Integration of transcriptome-wide association study with neuronal dysfunction assays provides functional genomics evidence for Parkinson's disease genes.

Genome-wide association studies (GWAS) have markedly advanced our understanding of the genetics of Parkinson's disease (PD), but they currently do not account for the full heritability of PD. In many cases it is difficult to unambiguously identify a specific gene within each locus because GWAS does not provide functional information on the identified candidate loci. Here we present an integrative approach that combines transcriptome-wide association study (TWAS) with high-throughput neuronal dysfunction analyses in Drosophila to discover and validate candidate PD genes. We identified 160 candidate genes whose misexpression is associated with PD risk via TWAS. Candidates were validated using orthogonal in silico methods and found to be functionally related to PD-associated pathways (i.e. endolysosome). We then mimicked these TWAS-predicted transcriptomic alterations in a Drosophila PD model and discovered that 50 candidates can modulate α-Synuclein(α-Syn)-induced neurodegeneration, allowing us to nominate new genes in previously known PD loci. We also uncovered additional novel PD candidate genes within GWAS suggestive loci (e.g. TTC19, ADORA2B, LZTS3, NRBP1, HN1L), which are also supported by clinical and functional evidence. These findings deepen our understanding of PD, and support applying our integrative approach to other complex trait disorders.

OmicNavigator: open-source software for the exploration, visualization, and archival of omic studies.

BACKGROUND: The results of high-throughput biology ('omic') experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival. However, an opportunity remains for open-source software that can archive and present the results of omic analyses with broad accommodation of study-specific analytical approaches and visualizations with useful exploration features. RESULTS: We present OmicNavigator, an R package for the archival, visualization and interactive exploration of omic studies. OmicNavigator enables bioinformaticians to create web applications that interactively display their custom visualizations and analysis results linked with app-derived analytical tools, graphics, and tables. Studies created with OmicNavigator can be viewed within an interactive R session or hosted on a server for shared access. CONCLUSIONS: OmicNavigator can be found at https://github.com/abbvie-external/OmicNavigator.

The impact of marital status on tumor aggressiveness, treatment, and screening among black and white men diagnosed with prostate cancer.

PURPOSE: To examine the association of marital status with prostate cancer outcomes in a racially-diverse cohort. METHODS: The study population consisted of men (1010 Black; 1070 White) with incident prostate cancer from the baseline North Carolina-Louisiana Prostate Cancer (PCaP) cohort. Marital status at time of diagnosis and screening history were determined by self-report. The binary measure of marital status was defined as married (including living as married) vs. not married (never married, divorced/separated, or widowed). High-aggressive tumors were defined using a composite measure of PSA, Gleason Score, and stage. Definitive treatment was defined as receipt of radical prostatectomy or radiation. Multivariable logistic regression was used to examine the association of marital status with (1) high-aggressive tumors, (2) receipt of definitive treatment, and (3) screening history among Black and White men with prostate cancer. RESULTS: Black men were less likely to be married than White men (68.1% vs. 83.6%). Not being married (vs. married) was associated with increased odds of high-aggressive tumors in the overall study population (adjusted Odds Ratio (aOR): 1.56; 95% Confidence Interval (CI): 1.20-2.02) and both Black and White men in race-stratified analyses. Unmarried men were less likely to receive definitive treatment in the overall study population (aOR: 0.68; 95% CI: 0.54-0.85). In race-stratified analyses, unmarried Black men were less likely to receive definitive treatment. Both unmarried Black and White men were less likely to have a history of prostate cancer screening than married men. CONCLUSION: Lower rates of marriage among Black men might signal decreased support for treatment decision-making, symptom management, and caregiver support which could potentially contribute to prostate cancer disparities.

Reducing racial and ethnic disparities in cardiovascular outcomes among cancer survivors.

PURPOSE OF REVIEW: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities. RECENT FINDINGS: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively.

Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly observed event following the administration of iodinated contrast. It presents as a spectrum of neurological symptoms that closely mimic ischaemic stroke, however, CIN remains a poorly understood clinical phenomenon. An appreciation of the underlying pathophysiological mechanisms is essential to improve clinical understanding and enhance decision-making. METHODS: A broad literature search of Medline (1946 to December 2022) and Embase (1947 to December 2022) was conducted. Articles discussing the pathophysiology of CIN were reviewed. SUMMARY: The pathogenesis of CIN appears to be multifactorial. A key step is likely blood-brain barrier (BBB) breakdown due to factors including ischaemic stroke, uncontrolled hypertension, and possibly contrast agents themselves, among others. This is followed by passage of contrast agents across the BBB, leading to chemotoxic sequelae on neural tissue. KEY MESSAGES: This review provides a clinically oriented review on the pathophysiology of CIN to enhance knowledge and improve decision-making among clinicians.

Patient Characteristics Associated with Telemedicine Use for Diabetes Mellitus Care: Experience of a University Health System.

OBJECTIVES: The objective was to understand the characteristics of patients who used telemedicine for diabetes management to inform future implementation of telemedicine. METHODS: We examined patient characteristics associated with telemedicine use for diabetes mellitus (DM) care between March 1, 2020 and April 1, 2021 (the coronavirus disease 2019 pandemic period) in a large university health system when telemedicine visits increased rapidly. Logistic regression models assessed patient characteristics associated with telemedicine visits and delays in DM process measures (hemoglobin A1c checks, nephropathy, and retinopathy evaluations) during the pandemic period after adjusting for potential confounders and corresponding values before the pandemic period (March 1, 2019-February 29, 2020). RESULTS: A total of 45,159 patients were seen from 987,791 visits during the pandemic period. The number of visits averaged one visit less during the pandemic period than before the pandemic period. Approximately 5.4% of patients used telemedicine during the pandemic period from 42,750 visits. The mean (standard deviation) telemedicine visit was 1.28 (0.91). Men, Asian, Black, and other race (vs White), having Medicare or uninsured (vs private insurance), were less likely to use telemedicine. Patients with more visits before the pandemic period were more likely to use telemedicine and less likely to experience a delay in DM process measures during the pandemic period. Telemedicine users were 18% less likely to experience a delay in nephropathy visits than nonusers, but without difference for other process measures. CONCLUSIONS: Race, sex, insurance, and prepandemic in-person visits were associated with telemedicine use for DM management in a large health system. Telemedicine use was not associated with delays in hemoglobin A1c testing, nephropathy, and retinopathy assessments. Understanding reasons for not using telemedicine is important to be able to deliver equitable DM care.

Exploring the intersectionality of race/ethnicity with rurality on breast cancer outcomes: SEER analysis, 2000-2016.

PURPOSE: Disparities in breast cancer survival have been observed within marginalized racial/ethnic groups and within the rural-urban continuum for decades. We examined whether there were differences among the intersectionality of race/ethnicity and rural residence on breast cancer outcomes. METHODS: We performed a retrospective analysis among 739,448 breast cancer patients using Surveillance Epidemiology and End Results (SEER) 18 registries years 2000 through 2016. We conducted multilevel logistic-regression and Cox proportional hazards models to estimate adjusted odds ratios (AORs) and hazard ratios (AHRs), respectively, for breast cancer outcomes including surgical treatment, radiation therapy, chemotherapy, late-stage disease, and risk of breast cancer death. Rural was defined as 2013 Rural-Urban Continuum Codes (RUCC) of 4 or greater. RESULTS: Compared with non-Hispanic white-urban (NH-white-U) women, NH-black-U, NH-black-rural (R), Hispanic-U, and Hispanic-R women, respectively, were at increased odds of no receipt of surgical treatment (NH-black-U, AOR = 1.98, 95% CI 1.91-2.05; NH-black-R, AOR = 1.72, 95% CI 1.52-1.94; Hispanic-U, AOR = 1.58, 95% CI 1.52-1.65; and Hispanic-R, AOR = 1.40, 95% CI 1.18-1.67), late-stage diagnosis (NH-black-U, AOR = 1.32, 95% CI 1.29-1.34; NH-black-R, AOR = 1.29, 95% CI 1.22-1.36; Hispanic-U, AOR = 1.25, 95% CI 1.23-1.27; and Hispanic-R, AOR = 1.17, 95% CI 1.08-1.27), and increased risks for breast cancer death (NH-black-U, AHR = 1.46, 95% CI 1.43-1.50; NH-black-R, AHR = 1.42, 95% CI 1.32-1.53; and Hispanic-U, AHR = 1.10, 95% CI 1.07-1.13). CONCLUSION: Regardless of rurality, NH-black and Hispanic women had significantly increased odds of late-stage diagnosis, no receipt of treatment, and risk of breast cancer death.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations.

