Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged ≥60 years: A phase 1, randomized, observer-blind, placebo-controlled trial.

BACKGROUND: Respiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged ≥60 years of Japanese descent. METHODS: In this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 µg or placebo. Solicited local and systemic adverse reactions (ARs) were collected within 7 days following injection. Unsolicited adverse events (AEs) were collected up to 28 days after injection; AEs of special interest, medically attended AEs, and serious AEs were collected through end of study. Immunogenicity was assessed at baseline and months 1, 2, 3, and 6 following injection. RESULTS: Twenty-five adults of Japanese descent aged ≥60 years received one injection of mRNA-1345 100 µg (n = 21) or placebo (n = 4). mRNA-1345 was well-tolerated; the most common local and systemic solicited ARs were injection site pain, and fatigue and myalgia, respectively, which were generally mild to moderate and transient. No serious AEs were reported. Neutralizing (nAb) and binding (bAb) antibodies were detectable at baseline, consistent with prior RSV exposure. mRNA-1345 boosted RSV nAb titers and preF bAb concentrations 1 month post-injection (geometric mean fold rise: RSV-A nAb, 11.2; RSV-B nAb, 6.6; preF bAb, 9.1). Titers among mRNA-1345 recipients remained above baseline through 6 months. CONCLUSIONS: mRNA-1345 100 µg was well-tolerated among older adults of Japanese descent and induced nAbs and bAbs which were durable through 6 months, supporting its continued development. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04528719.

Frailty in patients with ovarian cancer and the role of healthcare access, race, and ethnicity.

OBJECTIVE: Ovarian cancer has poor 5-year survival, particularly among non-Hispanic (NH) Black patients. Efforts to identify patients at high-risk of functional limitations and frailty may improve outcomes. In this study, we examined how healthcare access (HCA) and race/ethnicity relate to frailty among patients with ovarian cancer. METHODS: We identified Hispanic, NH Black, and NH White patients diagnosed at ages ≥6 5 years with ovarian cancer between 2009 and 2015 using SEER-Medicare. Log-binomial regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between HCA and race/ethnicity with pre- or post-diagnosis frailty, adjusting for age and comorbidities. RESULTS: A total of 6041 patients with ovarian cancer were included, including 91.8% NH White, 6.6% NH Black, and 1.7% Hispanic. Pre-diagnosis, 14.7% of patients were defined as frail (NH White: 14.3%; NH Black: 17.9%; Hispanic: 20.8%). Post-diagnosis, frailty prevalence increased to 58.8% (NH White: 58.2%; NH Black: 65.2%; Hispanic: 70.2%). No statistically significant associations were observed between race/ethnicity and pre- or post-diagnosis frailty in fully adjusted models. After adjustment for patient characteristics and healthcare accessibility and availability, higher healthcare affordability was associated with a decreased prevalence of pre-diagnosis frailty (PR: 0.91, 95% CI: 0.8 5, 0.98). CONCLUSIONS: Patients with ovarian cancer have a high prevalence of frailty after diagnosis, particularly NH Black and Hispanic patients. Improving healthcare affordability may prevent or help manage frailty in Medicare patients, improve receipt of cancer treatment, and increase cancer survival.

Enhanced Recovery After Surgery (ERAS) Society Recommendations for Neonatal Perioperative Care.

Importance: Neonates requiring surgery are often cared for in neonatal intensive care units (NICUs). Despite a breadth of surgical pathology, neonates share many perioperative priorities that allow for the development of unit-wide evidence-based Enhanced Recovery After Surgery (ERAS) recommendations. Observations: The guideline development committee included pediatric surgeons, anesthesiologists, neonatal nurses, and neonatologists in addition to ERAS content and methodology experts. The patient population was defined as neonates (first 28 days of life) undergoing a major noncardiac surgical intervention while admitted to a NICU. After the first round of a modified Delphi technique, 42 topics for potential inclusion were developed. There was consensus to develop a search strategy and working group for 21 topic areas. A total of 5763 abstracts were screened, of which 98 full-text articles, ranging from low to high quality, were included. A total of 16 recommendations in 11 topic areas were developed with a separate working group commissioned for analgesia-related recommendations. Topics included team communication, preoperative fasting, temperature regulation, antibiotic prophylaxis, surgical site skin preparation, perioperative ventilation, fluid management, perioperative glucose control, transfusion thresholds, enteral feeds, and parental care encouragement. Although clinically relevant, there were insufficient data to develop recommendations concerning the use of nasogastric tubes, Foley catheters, and central lines. Conclusions and Relevance: Despite varied pathology, neonatal perioperative care within NICUs allows for unit-based ERAS recommendations independent of the planned surgical procedure. The 16 recommendations within this ERAS guideline are intended to be implemented within NICUs to benefit all surgical neonates.

Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use.

ABSTRACT: Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were ≥18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using χ 2 tests for categorical variables and t -tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n = 808) were 53.6 (SD ± 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly ( P < 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly ( P = 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.

Impact of comprehensive medication reviews on potentially inappropriate medication discontinuation in Medicare beneficiaries.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic subgroups. Medicare's nationwide medication therapy management (MTM) program requires that Part D plans offer an annual comprehensive medication review (CMR) to all beneficiaries who qualify, and provides a platform to reduce PIM use. The objective of this study was to assess the impact of CMR on PIM discontinuation in Medicare beneficiaries and whether this differed by race or ethnicity. METHODS: Retrospective cohort study of community-dwelling Medicare Part D beneficiaries ≥66 years of age who were eligible for MTM from 2013 to 2019 based on 5% Medicare fee-for-service claims data linked to the 100% MTM data file. Among those using a PIM, MTM-eligible CMR recipients were matched to non-recipients via sequential stratification. The probability of PIM discontinuation was estimated using regression models that pooled yearly subcohorts accounting for within-beneficiary correlations. The most common PIMs that were discontinued after CMR were reported. RESULTS: We matched 24,368 CMR recipients to 24,368 CMR non-recipients during the observation period. Median age was 74-75, 35% were males, most were White beneficiaries (86%-87%), and the median number of PIMs was 1. In adjusted analyses, CMR receipt was positively associated with PIM discontinuation (adjusted relative risk [aRR]: 1.26, 95% CI: 1.20-1.32). There was no evidence of differential impact of CMR by race or ethnicity. The PIMs most commonly discontinued after CMR were glimepiride, zolpidem, digoxin, amitriptyline, and nitrofurantoin. CONCLUSIONS: Among Medicare beneficiaries who are using a PIM, CMR receipt was associated with PIM discontinuation, suggesting that greater CMR use could facilitate PIM reduction for all racial and ethnic groups.

Association of Patient-Reported Social Needs with Emergency Department Visits and Hospitalizations Among Federally Qualified Health Center Patients.

BACKGROUND: Health care systems are increasingly screening for unmet social needs. The association between patient-reported social needs and health care utilization is not well understood. OBJECTIVE: To investigate the association between patient-reported social needs, measured by the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), and inpatient and emergency department (ED) utilization. DESIGN: This cohort study analyzed merged 2017-2019 electronic health record (EHR) data across multiple health systems. PARTICIPANTS: Adult patients from a federally qualified health center (FQHC) in central North Carolina who completed PRAPARE as part of a primary care visit with behavioral health services. MAIN MEASURES: The count of up to 12 unmet social needs, aggregated as 0, 1, 2, or 3 + . Outcomes include the probability of an ED visit and hospitalization 12 months after PRAPARE assessment, modeled by logistic regressions controlling for age, sex, race, ethnicity, comorbidity burden, being uninsured, and prior utilization in the past 12 months. KEY RESULTS: The study population consisted of 1924 adults (38.7% male, 50.1% Black, 36.3% Hispanic, 55.9% unemployed, 68.2% of patients reported 1 + needs). Those with more needs were younger, more likely to be unemployed, and experienced greater comorbidity burden. 35.3% of patients had ED visit(s) and 36.3% had hospitalization(s) 1 year after PRAPARE assessment. In adjusted analysis, having 3 + needs was associated with a percentage point increase in the predicted probability of hospitalization (average marginal effect 0.06, SE 0.03, p < 0.05) compared with having 0 needs. Similarly, having 2 needs (0.07, SE 0.03, p < 0.05) or 3 + needs (0.06, SE 0.03, p < 0.05) was associated with increased probability of ED visits compared to 0 needs. CONCLUSIONS: Patient-reported social needs were common and associated with health care utilization patterns. Future research should identify interventions to address unmet social needs to improve health and avoid potentially preventable escalating medical intervention.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

We outside: Modeling equity-centered, antiracist, community-driven partnerships in resident education.

