Three-Year Outcomes of 6-Month Paliperidone Palmitate in Adults With Schizophrenia: An Open-Label Extension Study of a Randomized Clinical Trial.

Importance: Long-acting injectable (LAI) antipsychotics have the potential to improve adherence and symptom control in patients with schizophrenia, promoting long-term recovery. Paliperidone palmitate (PP) once every 6 months is the first and currently only LAI antipsychotic with an extended dosing interval of 6 months. Objective: To assess long-term outcomes of PP received once every 6 months in adults with schizophrenia. Design, Setting, and Participants: In a 2-year open-label extension (OLE) study of a 1-year randomized clinical trial (RCT), eligible adults with schizophrenia could choose to continue PP every 6 months if they had not experienced relapse after receiving PP once every 3 or 6 months in the 1-year, international, multicenter, double-blind, randomized noninferiority trial. The present analysis focused on patients receiving PP every 6 months in the double-blind trial through the OLE study (November 20, 2017, to May 3, 2022). Intervention: Patients received a dorsogluteal injection of PP on day 1 and once every 6 months up to month 30. Main Outcomes and Measures: End points included assessment of relapse and change from the double-blind trial baseline to the OLE end point in Positive and Negative Syndrome Scale (PANSS) total and subscale, Clinical Global Impression-Severity (CGI-S) Scale, and Personal Social Performance (PSP) Scale scores. Treatment-emergent adverse events (TEAEs), injection site evaluations, and laboratory tests were also assessed. Results: Among 121 patients (83 [68.6%] male), mean (SD) age at baseline was 38.6 (11.24) years and mean (SD) duration of illness was 11.0 (9.45) years. At screening of the double-blind study, 101 patients (83.5%) were taking an oral antipsychotic and 20 (16.5%) were taking an LAI antipsychotic. Altogether, 5 of 121 patients (4.1%) experienced relapse during the 3-year follow-up; reasons for relapse were psychiatric hospitalization (2 [1.7%]), suicidal or homicidal ideation (2 [1.7%]), and deliberate self-injury (1 [0.8%]). Patients treated with PP every 6 months were clinically and functionally stable, and outcomes were well maintained, evidenced by stable scores on the PANSS (mean [SD] change, -2.6 [9.96] points), CGI-S (mean [SD] change, -0.2 [0.57] points), and PSP (mean [SD] change, 3.1 [9.14] points) scales over the 3-year period. In total, 101 patients (83.5%) completed the 2-year OLE. At least 1 TEAE was reported in 97 of 121 patients (80.2%) overall; no new safety or tolerability concerns were identified. Conclusions and Relevance: In a 2-year OLE study of a 1-year RCT, results supported favorable long-term outcomes of PP once every 6 months for up to 3 years in adults with schizophrenia.

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

'Letting it be': a grounded theory about dementia care in Fiji.

OBJECTIVES: This research study aimed to discover how dementia affecting older people was perceived, experienced, and managed by stakeholders in the Pacific Island country of Fiji. METHOD: A transformational grounded theory approach was used. Semi-structured interviews and focus groups with key stakeholders in the major towns of Suva, Lautoka, and Nadi were carried out. Transcripts were analysed in line with transformational grounded theory methods. RESULTS: A total of 50 participants (40 service providers, eight family caregivers, one person with dementia, and one village elder) shared their views and experiences about dementia. A grounded theory about dementia care management was constructed. 'Letting it be' is the grounding socio-cultural construct that interweaves and binds together the processes of dementia care management. It expresses a compassionate approach to caring for older people with dementia that involves searching for knowledge and support, and application of traditional care practices within the strength of family and community networks. CONCLUSION: In Fiji, support for dementia centres on the integration of community understandings, and promotion of cultural values of wellbeing and care, with service provision. It also focuses on support for families and communities through social welfare, community networks, and education.

Biexponential I = 3/2 Spin-Lattice Relaxation in the Solid State: Multiple-Quantum 7Li NMR as a Probe of Fast Ion Dynamics.

