Trends in use of intensive care during hospitalizations at the end-of-life among older adults with advanced cancer.

BACKGROUND: High-intensity end-of-life (EOL) care, marked by admission to intensive care units (ICUs) or in-hospital death, can be costly and burdensome. Recent trends in use of ICUs, life-sustaining treatments (LSTs), and noninvasive ventilation (NIV) during EOL hospitalizations among older adults with advanced cancer and patterns of in-hospital death are unknown. METHODS: We used SEER-Medicare data (2003-2017) to identify beneficiaries with advanced solid cancer (summary stage 7) who died within 3 years of diagnosis. We identified EOL hospitalizations (within 30 days of death), classifying them by increasing intensity of care into: (1) without ICU; (2) with ICU but without LST (invasive mechanical ventilation, tracheostomy, gastrostomy, acute dialysis) or NIV; (3) with ICU and NIV but without LST; and (4) with ICU and LST use. We constructed a multinomial regression model to evaluate trends in risk-adjusted hospitalization, overall and across hospitalization categories, adjusting for sociodemographics, cancer characteristics, comorbidities, and frailty. We evaluated trends in in-hospital death across categories. RESULTS: Of 226,263 Medicare beneficiaries with advanced cancer, 138,305 (61.1%) were hospitalized at EOL [Age, Mean (SD):77.9(7.1) years; 45.5% female]. Overall, EOL hospitalizations remained high throughout, from 78.1% (95% CI: 77.4, 78.7) in 2004 to 75.5% (95% CI: 74.5, 76.2) in 2017. Hospitalizations without ICU use decreased from 49.3% (95% CI: 48.5, 50.2) to 35.0% (95% CI: 34.2, 35.9) while hospitalizations with more intensive care increased, from 23.7% (95% CI: 23.0, 24.4) to 28.7% (95% CI: 27.9, 29.5) for ICU without LST or NIV, 0.8% (95% CI: 0.6, 0.9) to 3.8% (95% CI: 3.4, 4.1) for ICU with NIV but without LST, and 4.3% (95% CI: 4.0, 4.7) to 8.0% (95% CI: 7.5, 8.5) for ICU with LST use. Among those who experienced in-hospital death, the proportion receiving ICU care increased from 46.5% to 65.0%. CONCLUSIONS: Among older adults with advanced cancer, EOL hospitalization rates remained stable from 2004-2017. However, intensity of care during EOL hospitalizations increased as evidenced by increasing use of ICUs, LSTs, and NIV.

Costs of care during chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas.

High upfront cost may be a barrier to adopting chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory B-cell lymphoma. Data on the real-world costs are limited. Using the Blue Cross Blue Shield Axis database, we evaluated 271 commercially insured patients who received CAR-T therapy for B-cell lymphoma (median age = 58 years; men = 68%; diffuse large B-cell lymphoma = 87%; inpatient CAR-T therapy = 85%). Our peri-CAR-T period of interest was from 41 days before to 154 days after CAR-T therapy index divided into seven 28-day intervals. Median total costs were $608 100 (interquartile range, IQR = $534 100-$732 800); 8.5% of patients had total costs exceeding $1 million. The median cost of CAR-T therapy products was $402 500, and the median out-of-pocket copayment was $510. Monthly costs were highest during the month of CAR-T therapy administration (median = $521 500), with median costs below $25 000 in all other 28-day intervals. Costs of CAR-T therapy use were substantial, largely driven by product acquisition. Future studies should examine the relationship between costs, access, and financial outcomes.

Associations Between Prostate Magnetic Resonance Imaging, Genomic Testing, and Treatment for Localized Prostate Cancer.