Background: Community engagement is increasingly recognized as a necessity in addressing intractable racial and ethnic health disparities in the United States. However, institutions have not adequately trained resident physicians in developing symbiotic community partnerships that preserve community autonomy and identity without exploitation. Our goals were to highlight the experiences of expert academic emergency physicians in creating innovative, community-driven, and anti-racist solutions to achieving measurable equity in health outcomes and to introduce a novel framework entitled the Social Change Method to take a community-embedded intervention from concept to creation. Methods: The methodology was based on the development of a didactic session at the 2023 SAEM Annual Meeting. The three novel initiatives discussed were Emergency Medicine Remix (EMR); Trust, Research, Access, and Prevention (TRAP) Medicine; and The Health Equity Accelerator (HEA). A team of multi-institutional experts convened to develop the session objectives through priority setting. Results: Our expert panel discussed successes and challenges encountered while using evidence-informed strategies to conduct their community-based programming. Participant questions were centered on fostering sustainability, emphasizing the importance of carefully crafted interventions in the face of uncertain legislative challenges and strategies to empower others. Conclusions: Emergency medicine residency education should incorporate training on methods to leverage community partnerships to improve individual and community health outcomes. The Social Change Method can be used as a conceptual framework to generate easily re-creatable and scalable partnerships that establish trust and forge relationships that honor identity and autonomy without exploiting community members.

Comprehensive Medication Review Completion Rates and Disparities After Medicare Star Rating Measure.

Importance: Comprehensive medication reviews (CMRs) are offered to qualifying US Medicare beneficiaries annually to optimize medication regimens and therapeutic outcomes. In 2016, Medicare adopted CMR completion as a Star Rating quality measure to encourage the use of CMRs. Objective: To examine trends in CMR completion rates before and after 2016 and whether racial, ethnic, and socioeconomic disparities in CMR completion changed. Design, Setting, and Participants: This observational study using interrupted time-series analysis examined 2013 to 2020 annual cohorts of community-dwelling Medicare beneficiaries aged 66 years and older eligible for a CMR as determined by Part D plans and by objective minimum eligibility criteria. Data analysis was conducted from September 2022 to February 2024. Exposure: Adoption of CMR completion as a Star Rating quality measure in 2016. Main Outcome and Measures: CMR completion modeled via generalized estimating equations. Results: The study included a total of 561 950 eligible beneficiaries, with 253 561 in the 2013 to 2015 cohort (median [IQR] age, 75.8 [70.7-82.1] years; 90 778 male [35.8%]; 6795 Asian [2.7%]; 24 425 Black [9.6%]; 7674 Hispanic [3.0%]; 208 621 White [82.3%]) and 308 389 in the 2016 to 2020 cohort (median [IQR] age, 75.1 [70.4-80.9] years; 126 730 male [41.1%]; 8922 Asian [2.9%]; 27 915 Black [9.1%]; 7635 Hispanic [2.5%]; 252 781 White [82.0%]). The unadjusted CMR completion rate increased from 10.2% (7379 of 72 225 individuals) in 2013 to 15.6% (14 185 of 90 847 individuals) in 2015 and increased further to 35.8% (18 376 of 51 386 individuals) in 2020, in part because the population deemed by Part D plans to be MTM-eligible decreased by nearly half after 2015 (90 487 individuals in 2015 to 51 386 individuals in 2020). Among a simulated cohort based on Medicare minimum eligibility thresholds, the unadjusted CMR completion rate increased but to a lesser extent, from 4.4% in 2013 to 12.6% in 2020. Compared with White beneficiaries, Asian and Hispanic beneficiaries experienced greater increases in likelihood of CMR completion after 2016 but remained less likely to complete a CMR. Dual-Medicaid enrollees also experienced greater increases in likelihood of CMR completion as compared with those without either designation, but still remained less likely to complete CMR. Conclusion and Relevance: This study found that adoption of CMR completion as a Star Rating quality measure was associated with higher CMR completion rates. The increase in CMR completion rates was achieved partly because Part D plans used stricter eligibility criteria to define eligible patients. Reductions in disparities for eligible Asian, Hispanic, and dual-Medicaid enrollees were seen, but not eliminated. These findings suggest that quality measures can inform plan behavior and could be used to help address disparities.