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (<1.5 mm) being the only factor independently associated with both clinical and radiographic failures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chaudhary and Gemmete in this issue.

Perceived economic pressure and colorectal cancer-related perceptions among U.S. males (aged 45-75).

PURPOSE: To examine whether a greater perception of economic pressure would be associated with more-negative attitudes, greater perceived barriers, and lower subjective norms regarding colorectal cancer (CRC) and CRC screening among males aged 45-75 years. METHODS: We recruited 492 self-identified males aged 45-75 years living in the United States. We operationalized perceived economic pressure as a latent factor with three subscales: can't make ends meet, unmet material needs, and financial cutbacks. Our dependent variables were attitudes toward CRC and CRC screening, perceived barriers to completing a CRC screening exam, and subjective norms regarding CRC screening (e.g., how others value CRC screening). We tested a hypothesized model using structural equation modeling with maximum-likelihood estimation, adjusting for covariates, and made post-hoc modifications to improve model fit. RESULTS: Greater perceived economic pressure was associated with more-negative attitudes toward CRC and CRC screening (ß = 0.47, 95% CI: 0.37,0.57) and with greater perceived barriers to CRC screening (ß = 0.22, 95% CI: 0.11, 0.34), but was not significantly associated with subjective norms (ß = 0.07, 95% CI: - 0.05, 0.19). Perceived economic pressure was an indirect pathway by which lower-income and younger age were associated with more-negative attitudes and greater perceived barriers. CONCLUSIONS: Our study is one of the first to show that, among males, perceived economic pressure is associated with two social-cognitive mechanisms (i.e., negative attitudes, greater perceived barriers) that are known to influence CRC screening intent and, ultimately, CRC screening completion. Future research on this topic should employ longitudinal study designs.

Ethno-demographic disparities in humoral responses to the COVID-19 vaccine among healthcare workers.

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.

Social Determinants of Health and Racial Disparities in Cardiac Events in Breast Cancer.

BACKGROUND: Racial disparities have been reported for breast cancer and cardiovascular disease (CVD) outcomes. The determinants of racial disparities in CVD outcomes are not yet fully understood. We aimed to examine the impact of individual and neighborhood-level social determinants of health (SDOH) on the racial disparities in major adverse cardiovascular events (MACE; consisting of heart failure, acute coronary syndrome, atrial fibrillation, and ischemic stroke) among female patients with breast cancer. METHODS: This 10-year longitudinal retrospective study was based on a cancer informatics platform with electronic medical record supplementation. We included women aged ≥18 years diagnosed with breast cancer. SDOH were obtained from LexisNexis, and consisted of the domains of social and community context, neighborhood and built environment, education access and quality, and economic stability. Race-agnostic (overall data with race as a feature) and race-specific machine learning models were developed to account for and rank the SDOH impact in 2-year MACE. RESULTS: We included 4,309 patients (765 non-Hispanic Black [NHB]; 3,321 non-Hispanic white). In the race-agnostic model (C-index, 0.79; 95% CI, 0.78-0.80), the 5 most important adverse SDOH variables were neighborhood median household income (SHapley Additive exPlanations [SHAP] score [SS], 0.07), neighborhood crime index (SS = 0.06), number of transportation properties in the household (SS = 0.05), neighborhood burglary index (SS = 0.04), and neighborhood median home values (SS = 0.03). Race was not significantly associated with MACE when adverse SDOH were included as covariates (adjusted subdistribution hazard ratio, 1.22; 95% CI, 0.91-1.64). NHB patients were more likely to have unfavorable SDOH conditions for 8 of the 10 most important SDOH variables for the MACE prediction. CONCLUSIONS: Neighborhood and built environment variables are the most important SDOH predictors for 2-year MACE, and NHB patients were more likely to have unfavorable SDOH conditions. This finding reinforces that race is a social construct.