Spin-lattice relaxation measurements are used in 7Li NMR studies of materials of potential use in solid-state Li-ion batteries as a probe of ion mobility on a fast (nanosecond to picosecond) time scale. The relaxation behavior is often analyzed by assuming exponential behavior or, equivalently, a single T1 time constant. However, the spin-lattice relaxation of spin I = 3/2 nuclei, such as 7Li, is in general biexponential; this is a fundamental property of I = 3/2 nuclei and unrelated to any compartmentalization within the solid. Although the possibility of biexponential 7Li (and other I = 3/2 nuclei) spin-lattice relaxation in the solid state has been noted by a number of authors, it can be difficult to observe unambiguously using conventional experimental NMR techniques, such as inversion or saturation recovery. In this work, we show that triple-quantum-filtered NMR experiments, as previously exploited in I = 3/2 NMR of liquids, can be used in favorable circumstances to observe and readily quantify biexponential 7Li spin-lattice relaxation in solids with high ion mobility. We demonstrate a triple-quantum-filtered inversion-recovery experiment on the candidate solid electrolyte material Li2OHCl at 325 K, which has previously been shown to exhibit fast ion mobility, and we also introduce a novel triple-quantum-filtered saturation-recovery experiment. The results of these solid-state NMR experiments are less straightforward than those in liquids as a consequence of the unwanted direct excitation of triple-quantum coherences by the weak (compared with the unaveraged 7Li quadrupolar interaction) pulses used, but we show that this unwanted excitation can be accounted for and, in the example shown here, does not impede the extraction of the two 7Li spin-lattice relaxation times.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Inspiring diverse researchers in Virginia: Cultivating research excellence through a career-building program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations.

BACKGROUND: The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), PP 3-month (PP3M), and PP 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. The current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M and PP1M and compared relapse prevention rates with PP6M from an open-label extension (OLE) study in adult patients with schizophrenia. METHODS: PP6M data were derived from a single-arm, 24-month, OLE study (NCT04072575), which included patients with schizophrenia who completed a 12-month randomized, double-blind, noninferiority, phase-3 study (NCT03345342) without relapse. Patients in the PP3M and PP1M ECAs were identified from the IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as the PP6M cohort. RESULTS: A total of 178 patients were included in each cohort following propensity score matching. Most patients were men (>70%; mean age: 39-41 years). Time to relapse (primary analysis based on Kaplan-Meier estimates) was significantly delayed in the PP6M cohort (P < .001, log-rank test). The relapse rate was lower in the PP6M cohort (3.9%) vs PP3M (20.2%) and PP1M (29.8%) cohorts. Risk of relapse decreased significantly (P < .001) by 82% for PP6M vs PP3M (HR = 0.18 [95% CI = 0.08 to 0.40]), 89% for PP6M vs PP1M (HR = 0.11 [0.05 to 0.25]), and 35% for PP3M vs PP1M (HR = 0.65 [0.42 to 0.99]; P = .043). Sensitivity analysis confirmed findings from the primary analysis. Although the ECAs were matched to mimic the characteristics of the PP6M cohort, heterogeneity between the groups could exist due to factors including prior study participation, unmeasured confounders, variations in data capture and quality, and completeness of clinical information. CONCLUSIONS: In a clinical trial setting, PP6M significantly delayed time to relapse and demonstrated lower relapse rates compared with PP3M and PP1M treatments in real-world settings among adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

Assessment of GAFF and OPLS Force Fields for Urea: Crystal and Aqueous Solution Properties.

Molecular simulations such as Monte Carlo, molecular dynamics, and metadynamics have been used to provide insight into crystallization phenomena, including nucleation and crystal growth. However, these simulations depend on the force field used, which models the atomic and molecular interactions, to adequately reproduce relevant material properties for the phases involved. Two widely used force fields, the General AMBER Force Field (GAFF) and the Optimized Potential for Liquid Simulations (OPLS), including several variants, have previously been used for studying urea crystallization. In this work, we investigated how well four different versions of the GAFF force field and five different versions of the OPLS force field reproduced known urea crystal and aqueous solution properties. Two force fields were found to have the best overall performance: a specific urea charge-optimized GAFF force field and the original all-atom OPLS force field. It is recommended that a suitable testing protocol involving both solution and solid properties, such as that used in this work, is adopted for the validation of force fields used for simulations of crystallization phenomena.

Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

Inspiring Diverse Researchers in Virginia: Cultivating Research Excellence Through a Career Building Program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This year-long program provided education, coaching, mentoring, and sponsorship for underrepresented early-career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Building our research administrator workforce as our clinical and translational research programs become increasingly complex.

Introduction: Research administrators (RA's) are critical members of the research workforce. For purposes of this article, research administrators are personnel who support the development, compliance, management, and financial oversight of sponsored research. There are currently very few institutional career development and mentoring programs available to research administrators. Recruitment and retention of quality research administrators has been especially challenging across the country in recent years. Methods: In an effort to address this gap in training and to increase recruitment and retention, the integrated Translational Health Research Institute of Virginia (iTHRIV), a collaborative NIH-NCATS funded Clinical Translational Science Award (CTSA) hub, has developed an innovative program of workforce development and mentoring for research administrators. This article provides an overview of one institutional training and development initiative, the Research Administration Program for Training and Resources (RAPTR). RAPTR provides training, resources and mentoring to develop a Community of Practice. Results: The program provides a forum where research administrators can share ideas, practices, and challenges. Discussion: This manuscript describes the benefits and lessons learned from our early experience in this program. We highlight selected components that may be generalizable to other institutions and describe individualized components, which require local policies and processes.

Disseminating for impact: creating curriculum activities for translational dissemination for the clinical and translational research workforce.

There has been an increased focus on the practices associated with dissemination for the translation of research to clinical practice and ultimately, policy. Simultaneously, there has been attention placed on the role of the clinical research workforce in supporting optimal dissemination efforts for impact and societal benefit. Curriculums focused on education opportunities for dissemination for translational scientists have been under-reported. The Translational Science Benefits Model (TSBM) is a framework that has been developed to support assessment of clinical and translational research outcomes that measure impact (both in the clinical and community setting) beyond traditional citations in academic journals/bibliometric activities. The TSBM framework outlines more than 30 different facets of impact and can provide a basis for operationalizing broad impacts of research for translational and clinical scientists. Engagement science offers methods and modalities to work with individual stakeholders, and collaborators in a team science model, and engagement with external scholars and society. This article will describe the use of the TSBM framework and engagement science strategies to develop a translational dissemination framework with novel components for evaluation of dissemination and implementation activities. We propose using the translational dissemination framework to guide the development of an educational curriculum for the clinical research workforce. We outline the educational domains and proposed evaluation criteria essential in implementing this innovative translational dissemination educational content for the clinical and translational research workforce.

Earlier Use of Long-Acting Injectable Paliperidone Palmitate Versus Oral Antipsychotics in Patients With Schizophrenia: An Integrated Patient-Level Post Hoc Analysis.

Objective: To assess the efficacy and safety of paliperidone palmitate (PP) long-acting injectable antipsychotic (LAI) versus oral antipsychotic (OAP) treatment in adult patients diagnosed with schizophrenia (per DSM-IV or DSM-5 criteria) and varying duration of illness (0-3 years and > 3 years).Methods: Patient-level data from the PRIDE, PROSIPAL, and DREaM studies were included in a post hoc analysis. Efficacy and safety outcomes, including relapse assessments, Personal and Social Performance scale scores, Medication Satisfaction Questionnaire total scores, and treatment-emergent adverse events (TEAEs), were measured systematically. Treatment failure (TF) included relapses due to psychiatric hospitalizations, arrest or incarceration, suicidal or homicidal ideation or behavior, discontinuation due to inadequate efficacy and/or safety or tolerability, treatment supplementation due to inadequate efficacy, and significant worsening of symptoms.Results: Fewer TFs were observed with PP versus OAP in both the 0-3 years group (17.7% and 25.3%, respectively) and the > 3 years group (32.3% and 42.4%, respectively). Time to first TF was significantly longer with PP versus OAP treatment in both duration of illness groups. TEAE rates were similar between the PP and OAP groups, with no new safety signals identified.Conclusions: This post hoc analysis suggests that PP provides significant benefit in reducing TF or relapse compared with OAPs regardless of duration of illness and highlights the potential benefit of implementing PP earlier in the course of schizophrenia.Trial Registration: ClinicalTrials.gov identifiers NCT01157351 (PRIDE), NCT01081769 (PROSIPAL), and NCT02431702 (DREaM).