Global latitudinal gradients and the evolution of body size in dinosaurs and mammals.

Global climate patterns fundamentally shape the distribution of species and ecosystems. For example, Bergmann's rule predicts that homeothermic animals, including birds and mammals, inhabiting cooler climates are generally larger than close relatives from warmer climates. The modern world, however, lacks the comparative data needed to evaluate such macroecological rules rigorously. Here, we test for Bergmann's rule in Mesozoic dinosaurs and mammaliaforms that radiated within relatively temperate global climate regimes. We develop a phylogenetic model that accounts for biases in the fossil record and allows for variable evolutionary dispersal rates. Our analysis also includes new fossil data from the extreme high-latitude Late Cretaceous Arctic Prince Creek Formation. We find no evidence for Bergmann's rule in Mesozoic dinosaurs or mammaliaforms, the ancestors of extant homeothermic birds and mammals. When our model is applied to thousands of extant dinosaur (bird) and mammal species, we find that body size evolution remains independent of latitude. A modest temperature effect is found in extant, but not in Mesozoic, birds, suggesting that body size evolution in modern birds was influenced by Bergmann's rule during Cenozoic climatic change. Our study provides a general approach for studying macroecological rules, highlighting the fossil record's power to address longstanding ecological principles.

Health Care Access Dimensions and Racial Disparities in End-of-Life Care Quality among Patients with Ovarian Cancer.

This study investigated the association between health care access (HCA) dimensions and racial disparities in end-of-life (EOL) care quality among non-Hispanic Black (NHB), non-Hispanic White (NHW), and Hispanic patients with ovarian cancer. This retrospective cohort study used the Surveillance, Epidemiology, and End Results-linked Medicare data for women diagnosed with ovarian cancer from 2008 to 2015, ages 65 years and older. Health care affordability, accessibility, and availability measures were assessed at the census tract or regional levels, and associations between these measures and quality of EOL care were examined using multivariable-adjusted regression models, as appropriate. The final sample included 4,646 women [mean age (SD), 77.5 (7.0) years]; 87.4% NHW, 6.9% NHB, and 5.7% Hispanic. In the multivariable-adjusted models, affordability was associated with a decreased risk of intensive care unit stay [adjusted relative risk (aRR) 0.90, 95% confidence interval (CI): 0.83-0.98] and in-hospital death (aRR 0.91, 95% CI: 0.84-0.98). After adjustment for HCA dimensions, NHB patients had lower-quality EOL care compared with NHW patients, defined as: increased risk of hospitalization in the last 30 days of life (aRR 1.16, 95% CI: 1.03-1.30), no hospice care (aRR 1.23, 95% CI: 1.04-1.44), in-hospital death (aRR 1.27, 95% CI: 1.03-1.57), and higher counts of poor-quality EOL care outcomes (count ratio:1.19, 95% CI: 1.04-1.36). HCA dimensions were strong predictors of EOL care quality; however, racial disparities persisted, suggesting that additional drivers of these disparities remain to be identified. SIGNIFICANCE: Among patients with ovarian cancer, Black patients had lower-quality EOL care, even after adjusting for three structural barriers to HCA, namely affordability, availability, and accessibility. This suggests an important need to investigate the roles of yet unexplored barriers to HCA such as accommodation and acceptability, as drivers of poor-quality EOL care among Black patients with ovarian cancer.

Bone microarchitectural alterations associated with spinal cord injury: Relation to sex hormones, metabolic factors, and loading.

