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Stephanie H Noh,1– 3 Andrew K Smith,1– 3 Austin R Fox,1– 3 Kevin M Gustafson,1– 3 Changyow C Kwan,1– 3 Ken Y Lin,1,2,4 Sameh Mosaed1,2 1University of California, Irvine School of Medicine, Irvine, CA, 92617, USA; 2Gavin Herbert Eye Institute, Department of Ophthalmology, UC Irvine, Irvine, CA, 92617, USA; 3Tibor Rubin Veteran Affairs Medical Center, Long Beach, CA, 90822, USA; 4Department of Biomedical Engineering, UC Irvine, Irvine, CA, 92617, USACorrespondence: Stephanie H Noh, Gavin Herbert Eye Institute, University of California, Irvine, USA, 850 Health Sciences Road, Irvine, CA, 92617, USA, Tel +1-951-751-7971, Fax +1-949-824-2073, Email shnoh1@hs.uci.eduPurpose: To compare outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle.Patients and methods: This was a prospective, non-randomized, interventional comparison study done at the Veteran Affairs Hospital in Long Beach, California. All patients underwent cataract surgery with intraocular lens implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA, USA), either superiorly or inferiorly. Pre- and post-operative intraocular pressure using Goldmann applanation tonometry and best corrected visual acuity were obtained and compared using paired t-tests. Patients were excluded if they had any prior intraocular surgery or prior laser trabeculoplasty procedures.Results: 38 eyes from 29 patients were analyzed. 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean postoperative IOP for the superior group decreased 24% to 13.3 ± 2.8 mmHg while the inferior group decreased 26% to 13.1 ± 2.2 mmHg (p = 0.92). Mean preoperative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64).Conclusion: There was no statistical difference in efficacy between superior versus inferior canaloplasty/trabeculotomy with OMNI. Therefore, surgeons can perform the procedure in the direction that is most comfortable for them without affecting outcomes.Keywords: OMNI, canaloplasty, trabeculotomy, goniotomy, MIGS

Andrew K Smith,1– 3 Changyow C Kwan,1– 3 Austin Fox,1– 3 Stephanie Noh,1– 3 Kevin Gustafson,1– 3 Ken Y Lin,1,2,4 Sameh Mosaed1,2 1School of Medicine, University of California, Irvine, CA, USA; 2Department of Ophthalmology, Gavin Herbert Eye Institute, Irvine, CA, USA; 3Department of Ophthalmology, Tibor Rubin Veteran Affairs Medical Center, Long Beach, CA, USA; 4Department of Biomedical Engineering, University of California, Irvine, CA, USACorrespondence: Andrew K Smith, Gavin Herbert Eye Institute, University of California, 850 Health Sciences Road, Irvine, CA, 92697-4375, USA, Tel +1-949-824-7944, Fax +1-949-824-2073, Email andrewks@hs.uci.eduPurpose: To evaluate outcomes of new adopters of the OMNI® Surgical System (Sight Sciences, Inc.) by prospectively evaluating intermediate-term outcomes of patients operated by trainees.Patients and Methods: This was a prospective study of surgeries performed by trainees on patients with open angle glaucoma undergoing simultaneous cataract surgery and ab interno canaloplasty and trabeculotomy using the OMNI Surgical System. Pre-operative intraocular pressure (IOP) and number of glaucoma medications were recorded. Only patients with a minimum of 6-month follow up were included. Baseline IOP was used to separate subjects into two groups: Group 1 (IOP ≥ 18 mmHg) and Group 2 (IOP < 18 mmHg). Mean decrease in IOP and medications was calculated and compared with paired t-tests for the overall sample as well as the subgroups. Success was defined as those with a ≥ 20% reduction from pre-operative IOP or with an IOP ≤ 18 mmHg and ≥ 6 mmHg and on the same or fewer number of medications while not requiring additional surgery. Adverse events were also recorded.Results: Forty-two eyes of 31 patients were included. Mean pre-operative IOP was 17.2 ± 4.8 mmHg and mean number of medications was 2.4 ± 1.2. The primary endpoint was reached in 83.3% of patients at 12 months. IOP was reduced by 22.3% to 13.4 ± 2.4 (p< 0.001). Mean number of medications decreased to 1.7 ± 1.6 (p< 0.001). Group 1 mean IOP decreased 35.4% from 22.2 ± 4.6 mmHg to 14.3 ± 2.8 mmHg (p< 0.001). Group 2 mean number of medications decreased from 2.3 ± 1.1 to 1.6 ± 1.5 (p< 0.001).Conclusion: When operated on by the novice MIGS surgeon, the OMNI device provides effective IOP and glaucoma medication reduction with minimal adverse events. Efficacy and safety of the device in the hands of trainees was comparable to experienced glaucoma surgeons suggesting its ease of adoption.Keywords: OMNI, canaloplasty, trabeculotomy, goniotomy, MIGs, minimally invasive glaucoma surgeries

Sasha E Parets,1 Anna K Knight,2 Alicia K Smith,1,2 1Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; 2Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA Abstract: Preterm birth (PTB;