Investigating the association between educational attainment and allostatic load with risk of cancer mortality among African American women.

BACKGROUND: African American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. Studies suggest that AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined the joint effect of educational attainment and AL status with long-term risk of cancer mortality, and whether education moderated the association between AL and cancer mortality. METHODS: We performed a retrospective analysis among 4,677 AA women within the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 with follow-up data through December 31, 2019. We fit weighted Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, income, and smoking status). RESULTS: AA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24-7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, this effect attenuated (age-adjusted HR: 1.11; 95% CI: 0.45-2.74). AA women with high AL had 2.3-fold increased risk of cancer death (fully adjusted HR: 2.26; 95% CI: 1.10-4.57) when compared to AA with low AL, specifically among women with high school diploma or equivalent and without history of cancer. CONCLUSIONS: Our findings suggest that high allostatic load is associated with a higher risk of cancer mortality among AA women with lower educational attainment, while no such association was observed among AA women with higher educational attainment. Thus, educational attainment plays a modifying role in the relationship between allostatic load and the risk of cancer death for AA women. Higher education can bring several benefits, including improved access to medical care and enhanced medical literacy, which in turn may help mitigate the adverse impact of AL and the heightened risk of cancer mortality among AA women.

Specialty preference for cardiovascular prevention practice in the Southeast US and role of a preventive cardiologist.

INTRODUCTION: Cardiovascular disease (CVD) prevention is practiced concurrently by providers from several specialties. Our goal was to understand providers' preference of specialties in CVD prevention practice and the role of preventive cardiologists. MATERIALS AND METHODS: Between 11 October 2021 and 1 March 2022, we surveyed providers from internal medicine, family medicine, endocrinology, and cardiology specialties to examine their preference of specialties in managing various domains of CVD prevention. We examined categorical variables using Chi square test and continuous variables using t or analysis of variance test. RESULTS: Of 956 invitees, 263 from 21 health systems and 9 states responded. Majority of respondents were women (54.5%), practicing physicians (72.5%), specializing in cardiology (43.6%), and working at academic centers (51.3%). Respondents favored all specialties to prescribe statins (43.2%), ezetimibe (37.8%), sodium-glucose cotransporter-2 (SGLT2) inhibitors (30.5%), and aspirin in primary prevention (36.3%). Only 7.9% and 9.5% selected cardiologists and preventive cardiologists, respectively, to prescribe SGLT2 inhibitors. Most preferred specialists (i.e. cardiology and endocrinology) to manage advanced lipid disorders, refractory hypertension, and premature coronary heart disease. The most common conditions selected for preventive cardiologists to manage were genetic lipid disorders (17%), cardiovascular risk assessment (15%), dyslipidemia (13%), and refractory/resistant hypertension (12%). CONCLUSIONS: For CVD prevention practice, providers favored all specialties to manage common conditions, specialists to manage complex conditions, and preventive cardiologists to manage advanced lipid disorders. Cardiologists were least preferred to prescribe SGLT2 inhibitor. Future research should explore reasons for selected CVD prevention practice preferences to optimize care coordination and for effective use of limited expertise.

How Attributes of Place Threaten Community Trust in the American South: Opportunities for Improving Pandemic-Related Communication.

Trust and mistrust influence the utilization of health services, the quality of overall healthcare, and the prevalence of health disparities. Trust has significant bearing on how communities, and the individuals within them, perceive health information and recommendations. The People and Places Framework is utilized to answer what attributes of place threaten community trust in public health and medical recommendations.Augusta-Richmond County is ranked among the least healthy counties in Georgia despite being home to the best healthcare-to-residence ratios and a vast array of healthcare services. Semi-structured interviews were conducted with 31 neighborhood residents. Data were analyzed using the Sort & Sift, Think & Shift method. Threats to community trust were identified within four local-level attributes of place: availability of products and services, social structures, physical structures, and cultural and media messages. We found a broader web of services, policies, and institutions, beyond interactions with health care, that influence the trust placed in health officials and institutions. Participants spoke to both a potential lack of trust (e.g. needs not being met, as through lack of access to services) and mistrust (e.g. negative motives, such as profit seeking or experimentation). Across the four attributes of place, residents expressed opportunities to build trust. Our findings highlight the importance of examining trust at the community level, providing insight into an array of factors that impact trust at a local level, and extend the work on trust and its related constructs (e.g. mistrust). Implications for improving pandemic-related communication through community relationship building are presented.