INTRODUCTION: Although prostate MRI and tissue-based gene expression (genomic) tests improve staging and estimates of prostate cancer prognosis, their association with the intensity of treatment patients receive is not well understood. METHODS: We performed a retrospective cohort study of Medicare beneficiaries diagnosed with clinically localized prostate cancer in 2013 through 2017 in the Surveillance, Epidemiology, and End Results database. The primary study outcome was the receipt of treatment intensification in the first 12 months after diagnosis (defined as the addition of androgen deprivation therapy among patients receiving radiation or pelvic lymphadenectomy among those undergoing radical prostatectomy). We assessed associations between the receipt of prostate MRI and genomic testing and treatment intensification, adjusting for clinical and sociodemographic factors and further stratifying the analyses by risk status. RESULTS: We identified 37,064 patients with clinically localized prostate cancer, including 6,398, 22,011, and 5976 with low, intermediate, and high D'Amico-risk disease, respectively. Among all treated patients, receipt of prostate MRI was associated with increased odds of treatment intensification (odds ratio 1.76, 95% CI 1.65-1.88, P < .001). In contrast, genomic testing was not significantly associated. Among treated patients with high-risk disease, genomic testing was associated with decreased odds of intensified treatment (odds ratio 0.59, 95% CI 0.35-1.00, P = .05). CONCLUSIONS: Prostate MRI was associated with intensified treatment across risk strata, while genomic testing was associated with lower intensity of treatment among high-risk disease. Additional study is needed to determine whether use of imaging and risk stratification tools leads to improved long-term patient outcomes.

Cost trends of Metastatic Renal Cell Carcinoma Therapy: the impact of oral anticancer agents and immunotherapy.

BACKGROUND: Immunotherapy (IO) and oral anticancer agents (OAA) have improved outcomes for metastatic renal cell carcinoma (mRCC) but there is a need to understand real-world costs from the perspective of payers and patients. METHODS: We used retrospective fee-for-service Medicare 100% claims data to study patients diagnosed with mRCC in 2015-2019. We identified initial treatment type and costs (the year after diagnosis) and analyzed differences in monthly and 12-month costs over time and between OAA, IO, and combination groups and the association between OOP costs and adherence. RESULTS: We identified 15,407 patients with mRCC (61% male; 85% non-Hispanic white). 6,196 received OAA, IO or combination OAA/IO as initial treatment. OAA use decreased (from 31% to 11%) with a simultaneous rise in patients receiving IO (3% to 26%) or combination IO/OAA therapy (1% to 11%). Medicare payments for all patients with mRCC increased by 41%, from $60,320 (95% CI: 58,260-62,380) in 2015 to $85,130 (95% CI: 82,630-87,630) in 2019. Payments increased in patients who received OAA, IO or combination OAA/IO but were stable in those with other/no treatment. Initial higher OOP responsibility ($200-$1000) was associated with 13% decrease in percent days covered in patients receiving OAA in the first 90 days of treatment, compared to those whose OOP responsibility was <$200. CONCLUSION: From 2015-2019, costs for Medicare patients with mRCC rose substantially due to more patients receiving IO or IO/OAA combined therapy and increases in costs among those receiving those therapies. Increased OOP costs was associated with decreased adherence.

Expanding Genetic Counselor Roles: A Model for Global Research Development.

PURPOSE: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs' evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities. METHODS: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children's Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position. Data were organized using the "My Bibliography" tool on the National Center for Biotechnology Information website and a Research Electronic Data Capture database created to initially collect manuscripts published through 30 June 2020. A subsequent survey captured publications through 5 February 2024. RESULTS: An amount of 52 of 120 (43%) GCs shared their curriculum vitae/papers. 992 unique publications were identified from 1986 to 2024. Since 2013, no less than 32 papers were published annually by Section members and no less than 10 GCs contributed to publications yearly. Impact factors typically averaged >5.0 per year. Areas of foci diversified considerably since 2015. CONCLUSIONS: Here, we establish that GCs indeed contribute to scholarly work as evidenced by the number of publications alone. The establishment of an academic home may have contributed, given publications increased concurrent to launching the Section, providing a model for organizing GCs at institutions nationally and internationally. Highlighting such achievements will foster the expansion of GC roles in the era of precision genomic medicine and therapy. Considering ways to support GCs towards expanding these activities is equally important.