BACKGROUND: As our society ages, improving medical care for an older population will be crucial. Discrimination in healthcare may contribute to substandard experiences with the healthcare system, increasing the burden of poor health in older adults. Few studies have focused on the presence of healthcare discrimination and its effects on older adults. OBJECTIVE: We aimed to examine the relationship between healthcare discrimination and new or worsened disability. DESIGN: This was a longitudinal analysis of data from the nationally representative Health and Retirement Study administered in 2008 with follow-up through 2012. PARTICIPANTS: Six thousand and seventeen adults over the age of 50 years (mean age 67 years, 56.3 % female, 83.1 % white) were included in this study. MAIN MEASURES: Healthcare discrimination assessed by a 2008 report of receiving poorer service or treatment than other people by doctors or hospitals (never, less than a year=infrequent; more than once a year=frequent). Outcome was self-report of new or worsened disability by 2012 (difficulty or dependence in any of six activities of daily living). We used a Cox proportional hazards model adjusting for age, race/ethnicity, gender, net worth, education, depression, high blood pressure, diabetes, cancer, lung disease, heart disease, stroke, and healthcare utilization in the past 2 years. KEY RESULTS: In all, 12.6 % experienced discrimination infrequently and 5.9 % frequently. Almost one-third of participants (29 %) reporting frequent healthcare discrimination developed new or worsened disability over 4 years, compared to 16.8 % of those who infrequently and 14.7 % of those who never experienced healthcare discrimination (p < 0.001). In multivariate analyses, compared to no discrimination, frequent healthcare discrimination was associated with new or worsened disability over 4 years (aHR = 1.63, 95 % CI 1.16–2.27). CONCLUSIONS: One out of five adults over the age of 50 years experiences discrimination in healthcare settings. One in 17 experience frequent healthcare discrimination, and this is associated with new or worsened disability by 4 years. Future research should focus on the mechanisms by which healthcare discrimination influences disability in older adults to promote better health outcomes for an aging population.

© 2015 The Author(s) BACKGROUND: As our society ages, improving medical care for an older population will be crucial. Discrimination in healthcare may contribute to substandard experiences with the healthcare system, increasing the burden of poor health in

Hydrogen-Deuterium exchange mass spectrometry's (HDX-MS) utility in identifying and characterizing protein-small molecule interaction sites has been established. The regions that are seen to be protected from exchange upon ligand binding indicate regions that may be interacting with the ligand, giving a qualitative understanding of the ligand binding pocket. However, quantitatively deriving an accurate high-resolution structure of the protein-ligand complex from the HDX-MS data remains a challenge, often limiting its use in applications such as small molecule drug design. Recent efforts have focused on the development of methods to quantitatively model Hydrogen-Deuterium exchange (HDX) data from computationally modeled structures to garner atomic level insights from peptide-level resolution HDX-MS. One such method, HDX ensemble reweighting (HDXer), employs maximum entropy reweighting of simulated HDX data to experimental HDX-MS to model structural ensembles. In this study, we implement and validate a workflow which quantitatively leverages HDX-MS data to accurately model protein-small molecule ligand interactions. To that end, we employ a strategy combining computational protein-ligand docking, molecular dynamics simulations, HDXer, and dimensional reduction and clustering approaches to extract high-resolution drug binding poses that most accurately conform with HDX-MS data. We apply this workflow to model the interaction of ERK2 and FosA with small molecule compounds and inhibitors they are known to bind. In five out of six of the protein-ligand pairs tested, the HDX derived protein-ligand complexes result in a ligand root-mean-square deviation (RMSD) within 2.5 Å of the known crystal structure ligand.

Background: Social constructs like race can affect how patients are perceived and impact care. This study investigated whether mentions of race in notes for critically ill patients differed according to patients' race., Methods: This retrospective cohort study included intensive care unit notes for adults (≥18 years old) admitted to any of 6 intensive care units at University of California, San Francisco, from 2012 through 2020. Notes were linked to National Provider Identifier records to obtain note writer characteristics. Logistic regression analysis with robust SEs clustered on note writers was adjusted for patient-, note- and clinician-level characteristics. Any race or ethnicity mention was the outcome of interest., Results: Among 5573 patients with 292 457 notes by 9742 unique note writers, 3225 patients (57.9%) self-reported their race as White, 997 (17.9%) as Asian, 860 (15.4%) as Latinx, and 491 (8.8%) as Black. Note writers documented race/ethnicity for 20.8% of Black, 10.9% of Latinx, 9.1% of White, and 4.4% of Asian patients. Black patients were more likely than White patients to have race mentioned in notes (adjusted odds ratio, 2.05 [95% CI, 1.49-2.82])., Conclusions: Black patients were more than twice as likely as White patients to have race mentioned in notes. Note language containing information on social constructs has consequences for clinicians and patients reading notes and for algorithms trained on clinical notes., (©2024 American Association of Critical-Care Nurses.)

