Pathogenic Germline Variants in 10,389 Adult Cancers.

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer.

Implementing Patient-Centered Outcomes Research Institute Stakeholder Engagement Principles in Models of Palliative Care Delivery and Advance Care Planning Research.

BACKGROUND: Given the many challenges of conducting research that addresses the palliative and end-of-life care needs of patients with serious illnesses, stakeholder engagement starting from the moment of study conceptualization and design is critical to ensure successful participant recruitment, data collection, intervention delivery, data analysis, and dissemination. METHODS: Guided by a conceptual model published by the Patient-Centered Outcomes Research Institute (PCORI) entitled, "Measuring What Matters for Advancing the Science and Practice of Engagement"14 and with the support of a PCORI Engagement Officer, representatives from 9 PCORI-funded study teams formed a working group to survey team members and review, outline, and describe key lessons learned and best practices for promoting stakeholder engagement in palliative care research. RESULTS: Almost all study teams engaged with patients/caregivers, clinicians, researchers, and health care system experts as stakeholder partners. About half the teams also included payers and training institutions as part of their stakeholder advisors as well as a range of content experts. Study teams relied on a variety of support structures and resources, and they employed 10 distinct methods for maintaining engagement. All engagement methods were generally considered to be effective by teams who used the method, though there was some variability in team-rated engagement quality of each method. Nine barriers to stakeholder engagement were identified across the 9 studies as well as 9 strategies (or facilitators) to overcome these barriers. We share examples of how stakeholder engagement impacted studies in all phases, including the preparatory phase, study initiation phase, execution phase, and data analysis/dissemination phase. CONCLUSIONS: Teams utilized a variety of resources and support structures as well as capitalized on multiple engagement methods for fostering stakeholder engagement, resulting in a high level of collaboration and integration.

Notes from the Field: Mpox Cluster Caused by Tecovirimat-Resistant Monkeypox Virus - Five States, October 2023-February 2024.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat† (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

Associations between Medicaid enrollment and diagnosis stage and survival among pediatric cancer patients.

BACKGROUND: Medicaid-associated disparities in childhood and adolescent (pediatric) cancer diagnosis stage and survival have been reported. However, a key limitation of prior studies is the assessment of health insurance at a single time point. To evaluate Medicaid-associated disparities more robustly, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid linked data to examine diagnosis stage and survival disparities in those (i) Medicaid-enrolled and (ii) with discontinuous and continuous Medicaid enrollment. METHODS: SEER-Medicaid linked data from 2006 to 2013 were obtained on cases diagnosed from 0 to 19 years. Medicaid enrollment was classified as enrolled versus not enrolled, with further classifications as continuous when enrolled 6 months before through 6 months after diagnosis, and discontinuous when not enrolled continuously for this period. We used multinomial logistic and Cox proportional hazards regression models to determine associations between enrollment measures, diagnosis stage, and cancer death adjusted for covariates. RESULTS: Among 21,502 cases, a higher odds of distant stage diagnoses were observed in association with Medicaid enrollment (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.48-1.65), with the highest odds for discontinuous enrollment (OR = 2.0, 95% CI: 1.86-2.15). Among 30,654 cases, any Medicaid enrollment, continuous enrollment, and discontinuous enrollment were associated with 1.68 (95% CI: 1.35-2.10), 1.66 (95% CI: 1.35-2.05), and 1.89 (95% CI: 1.54-2.33) times higher hazards of cancer death versus no enrollment, respectively. CONCLUSIONS: Medicaid enrollment, particularly discontinuous enrollment, is associated with a higher  distant stage diagnosis odds and risk of death. This study supports the critical need for consistent health insurance coverage in children and adolescents.

Priority areas for outcomes improvement among older adults undergoing inpatient general surgery inclusive of geriatric-pertinent complications.

