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1.
JAMA Intern Med ; 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38648065

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.

2.
Public Health Nutr ; 27(1): e124, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38680073

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.


Nutrition Policy , Humans , Cross-Sectional Studies , Child, Preschool , Victoria , Child Day Care Centers/standards , Health Promotion/methods , Female , Male
3.
Nat Genet ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671320

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.

4.
Reg Anesth Pain Med ; 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38580338

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.

5.
Health Place ; 87: 103243, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38663339

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.

6.
JCO Precis Oncol ; 8: e2300567, 2024 Apr.
Article En | MEDLINE | ID: mdl-38579192

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.


Antineoplastic Agents , Circulating Tumor DNA , Prostatic Neoplasms , Male , Humans , Retrospective Studies , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/drug therapy , Circulating Tumor DNA/genetics , Antineoplastic Agents/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , High-Throughput Nucleotide Sequencing/methods
7.
JCO Precis Oncol ; 8: e2300634, 2024 Apr.
Article En | MEDLINE | ID: mdl-38662984

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.


Dipeptides , Lutetium , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Retrospective Studies , Aged , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/drug therapy , Lutetium/therapeutic use , Dipeptides/therapeutic use , Heterocyclic Compounds, 1-Ring/therapeutic use , Prostate-Specific Antigen/blood , Antigens, Surface/genetics , Cohort Studies , Glutamate Carboxypeptidase II/genetics
8.
Methods Cell Biol ; 183: 355-380, 2024.
Article En | MEDLINE | ID: mdl-38548419

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.


Cytokines , Immunotherapy, Adoptive , Mice , Animals , Immunotherapy, Adoptive/methods , Bryostatins , Ionomycin/pharmacology , Lymph Nodes , Lymphocyte Activation , Mice, Inbred C57BL
9.
Article En | MEDLINE | ID: mdl-38383885

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.

10.
Sci Rep ; 14(1): 4815, 2024 02 27.
Article En | MEDLINE | ID: mdl-38413683

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.


Bryophyta , Calluna , Fires , Wildfires , Ecosystem , Soil
11.
Animals (Basel) ; 14(3)2024 Jan 25.
Article En | MEDLINE | ID: mdl-38338030

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.

12.
JAMA Surg ; 159(4): 438-444, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38381415

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.


Aftercare , Patient Discharge , Humans , Hospitalization , Patient Transfer , Pain
13.
Health Aff (Millwood) ; 43(2): 234-241, 2024 Feb.
Article En | MEDLINE | ID: mdl-38315919

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.


Breast Neoplasms , Ill-Housed Persons , Veterans , Adult , Humans , United States , Aged , Female , Housing
15.
JAMA Netw Open ; 6(12): e2349143, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-38127343

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.


Breast Neoplasms , Colorectal Neoplasms , Lung Neoplasms , Veterans , United States/epidemiology , Male , Humans , Aged , Female , Retrospective Studies , Housing , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/therapy
16.
Res Sq ; 2023 Aug 10.
Article En | MEDLINE | ID: mdl-37609284

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: To our knowledge, this is the largest real-world clinicogenomics database-driven study exploring the development of ARalterations 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.

17.
Digit Health ; 9: 20552076231183555, 2023.
Article En | MEDLINE | ID: mdl-37426589

Objective: Mild traumatic brain injuries (mTBIs) are common and may result in persisting symptoms. Mobile health (mHealth) applications enhance treatment access and rehabilitation. However, there is limited evidence to support mHealth applications for individuals with an mTBI. The primary purpose of this study was to evaluate user experiences and perceptions of the Parkwood Pacing and Planning™ application, an mHealth application developed to help individuals manage their symptoms following an mTBI. The secondary purpose of this study was to identify strategies to improve the application. This study was conducted as part of the development process for this application. Methods: A mixed methods co-design encompassing an interactive focus group and a follow-up survey was conducted with patient and clinician-participants (n = 8, four per group). Each group participated in a focus group consisting of an interactive scenario-based review of the application. Additionally, participants completed the Internet Evaluation and Utility Questionnaire (UQ). Qualitative analysis on the interactive focus group recordings and notes was performed using phenomenological reflection through thematic analyses. Quantitative analysis included descriptive statistics of demographic information and UQ responses. Results: On average, clinician and patient-participants positively rated the application on the UQ (4.0 ± .3, 3.8 ± .2, respectively). User experiences and recommendations for improving the application were categorized into four themes: simplicity, adaptability, conciseness, and familiarity. Conclusion: Preliminary analyses indicates patients and clinicians have a positive experience when using the Parkwood Pacing and Planning™ application. However, modifications that improve simplicity, adaptability, conciseness, and familiarity may further improve the user's experience.