Introduction: Among older adults without cancer, living alone is associated with poor health outcomes. However, among older adults with non-small cell lung cancer (NSCLC) who live alone, data on function, cognition, and quality of life (QOL) during systemic treatment remain limited., Materials and Methods: We enrolled adults aged ≥65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen with non-curative intent. Patients completed geriatric assessments including instrumental activities of daily living (IADL), Montreal Cognitive Assessment, and QOL pretreatment and at 1, 2, 4, and 6 months, or until treatment discontinuation, whichever occurred earlier. We categorized change in IADL, cognition, and QOL as stable/improved, declined with recovery, or declined without recovery using clinically meaningful definitions of change. We used multinomial logistic regression to compare change between patients who lived alone versus with others., Results: Among 149 patients, median age was 73; 21% lived alone. Pretreatment IADL, cognition, and QOL scores were similar between older adults who lived alone versus with others. During NSCLC treatment, older adults who lived alone had similar trajectories of function (52% functional decline vs 38%), cognition (43% cognitive decline vs 50%), and QOL (45% QOL decline vs 44%) compared with those who lived with others. In unadjusted analyses, patients who lived alone were more likely to develop functional decline with recovery (reference category: stable/improved function) than those who lived with others (relative risk ratio 4.07, 95% CI 1.14-14.6, p = 0.03). However, this association was not observed after adjusting for age, race, prior NSCLC treatment, current treatment group, and pretreatment geriatric assessment differences. There were no differences in cognitive or QOL trajectories in unadjusted or adjusted analyses., Discussion: Approximately half of older adults with advanced NSCLC who lived alone were able to maintain their function, cognition, and QOL during NSCLC treatment, which was similar to older adults who lived with others. Many older adults with advanced NSCLC who live alone can receive systemic treatment with individualized supportive care., Competing Interests: Declaration of Competing Interest SS reported conflicts of interest outside the submitted work (consultant/advisory to Oncohost). AIV reported conflicts of interest outside the submitted work (consultant/advisory to Merus and AstraZeneca). LCS has received research funding from AstraZeneca awarded directly to her institution. MLW reported conflicts of interest outside of the submitted work (royalties from UpToDate; immediate family member is an employee of Genentech with stock ownership). The remaining authors have no conflicts to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A metaphor conceptualizes one, typically abstract, experience in terms of another, more concrete, experience with the goal of making it easier to understand. Although combat metaphors have been well described in some health contexts, they have not been well characterized in the setting of critical illness., Research Question: How do clinicians use combat metaphors when describing critically ill patients and families in the electronic health record?, Study Design and Methods: We included notes written about patients aged 18 years or older admitted to ICUs within a large hospital system from 2012 through 2020. We developed a lexicon of combat words and isolated note segments that contained any combat mentions. Combat mentions were defined systematically as a metaphor or not across two coders. Among combat metaphors, we used a grounded theory approach to construct a conceptual framework around their use., Results: Across 6,404 combat-related mentions, 5,970 were defined as metaphors (Cohen κ, 0.84). The most common metaphors were "bout" (26.2% of isolated segments), "combat" (18.5%), "confront" (17.8%), and "struggle" (17.5%). We present a conceptual framework highlighting how combat metaphors can present as identity ("mom is a fighter") and process constructs ("struggling to breathe"). Identity constructs usually were framed around: (1) hope, (2) internal strength, (3) contextualization of current illness based on prior experiences, or (4) a combination thereof. Process constructs were used to describe: (1) "fighting for" (eg, working toward) a goal, (2) "fighting against" an unwanted force, or (3) experiencing internal turmoil., Interpretation: We provide a novel conceptual framework around the use of combat metaphors in the ICU. Further studies are needed to understand intentionality behind their use and how they impact clinician behaviors and patient and caregiver emotional responses., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Published by Elsevier Inc.)

Objective: To explore the policies of key organisations in Australian health and medical research on defining, collecting, analysing, and reporting data on sex and gender, and to identify barriers to and facilitators of developing and implementing such policies., Study Design: Mixed methods study: online planning forum; survey of organisations in Australian health and medical research, and internet search for policies defining, collecting, analysing, and reporting data by sex and gender in health and medical research., Setting, Participants: Australia, 19 May 2021 (planning forum) to 12 December 2022 (final internet search)., Main Outcome Measures: Relevant webpages and documents classified as dedicated organisation-specific sex and gender policies; policies, guidelines, or statements with broader aims, but including content that met the definition of a sex and gender policy; and references to external policies., Results: The online planning forum identified 65 relevant organisations in Australian health and medical research; twenty participated in the policy survey. Seven organisations reported at least one relevant policy, and six had plans to develop or implement such policies during the following two years. Barriers to and facilitators of policy development and implementation were identified in the areas of leadership, language and definitions, and knowledge skills and training. The internet search found that 57 of the 65 organisations had some form of sex and gender policy, including all ten peer-reviewed journals and five of ten research funders; twelve organisations, including eight peak body organisations, had published dedicated sex and gender policies on their websites., Conclusion: Most of the organisations included in our study had policies regarding the integration of sex and gender in health and medical research. The implementation and evaluation of these policies is necessary to ensure that consideration of sex and gender is adequate during all stages of the research process., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: National guidelines recognize lifetime trauma as relevant to clinical care for adults nearing the end of life. We determined the prevalence of early life and cumulative trauma among persons at the end of life by gender and birth cohort, and the association of lifetime trauma with end-of-life physical, mental, and social well-being., Methods: We used nationally representative Health and Retirement Study data (2006-2020), including adults age > 50 who died while enrolled (N = 6495). Early life and cumulative traumatic events were measured using an 11-item traumatic events scale (cumulative trauma: 0-5+ events over the lifespan). We included six birth cohorts (born <1924; children of depression [1924-1930]; HRS cohort [1931-1941]; war babies [1942-1947]; early baby-boomers [1948-1953]; mid-baby boomers [1954-1959]). End-of-life outcomes included validated measures of physical (pain, fatigue, dyspnea), mental (depression, life satisfaction), and social (loneliness, social isolation) needs. We report the prevalence of lifetime trauma by gender and birth cohort and the adjusted probability of each end-of-life outcome by trauma using multivariable logistic regression., Results: The mean age at death was 78 years (SD = 11.1) and 52% were female. Lifetime trauma was common (0 events: 19%; 1-2: 47%; 3-4: 25%; 5+: 9%), with variation in individual events (e.g., death of a child, weapons in combat) by gender and birth cohort. After adjustment, increasing cumulative trauma was significantly associated (p-value<0.001) with higher reports of end-of-life moderate-to-severe pain (0 events: 46%; 1-2 events: 50%; 3-4 events: 57%; 5+ events: 60%), fatigue (58%; 60%; 66%; 69%), dyspnea (46%; 51%; 56%; 58%), depression (24%; 33%; 37%; 40%), loneliness (12%; 17%; 19%; 22%), and lower life satisfaction (73%; 63%; 58%; 54%)., Conclusion: Older adults in the last years of life report a high prevalence of lifetime traumatic events which are associated with worse end-of-life physical and psychosocial health. A trauma-informed approach to end-of-life care and management of physical and psychosocial needs may improve a patient's quality of life., (© 2024 The American Geriatrics Society.)

