Are community oncology practices with/without clinical research programs different? A comparison of patient and practice characteristics.

PURPOSE: Expanding access to clinical trials in community settings is a potential approach to addressing disparities in accrual of historically underrepresented populations. However, little is known about the characteristics of practices that do not participate in research. We investigated differences in patient and practice characteristics of US community oncology practices with high vs low engagement in clinical research. METHODS: We included patients from a real-world, nationwide electronic health record-derived, de-identified database who received active treatment for cancer at community oncology practices between 11/1/17 and 10/31/22. We assessed patient and practice characteristics and their associations with high vs low research engagement using descriptive analyses and logistic regression models. RESULTS: Seventy (39.3%) of 178 practices had high research engagement, treated 57.8% of the overall 568,540 patient cohort, and enrolled 3.25% of their patients on cancer treatment trials during the five-year observation period (v 0.27% enrollment among low engagement practices). Practices with low vs high research engagement treated higher proportions of the following patient groups: ages > =75 (24.2% v 21.8%), non-Latinx Black (12.6% v10.3%) or Latinx (11.6% v 6.1%), were within the lowest socioeconomic status quintile (21.9% v 16.5%), and were uninsured or had no documented insurance (22.2% v 13.6%). CONCLUSION: Patient groups historically underrepresented in oncology clinical trials are more likely to be treated at community practices with limited or no access to trials. These results suggest that investments to expand the clinical research footprint among practices with low research engagement could help address persistent inequities in trial representation.

Changes in Emergency Contraceptive Fills After Massachusetts' Statewide Standing Order.

This study examines whether policies that reduce prescribing barriers may improve access to emergency contraceptives, particularly ulipristal.

Benefits and Harms of Proposed Social Media Legislation.

This Viewpoint identifies potential strategies to address issues in adolescents' use of social media and cautions against the premature adoption of some strategies, such as parental permissions and age restrictions.

3-Hydroxykynurenine targets kainate receptors to promote defense against infection.

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

Use of Oral and Emergency Contraceptives After the US Supreme Court's Dobbs Decision.

Importance: The US Supreme Court Dobbs v Jackson Women's Health Organization decision allowed states to strengthen restrictions on abortion access, triggering the closure of family planning clinics and leading to confusion about the legality of emergency contraceptives (ECs). Objectives: To evaluate the association between the Dobbs decision and fills for oral and emergency contraceptives in states that enacted the most restrictive abortion policies after Dobbs. Design, Setting, and Participants: This cohort study used data on contraceptive fills for women of reproductive age (15-49 years) in the US from IQVIA's National Prescription Audit PayerTrak and data from the Guttmacher Institute were used to categorize changes in abortion restrictions in each state. A difference-in-differences analysis compared changes in monthly fill rates for daily oral contraceptive pills (OCPs) and ECs in states that became most restrictive (implemented a full abortion ban after Dobbs) and comparison states (kept a medium level of abortion restrictions after Dobbs) before (March 2021 to November 2021) and after (July 2022 to October 2023) the Dobbs decision. Exposure: State-level abortion restrictions. Main Outcomes and Measures: Monthly fills of OCPs and ECs per 100 000 women of reproductive age. Results: Between March 2021 and October 2023, 142.8 million prescriptions for OCPs and 904 269 prescriptions for ECs were dispensed at US retail pharmacies. Before Dobbs, trends in monthly fill rates were similar for OCPs and ECs between the most restrictive and comparison states. After the Dobbs decision, states that became the most restrictive experienced an additional 4.1% decline in OCP fills with 285.9 fewer fills per 100 000 (95% CI, -495.8 to -6.8; P = .04). In contrast to OCPs, fills for ECs increased during the first year after Dobbs (July 2022 to June 2023) in both groups of states. However, 1 year after Dobbs (July 2023 to October 2023), the most restrictive states experienced an additional 65% decrease in emergency contraceptive fills with 13.2 fewer fills per 100 000 (95% CI, -27.2 to -4.1; P = .01). Conclusions and Relevance: In this cohort study of prescriptions filled at US pharmacies, the Dobbs decision was associated with declines in oral contraceptives, particularly ECs, in states enacting the most restrictive abortion policies. Given the important role of OCPs and ECs in preventing pregnancy and the need for abortion, efforts to improve access may be needed, especially in states where legal abortion is no longer an option.