BACKGROUND: Comprehensive studies on priority areas for improving geriatric surgery outcomes, inclusive of geriatric-pertinent data, are limited. METHODS: The ACS NSQIP geriatric database (2014-2018) was used to abstract older adults (≥65 years) undergoing inpatient general surgery procedures. Thirty-day complication, functional decline, and mortality rates were analyzed, with a focus on two geriatric-pertinent complications: delirium and new/worsening pressure ulcers. RESULTS: There were 9062 patients; 41.9% were ≥75 years. Mean age was 73.9 years. The majority of patients were female (54.0%), White (77.7%), and had independent functional status before surgery (94.0%). Overall 30-day complication, functional decline, and mortality rates were 33.6%, 34.5%, and 3.5%, respectively; failure to the rescue rate was 9.7%. Including geriatric-pertinent complications increased the overall complication rate by 20.4%. Delirium emerged as the leading complication (11.9%), followed by bleeding (11.1%), and wound-related complications (10.1%); these three accounted for 53.7% of complications. Delirium and pressure ulcers were associated with a >50% rate of postoperative functional decline (52.0% and 71.4%, respectively); pressure ulcers were also notable for a 25.5% failure to the rescue rate. Both were also among complications most likely to occur following the 3 most common procedures (colorectal surgery, pancreatic resections, and exploratory laparotomy), which overall accounted for approximately 79.6% of complications, 73.4% of patients experiencing functional decline, and 82.3% of mortality. CONCLUSIONS: Delirium is the leading complication among older adults undergoing inpatient surgery. Overall, a small number of complications and procedure groups account for most surgical morbidity and mortality among older adults and thus constitute priority areas for outcomes improvement.

Impact of environment on pediatric and adult brain tumors: The 2023 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology including surveillance, classification, methodology, etiology, and factors associated with morbidity and mortality. The 2023 annual BTEC meeting entitled "Impact of Environment on Pediatric and Adult Brain Tumors" was held in Lexington, KY, USA on May 22 - 24, 2023. The meeting gathered scientists from the United States, Canada, Australia, and Europe and included four keynote sessions covering genomic, epigenomic, and metabolomic considerations in brain tumor epidemiology, cancer clusters, environmental risk factors, and new approaches to cancer investigation. The meeting also included three abstract sessions and a brainstorming session. A summary of the meeting content is included in this report.

Occurrence and Predictors of Postoperative Preauricular and Masticatory Muscle Pain Symptoms After Surgical Removal of Third Molars: A Single-Blind Randomized Controlled Trial Comparing Dental Assistants Supporting the Mandible and the Restful Jaw Device.

BACKGROUND: During third molar removal, the mandible is supported by a dental assistant (DA) to counter downward forces during surgery, and with sedation, to maintain airway patency. The Restful Jaw device (PEP Design; Saint Paul) provides this support instead of the DA. PURPOSE: This study compared the occurrence of postoperative preauricular and masticatory muscle pain symptoms (PMMPS) between the device and DAs providing mandibular support, using two outcome measures. Secondary aims identify predictors of outcome and providers' opinions of the device. STUDY DESIGN, SETTING, SAMPLE: In this multisite, single-blind, two-arm parallel randomized trial, participants without preoperative PMMPS had surgical removal of third molars, with sedation and bite blocks were randomly assigned to manual support or the device. EXPOSURE VARIABLE: The exposed group was randomly assigned to the device and the nonexposed group to manual support. MAIN OUTCOME VARIABLE(S): The primary outcome was patient-reported PMMPS. Two secondary outcomes were pain assessed with the temporomandibular disorder Pain Screener and providers' views on the device. Outcomes were assessed at 1-, 3-, and 6-month postsurgery. COVARIATES: The covariates are baseline demographics (eg, sex), clinical characteristics (eg, eruption status), and third molar surgeries. ANALYSES: For occurrence of pain, generalized estimating equations assessed differences between groups. Logistic regression analysis assessed predictors of pain at 1 month, per the Screener. The level for statistical significance was 5%. RESULTS: Enrollment was 86 and 83 participants in the device and DA groups, respectively. The average age was 20.8 years; the majority were female (65%) and Caucasian (66%). The retention rate was ≥95.9%. The groups did not differ significantly for occurrence of pain using the primary and secondary outcome measures at any follow-up (P ≥ .46). Fully impacted molars were associated with occurrence of pain (odds ratio = 3.44; 95% confidence interval 1.49-7.92; P = .004). CONCLUSION AND RELEVANCE: Occurrence of pain using the primary and secondary outcome measures did not differ significantly between groups at any follow-up and was associated with removal of fully impacted third molars. Four out of five surgeons reported wanting to use the device on a regular basis when performing this procedure in sedated patients.

Repeated Exposure to COVID-19 Misinformation: A Longitudinal Analysis of Prevalence and Predictors in a Community Sample.