CONTEXT: People living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. OBJECTIVE: To determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DESIGN: Cross-sectional analyses of bone properties in people with SCI. PARTICIPANTS: Twenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). OUTCOME MEASURES: Distal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (µFEA); sex hormones; metabolic and inflammatory markers. RESULTS: The mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score - 3.3), trabecular (-2.93), and cortical vBMD (-1.87), and Failure Load by µFEA (-2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (ß = 0.77, p = 0.02), thickness (ß = 0.52, p = 0.04) and number (ß = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (ß = 0.59, p = 0.01), trabecular thickness (ß = 0.43, p = 0.04), cortical thickness (ß = 0.63, p = 0.01) and cortical porosity (ß = 0.74 p = 0.04). CONCLUSIONS: Radius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading. CLINICALTRIALS: gov registration #: (NCT03576001).

Safety, Tolerability and Immunogenicity of a mRNA-based RSV Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial.

BACKGROUND: Respiratory syncytial virus (RSV) presents a global health concern. A lipid nanoparticle-encapsulated mRNA-based RSV vaccine (mRNA-1345) encoding the membrane-anchored RSV prefusion stabilised F glycoprotein (preF) is under clinical investigation. METHODS: This phase 1, randomized, observer-blind, placebo-controlled dose escalation study assessed safety and immunogenicity of mRNA-1345 in healthy adults aged 18-49 years (NCT04528719). Participants were randomized to receive one dose of mRNA-1345 (50, 100, or 200 µg) or placebo, or 3 doses of mRNA-1345 (100 µg) or placebo 56 days apart. RESULTS: mRNA-1345 was well-tolerated at all dose levels. The most common solicited adverse reactions were pain, headache, fatigue, myalgia, or chills, which were all generally mild to moderate. A single injection of mRNA-1345 boosted RSV neutralizing antibody titers (geometric mean fold rise [GMFR]: RSV-A, 20.0 to 23.5; RSV-B, 11.7 to 16.0) and RSV preF binding antibody concentrations (GMFR: 16.1 to 21.8) at 1 month post injection, with no apparent dose response. Antibody levels remained above baseline through 6 months. Sequential doses of 100 µg were well tolerated but did not further boost antibody levels. CONCLUSIONS: A single mRNA-1345 injection demonstrated an acceptable safety profile in younger adults and induced a durable neutralizing antibody response, supporting its continued development.

Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase I Clinical Trial in Healthy Older Adults.

BACKGROUND: An mRNA-based RSV vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults. METHODS: This phase 1, randomized, observer-blind, placebo-controlled, dose-ranging study evaluated safety, reactogenicity, and immunogenicity of mRNA-1345 in adults 65-79 years (NCT04528719). Participants were randomized to receive 1-dose of mRNA-1345 (12.5, 25, 50, 100, or 200-µg) or placebo and matched mRNA-1345 booster or placebo at 12-months. RESULTS: Overall, 298 participants received the first injection; 247 received the 12-month booster injection. mRNA-1345 was generally well-tolerated after both injections, with the most frequently reported solicited adverse reactions being injection-site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection than the first injection but similar severity, time-to-onset, and duration. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers (nAb) and prefusion-F-binding antibody (preF-bAb) concentrations at 1-month (geometric mean-fold rises: RSV-A, 10.2-16.5; RSV-B, 5.3-12.5; preF-bAb, 7.2-12.1). RSV antibody levels remained above baseline through 12-months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B nAb titers and preF-bAb concentrations; titers post-booster injection were numerically lower compared to titers after the first-dose, with overlapping 95% CIs. CONCLUSIONS: mRNA-1345 was well-tolerated and immunogenic following a single injection and a 12-month booster. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04528719.

Factors Associated With Interest in Engaging in Psychological Interventions for Pain Management.

