Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.

BACKGROUND: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown. METHODS: We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status. RESULTS: Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups. CONCLUSIONS: Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.

Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

BACKGROUND: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g. traumatic brain and spinal cord injury), but evidence is lacking for other moderately severe or major trauma. METHODS: ROWTATE is an individually randomised controlled multicentre pragmatic trial of early VR and psychological support in trauma patients. It includes an internal pilot, economic evaluation, a process evaluation and an implementation study. Participants will be screened for eligibility and recruited within 12 weeks of admission to eight major trauma centres in England. A total of 722 participants with ISS > 8 will be randomised 1:1 to VR and psychological support (where needed, following psychological screening) plus usual care or to usual care alone. The ROWTATE VR intervention will be provided within 2 weeks of study recruitment by occupational therapists and where needed, by clinical psychologists. It will be individually tailored and provided for ≤ 12 months, dependent on participant need. Baseline assessment will collect data on demographics, injury details, work/education status, cognitive impairment, anxiety, depression, post-traumatic distress, disability, recovery expectations, financial stress and health-related quality of life. Participants will be followed up by postal/telephone/online questionnaires at 3, 6 and 12 months post-randomisation. The primary objective is to establish whether the ROWTATE VR intervention plus usual care is more effective than usual care alone for improving participants' self-reported return to work/education for at least 80% of pre-injury hours at 12 months post-randomisation. Secondary outcomes include other work outcomes (e.g. hours of work/education, time to return to work/education, sickness absence), depression, anxiety, post-traumatic distress, work self-efficacy, financial stress, purpose in life, health-related quality of life and healthcare/personal resource use. The process evaluation and implementation study will be described elsewhere. DISCUSSION: This trial will provide robust evidence regarding a VR intervention for a major trauma population. Evidence of a clinically and cost-effective VR intervention will be important for commissioners and providers to enable adoption of VR services for this large and important group of patients within the NHS. TRIAL REGISTRATION: ISRCTN: 43115471. Registered 27/07/2021.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

PURPOSE: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). METHODS: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. RESULTS: Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. CONCLUSION: Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.

Complex Patterns of Antihypertensive Treatment Changes in Long-Term Care Residents.

OBJECTIVES: Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 24,870 Department of Veterans Affairs (VA) nursing home residents aged ≥65 years with long-term stays (≥180 days) from 2006 to 2019. METHODS: We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission. RESULTS: More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years). CONCLUSIONS AND IMPLICATIONS: Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes.

Use of natural language processing method to identify regional anesthesia from clinical notes.

INTRODUCTION: Accurate data capture is integral for research and quality improvement efforts. Unfortunately, limited guidance for defining and documenting regional anesthesia has resulted in wide variation in documentation practices, even within individual hospitals, which can lead to missing and inaccurate data. This cross-sectional study sought to evaluate the performance of a natural language processing (NLP)-based algorithm developed to identify regional anesthesia within unstructured clinical notes. METHODS: We obtained postoperative clinical notes for all patients undergoing elective non-cardiac surgery with general anesthesia at one of six Veterans Health Administration hospitals in California between January 1, 2017, and December 31, 2022. After developing and executing our algorithm, we compared our results to a frequently used referent, the Corporate Data Warehouse structured data, to assess the completeness and accuracy of the currently available data. Measures of agreement included sensitivity, positive predictive value, false negative rate, and accuracy. RESULTS: We identified 27,713 procedures, of which 9310 (33.6%) received regional anesthesia. 96.6% of all referent regional anesthesia cases were identified in the clinic notes with a very low false negative rate and good accuracy (false negative rate=0.8%, accuracy=82.5%). Surprisingly, the clinic notes documented more than two times the number of regional anesthesia cases that were documented in the referent (algorithm n=9154 vs referent n=4606). DISCUSSION: While our algorithm identified nearly all regional anesthesia cases from the referent, it also identified more than two times as many regional anesthesia cases as the referent, raising concerns about the accuracy and completeness of regional anesthesia documentation in administrative and clinical databases. We found that NLP was a promising alternative for identifying clinical information when existing databases lack complete documentation.

Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations.

PURPOSE: There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB. RESULTS: Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients. CONCLUSION: Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

Nutrition environments in early childhood education: do they align with best practice?

OBJECTIVE: To assess the comprehensiveness (scope of nutrition guidance) and strength (clarity of written language) of centre-based nutrition policies (CBNP) within early childhood education (ECE) centres. To also consider the applicability of an existing CBNP assessment tool and policy alignment with best practice food provision and feeding practices. DESIGN: Cross-sectional online study to assess written ECE CNBP using the Wellness Child Care Assessment Tool. SETTING: Licenced ECE centres in the state of Victoria, Australia. PARTICIPANTS: ECE centres (operating at least 8 h per d, 48 weeks per annum), stratified by location (rural and metropolitan), centre management type (profit and not-for-profit) and socio-economic area (low, middle, high). RESULTS: Included individual CBNP (n 118), predominantly from metropolitan centres (56 %) and low-medium socio-economic areas (78 %). Policies had low overall Wellness Child Care Assessment Tool scores, particularly strength scores which were low across all four domains (i.e. nutrition education, nutrition standards, health promotion and communication/evaluation). The nutrition standards domain had the lowest strength score. The communication/evaluation domain had the lowest comprehensiveness score. Content analysis indicated low scores may relate to the Wellness Child Care Assessment Tool applicability for the Australian context due to differences in best practice guidance. CONCLUSION: Despite the presence of written nutrition policies in ECE centres, many showed weak language and lacked comprehensiveness and strength. This may relate to poor implementation of best practice food provision or feeding practices. Low scores, however, may partly stem from using an assessment tool that is not country-specific. The redevelopment of country-specific tools to assess ECE CNBP may be warranted.

Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response to 177Lu-PSMA-617: A Retrospective Multicenter Cohort Study.

PURPOSE: While 177Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes. METHODS: This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups. RESULTS: One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53, RB1, or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA50 response, PSA PFS, and OS. CONCLUSION: Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents.

Importance: Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents. Objective: To assess the association between antihypertensive medication initiation and risk of fracture. Design, Setting, and Participants: This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023. Exposure: Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy. Main Outcome and Measures: The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching. Results: Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score-matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]). Conclusions and Relevance: Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

Effects of residential socioeconomic polarization on high blood pressure among nursing home residents.

OBJECTIVE: Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home. METHODS: 41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders. RESULTS: We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain. CONCLUSIONS: We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.

Adoptive immunotherapy with cells from tumor-draining lymph nodes activated and expanded in vitro.

Tumor-draining lymph nodes (tumor-DLNs) provide a rich source of tumor-reactive lymphocytes which can be used in adoptive immunotherapy (AIT) and that circumvent the need to resect autologous tumor, without the challenges and shortcomings associated with using autologous tumor or anti-CD3 monoclonal antibody. Bryostatin/Ionomycin (Bryo/Io) provide a useful method of activating tumor-DLNs such that they can readily be expanded to sufficient numbers to be used in AIT, and growing the tumor-DLN lymphocytes in the gamma chain cytokines IL-7 plus IL-15 is superior to IL-2 in terms of T cell numbers and phenotype. AIT with these cells induces tumor regression and provides protection against metastases and future tumor challenge. Here, we provide a stepwise protocol to sensitize tumor-DLN cells in donor mice, activate tumor-DLN T cells ex vivo using Bryo/Io, expansion of these cells in gamma chain cytokines and adoptive transfer of the expanded cells back into tumor-bearing hosts. Methods relevant to these experiments, such as injecting tumor cells intravenously and monitoring for pulmonary metastases, tumor volume measurement and resection, and use of luciferase-expressing tumor cells to monitor for metastases following resection, are described in detail. The methods outlined herein can be easily adapted to suit similar experiments across multiple tumor cell lines and syngeneic mouse models.

Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.

BACKGROUND: AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. METHODS: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. RESULTS: In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%). CONCLUSION: In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.