Racialized economic segregation and inequities in treatment initiation and survival among patients with metastatic breast cancer.

PURPOSE: Racialized economic segregation, a form of structural racism, may drive persistent inequities among patients with breast cancer. We examined whether a composite area-level index of racialized economic segregation was associated with real-world treatment and survival in metastatic breast cancer (mBC). METHODS: We conducted a retrospective cohort study among adult women with mBC using a US nationwide electronic health record-derived de-identified database (2011-2022). Population-weighted quintiles of the index of concentration at the extremes were estimated using census tract data. To identify inequities in time to treatment initiation (TTI) and overall survival (OS), we employed Kaplan-Meier methods and estimated hazard ratios (HR) adjusted for clinical factors. RESULTS: The cohort included 27,459 patients. Compared with patients from the most privileged areas, those from the least privileged areas were disproportionately Black (36.9% vs. 2.6%) or Latinx (13.2% vs. 2.6%) and increasingly diagnosed with de novo mBC (33.6% vs. 28.9%). Those from the least privileged areas had longer median TTI than those from the most privileged areas (38 vs 31 days) and shorter median OS (29.7 vs 39.2 months). Multivariable-adjusted HR indicated less timely treatment initiation (HR 0.87, 95% CI 0.83, 0.91, p < 0.01) and worse OS (HR 1.19, 95% CI 1.13, 1.25, p < 0.01) among those from the least privileged areas compared to the most privileged areas. CONCLUSION: Racialized economic segregation is a social determinant of health associated with treatment and survival inequities in mBC. Public investments directly addressing racialized economic segregation and other forms of structural racism are needed to reduce inequities in cancer care and outcomes.

Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials.

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).

Preconditioning with selective autoretroperfusion: In vivo and in silico evidence of washout hypothesis.

Introduction: Prompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10 min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis. Methods: AMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10 min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect. Results: SARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2 min during retroperfusion, suggest a "washout" effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers. Discussion: RI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.

Increasing Rates of Bowel Resection Surgery for Stricturing Crohn's Disease in the Biologic Era.

BACKGROUND: The era of biologics is associated with declining rates of surgery for Crohn's disease (CD), but the impact on surgery for stricturing CD is unknown. Our study aimed to assess nationwide trends in bowel resection surgery for obstruction in CD since the introduction of infliximab for CD in 1998. METHODS: Using the Nationwide Inpatient Sample, we performed a nationwide analysis, identifying patients hospitalized for CD who underwent bowel resection for an indication of obstruction between 1998 and 2020 (era of biologics). Longitudinal trends in all CD-related resections and resection for obstruction were evaluated. Multivariable logistic regression identified patient and hospital characteristics associated with bowel resection surgery for obstruction. RESULTS: Hospitalizations for all CD-related resections decreased from 12.0% of all hospitalizations in 1998 to 6.9% in 2020, while hospitalizations for CD-related resection for obstructive indication increased from 1.3% to 2.0%. The proportion of resections for obstructive indication amongst all CD-related bowel resections increased from 10.8% in 1998 to 29.1% in 2020. In the multivariable models stratified by elective admission, the increasing year was associated with risk of resection for obstructive indication regardless of urgency (nonelective model: odds ratio, 1.01; 95% CI, 1.00-1.02; elective model: odds ratio, 1.06; 95% CI, 1.04-1.08). CONCLUSIONS: In the era of biologics, our findings demonstrate a decreasing annual rate of CD-related bowel resections but an increase in resection for obstructive indication. Our findings highlight the effect of medical therapy on surgical rates overall but suggest limited impact of current medical therapy on need of resection for stricturing disease.

In our nationwide analysis, rates of bowel resection for patients with Crohn's disease have declined since the approval of infliximab in 1998. However, rates of resection for obstruction in patients with Crohn's disease continue to increase.

Addressing Culturally Based Hidden Bias and RacisM (A-CHARM) Using Simulation Experiences, Nik's Story: A Quasi-Experimental Study.