Predictors of aneurysmal occlusion following intracranial aneurysms treatment with pipeline embolization device.

PURPOSE: Pipeline embolization device (PED) is thought to induce aneurysmal occlusion through diversion of flow away from the aneurysmal sac with subsequent thrombosis and endothelialization. The impact of different factors especially hypertension (HTN)-a known predisposing factor to hypercoagulability and altered endothelial function-on aneurysmal occlusion after flow diversion has not been studied. We sought to determine predictors of aneurysmal occlusion following PED treatment focusing on impact of blood pressure. METHODS: Database of patients with cerebral aneurysms treated with PED from 2013 to 2019 at our institution was retrospectively reviewed. Patients were defined as hypertensive if (1) they had a documented history of HTN requiring anti-HTN medications or (2) average systolic blood pressure on three measurements was > 130 mmHg. The primary outcome was aneurysm occlusion status at the last imaging follow-up. Multivariable logistic regression model was constructed to assess the effect of HTN on occlusion, controlling for age, smoking, aneurysmal size, fusiform morphology, posterior circulation location, and incorporated branches. RESULTS: A total of 331 aneurysms in 294 patients were identified for this analysis. The mean age was 59 years (79.9% female). Fifty-five percent of the cohort were classified as hypertensive. When controlling for other potential confounders, hypertensive patients trended toward higher odds of achieving complete occlusion compared to non-hypertensive patients (OR = 2.05; 95% CI = 0.99-4.25; p = 0.052). Meanwhile, age (OR = 0.91; 95% CI = 0.88-0.95; p < 0.001) and an incorporated branch into an aneurysm (OR = 0.22; 95% CI = 0.08-0.58; p < 0.002) were associated with decreased odds for complete aneurysmal occlusion. CONCLUSION: Hypertensive patients show a trend toward higher odds of achieving complete occlusion when controlling for potential confounders. The HTN-induced hypercoagulable state, enhanced endothelial activation, and altered extracellular matrix regulation might be the contributing factors. Further research is warranted to explore clinical implications of these findings.

Polycystic Ovary Syndrome: Common Questions and Answers.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age. Its complex pathophysiology includes genetic and environmental factors that contribute to insulin resistance in patients with this disease. The diagnosis of PCOS is primarily clinical, based on the presence of at least two of the three Rotterdam criteria: oligoanovulation, hyperandrogenism, and polycystic ovaries on ultrasonography. PCOS is often associated with hirsutism, acne, anovulatory menstruation, dysglycemia, dyslipidemia, obesity, and increased risk of cardiovascular disease and hormone-sensitive malignancies (e.g., at least a twofold increased risk of endometrial cancer). Lifestyle modification, including caloric restriction and increased physical activity, is the foundation of therapy. Subsequent management decisions depend on the patient's desire for pregnancy. In patients who do not want to become pregnant, oral contraceptives are first-line therapy for menstrual irregularities and dermatologic complications such as hirsutism and acne. Antiandrogens such as spironolactone are often added to oral contraceptives as second-line agents. In patients who want to become pregnant, first-line therapy is letrozole for ovulation induction. Metformin added to lifestyle management is first-line therapy for patients with metabolic complications such as insulin resistance. Patients with PCOS are at increased risk of depression and obstructive sleep apnea, and screening is recommended.

Availability of Specialty Services for Cardiovascular Prevention Practice in the Southeastern United States.