Belief in health misinformation can affect individual health decisions and actions. Repeated exposure to the same misinformation strengthens its impact, yet little is known about how commonly repeated exposure occurs. To estimate the prevalence, we tracked exposure to 5 inaccurate COVID-19 claims every week for up to 23 consecutive weeks in a racially diverse panel of adults (n = 213). Repeated exposure was common: across the 5 claims, 10%-43% of respondents reported hearing the misinformation in ≥ 3 different weeks. Frontline workers were more likely than other community members to experience repeated exposure, with adjusted incidence rate ratios (IRRs) ranging from 1.8 to 4.9 across the 4 items. Repeated exposure was most common among older adults. Adjusted IRR for those ages ≥ 50 versus 18-29 years ranged from 1.8 to 2.5 per misinformation claim. Public health planning efforts to counter health misinformation should anticipate multiple exposures to the same false claim, especially in certain subgroups.

Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms.

OBJECTIVES: While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months. DESIGN: Prospective cohort study. SETTING: Six adult medical and surgical ICUs. PARTICIPANTS: Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0-63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15). CONCLUSIONS: Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.

Health Insurance Coverage and Racial/Ethnic Disparities in US Childhood and Adolescent Cancer Survival.

OBJECTIVE: To evaluate potential effect modification by health insurance coverage on racial and ethnic disparities in cancer survival among US children and adolescents. STUDY DESIGN: Data from 54 558 individuals diagnosed with cancer at ≤ 19 years between 2004 and 2010 were obtained from the National Cancer Database. Cox proportional hazards regression was used for analyses. An interaction term between race/ethnicity and health insurance type was included to examine racial/ethnic disparities in survival by each insurance status category. RESULTS: Racial/ethnic minorities experienced a 14%-42% higher hazard of death compared with non-Hispanic Whites (NHWs) with magnitudes varying by health insurance type (Pinteraction < .001). Specifically, among those reported as privately insured, the hazard of death was higher for non-Hispanic Blacks (NHBs) (hazard ratio [HR] = 1.48, 95% CI: 1.36-1.62), non-Hispanic American Indian/Alaskan Natives (HR = 1.99, 95% CI: 1.36-2.90), non-Hispanic Asians or Pacific Islanders (HR = 1.30, 95% CI: 1.13-1.50), and Hispanics (HR = 1.28, 95% CI: 1.17-1.40) vs NHWs. Racial/ethnic disparities in survival among those reported as covered by Medicaid were present for NHBs (HR = 1.30, 95% CI: 1.19-1.43) but no other racial/ethnic minorities (HR ranges: 0.98∼1.00) vs NHWs. In the uninsured group, the hazard of death for NHBs (HR = 1.68, 95% CI: 1.26-2.23) and Hispanics (HR = 1.27, 95% CI: 1.01-1.61) was higher vs NHWs. CONCLUSIONS: Disparities in survival exist across insurance types, particularly for NHB childhood and adolescent cancer patients vs NHWs with private insurance. These findings provide insights for research and policy, and point to the need for more efforts on promoting health equity while improving health insurance coverage.

Facility patient volume and survival among individuals diagnosed with malignant central nervous system tumors.

PURPOSE: Prior research indicates that the volume of central nervous system (CNS) tumor patients seen by a facility is associated with outcomes. However, most studies have focused on short-term survival and specific CNS tumor subtypes. Our objective was to examine whether facility CNS tumor patient volume is associated with longer-term CNS tumor survival overall and by subtype. METHODS: We obtained National Cancer Database (NCDB) data including individuals diagnosed with CNS tumors from 2004 to 2016. Analyses were stratified by age group (0-14, 15-39, 40-64, and ≥ 65 years) and tumor type. We used Cox Proportional Hazards (PH) regression and restricted mean survival time (RMST) analyses to examine associations between survival and facility patient volume percentile category adjusting for potential confounding factors. RESULTS: Our analytic dataset included data from 130,830 individuals diagnosed with malignant first primary CNS tumors. We found a consistently reduced hazard rate of death across age groups for individuals reported by higher vs. lower (> 95th vs. ≤ 70th percentile) volume facilities (hazard ratio (HR)0-14 = 0.78, 95% confidence interval (CI) 0.64-0.95; HR15-39 = 0.87, 95% CI 0.78-0.96; HR40-64 = 0.82, 95% CI 0.76-0.88; HR≥65 = 0.80, 95% CI 0.75-0.86). Significantly longer survival times within 5 years for higher vs. lower volume facilities were observed ranging from 1.20 months (15-39) to 3.08 months (40-64) higher. Associations varied by CNS tumor subtype for all age groups. CONCLUSIONS: These results suggest facility factors influence CNS tumor survival with longer survival for patients reported by higher volume facilities. Understanding these factors will be critical to developing strategies that eliminate modifiable differences in survival times.