Diurnal fuel moisture content variations of live and dead Calluna vegetation in a temperate peatland.

The increasing frequency and severity of UK wildfires, attributed in part to the effects of climate change, highlights the critical role of fuel moisture content (FMC) of live and dead vegetation in shaping wildfire behaviour. However, current models used to assess wildfire danger do not perform well in shrub-type fuels such as Calluna vulgaris, requiring in part an improved understanding of fuel moisture dynamics on diurnal and seasonal scales. To this end, 554 samples of upper live Calluna canopy, live Calluna stems, upper dead Calluna canopy, dead Calluna stems, moss, litter and organic layer (top 5 cm of organic material above mineral soil) were sampled hourly between 10:00 and 18:00 on seven days from March-August. Using a novel statistical method for investigating diurnal patterns, we found distinctive diurnal and seasonal trends in FMC for all fuel layers. Notably, significant diurnal patterns were evident in dead Calluna across nearly all sampled months, while diurnal trends in live Calluna canopy were pronounced in March, June, and August, coinciding with the peak occurrence of UK wildfires. In addition, the moisture content of moss and litter was found to fluctuate above and below their relative ignition thresholds throughout the day on some sampling days. These findings underscore the impact of diurnal FMC variations on wildfire danger during early spring and late summer in Calluna dominated peatlands and the need to consider such fluctuations in management and fire suppression strategies.

Mapping the Discharge Process After Surgery.

Importance: Care transition models are structured approaches used to ensure the smooth transfer of patients between health care settings or levels of care, but none currently are tailored to the surgical patient. Tailoring care transition models to the unique needs of surgical patients may lead to significant improvements in surgical outcomes and reduced care fragmentation. The first step to developing surgical care transition models is to understand the surgical discharge process. Objective: To map the surgical discharge process in a sample of US hospitals and identify key components and potential challenges specific to a patient's discharge after surgery. Design, Setting, and Participants: This qualitative study followed a cognitive task analysis framework conducted between January 1, 2022, and April 1, 2023, in Veterans Health Administration (VHA) hospitals. Observations (n = 16) of discharge from inpatient care after a surgical procedure were conducted in 2 separate VHA surgical units. Interviews (n = 13) were conducted among VHA health care professionals nationwide. Exposure: Postoperative hospital discharge. Main Outcomes and Measures: Data were coded according to the principles of thematic analysis, and a swim lane process map was developed to represent the study findings. Results: At the hospitals in this study, the discharge process observed for a surgical patient involved multidisciplinary coordination across the surgery team, nursing team, case managers, dieticians, social services, occupational and physical therapy, and pharmacy. Important components for a surgical discharge that were not incorporated in the current care transition models included wound care education and supplies; pain control; approvals for nonhome postdischarge locations; and follow-up plans for wounds, ostomies, tubes, and drains at discharge. Potential challenges to the surgical discharge process included social situations (eg, home environment and caregiver availability), team communication issues, and postdischarge care coordination. Conclusions and Relevance: These findings suggest that current and ongoing studies of discharge care transitions for a patient after surgery should consider pain control; wounds, ostomies, tubes, and drains; and the impact of challenging social situations and interdisciplinary team coordination on discharge success.

Factors Associated with Reproductive Success in Captive Vancouver Island Marmots (Marmota vancouverensis).

The Vancouver Island marmot (Marmota vancouverensis) is Canada's most endangered endemic mammal. In 1997, a conservation breeding-for-release program was established to supplement wild marmot populations. Retrospective analyses of captive breeding studbook records since 2000 indicate the age of the sire and the dam significantly impacted the odds of successfully weaning a litter. Dams and sires between 5 and 7 years of age had more than double the odds of reproductive success compared to older animals. Successful reproduction by the dam in the previous year also doubled the odds of successfully weaning a litter in subsequent years. Assessment of adrenal function via fecal glucocorticoid analyses indicated established breeding pairs had decreased stress compared to new pairs (5.74 ± 0.28 ng/g vs. 7.60 ± 0.34 ng/g; p < 0.0001). Pairs that were ultimately successful at weaning pups in a breeding season had decreased stress compared to unsuccessful pairs (6.05 ± 0.34 ng/g vs. 7.22 ± 0.28 ng/g; p = 0.0006). These endocrine results suggest social buffering via familiarity and breeding/pair bond formation may be decreasing stress in established and successful pairs, respectively. The results of this study will be used to assist in the captive breeding management of this species to optimise numbers of animals produced to supplement the wild populations.