NINDS Health Equity Strategic Planning Process Overview, High-Level Recommendations, and Guide.

Neurologic mortality is increasing in the United States and is occurring in an inequitable manner. There is a major need for innovative research strategies to eliminate these inequities. In 2020, the National Institute of Neurological Disorders and Stroke (NINDS) embarked on a health equity strategic planning process, which culminated in a 3-day public workshop and research recommendations provided by a working group of its National Advisory Neurological Disorders and Stroke Council (NANDSC WG) to the NINDS. This Neurology® supplement is dedicated to the NINDS health equity strategic planning process. As cochairs of the NANDS WG, we developed this summary to provide an overview of the process and a guide for navigating this special issue. Detailed recommendations from the NANDS WG are distributed throughout various articles in this supplement and supported with extensive commentary on the state of the science in health equity. Consolidated high-level recommendations from this process are presented at the end of this article.

The Lives Lost to Inequities: Avertable Deaths From Neurologic Diseases in the Past Decade.

BACKGROUND AND OBJECTIVES: Mortality rates for neurologic diseases are increasing in the United States, with large disparities across geographical areas and populations. Racial and ethnic populations, notably the non-Hispanic (NH) Black population, experience higher mortality rates for many causes of death, but the magnitude of the disparities for neurologic diseases is unclear. The objectives of this study were to calculate mortality rates for neurologic diseases by race and ethnicity and-to place this disparity in perspective-to estimate how many US deaths would have been averted in the past decade if the NH Black population experienced the same mortality rates as other groups. METHODS: Mortality rates for deaths attributed to neurologic diseases, as defined by the International Classification of Diseases, were calculated for 2010 to 2019 using death and population data obtained from the Centers for Disease Control and Prevention and the US Census Bureau. Avertable deaths were calculated by indirect standardization: For each calendar year of the decade, age-specific death rates of NH White persons in 10 age groups were multiplied by the NH Black population in each age group. A secondary analysis used Hispanic and NH Asian populations as the reference groups. RESULTS: In 2013, overall age-adjusted mortality rates for neurologic diseases began increasing, with the NH Black population experiencing higher rates than NH White, NH American Indian and Alaska Native, Hispanic, and NH Asian populations (in decreasing order). Other populations with higher mortality rates for neurologic diseases included older adults, the male population, and adults older than 25 years without a high school diploma. The gap in mortality rates for neurologic diseases between the NH Black and NH White populations widened from 4.2 individuals per 100,000 in 2011 to 7.0 per 100,000 in 2019. Over 2010 to 2019, had the NH Black population experienced the neurologic mortality rates of NH White, Hispanic, or NH Asian populations, 29,986, 88,407, or 117,519 deaths, respectively, would have been averted. DISCUSSION: Death rates for neurologic diseases are increasing. Disproportionately higher neurologic mortality rates in the NH Black population are responsible for a large number of excess deaths, making research and policy efforts to address the systemic causes increasingly urgent.

Democratising data to address health system inequities in Australia.