18.
J Am Heart Assoc ; 12(14): e029910, 2023 07 18.
Article En | MEDLINE | ID: mdl-37421288

Background Cardiovascular procedural treatments were deferred at scale during the COVID-19 pandemic, with unclear impact on patients presenting with non-ST-segment-elevation myocardial infarction (NSTEMI). Methods and Results In a retrospective cohort study of all patients diagnosed with NSTEMI in the US Veterans Affairs Healthcare System from January 1, 2019 to October 30, 2022 (n=67 125), procedural treatments and outcomes were compared between the prepandemic period and 6 unique pandemic phases: (1) acute phase, (2) community spread, (3) first peak, (4) post vaccine, (5) second peak, and (6) recovery. Multivariable regression analysis was performed to assess the association between pandemic phases and 30-day mortality. NSTEMI volumes dropped significantly with the pandemic onset (62.7% of prepandemic peak) and did not revert to prepandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention and coronary artery bypass grafting volumes declined proportionally. Compared with the prepandemic period, patients with NSTEMI experienced higher 30-day mortality during Phases 2 and 3, even after adjustment for COVID-19-positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted odds ratio for Phases 2 and 3 combined, 1.26 [95% CI, 1.13-1.43], P<0.01). Patients receiving Veterans Affairs-paid community care had a higher adjusted risk of 30-day mortality compared with those at Veterans Affairs hospitals across all 6 pandemic phases. Conclusions Higher mortality after NSTEMI occurred during the initial spread and first peak of the pandemic but resolved before the second, higher peak-suggesting effective adaptation of care delivery but a costly delay to implementation. Investigation into the vulnerabilities of the early pandemic spread are vital to informing future resource-constrained practices.


COVID-19 , Myocardial Infarction , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Pandemics , Non-ST Elevated Myocardial Infarction/epidemiology , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/diagnosis , Retrospective Studies , Veterans Health , Treatment Outcome , COVID-19/epidemiology , Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/therapy
19.
JAMA Netw Open ; 6(7): e2323884, 2023 07 03.
Article En | MEDLINE | ID: mdl-37459100

This cross-sectional study using survey data investigates the association between level of reliance on the Department of Veterans Affairs for health care and self-reported health by type of insurance coverage among VA enrollees.


Veterans , Humans , United States , Self Report , Delivery of Health Care , Patient Acceptance of Health Care , United States Department of Veterans Affairs
20.
Am J Pharm Educ ; 87(7): 100084, 2023 07.
Article En | MEDLINE | ID: mdl-37380256

OBJECTIVE: To investigate Year 4 Master of Pharmacy students' understanding and sense of professional identity (PI) and explore the factors that positively and negatively impact PI formation in the undergraduate program. METHODS: Three focus groups were conducted in January 2022 with 5-8 participants per group. Audio from the focus groups was recorded and recordings were transcribed verbatim. Reflexive thematic analysis was employed to construct themes and subthemes. RESULTS: Four themes, with associated subthemes, were generated. The themes were 'Understanding PI', 'Experience of Master of Pharmacy degree', 'Interaction and comparison with others,' and 'Development of self'. CONCLUSION: Participant understanding of PI reflected the wider literature, including ambiguity as to what it means to a pharmacist in training. The lens of legitimate peripheral participation in a community of practice was used to reflect on curricular and educational approaches to support undergraduate PI formation. Participants expressed that patient-focused learning experiences and opportunities to participate in authentic professional activities alongside peers and more experienced members of the pharmacy community positively contribute to PI formation. This suggests that a sociocultural perspective where learning is viewed as legitimate peripheral participation in a community of practice provides a valid theoretical basis to underpin curriculum design.


Community Pharmacy Services , Education, Pharmacy , Students, Pharmacy , Humans , Educational Status , Curriculum
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