BACKGROUND/PURPOSE: Racism and hidden bias experienced by underrepresented nursing students contribute to a loss of confidence and anxiety. The A-CHARM nursing project developed virtual simulation experiences for nursing students to practice how to address racism. 'Nik's Story' virtual simulation was created as part of the A-CHARM project. The purpose of this study was to examine the effectiveness of an education intervention, that included Nik's story, on cultural humility and cultural diversity awareness. METHOD: This quasi-experimental study included a convenience sample of final year nursing students. After informed consent, participants completed a pre-intervention questionnaire that included the Cultural Humility Scale "context for difference in perspective" subscale, and the Cultural Diversity Awareness questionnaire to assess baseline knowledge. Students participated in an education intervention that included a lecture, Nik's story virtual simulation experience, a debrief and then completed a post-education/simulation questionnaire that included usability/learner engagement questions and the Cultural Humility Scale "context for difference in perspective" subscale, and the Cultural Diversity Awareness questionnaire. RESULTS: Forty-seven students consented and completed the pre/post intervention questionnaire. Participants rated the effectiveness, engagement and usability of the simulation experience highly. There was a significant positive change in cultural humility "context for difference in perspective" subscale (pre-scores = 6.9, SD = 3.3; post-scores = 31.0, SD = 3.8, p < 0.001), and cultural diversity awareness (pre-scores = 95.4, SD = 8.9; post-scores = 103.4, SD = 9.8, p < 0.001). DISCUSSION: This intervention was effective in improving cultural humility and cultural diversity awareness in nursing students. CONCLUSION: Simulation experiences regarding racism in the clinical setting provide a strategy for students to learn how to professionally navigate unwanted experiences.

Diagnoses and Treatment of Behavioral and Psychological Symptoms of Dementia Among Racially and Ethnically Diverse Persons Living with Dementia.

Background: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD. Objective: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD. Methods: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use. Results: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants. Conclusions: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.

Sociodemographic inequities in COVID-19 vaccination among adults in the United States, 2022.

BACKGROUND: Despite the availability of COVID-19 vaccines since December 2020, sociodemographic inequities in vaccination and preventable COVID-related deaths persist. To inform efforts for equitable COVID-19 vaccination campaigns, a comprehensive national evaluation of existing inequities is necessary. OBJECTIVE: To examine sociodemographic inequities in COVID-19 vaccination receipt using data from the 2022 National Health Interview Survey (NHIS). METHODS: This secondary data analysis used cross-sectional nationally-representative data from the 2022 NHIS to assess vaccination inequities among 27,126 adults. Separate Poisson regressions adjusted for clinical factors (e.g., age, sex, high-risk health conditions) were used to evaluate vaccination inequities across sociographic factors (e.g., race/ethnicity, poverty, health insurance). RESULTS: In 2022, 79.6% of adults received at ≥ 1 vaccine dose, 75.0% received ≥ 2 doses ("fully vaccinated"), 45.7% received ≥ 3 doses (≥ 1 booster), and 17.2% received ≥ 4 doses (≥ 2 boosters). Marked inequities were evident in COVID-19 vaccination across primary and booster doses, especially receipt of at least 1 booster dose (≥ 3 doses). Black (35.7%, prevalence ratio [PR] 0.78 [95% CI 0.74-0.83]) and Latinx (35.5%, PR 0.82 [CI 0.78-0.86]) adults were less likely to receive ≥ 3 doses than Asian (66.5%, PR 1.41 [CI 1.35-1.48]) and White (48.8%) adults. Poverty (31.1% [PR 0.65 {CI 0.61-0.69}] vs. 50.7%) and food insecurity (27.1% [PR 0.63 {CI 0.58-0.68}] vs. 47.3%) were negatively associated with receipt of ≥ 3 vaccine doses. Adults without usual source of care (24.9%, PR 0.61 [CI 0.57-0.65]) or health insurance (17.4%, PR 0.40 [CI 0.36-0.45]) had much lower rates of ≥ 3 doses than those with appropriate health care access (48.7% and 51.9%, respectively). CONCLUSION: As of 2022, 1-in-5 U.S. adults remain unvaccinated, and more than half have not received any recommended booster doses. Economically/socially marginalized populations-including Black and Latinx adults and those with structural barriers such as poverty, food insecurity, and poor health care access-were less likely to receive a booster. Addressing these vaccination inequities is crucial to achieve equitable COVID-19 protection and reduce preventable deaths among economically/socially marginalized populations.

Femoral neck width genetic risk score is a novel independent risk factor for hip fractures.

Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29-1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30-1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05-1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06-1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction.