Adolescent Sexuality.

Adolescence is a unique time where there are many developmental changes occurring. Teenagers are striving to establish their personal identity as they are also developing a better understanding of their gender and sexual identity while navigating social expectations both in person and online. Therefore, clinicians must continue to support adolescent patients and their families by providing accurate and timely information so that they can have the tools they need to avoid the pitfalls of an uninformed adolescent experience.

Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma.

Importance: Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. Objective: To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Exposures: Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). Main Outcomes and Measures: The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. Results: The sample included 15 407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12 966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. Conclusions and Relevance: In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.

Optimizing Vaccine Trials for Enteric Diseases: The Enterics for Global Health (EFGH) Shigella Surveillance Study.

In this introductory article, we describe the rationale for the Enterics for Global Health (EFGH) Shigella surveillance study, which is largely to optimize the design and implementation of pivotal Shigella vaccine trials in the target population of infants and young children living in low- and middle-income countries. Such optimization will ideally lead to a shorter time to vaccine availability in the target population. We also provide a brief description of the articles included in the supplement.

Uptake of Genetic Research Results and Patient-Reported Outcomes With Return of Results Incorporating Web-Based Predisclosure Education.

PURPOSE: We developed a web-based education intervention as an alternative to predisclosure education with a genetic counselor (GC) to reduce participant burden and provider costs with return of genetic research results. METHODS: Women at three sites who participated in 11 gene discovery research studies were contacted to consider receiving cancer genetic research results. Participants could complete predisclosure education through web education or with a GC. Outcomes included uptake of research results, factors associated with uptake, and patient-reported outcomes. RESULTS: Of 819 participants, 178 actively (21.7%) and 167 passively (20.4%) declined return of results; 474 (57.9%) were enrolled. Most (60.3%) received results although this was lower than the 70% uptake we hypothesized. Passive and active decliners were more likely to be Black, to have less education, and to have not received phone follow-up after the invitation letter. Most participants selected web education (88.5%) as an alternative to speaking with a GC, but some did not complete or receive results. Knowledge increased significantly from baseline to other time points with no significant differences between those who received web versus GC education. There were no significant increases in distress between web and GC education. CONCLUSION: Interest in web-based predisclosure education for return of genetic research results was high although it did not increase uptake of results. We found no negative patient-reported outcomes with web education, suggesting that it is a viable alternative delivery model for reducing burdens and costs of returning genetic research results. Attention to attrition and lower uptake of results among Black participants and those with less formal education are important areas for future research.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age. DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. PATIENTS: Women 70 years and older who had been recently screened. MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. PRIMARY FUNDING SOURCE: National Cancer Institute.

Development of an Electronic Health Record-Based Clinical Decision Support Tool for Patients With Lynch Syndrome.

PURPOSE: To develop an electronic health record (EHR)-based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS: Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION: We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS.

Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This commentary provides recommendations for cancer surveillance, risk-reducing strategies, and genetic counseling considerations for TGD patients with LS.

Taking on Typhoid: Eliminating Typhoid Fever as a Global Health Problem.

Typhoid fever is a significant global health problem that impacts people living in areas without access to clean water and sanitation. However, collaborative international partnerships and new research have improved both knowledge of the burden in countries with endemic disease and the tools for improved surveillance, including environmental surveillance. Two typhoid conjugate vaccines (TCVs) have achieved World Health Organization prequalification, with several more in the development pipeline. Despite hurdles posed by the coronavirus disease 2019 pandemic, multiple TCV efficacy trials have been conducted in high-burden countries, and data indicate that TCVs provide a high degree of protection from typhoid fever, are safe to use in young children, provide lasting protection, and have the potential to combat typhoid antimicrobial resistance. Now is the time to double down on typhoid control and elimination by sustaining progress made through water, sanitation, and hygiene improvements and accelerating TCV introduction in high-burden locations.

Disparities in immune and targeted therapy utilization for older US patients with metastatic renal cell carcinoma.