Understanding the health status of a population or community is crucial to equitable service planning. Among other uses, data on health status can help local and national planners and policy makers understand patterns and trends in current or emerging health and well-being, especially how disparities relating to geography, ethnicity, language and living with disability influence access to services. In this practice paper we draw attention to the nature of Australia's health data challenges and call for greater 'democratisation' of health data to address health system inequities. Democratisation implies the need for greater quality and representativeness of health data as well as improved access and usability that enable health planners and researchers to respond to health and health service disparities efficiently and cost-effectively. We draw on learnings from two practice examples, marred by inaccessibility, reduced interoperability and limited representativeness. We call for renewed and urgent attention to, and investment in, improved data quality and usability for all levels of health, disability and related service delivery in Australia.

Twenty-Year Disparity Trends in United States Stroke Death Rate by Age, Race/Ethnicity, Geography, and Socioeconomic Status.

BACKGROUND AND OBJECTIVES: In 2017, the Centers for Disease Control and Prevention (CDC) issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis was to understand whether social determinants of health have influenced trends in stroke mortality. METHODS: We performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults from 1999 to 2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age (35-64 years [younger] and 65 years or older [older]) and then by county-level social determinants of health. We reported stroke death rate by county and the percentage change in stroke death rate during 2014-2018 compared with that during 2009-2013. RESULTS: We included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 (p < 0.001), and the slope of the decrease in stroke death rate tapered for older individuals (p < 0.001). During the 20-year period of our study, counties with a high social deprivation index and ≥10% Black residents consistently had the highest rates of stroke death in both age groups. Comparing stroke death rate during 2014-2018 with that during 2009-2013, larger increases in younger individuals' stroke death rate were seen in counties with ≥90% (vs <90%) non-Hispanic White individuals (3.2% mean death rate change vs 1.7%, p < 0.001), rural (vs urban) populations (2.6% vs 2.0%, p = 0.019), low (vs high) proportion of medical insurance coverage (2.9% vs 1.9%, p = 0.002), and high (vs low) substance abuse and suicide mortality (2.8 vs 1.9%, p = 0.008; 3.3% vs 1.5%, p < 0.001). In contrast to the younger individuals, in older individuals, the associations with increased death rates were with more traditional social determinants of health such as the social deprivation index, urban location, unemployment rate, and proportion of Black race and Hispanic ethnicity residents. DISCUSSION: Improvements in the stroke death rate in the United States are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger vs older individuals. These findings may inform targeted public health strategies.

Childhood Cancer Survivors' Reported Late Effects, Motivations for Seeking Survivorship Care, and Patterns of Attendance.

BACKGROUND: Childhood cancer survivors are vulnerable to long-term treatment-related health conditions, which can lead to poor quality of life. Little data exist on the overall health of long-term Australian and New Zealand childhood cancer survivors or on survivors' motivations for attending survivorship clinics. METHODS: This study administers a cross-sectional questionnaire to long-term survivors ≥5 years from their primary diagnosis. We compared participant-reported number of late effects by a cancer diagnosis, and identified clinical (eg, treatment) and demographic (eg, age) factors that were associated with late effects burden and engagement in cancer survivorship care. RESULTS: A total of 634 participants completed questionnaires (48% male, mean age = 21.7 years). Most participants (79%) reported at least one cancer-related late effect, most commonly fatigue (40%) and memory/learning difficulties (34%). Brain tumor survivors reported a higher total number of late effects than survivors with other diagnoses (mean = 5.7 vs. 3.2, P < .001). Participants' most commonly reported motivators for engaging in care were to understand problems that may occur later in life because of their cancer and/or treatment (98.5%) and to get reassurance about one's health (97.4%). The proportion of survivors endorsing each motivating factor was similar across cancer diagnoses, with the exception of learning more about insurance and pensions (highest in brain tumor survivors = 80%). In multivariable analyses, survivors were more likely to report being engaged in survivorship care if they were younger (P < .001), less time had elapsed since their diagnosis (P < .001), or they reported a higher number of motivating factors (P = .016). CONCLUSION: Survivors report a range of health problems decades after treatment completion. Understanding the burden of late effects, and motivators for seeking survivorship care to manage these health problems, is important for ensuring that tailored interventions or services are available to meet the needs of this growing population and to design effective models of survivorship care.