Initiating pre-exposure prophylaxis in the inpatient setting: a quality improvement project.

Many patients who are at high risk of HIV transmission do not receive pre-exposure prophylaxis (PrEP). HIV risk counselling and PrEP initiation have historically been limited to outpatient settings. Here we describe a novel quality improvement project at San Francisco's main safety-net hospital designed to incorporate universal screening for active HIV risk factors and PrEP initiation into standard inpatient care. Interventions included education sessions and dissemination of clinical materials to increase providers' knowledge and comfort with HIV risk screening, prevention counselling and prescribing PrEP. We implemented new workflows on the inpatient medicine service to encourage providers to universally screen all patients at the time of admission and initiate PrEP for appropriate patients during their hospitalisation. Over the first 9 months of the initiative, 14 inpatients were started on PrEP during their admission. As PrEP was initiated in particularly vulnerable patients, using inpatient admissions to engage at-risk patients in HIV prevention may help to reduce disparities in HIV outcomes.

History of Incarceration and Its Association With Geriatric and Chronic Health Outcomes in Older Adulthood.

Importance: Although incarcerated older adults experience higher rates of chronic disease and geriatric syndromes, it is unknown whether community-dwelling older adults with a history of incarceration are also at risk for worse health outcomes. Objective: To evaluate the association between a history of incarceration and health outcomes, including chronic health conditions and geriatric syndromes, in older age. Design, Setting, and Participants: This cross-sectional study using population-based data from the nationally representative Health and Retirement Study included US community-dwelling adults aged 50 years or older who completed the 2012 or 2014 survey waves assessing self-reported history of incarceration. Statistical analysis was completed from December 2021 to July 2022. Exposures: Self-reported history of incarceration. Main Outcomes and Measures: Geriatric health outcomes included cognitive impairment, mobility impairment, vision impairment, hearing impairment, urinary incontinence, and impairment of activities of daily living (ADLs). Chronic health outcomes included high blood pressure, diabetes, chronic lung disease, heart disease, stroke, mental health conditions, heavy alcohol use, and self-reported health. Survey weights were applied to adjust for the survey design. Results: Among 13 462 participants, 946 (7.6%) had experienced incarceration (mean [SD] age, 62.4 [7.8] years); compared with 12 516 people with no prior incarceration (mean [SD] age, 66.7 [10.0] years), previously incarcerated adults were more likely to be male (83.0% vs 42.8%; P < .001) and in the lowest quartile of wealth (44.1% vs 21.4%; overall P < .001). After adjusting for age, sex, race and ethnicity, wealth, educational attainment, and uninsured status, a history of incarceration was associated with a 20% to 80% increased risk of all geriatric syndromes evaluated, including impairment of ADLs (relative risk [RR], 1.62; 95% CI, 1.40-1.88) and hearing impairment (RR, 1.22; 95% CI, 1.04-1.44). Incarceration was also associated with increased risk of some chronic diseases, including chronic lung disease (RR, 1.56; 95% CI, 1.27-1.91), mental health conditions (RR, 1.80; 95% CI, 1.55-2.08), and heavy alcohol use (RR, 2.13; 95% CI, 1.59-2.84). Prior incarceration was not associated with diabetes or cardiovascular conditions. Conclusions and Relevance: In this study, at least 1 in 15 older US adults reported a history of incarceration in their lifetime. Past incarceration was associated with many chronic diseases and geriatric syndromes even after accounting for socioeconomic status. These findings suggest that attention to incarceration history may be an important consideration in understanding and mitigating health risks in older age.

Public Health and Prisons: Priorities in the Age of Mass Incarceration.

Mass incarceration is a sociostructural driver of profound health inequalities in the United States. The political and economic forces underpinning mass incarceration are deeply rooted in centuries of the enslavement of people of African descent and the genocide and displacement of Indigenous people and is inextricably connected to labor exploitation, racial discrimination, the criminalization of immigration, and behavioral health problems such as mental illness and substance use disorders. This article focuses on major public health crises and advances in state and federal prisons and discusses a range of practical strategies for health scholars, practitioners, and activists to promote the health and dignity of incarcerated people. It begins by summarizing the historical and sociostructural factors that have led to mass incarceration in the United States. It then describes the ways in which prison conditions create or worsen chronic, communicable, and behavioral health conditions, while highlighting priority areas for public health research and intervention to improve the health of incarcerated people, including decarceral solutions that can profoundly minimize-and perhaps one day help abolish-the use of prisons.

Strategies for Addressing Vaccine Hesitancy Within California State Prisons in 2021 and Beyond.

Although widespread vaccination in correctional facilities is crucial for preventing COVID-19 morbidity and mortality in these institutions and their surrounding communities, there are little data on how to effectively perform vaccine outreach to people experiencing incarceration who remain unvaccinated. In this article, we describe lessons learned from a successful vaccine education initiative in California state prisons and describe opportunities for application to other correctional settings. (Am J Public Health. 2022;112(11):1543-1545. https://doi.org/10.2105/AJPH.2022.307042).