Subgroup analyses conducted among U.S. national survey data have estimated that 27 to 34% of adults aged ≥65 years have chronic pain. However, none of these studies focused specifically on older adults or examined disparities in chronic pain in those aged ≥65 years. To obtain current information on the prevalence and sociodemographic correlates of chronic pain in U.S. older adults, a cross-sectional analysis was conducted of data collected from 3,505 older adults recruited from the AmeriSpeak Panel. Chronic pain was defined as pain on most or every day in the last 3 months. Nationally representative chronic pain prevalence estimates were computed by incorporating study-specific survey design weights. Logistic regression analyses evaluated differences in chronic pain status as a function of sociodemographic characteristics (eg, gender, race/ethnicity, and socioeconomic status). The results indicated that 37.8% of older adults reported chronic pain. Compared with White older adults, Black (odds ratio [OR] = .6, 95% CI: .4-.8) and Asian (OR = .2, 95% CI: .1-.8) older adults were less likely to report chronic pain. The prevalence of chronic pain was also lower among those who reported the highest (vs lowest) household income (OR = .6, 95% CI: .4-.8). Those who were not working due to disability (vs working as a paid employee) were more likely to report chronic pain (OR = 3.2, 95% CI: 2.1-5.0). This study was the first to recruit a large, representative sample of older adults to estimate the prevalence of chronic pain and extends prior work by identifying subgroups of older adults that are disproportionately affected. PERSPECTIVE: This study was the first to estimate the prevalence and sociodemographic correlates of chronic pain among a large, representative sample of U.S. older adults. The findings underscore the high prevalence of chronic pain and highlight disparities in chronic pain prevalence rates among this historically understudied population., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not., Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts., Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD., Conclusion: The inclusion of exposure variables adds to the predictive power of MRS. Classification-based MRS may be useful in predicting risk of future PTSD in populations with anticipated trauma exposure. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting PTSD and, relatedly, improve their performance in independent cohorts., (© 2024. The Author(s).)

Background: Ovarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells., Materials and Methods: Here, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervicovaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle., Results: Our findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5- cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and cytokines (IL-5 and IL-6) were correlated with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycle., Conclusion: Overall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Govindaraj, Tyree, Herring, Rahman, Babu, Ibegbu, Young, Mehta, Haddad, Smith and Velu.)

Borderline Personality Disorder (BPD) is characterized by rapidly shifting emotional, interpersonal, and behavioral symptoms, and is often co-morbid with mood and anxiety disorders. Females are more likely to be diagnosed with BPD than males and exhibit greater functional impairment. Hormonal fluctuations, particularly in estrogen levels, may influence the manifestation of BPD symptoms. Here we investigated the influence of estrogen-suppressing contraceptives on behavioral and functional difficulties in BPD. The analytical sample included 348 females ages 18-50 undergoing residential treatment for psychiatric disorders, with 131 having a BPD diagnosis. Patients were categorized based on their contraceptive method: 1) Estrogen-suppressing contraceptives (N=145) and 2) Naturally cycling (N=203). Interaction models tested the impact of estrogen-suppressing contraceptives on the relationship between BPD diagnosis and behavioral and functional difficulties at admission and discharge, assessed by the four Behavior and Symptom Identification Scale (BASIS-32) domains: difficulties in relationships, daily living, depression/anxiety, and impulsivity. Females with a BPD diagnosis were more likely to use estrogen-suppressing contraceptives compared to those without BPD (p=0.04). However, estrogen-suppressing contraceptive use was not associated with behavioral and functional difficulties at admission, discharge, or over time. Estrogen-suppressing contraceptives moderated the association between BPD diagnosis and difficulties in relationships (p=0.004), difficulties in daily living (p=0.01), and depression/anxiety symptoms (p=0.004). Patients with BPD expressed increased behavioral and functional difficulties at admission, discharge, and over time only if naturally cycling (p<0.003). Our findings suggest that estrogen-suppressing contraceptives may help to regulate the rapidly shifting emotional, interpersonal, and behavioral symptoms in females with BPD by stabilizing estrogen levels.