Disparities in metastatic renal cell carcinoma (mRCC) outcomes persist in the era of oral anticancer agents (OAAs) and immunotherapies (IOs). We examined variation in the utilization of mRCC systemic therapies among US Medicare beneficiaries from 2015 to 2019. Logistic regression models evaluated the association between therapy receipt and demographic covariates including patient race, ethnicity, and sex. In total, 15 407 patients met study criteria. After multivariable adjustment, non-Hispanic Black race and ethnicity was associated with reduced IO (adjusted relative risk ratio [aRRR] = 0.76, 95% confidence interval [CI] = 0.61 to 0.95; P = .015) and OAA receipt (aRRR = 0.76, 95% CI = 0.64 to 0.90; P = .002) compared with non-Hispanic White race and ethnicity. Female sex was associated with reduced IO (aRRR = 0.73, 95% CI = 0.66 to 0.81; P < .001) and OAA receipt (aRRR = 0.74, 95% CI = 0.68 to 0.81; P < .001) compared with male sex. Thus, disparities by race, ethnicity, and sex were observed in mRCC systemic therapy utilization for Medicare beneficiaries from 2015 to 2019.

Impact of the COVID-19 pandemic on obstetrical care at a tertiary care facility in Mombasa, Kenya: Time-series analyses and staff perspectives.

The COVID-19 pandemic caused disruption in healthcare delivery due to reductions in both health facility capacity and care-seeking behavior. For women experiencing obstetric complications, access to comprehensive emergency obstetric care is critical for maternal and child health. In Kenya, pandemic-related restrictions began in March 2020 and were compounded by a healthcare worker strike in December 2020. We examined medical record data at Coast General Teaching and Referral Hospital, a large public hospital, and conducted staff interviews to understand how healthcare disruptions impacted care delivery and perinatal outcomes. Routinely collected data from all mother-baby dyads admitted to the Labor and Delivery Ward from January 2019 through March 2021 were included in interrupted time-series analyses. Outcomes included number of admissions and proportion of deliveries that resulted in caesarean sections and adverse birth outcomes. Interviews were conducted with nurses and medical officers to understand how the pandemic impacted clinical care. Pre-pandemic, the ward averaged 810 admissions/month, compared to 492 admissions/month post-pandemic (average monthly decrease: 24.9 admissions; 95% CI: -48.0, -1.8). The proportion of stillbirths increased 0.3% per month during the pandemic compared to the pre-pandemic period (95% CI: 0.1, 0.4). No significant differences were seen in the proportion of other adverse obstetrical outcomes. Interview results suggested that pandemic-related disruptions included reduced access to surgical theaters and protective equipment, and absence of COVID-19 guidelines. While these disruptions were perceived as impacting care for high-risk pregnancies, providers believed that overall quality of care did not diminish during the pandemic. However, they expressed concern about a likely increase in at-home births. In conclusion, while the pandemic had minimal adverse impact on hospital-based obstetrical outcomes, it reduced the number of patients able to access care. Emergency preparedness guidelines and public health messaging promoting timely obstetrical care are needed to ensure continuation of services during future healthcare disruptions.

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials.

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.

Genetic testing in privately insured women with surgically treated breast cancer.

PURPOSE: Rates of BRCA1 and BRCA2 prevalence among women with breast cancer vary by age, hormone receptor status, and family history. Recommendations for genetic testing have varied between overlapping guidelines, payor coverage policies, and have evolved over time, resulting in unclear implications for adoption into routine breast cancer care. METHODS: Using a large, private insurer database, we examined rates of BRCA1/BRCA2 genetic testing in women with newly diagnosed invasive breast cancer undergoing surgery from 2015 through 2019. RESULTS: Testing increased among women 50 years or older from 26 to 38%, remained stable at 66% in both 2015 and 2019 in the under 50 population, and was slightly decreased in women under age 45 years. CONCLUSION: Among privately insured patients with breast cancer, rates are increasing in older women, but appear persistently underused in younger women.