OBJECTIVES: A comprehensive cardiovascular disease (CVD) prevention approach should address patients' medical, behavioral, and psychological issues. The aim of this study was to understand the clinician-reported availability of a pertinent CVD preventive workforce across various specialties using a survey study in the southeastern United States, an area with a disproportionate burden of CVD and commonly known as the Stroke Belt. METHODS: We surveyed physicians, advanced practice providers (APPs), and pharmacists in internal medicine, family medicine, endocrinology, and cardiology regarding available specialists in CVD preventive practice. We examined categorical variables using the χ2 test and continuous variables using the t test/analysis of variance. RESULTS: A total of 263 clinicians from 21 health systems participated (27.6% response rate, 91.5% from North Carolina). Most were women (54.5%) and physicians (72.5%) specializing in cardiology (43.6%) and working at academic centers (51.3%). Overall, most clinicians stated having adequate specialist services to manage hypertension (86.6%), diabetes mellitus (90.1%), and dyslipidemia (84%), with >50% stating having adequate specialist services for obesity, smoking cessation, diet/nutrition, and exercise counseling. Many reported working with an APP (69%) or a pharmacist (56.5%). Specialist services for exercise therapy, psychology, behavioral counseling, and preventive cardiology were less available. When examined across the four specialties, the majority reported having adequate specialist services for hypertension, diabetes mellitus, obesity, dyslipidemia, and diet/nutrition counseling. Providers from all four specialties were less likely to work with exercise therapists, psychologists, behavioral counselors, and preventive cardiologists. CONCLUSIONS: A majority of providers expressed having adequate specialists for hypertension, diabetes mellitus, dyslipidemia, obesity, smoking cessation, diet/nutrition, and exercise counseling. Most worked together with APPs and pharmacists but less frequently with exercise therapists, psychologists, behavioral counselors, and preventive cardiologists. Further research should explore approaches to use and expand less commonly available specialists for optimal CVD preventive care.

Characterization of Head Acceleration Exposure During Youth Football Practice Drills.

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11-13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices.

Repeat Flow Diversion for Cerebral Aneurysms Failing Prior Flow Diversion: Safety and Feasibility From Multicenter Experience.

BACKGROUND: Aneurysmal persistence after flow diversion (FD) occurs in 5% to 25% of aneurysms, which may necessitate retreatment. There are limited data on safety/efficacy of repeat FD-a frequently utilized strategy in such cases. METHODS: A series of consecutive patients undergoing FD retreatment from 15 centers were reviewed (2011-2019), with inclusion criteria of repeat FD for the same aneurysm at least 6 months after initial treatment, with minimum of 6 months post-retreatment imaging. The primary outcome was aneurysmal occlusion, and secondary outcome was safety. A multivariable logistic regression model was constructed to identify predictors of incomplete occlusion (90%-99% and <90% occlusion) versus complete occlusion (100%) after retreatment. RESULTS: Ninety-five patients (median age, 57 years; 81% women) harboring 95 aneurysms underwent 198 treatment procedures. Majority of aneurysms were unruptured (87.4%), saccular (74.7%), and located in the internal carotid artery (79%; median size, 9 mm). Median elapsed time between the first and second treatment was 12.2 months. Last available follow-up was at median 12.8 months after retreatment, and median 30.6 months after the initial treatment, showing complete occlusion in 46.2% and near-complete occlusion (90%-99%) in 20.4% of aneurysms. There was no difference in ischemic complications following initial treatment and retreatment (4.2% versus 4.2%; P>0.99). On multivariable regression, fusiform morphology had higher nonocclusion odds after retreatment (odds ratio [OR], 7.2 [95% CI, 1.97-20.8]). Family history of aneurysms was associated with lower odds of nonocclusion (OR, 0.18 [95% CI, 0.04-0.78]). Likewise, positive smoking history was associated with lower odds of nonocclusion (OR, 0.29 [95% CI, 0.1-0.86]). History of hypertension trended toward incomplete occlusion (OR, 3.10 [95% CI, 0.98-6.3]), similar to incorporated branch into aneurysms (OR, 2.78 [95% CI, 0.98-6.8]). CONCLUSIONS: Repeat FD for persistent aneurysms carries a reasonable success/safety profile. Satisfactory occlusion (100% and 90%-99% occlusion) was encountered in two-thirds of patients, with similar complications between the initial and subsequent retreatments. Fusiform morphology was the strongest predictor of retreatment failure.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.