Importance: The widowhood effect, in which mortality increases and function decreases in the period following spousal death, may be heightened in older adults with functional impairment and serious illnesses, such as cancer, dementia, or organ failure, who are highly reliant on others, particularly spouses, for support. Yet there are limited data on widowhood among people with these conditions., Objective: To determine the association of widowhood with function and mortality among older adults with dementia, cancer, or organ failure., Design, Setting, and Participants: This longitudinal cohort study used population-based, nationally representative data from the Health and Retirement Study database linked to Medicare claims from 2008 to 2018. Participants were married or partnered community-dwelling adults aged 65 years and older with and without cancer, organ failure, or dementia and functional impairment (function score <9 of 11 points), matched on widowhood event and with follow-up until death or disenrollment. Analyses were conducted from September 2021 to May 2024., Exposure: Widowhood., Main Outcomes and Measures: Function score (range 0-11 points; 1 point for independence with each activity of daily living [ADL] or instrumental activity of daily living [IADL]; higher score indicates better function) and 1-year mortality., Results: Among 13 824 participants (mean [SD] age, 70.1 [5.5] years; 6416 [46.4%] female; mean [SD] baseline function score, 10.2 [1.6] points; 1-year mortality: 0.4%) included, 5732 experienced widowhood. There were 319 matched pairs of people with dementia, 1738 matched pairs without dementia, 95 matched pairs with cancer, 2637 matched pairs without cancer, 85 matched pairs with organ failure, and 2705 matched pairs without organ failure. Compared with participants without these illnesses, widowhood was associated with a decline in function immediately following widowhood for people with cancer (change, -1.17 [95% CI, -2.10 to -0.23] points) or dementia (change, -1.00 [95% CI, -1.52 to -0.48] points) but not organ failure (change, -0.84 [95% CI, -1.69 to 0.00] points). Widowhood was also associated with increased 1-year mortality among people with cancer (hazard ratio [HR], 1.08 [95% CI, 1.04 to 1.13]) or dementia (HR, 1.14 [95% CI, 1.02 to 1.27]) but not organ failure (HR, 1.02 [95% CI, 0.98 to 1.06])., Conclusions and Relevance: This cohort study found that widowhood was associated with increased functional decline and increased mortality in older adults with functional impairment and dementia or cancer. These findings suggest that persons with these conditions with high caregiver burden may experience a greater widowhood effect.

Study Question: Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation?, Summary Answer: Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes., What Is Known Already: In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes., Study Design, Size, Duration: Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016)., Participants/materials, Setting, Methods: Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol., Main Results and Role of Chance: Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: -23.8%; 95% CI: -39.9%, -3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response., Limitations, Reasons for Caution: Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types., Wider Implications of the Findings: Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment., Study Funding/competing Interest(s): The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870)., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS)., Methods: We identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients., Results: Two hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively)., Conclusions: Despite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-165/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Spouses of persons living with dementia may face heightened psychosocial distress in the years immediately before and after their partner's death. We compared the psychosocial needs of spouses of partners with dementia with spouses of partners with non-impaired cognition nearing and after the end of life, focusing on loneliness, depression, life satisfaction, and social isolation., Methods: We used nationally representative Health and Retirement Study married couples data (2006-2018), restricting to spouses 50+ years old. We included 2098 spouses with data on loneliness and depressive symptoms 2 years before and after the partner's death. We additionally examined a subset of spouses (N = 1113) with available data on life satisfaction and social isolation 2 years before their partner's death. Cognitive status of partners was classified as non-impaired cognition, cognitive impairment not dementia (cognitive impairment), and dementia. We used multivariable logistic regression to determine: 1) the change in loneliness and depression for spouses pre- and post-partner's death, and 2) life satisfaction and social isolation 2 years before the partner's death., Results: Spouses were on average 73 years old (SD: 10), 66% women, 7% Black, 7% Hispanic non-White, 24% married to persons with cognitive impairment, and 19% married to partners with dementia. Before their partner's death, spouses married to partners with dementia experienced more loneliness (non-impaired cognition: 8%, cognitive impairment: 16%, dementia: 21%, p-value = 0.002) and depressive symptoms (non-impaired cognition: 20%, cognitive impairment: 27%, dementia: 31%, p-value < 0.001), and after death a similar prevalence of loneliness and depression across cognitive status. Before their partner's death, spouses of partners with dementia reported less life satisfaction (non-impaired cognition: 74%, cognitive impairment: 68%; dementia: 64%, p-value = 0.02) but were not more socially isolated., Conclusion: Results emphasize a need for clinical and policy approaches to expand support for the psychosocial needs of spouses of partners with dementia in the years before their partner's death rather than only bereavement., (© 2024 The American Geriatrics Society.)