Pediatric cancer patient emergency department visits and disposition by sociodemographic and economic characteristics.

BACKGROUND: Limited research has been conducted on cancer-related emergency department (ED) patterns among pediatric cancer patients, including whether there are differences in the characteristics of individuals who seek ED care for cancer complications. The objectives of this study were to determine whether rates and disposition of cancer-related ED visits and hospital admissions in childhood cancer patients differ by sociodemographic factors. METHODS: A cross-sectional analysis of ED encounters with a cancer diagnosis code among patients aged 0-19 years from the 2019 National Emergency Department Sample (NEDS) was conducted. Weighted logistic regression models were utilized to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a primary cancer-related encounter, and hospital admission overall and by subgroup characteristics. RESULTS: Of the unweighted 6,801,711 ED encounters in children aged 0-19 years, 10,793 were classified as visits by cancer patients. ED encounters of Hispanic versus non-Hispanic White pediatric cancer patients had higher odds of having a cancer-related primary diagnosis (OR = 1.15, 95% CI: 1.04-1.27). ED encounters of non-Hispanic Black pediatric patients and those in the lowest zip code income quartile had higher odds of hospital admission (OR = 1.28, 95% CI: 1.08-1.53; OR = 1.30, 95% CI: 1.15-1.46), while rurality was associated with lower odds of hospital admission (OR = 0.69, 95% CI: 0.57-0.83). CONCLUSION: These results suggest that pediatric cancer patients from certain under-resourced communities are more likely to use the ED for cancer treatment complications, and their encounters are more likely to result in admission to the hospital.

Pediatric brain tumors: Origins, epidemiology, and classification - The 2022 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization that fosters collaboration among scientists focused on understanding the epidemiology of brain tumors with interests ranging from the etiology of brain tumor development and outcomes to the control of morbidity and mortality. The 2022 annual BTEC meeting with the theme "Pediatric Brain Tumors: Origins, Epidemiology, and Classification" was held in Lyon, France on June 20 - 22, 2022. Scientists from North America and Europe presented recent research and progress in the field. The meeting content is summarized in this report.

Normalization of Prevention Principles and Practices to Reduce Substance Use Disorders Through an Integrated Dissemination and Implementation Framework.

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization."

Acceptability of a Serious Illness Conversation Guide to Black Americans: Results from a focus group and oncology pilot study.

OBJECTIVES: Serious illness conversations (SICs) can improve the experience and well-being of patients with advanced cancer. A structured Serious Illness Conversation Guide (SICG) has been shown to improve oncology patient outcomes but was developed and tested in a predominantly White population. To help address disparities in advanced cancer care, we aimed to assess the acceptability of the SICG among African Americans with advanced cancer and their clinicians. METHODS: A two-phase study conducted in Charleston, SC, included focus groups to gather perspectives on the SICG in Black Americans and a single-arm pilot study of a revised SICG with surveys and qualitative exit interviews to evaluate patient and clinician perspectives. We used descriptive analysis of survey results and thematic analysis of qualitative data. RESULTS: Community-based and patient focus group participants (N = 20) reported that a simulated conversation using an adapted SICG built connection, promoted control, and fostered consideration of religious faith and family. Black patients with advanced cancer (N = 23) reported that SICG-guided conversations were acceptable, helpful, and promoted conversations with loved ones. Oncologists found conversations feasible to implement and skill-building, and also identified opportunities for training and implementation that could support meeting the needs of their patients with low health literacy. An adapted SICG includes language to assess the strength and affirm the clinician-patient relationship. SIGNIFICANCE OF RESULTS: An adapted structured communication tool to facilitate SIC, the SICG, appears acceptable to Black Americans with advanced cancer and seems feasible for use by oncology clinicians working with this population. Further testing in other marginalized populations may address disparities in advanced cancer care.

Advancing Equity in Cancer Research: Opportunities for Sponsors, Institutions, and Investigators.

Numerous studies have documented patient-level barriers to research participation that are often connected to social determinants of health. As described in this paper, to significantly move the needle toward greater diversity and inclusion in cancer research, it will take a full commitment to integrating an equity lens across the cancer research ecosystem, specifically among sponsors, institutions, and investigators.

The impact of health insurance coverage on racial/ethnic disparities in US childhood and adolescent cancer stage at diagnosis.