OBJECTIVE: Engagement in evidence-based psychological interventions for pain management is low. Identifying characteristics associated with interest in interventions can inform approaches to increase uptake and engagement. The purpose of this study was to examine factors associated with interest in psychological interventions among persons with chronic noncancer pain receiving prescription opioids. METHODS: Participants with chronic noncancer pain and a new 30 to 90 day opioid prescription were recruited from 2 health systems. Participants (N=845) completed measures regarding pain, opioid use, psychiatric symptoms, emotional support, and interest in psychological interventions for pain management. RESULTS: There were 245 (29.0%) participants who reported a high interest in psychological interventions for pain management. In bivariate analyses, variables associated with interest included younger age, female sex, greater pain severity, greater pain interference, greater number of pain sites, lower emotional support, depression, anxiety, and post-traumatic stress disorder ( P <0.05). In a multivariate model, greater pain severity (odds ratio [OR]=1.17; CI: 1.04-1.32), depression (OR=2.10; CI: 1.39-3.16), post-traumatic stress disorder (OR=1.85; CI: 1.19-2.95), and lower emotional support (OR=0.69; CI: 0.5-0.97) remained statistically significant. DISCUSSION: The rate of interest in psychological interventions for pain management was low, which may indicate that patients initiating opioid treatment of chronic noncancer pain have low interest in psychological interventions. Greater pain severity and psychiatric distress were related to interest, and patients with these characteristics may especially benefit from psychological interventions. Providers may want to refer to psychological interventions before or when opioids are initiated. Additional work is needed to determine whether this would reduce long-term opioid use.

Characteristics, healthcare utilization, and outcomes of patients with HER2-low breast cancer.

PURPOSE: Treatment for HER2-low [defined as ImmunoHistoChemistry (IHC) 1 + or 2 + and negative/normal in Situ Hybridization (ISH)] breast cancer patients is rapidly evolving, yet we lack critical information about the HER2-low population. METHODS: We conducted a retrospective cohort study of women aged 18 years or older diagnosed with breast cancer between 2010 and 2016 in North Carolina. Analyses were conducted for the overall cohort and a stage IV sub-cohort. We examined demographic and clinical characteristics, and characterized prevalence of HER2-low disease and healthcare utilization. We estimated adjusted rate ratios for the association between HER2 classifications and utilization outcomes, and hazard ratios for 3-year all cause mortality (stage IV only). RESULTS: The overall and stage IV cohorts included 12,965 and 635 patients, respectively. HER2-low patients represented more than half of both cohorts (59% overall, 53% stage IV). HER2-low patients were more likely than IHC 0 patients to have hormone receptor (HR)-positive disease. In the stage IV cohort, HER2-low patients were more likely to be Black (26% vs. 16% IHC 0, p = 0.0159). In both cohorts, rates of hospitalizations were slightly higher among HER2-low patients. There were no survival differences between HER2-low and IHC 0 among stage IV patients. CONCLUSION: New treatment options for HER2-low breast cancer may have potential for significant impact at the population level particularly for patients with stage IV disease. In light of racial differences between HER2-low and IHC 0 patients observed in our cohort, research- and practice-based efforts to ensure equitable adoption of new treatment guidelines for patients with HER2-low metastatic breast cancer will be essential.

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 µg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

Atrial fibrillation as a novel risk factor for retinal stroke: A protocol for a population-based retrospective cohort study.

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

Association of educational attainment with cancer mortality in a national cohort study of black and white adults: A mediation analysis.

Background: Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown. Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated the associations of participant and parental/caregiver education with cancer mortality using Cox proportional hazards models, adjusting for socio-demographic characteristics and health conditions. We used principal components analysis to generate indices of measures representing the social determinants of health (SDOH) and health behaviors. We used structural equation modeling to determine if the association between educational attainment and cancer mortality was mediated by these domains. Results: Among 30,177 REGARDS participants included in this analysis, 3798 (12.6%) had less than a high school degree. In fully adjusted models, those without a high school education experienced about 50% greater risk of death than high school graduates and higher (White participants HR: 1.47; 95% CI: 1.23, 1.76 and Black HR: 1.54; 95% CI: 1.33, 1.79). There was evidence of a modest mediation effect for the association between education and cancer mortality by the SDOH domain score (White total effect HR: 1.25; 95% CI: 1.18, 1.33, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.21; 95% CI: 1.14, 1.28 and Black total effect HR: 1.24; 95% CI: 1.18, 1.29, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.19; 95% CI: 1.14, 1.24). There was no evidence of mediation by the health behaviors score. No significant associations were found for female caregiver/mother's or male caregiver/father's education (N = 13,209). Conclusions: In conclusion, participant education was strongly associated with cancer mortality, and this association was partially mediated by the SDOH domain score.