There are multiple ongoing and planned clinical trials that are evaluating novel therapies to treat patients with BCG-unresponsive high grade nonmuscle invasive bladder cancer (NMIBC). Importantly, there is considerable variation in surveillance strategies between these clinical trials, specifically with regards to the use of advanced imaging, enhanced cystoscopy, and mandatory biopsies, which could impact landmark efficacy assessments of investigational agents. To present guideline recommendations for the standardization of cystoscopic evaluation, surveillance, and efficacy assessments for patients with BCG-unresponsive NMIBC participating in clinical trials. On September 29, 2023 at the annual meeting of the International Bladder Cancer Network, a breakout session was convened, during which representatives from various disciplines discussed potential guidance statements with opportunity for discussion and comment. A set of statements regarding use of white light and enhanced cystoscopy were developed to help guide a pragmatic approach to surveillance and efficacy assessments of patients in clinical trials. The use of "for cause" and "mandatory" biopsies was also addressed. A standard approach to evaluation of patients within the context of clinical trials is necessary to accurately assess the efficacy of novel agents, especially within single arm trials that lack an appropriate comparator. Additionally, the utilization and timing of mandatory biopsies is critical, as these biopsies may impact both disease evaluations and the determination of duration of response., Competing Interests: Declaration of competing interest Yair Lotan Consultant: Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, verity pharmaceutics, virtuoso surgical, Stimit, Urogen, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab, Promis Diagnostics, Valar labs, Uroessentials Piyush Agarwal Consultant: AstraZeneca; Aura Bioscience; Janssen Pharmaceuticals, Inc.; Nonagen Bioscience; UroGen Pharma; and Verity Pharmaceuticals. Spouse is employed by Pfizer Peter Black Advisory board : AbbVie, AstraZeneca, Astellas, Bayer, BMS, Combat, EMD-Serono, Ferring, Janssen, Merck, Nonagen, Nanobot, NanOlogy, Pfizer, Photocure, Prokarium, Sumitomo, TerSera, Tolmar, Verity Speaker's bureau: Janssen, TerSera, Bayer, Pfizer Shared patent with: Veracyte Rian Dickstein Consultant: AstraZeneca, Bristol Myers Squibb, Ferring, Janssen, ImmunityBio, Olympus, Specialty Networks, UroGen Ashish Kamat Honoraria: Tesaro, AstraZeneca Consulting or Advisory Role: Photocure, Merck, Theralase, CG Oncology, US Biotest, Eisai, Imagin Medical, Medac, Asieris Pharmaceuticals, Sesen Bio, Bristol Myers Squibb, EnGene, Janssen, Seagen, FerGene, Biological Dynamics, Roche, Urogen pharma, Protara Therapeutics, Astellas Pharma, Incyte, Arquer Diagnostics, Cystotech, Imvax, Nonagen Bioscience, Pfizer Research Funding: FKD Therapies, Photocure, Merck, Bristol Myers Squibb, Adolor, Heat Biologics, SWOG, Seagen, Janssen/Taris, NIH, The Leo & Anne Albert Institute for Bladder Cancer Care and Research (AIBCCR), Patient-Centered Outcomes Research Institute (PCORI) Patent: CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) joint with UT MD Anderson Cancer Center Byron Lee: none Vikram M Narayan: Consultant: Ferring Research Funding: Merck, Janssen, Photocure Sima Porten: consultant: stryker SAB: Oncuria, ProTara research funding: Oncuria , Photocure, KDx Sarah P Psutka Medical steering committee/Ad Board: Janssen Ad Board: Immunity Bio Armine K. Smith: consultant Amgen, Photocure, Urogen, and CG Oncology Robert S Svatek: Consultant: CG Oncology, Verity pharmaceuticals Stephen B. Williams: consultant: Valar, Merck, Janssen, Photocure Solomon Woldu: consultant: Urogen, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions., Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress., Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB . Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels., Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD., Competing Interests: Competing interests CYC is an employee of Biogen. NPD has served on scientific advisory boards for BioVie Pharma, Circular Genomics and Sentio Solutions for unrelated work. NRN serves as an unpaid member of the Ilumivu advisory board. SAMR receives support from the Wounded Warrior Project (WWP), Department of Veterans Affairs (VA), National Institute of Health (NIH), McCormick Foundation, Tonix Pharmaceuticals, Woodruff Foundation, and Department of Defense (DOD). Dr. Rauch receives royalties from Oxford University Press and American. KJR serves as a consultant for Acer, Bionomics, and Jazz Pharma; SABs for Sage, Boehringer Ingelheim, and Senseye. DJS has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. MBS has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Delix Therapeutics, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. MBS has stock options in Oxeia Biopharmaceuticals and EpiVario. MBS has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). MBS has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. MBS is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America.