BACKGROUND: Racial/ethnic minority children and adolescents are more likely to have an advanced cancer diagnosis compared with non-Hispanic Whites, which may relate to the lack of consistent health care access. This study aims to describe racial/ethnic disparities in cancer diagnosis stage among children and adolescents and assess whether health insurance mediates these disparities. METHODS: Data on individuals ≤19 years of age diagnosed with primary cancers from 2007 to 2016 were obtained from the Surveillance, Epidemiology, and End Results 18 database. Prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between race/ethnicity and cancer diagnosis stage were calculated using Poisson regression. Analyses addressing health insurance as a potential mediator were also performed. RESULTS: Compared with non-Hispanic Whites, racial/ethnic minorities had a higher prevalence of a distant cancer diagnosis, with PRs of 1.31 (95% CI, 1.23-1.40) for non-Hispanic Blacks, 1.14 (95% CI, 1.04-1.24) for non-Hispanic Asian/Pacific Islanders, and 1.15 (95% CI, 1.09-1.21) for Hispanics. These associations were attenuated when adjusting for health insurance, with PRs of 1.24 (95% CI, 1.16-1.33) for non-Hispanic Blacks, 1.11 (95% CI, 1.02-1.21) for non-Hispanic Asian/Pacific Islanders, and 1.07 (95% CI, 1.01-1.13) for Hispanics. Any Medicaid or no insurance at diagnosis mediated 49%, 22%, and 9% of the observed association with distant stage in Hispanics, non-Hispanic Blacks, and non-Hispanic Asian/Pacific Islanders, respectively. CONCLUSIONS: Disparities in cancer diagnosis stage in racial/ethnic minority children and adolescents may be partially explained by health insurance coverage. Further research is needed to understand the mechanisms.

Risk of suicide among individuals with a history of childhood cancer.

BACKGROUND: Previous studies have described suicidal ideation among survivors of childhood cancer, but small numbers of events limit the understanding of suicide risk. The objectives of this study were to assess whether childhood cancer survivors are at increased risk of suicide in comparison with the general population and to determine risk factors associated with risk in a population-based cohort. METHODS: First primary malignancies among individuals aged 0 to 19 years from 1975 to 2016 were identified from Surveillance, Epidemiology, and End Results (SEER) databases. Standardized mortality ratios (SMRs) of suicide were obtained via SEER*Stat software from SEER 9. Fine and Gray proportional hazards models were used to identify suicide-associated factors among childhood cancer patients included in SEER 18. RESULTS: In all, 96,948 childhood cancer cases and 89 suicides were identified. Across all attained ages, the suicide risk for individuals with a childhood cancer history (11.64 per 100,000 person-years) was similar to the risk for those without a cancer history (SMR, 1.14; 95% confidence interval [CI], 0.91-1.43). However, for survivors alive beyond the age of 28 years (the median age of death by suicide), the suicide risk was significantly elevated (suicides per 100,000 person-years, 22.43; SMR, 1.40; 95% CI, 1.02-1.87). Females (hazard ratio, 0.29; 95% CI, 0.18-0.59; P < .01) had lower risks than males. CONCLUSIONS: These results suggest that long-term childhood cancer survivors may be at increased suicide risk. Male sex is an independent risk factor for suicide. However, the absolute risk of suicide in older survivors is still low at ~1 per 5000 person-years. Future efforts should identify survivorship strategies to mitigate suicide risk.

The prevalence of onchocerciasis in Africa and Yemen, 2000-2018: a geospatial analysis.

BACKGROUND: Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission. METHODS: A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions. RESULTS: As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan. CONCLUSIONS: Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.

Polypharmacy in Palliative Care for Advanced Heart Failure: The PAL-HF Experience.

BACKGROUND: Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown. METHODS AND RESULTS: We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial of standard care vs interdisciplinary PC in advanced HF (N = 150). We describe differences in medication counts between arms at 2, 6, 12, and 24 weeks for HF (12 classes) and PC (6 classes) medications. General linear mixed models were used to evaluate associations between treatment arm and polypharmacy over time. The median age of the patients was 72 years (interquartile range 62-80 years), 47% were female, and 41% were Black. Overall, 48% had ischemic etiology, and 55% had an ejection fraction of 40% or less. Polypharmacy was present at baseline in 100% of patients. HF and PC medication counts increased in both arms, with no significant differences in counts by drug class at any time point between arms. CONCLUSIONS: In a trial of patients with advanced HF considered eligible for PC, polypharmacy was universal at baseline and increased during follow-up with no effect of the palliative intervention on medication counts relative to standard care.