Housing Status Changes Are Associated With Cancer Outcomes Among US Veterans.

Cancer is a leading cause of death in older unhoused adults. We assessed whether being unhoused, gaining housing, or losing housing in the year after cancer diagnosis is associated with poorer survival compared with being continuously housed. We examined all-cause survival in more than 100,000 veterans diagnosed with lung, colorectal, and breast cancer during the period 2011-20. Five percent were unhoused at the time of diagnosis, of whom 21 percent gained housing over the next year; 1 percent of veterans housed at the time of diagnosis lost housing. Continuously unhoused veterans and veterans who lost their housing had poorer survival after lung and colorectal cancer diagnosis compared with those who were continuously housed. There was no survival difference between veterans who gained housing after diagnosis and veterans who were continuously housed. These findings support policies to prevent and end homelessness in people after cancer diagnosis, to improve health outcomes.

Housing Status, Cancer Care, and Associated Outcomes Among US Veterans.

Importance: Cancer is a leading cause of death among older people experiencing homelessness. However, the association of housing status with cancer outcomes is not well described. Objective: To characterize the diagnosis, treatment, surgical outcomes, and mortality by housing status of patients who receive care from the US Department of Veterans Affairs (VA) health system for colorectal, breast, or lung cancer. Design, Setting, and Participants: This retrospective cohort study identified all US veterans diagnosed with lung, colorectal, or breast cancer who received VA care between October 1, 2011, and September 30, 2020. Data analysis was performed from February 13 to May 9, 2023. Exposures: Veterans were classified as experiencing homelessness if they had any indicators of homelessness in outpatient visits, clinic reminders, diagnosis codes, or the Homeless Operations Management Evaluation System in the 12 months preceding diagnosis, with no subsequent evidence of stable housing. Main Outcomes and Measures: The major outcomes, by cancer type, were as follows: (1) treatment course (eg, stage at diagnosis, time to treatment initiation), (2) surgical outcomes (eg, length of stay, major complications), (3) overall survival by cancer type, and (4) hazard ratios for overall survival in a model adjusted for age at diagnosis, sex, stage at diagnosis, race, ethnicity, marital status, facility location, and comorbidities. Results: This study included 109 485 veterans, with a mean (SD) age of 68.5 (9.7) years. Men comprised 92% of the cohort. In terms of race and ethnicity, 18% of veterans were Black, 4% were Hispanic, and 79% were White. A total of 68% of participants had lung cancer, 26% had colorectal cancer, and 6% had breast cancer. There were 5356 veterans (5%) experiencing homelessness, and these individuals more commonly presented with stage IV colorectal cancer than veterans with housing (22% vs 19%; P = .02). Patients experiencing homelessness had longer postoperative lengths of stay for all cancer types, but no differences in other treatment or surgical outcomes were observed. These patients also demonstrated higher rates of all-cause mortality 3 months after diagnosis for lung and colorectal cancers, with adjusted hazard ratios of 1.1 (95% CI, 1.1-1.2) and 1.3 (95% CI, 1.2-1.4) (both P < .001), respectively. Conclusions and Relevance: In this large retrospective study of US veterans with cancer, homelessness was associated with later stages at diagnosis for colorectal cancer. Differences in lung and colorectal cancer survival between patients with housing and those experiencing homelessness were present but smaller than observed in other settings. These findings suggest that there may be important systems in the VA that could inform policy to improve oncologic outcomes for patients experiencing homelessness.