Background: Children from families with low socioeconomic status (SES), as determined by income, experience several negative outcomes, such as higher rates of newborn mortality and behavioral issues. Moreover, associations between DNA methylation and low income or poverty status are evident beginning at birth, suggesting prenatal influences on offspring development. Recent evidence suggests neighborhood opportunities may protect against some of the health consequences of living in low income households. The goal of this study was to assess whether neighborhood opportunities moderate associations between household income (HI) and neonate developmental maturity as measured with DNA methylation., Methods: Umbilical cord blood DNA methylation data was available in 198 mother-neonate pairs from the larger CANDLE cohort. Gestational age acceleration was calculated using an epigenetic clock designed for neonates. Prenatal HI and neighborhood opportunities measured with the Childhood Opportunity Index (COI) were regressed on gestational age acceleration controlling for sex, race, and cellular composition., Results: Higher HI was associated with higher gestational age acceleration (B = .145, t = 4.969, p = 1.56x10-6, 95% CI [.087, .202]). Contrary to expectation, an interaction emerged showing higher neighborhood educational opportunity was associated with lower gestational age acceleration at birth for neonates with mothers living in moderate to high HI (B = -.048, t = -2.08, p = .03, 95% CI [-.092, -.002]). Female neonates showed higher gestational age acceleration at birth compared to males. However, within males, being born into neighborhoods with higher social and economic opportunity was associated with higher gestational age acceleration., Conclusion: Prenatal HI and neighborhood qualities may affect gestational age acceleration at birth. Therefore, policy makers should consider neighborhood qualities as one opportunity to mitigate prenatal developmental effects of HI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pilkay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Disasters experienced by an entire community provide opportunities to understand individual differences in risk for adverse health outcomes over time. DNA methylation (DNAm) differences may help to distinguish individuals at increased risk following large-scale disasters., Objective: To examine the association of epigenetic age acceleration with probable posttraumatic stress disorder (PTSD) and PTSD symptom severity in women., Design, Setting, and Participants: This prospective cohort study examined data from participants in the Women and Their Children's Health cohort, who were characterized longitudinally following the Deepwater Horizon oil spill (DHOS) in 2010 and through numerous hurricanes in the Gulf Coast region of the US. Wave 1 occurred August 6, 2012, through June 26, 2014, and wave 2 occurred September 2, 2014, through May 27, 2016. Data were analyzed between August 18 and November 4, 2023. Address-based sampling was used to recruit women aged 18 to 80 years and residing in 1 of the 7 Louisiana parishes surrounding the DHOS-affected region. Recruitment consisted of 2-stage sampling that (1) undersampled the 2 more urban parishes to maximize probability of participant oil exposure and (2) proportionally recruited participants across census tracts in the 5 other parishes closest to the spill., Exposure: Posttraumatic stress subsequent to the DHOS., Main Outcome and Measures: Epigenetic age acceleration was measured by DNAm assayed from survey wave 1 blood samples. Posttraumatic stress disorder was assessed using the PTSD Checklist for DSM-5 at survey wave 2, and lifetime trauma exposure was assessed using the Life Events Checklist for DSM-5. General linear models were used to examine the association between wave 1 DNAm age and wave 2 probable PTSD diagnosis and symptom severity., Results: A total of 864 women (mean [SD] age, 47.1 [12.0] years; 328 Black [38.0%], 19 American Indian [2.2%], 486 White [56.3%], and 30 of other racial groups, including uknown or unreported [3.5%]) were included. Black and American Indian participants had a higher age acceleration at wave 1 compared with White participants (β = 1.64 [95% CI, 1.02-2.45] and 2.34 [95% CI, 0.33-4.34], respectively), and they had higher PTSD symptom severity at wave 2 (β = 7.10 [95% CI, 4.62-9.58] and 13.08 [95% CI, 4.97-21.18], respectively). Epigenetic age acceleration at wave 1 was associated with PTSD symptom severity at wave 2 after adjusting for race, smoking, body mass index, and household income (β = 0.38; 95% CI, 0.11-0.65)., Conclusions and Relevance: In this cohort study, epigenetic age acceleration was higher in minoritized racial groups and associated with future PTSD diagnosis and severity. These findings support the need for psychoeducation about traumatic responses to increase the likelihood that treatment is sought before years of distress and entrenchment of symptoms and comorbidities occur.

Importance: The Palliative Performance Scale (PPS) is one of the most widely used prognostic tools for patients with serious illness. However, current prognostic estimates associated with PPS scores are based on data that are over a decade old., Objective: To generate updated prognostic estimates by PPS score, care setting, and illness category, and examine how well PPS predicts short- and longer-term survival., Design, Setting, and Participants: This prognostic study was conducted at a large academic medical center with robust inpatient and outpatient palliative care practices using electronic health record data linked with data from California Vital Records. Eligible participants included patients who received a palliative care consultation between January 1, 2018, and December 31, 2020. Data analysis was conducted from November 2022 to February 2024., Exposure: Palliative care consultation with a PPS score documented., Main Outcomes and Measures: The primary outcomes were predicted 1-, 6-, and 12-month mortality and median survival of patients by PPS score in the inpatient and outpatient settings, and performance of the PPS across a range of survival times. In subgroup analyses, mortality risk by PPS score was estimated in patients with cancer vs noncancer illnesses and those seen in-person vs by video telemedicine in the outpatient setting., Results: Overall, 4779 patients (mean [SD] age, 63.5 [14.8] years; 2437 female [51.0%] and 2342 male [49.0%]) had a palliative care consultation with a PPS score documented. Of these patients, 2276 were seen in the inpatient setting and 3080 were seen in the outpatient setting. In both the inpatient and outpatient settings, 1-, 6-, and 12-month mortality were higher and median survival was shorter for patients with lower PPS scores. Prognostic estimates associated with PPS scores were substantially longer (2.3- to 11.7-fold) than previous estimates commonly used by clinicians. The PPS had good ability to discriminate between patients who lived and those who died in the inpatient setting (integrated time-dependent area under the curve [iAUC], 0.74) but its discriminative ability was lower in the outpatient setting (iAUC, 0.67). The PPS better predicted 1-month survival than longer-term survival. Mortality rates were higher for patients with cancer than other serious illnesses at most PPS levels., Conclusions and Relevance: In this prognostic study, prognostic estimates associated with PPS scores were substantially longer than previous estimates commonly used by clinicians. Based on these findings, an online calculator was updated to assist clinicians in reaching prognostic estimates that are more consistent with modern palliative care practice and specific to the patient's setting and diagnosis group.

Background and Objectives: Emerging evidence suggests music-based interventions can improve the well-being of people living with dementia, but little is known about the ways in which music might support dementia caregiving relationships as part of everyday life at home. This study examined music engagement in the context of daily life to identify patterns of music engagement and potential targets for the design of music-based interventions to support well-being., Research Design and Methods: This ethnographic, in-home study of people living with dementia and their family and professional care partners used methods from ethnomusicology, including semistructured interviews and in-home participant observation with a focus on music engagement., Results: A total of 21 dyads were purposively recruited for diversity in terms of gender, ethnicity/race/heritage, caregiving relationship, and music experiences. Despite participants' diverse music preferences, 3 distinct music engagement patterns emerged. (a) Professional care partners intentionally integrated music listening and singing into daily life as part of providing direct care. (b) Family care partners, who had prior dementia care nursing experience or family music traditions, integrated music into daily life in ways that supported their personal relationships. (c) In contrast, family care partners, who lacked dementia care experience and had high levels of caregiver burden, disengaged from prior music-making., Discussion and Implications: The distinct music engagement patterns reflect different needs on the part of dyads. It is important to continue to support dyads who engage in music daily and to consider developing music-based interventions to support well-being among dyads who have become disengaged from music., (Published by Oxford University Press on behalf of The Gerontological Society of America 2023.)

