 0.01). Our subgroup analysis according to sex suggested that the association between CCI and risk of death was stronger in women.

The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.

BACKGROUND: Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. METHODS: Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. RESULTS: 76,095 patients were included in the analysis: 63.2% were <65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups. CONCLUSIONS: NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. IMPACT: The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

Associations of Total Body Fat Mass and Skeletal Muscle Index with All-Cause and Cancer-Specific Mortality in Cancer Survivors.

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06-1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22-1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23-2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39-6.06) compared to White people (aHR = 1.53, 95% CI = 1.19-1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

Low muscle mass is associated with a higher risk of all-cause and cardiovascular disease-specific mortality in cancer survivors.

OBJECTIVES: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. METHODS: We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. RESULTS: The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort. CONCLUSION: Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.

Personalised Lung Cancer Screening (PLuS) study to assess the importance of coexisting chronic conditions to clinical practice and policy: protocol for a multicentre observational study.

INTRODUCTION: Lung cancer is the leading cause of cancer death in the USA and worldwide, and lung cancer screening (LCS) with low-dose CT (LDCT) has the potential to improve lung cancer outcomes. A critical question is whether the ratio of potential benefits to harms found in prior LCS trials applies to an older and potentially sicker population. The Personalised Lung Cancer Screening (PLuS) study will help close this knowledge gap by leveraging real-world data to fully characterise LCS recipients. The principal goal of the PLuS study is to characterise the comorbidity burden of individuals undergoing LCS and quantify the benefits and harms of LCS to enable informed decision-making. METHODS AND ANALYSIS: PLuS is a multicentre observational study designed to assemble an LCS cohort from the electronic health records of ~40 000 individuals undergoing annual LCS with LDCT from 2016 to 2022. Data will be integrated into a unified repository to (1) examine the burden of multimorbidity by race/ethnicity, socioeconomic status and age; (2) quantify potential benefits and harms; and (3) use the observational data with validated simulation models in the Cancer Intervention and Surveillance Modeling Network (CISNET) to provide LCS outcomes in the real-world US population. We will fit a multivariable logistic regression model to estimate the adjusted ORs of comorbidity, functional limitations and impaired pulmonary function adjusted for relevant covariates. We will also estimate the cumulative risk of LCS outcomes using discrete-time survival models. To our knowledge, this is the first study to combine observational data and simulation models to estimate the long-term impact of LCS with LDCT. ETHICS AND DISSEMINATION: The study was approved by the Kaiser Permanente Southern California Institutional Review Board and VA Portland Health Care System. The results will be disseminated through publications and presentations at national and international conferences. Safety considerations include protection of patient confidentiality.