Femoral neck width (FNW) derived from DXA scans may provide useful information about hip fracture prediction, over and above that provided by BMD measurements. Therefore, we investigated whether FNW is related to hip fracture risk independently of BMD, using a genetic approach. FNW was derived from points automatically placed on the hip in DXA scans obtained from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank. Seventy-one distinct genetic factors were found to be associated with FNW. Individuals who were predicted by their genes to have greater FNW had a higher risk of hip but not forearm fractures. In contrast, those with greater genetically determined BMD of the femoral neck had a lower risk of both hip and forearm fractures. We conclude that the underlying biology regulating FNW and BMD of the femoral neck differs, and that FNW derived from DXA analyses may contribute clinically useful information beyond BMD for hip fracture prediction.

Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.

RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.

Mechanisms of coronary sinus reducer for treatment of myocardial ischemia: in silico study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) [up to 69% with near-complete coronary sinus (CS) occlusion] is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis; however, the redistribution of blood draining from the nonischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the nonischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.NEW & NOTEWORTHY Emerging coronary venous retroperfusion treatments, particularly coronary sinus reducer (CSR) for refractory angina linked to myocardial ischemia, show promise; however, their mechanisms of action are not well understood. We find that CSR's effectiveness varies with the severity of coronary stenosis. In moderate stenosis, CSR improves tissue oxygenation by increasing capillary transit time, whereas in severe stenosis, it redistributes blood from nonischemic to ischemic regions and reduces capillary flow heterogeneity.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

BACKGROUND: Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. METHODS AND RESULTS: A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. CONCLUSIONS: Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting.

Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB biogenesis.

Compatibility of the fungus Beauveria bassiana and Trichoplusia ni SNPV against the cabbage looper Trichoplusia ni: crop plant matters.

BACKGROUND: Microbial insecticides are an important weapon in insect pest management, but their use is still relatively limited. One approach for increasing their efficacy and use could be to combine different pathogens to increase pest mortality. However, little is known about whether increasing pathogen diversity will improve pest management. Here, we investigated the compatibility of two pathogens for the management of the cabbage looper, Trichoplusia ni, T. ni nucleopolyhedrovirus (TniSNPV) and the entomopathogenic fungus Beauveria bassiana, on two crops, tomato and broccoli. The pathogens were applied to individual plants using ultra low volume sprays, alone or in combination, either synchronously or asynchronously. Healthy third-instar T. ni larvae were introduced to the plants before application and collected by destructive sampling 24 h after the last pathogen application. RESULTS: Combined applications did not result in an increase in larval mortality compared to TniSNPV alone, although mortality was generally high. B. bassiana was considerably less effective on broccoli compared to tomato. In both the combined treatments, virus-induced mortality was approximately 50% lower when applied together with the fungus, while fungus-induced mortality was not affected by the virus, even when the virus was introduced 24 h before the fungus. CONCLUSION: While our results suggest that applying this combination of entomopathogens would not be beneficial for pest management, this study illustrates the need to consider the target crop as an important driver of the efficacy of both single and mixed pathogen applications in the field. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Bariatric surgery patients in AUD treatment in Norway-an exploratory cross-sectional study.

AIMS: Patients who have undergone some forms of bariatric surgery have increased risk of developing alcohol use disorder (AUD). In the present observational study, we compared patients with AUD who themselves reported to having undergone bariatric surgery with other patients in treatment for AUD. MATERIALS: One-hundred-and-six consecutively enrolled patients in residential treatment for AUD were asked if they had undergone bariatric surgery. Sociodemographics, mental health-related, and alcohol use-related parameters were compared between those who had and those who had not undergone bariatric surgery. RESULTS: Of the 106 patients with AUD, seven (6.6%; 95% confidence interval, 2.7%-13.1%) had undergone bariatric surgery. Six of seven patients had undergone such surgery were women (P < .001). The patients with AUD who had undergone bariatric surgery were similar to other patients with AUD on most other parameters, the exception being a larger number of alcohol units ingested to feel an effect of alcohol (adjusted odds ratio 7.1; 95% confidence interval 2.0-12.2; P = .007). CONCLUSION: The high number of patients with AUD that reported having undergone bariatric surgery emphasizes the risks following such a procedure. The overrepresentation of women may reflect than more women undergo such procedures. The unexpected finding that patients with AUD having undergone bariatric surgery seemed to need more alcohol to feel intoxicated warrants further research.