The increase in social media mental health (MH) campaigns provides an opportunity to improve awareness and attitudes toward MH. However, racial disparities remain in these social media campaigns. Black youth who participated in MH social media campaigns reported lower levels of improvement in stigma and help-seeking than their White peers. We employed a youth participatory action research (YPAR) process to expand on a previous community-wide MH social media campaign (A. Thompson et al., 2021), focusing on a Central Midwest community. We studied Black adolescents' perceptions of MH stigma and help-seeking to determine essential features of a culturally responsive MH social media campaign for Black youth. With a lead youth-research collaborator, the research team designed the following two-staged study. The first stage consisted of four semistructured focus group interviews (FGIs) ( N = 20), analyzed by using a rapid analysis strategy to obtain results for the development of the campaign. In the second stage, using YPAR's iterative and action-based process, five youth researchers collaborated with the research team on the campaign's design. Following the two stages, the researcher's thematic analysis resulted in three themes: (a) broadening horizons for campaign designers and MH professionals; (b) considering mistrust of schools and school personnel; and (c) diverse experiences, sustainability, and accessibility in a campaign. Findings indicated that while culturally responsive social media campaigns to promote MH can be designed, mistrust of adults in schools is likely to hinder the impact of such campaigns. Implications for school psychology practice and research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Older adults surviving critical illness often experience new or worsening functional impairments. Modifiable positive psychological constructs such as resilience may mitigate post-intensive care morbidity., Research Question: Is pre-ICU resilience associated with: (1) post-ICU survival; (2) the drop in functional independence during the ICU stay; or (3) the trend in predicted independence before vs after the ICU stay?, Study Design and Methods: This retrospective cohort study was performed by using Medicare-linked Health and Retirement Study surveys from 2006 to 2018. Older adults aged ≥ 65 years admitted to an ICU were included. Resilience was calculated prior to ICU admission. The resilience measure was defined from the Simplified Resilience Score, which was previously adapted and validated for the Health and Retirement Study. Resilience was scored by using the Leave-Behind survey normalized to a scale from 0 (lowest resilience) to 12 (highest resilience). Outcomes were survival and probability of functional independence. Survival was modeled by using Gompertz models and independence using joint survival models adjusting for sociodemographic and clinical variables. Average marginal effects were estimated to determine independence probabilities., Results: Across 3,409 patients aged ≥ 65 years old admitted to ICUs, preexisting frailty (30.5%) and cognitive impairment (24.3%) were common. Most patients were previously independent (82.7%). Mechanical ventilation occurred in 14.8% and sepsis in 43.2%. Those in the highest resilience group (vs lowest resilience) had a lower risk of post-ICU mortality (adjusted hazard ratio, 0.81; 95% CI, 0.70-0.94). Higher resilience was associated with greater likelihood of post-ICU functional independence (estimated probability of functional independence 5 years after ICU discharge in highest-to-lowest resilience groups (adjusted hazard ratio [95% CI]): 0.53 (0.33-0.74), 0.47 (0.26-0.68), 0.49 (0.28-0.70), and 0.36 (0.17-0.55); P < .01. Resilience was not associated with a difference in the drop in independence during the ICU stay or a difference in the pre-ICU vs post-ICU trend in predicted independence ., Interpretation: ICU survivors with higher resilience had increased rates of survival and functional independence, although the slope of functional decline before vs after the ICU stay did not differ according to resilience group., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Published by Elsevier Inc.)

Introduction: Transurethral resection of bladder tumour (TURBT) is one of the more common procedures performed by urologists. It is often described as an 'incision-free' and 'well-tolerated' operation. However, many patients experience distress and discomfort with the procedure. Substantial opportunity exists to improve the TURBT experience. An enhanced recovery after surgery (ERAS) protocol designed by patients with bladder cancer and their providers has been developed., Methods and Analysis: This is a single-centre, randomised controlled trial to investigate the effectiveness of an ERAS protocol compared with usual care in patients with bladder cancer undergoing ambulatory TURBT. The ERAS protocol is composed of preoperative, intraoperative and postoperative components designed to optimise each phase of perioperative care. 100 patients with suspected or known bladder cancer aged ≥18 years undergoing initial or repeat ambulatory TURBT will be enrolled. The change in Quality of Recovery 15 score, a measure of the quality of recovery, between the day of surgery and postoperative day 1 will be compared between the ERAS and control groups., Ethics and Dissemination: The trial has been approved by the Johns Hopkins Institutional Review Board #00392063. Participants will provide informed consent to participate before taking part in the study. Results will be reported in a separate publication., Trial Registration Number: NCT05905276., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown., Objective: To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US., Design, Setting, and Participants: This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023., Exposure: Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD)., Main Outcomes and Measures: Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants., Results: This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (β [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77)., Conclusions and Relevance: In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.