The Impact Of COVID-19 On The Health Of Incarcerated Older Adults In California State Prisons.

The number of older adults (age fifty-five or older) incarcerated in US prisons reached an all-time high just as COVID-19 entered correctional facilities in 2020. However, little is known about COVID-19's impact on incarcerated older adults. We compared COVID-19 outcomes between older and younger adults in California state prisons from March 1, 2020, to October 9, 2021. Adjusted odds ratios (aORs) revealed an increasing risk for adverse COVID-19 outcomes among older age groups (ages 55-64, 65-74, and 75 or older) compared with younger adults, including for documented infection (aOR, 1.3, 1.4, and 1.4, respectively) and hospitalization with COVID-19 (aOR, 4.6, 8.7, and 15.1, respectively). Moreover, although accounting for 17.3 percent of the California state prison population, older adults represented 85.8 percent of this population's COVID-19-related deaths. Yet a smaller percentage of older adults than younger adults were released from prison during the pandemic. The differential rates of morbidity and mortality experienced by incarcerated older adults should be considered in future pandemic response strategies regarding prisons.

A stepwise guide for healthcare professionals requesting compassionate release for patients who are incarcerated.

PURPOSE: Compassionate release is a process that allows for the early release or parole of some incarcerated people of advanced age, with life-limiting illness, complex medical care needs or significant functional decline. Despite the expansion of State and Federal compassionate release programs, this mechanism for release remains underutilized. Health-care professionals are central to the process of recommending compassionate release, but few resources exist to support these efforts. The purpose of this paper is to provide a guide for health-care professionals requesting compassionate release for patients who are incarcerated. DESIGN/METHODOLOGY/APPROACH: This study is stepwise guide for health-care professionals requesting compassionate release for patients who are incarcerated. FINDINGS: This study describes the role of the health-care professional in requesting compassionate release and offers guidance to help them navigate the process of preparing a medical declaration or request for compassionate release. ORIGINALITY/VALUE: No prior publications have created a step-wise guide of this nature to aid health-care professionals through the compassionate release process.

Factors Associated with Incarceration in Older Adults Experiencing Homelessness: Results from the HOPE HOME Study.

BACKGROUND: In the US, the median age of adults experiencing homelessness and incarceration is increasing. Little is known about risk factors for incarceration among older adults experiencing homelessness. To develop targeted interventions, there is a need to understand their risk factors for incarceration. OBJECTIVE: To examine the prevalence and risk factors associated with incarceration in a cohort of older adults experiencing homelessness. DESIGN: Prospective, longitudinal cohort study with interviews every 6 months for a median of 5.8 years. PARTICIPANTS: We recruited adults ≥50 years old and homeless at baseline (n=433) via population-based sampling. MAIN MEASURES: Our dependent variable was incident incarceration, defined as one night in jail or prison per 6-month follow-up period after study enrollment. Independent variables included socioeconomic status, social, health, housing, and prior criminal justice involvement. KEY RESULTS: Participants had a median age of 58 years and were predominantly men (75%) and Black (80%). Seventy percent had at least one chronic medical condition, 12% reported heavy drinking, and 38% endorsed moderate-severe use of cocaine, 8% of amphetamines, and 7% of opioids. At baseline, 84% reported a lifetime history of jail stays; 37% reported prior prison stays. During follow-up, 23% spent time in jail or prison. In multivariable models, factors associated with a higher risk of incarceration included the following: having 6 or more confidants (HR=2.13, 95% CI=1.2-3.7, p=0.007), remaining homeless (HR=1.72, 95% CI=1.1-2.8, p=0.02), heavy drinking (HR=2.05, 95% CI=1.4-3.0, p<0.001), moderate-severe amphetamine use (HR=1.89, 95% CI=1.2-3.0, p=0.006), and being on probation (HR=3.61, 95% CI=2.4-5.4, p<0.001) or parole (HR=3.02, 95% CI=1.5-5.9, p=0.001). CONCLUSIONS: Older adults experiencing homelessness have a high risk of incarceration. There is a need for targeted interventions addressing substance use, homelessness, and reforming parole and probation in order to abate the high ongoing risk of incarceration among older adults experiencing homelessness.

A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma.

BACKGROUND: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway frequently is activated in patients with urothelial carcinoma (UC). In the current study, the authors performed a phase 2 study evaluating the efficacy of the pan-isoform class I PI3K inhibitor buparlisib in patients with platinum-refractory metastatic UC. METHODS: Two cohorts were recruited: an initial genetically unselected cohort and a subsequent expansion cohort of patients with PI3K/Akt/mTOR pathway-altered tumors. The primary endpoint was the 2-month progression-free survival rate. A rate of ≥80% was considered promising using a Simon 2-stage minimax design. Secondary endpoints included safety and correlation of markers of PI3K pathway activation with outcome. RESULTS: Six of 13 evaluable patients within the initial cohort demonstrated stable disease and 1 demonstrated a partial response, which was below the cutoff of 9 patients required to proceed to stage 2. Three of the patients with stable disease and the patient with a partial response harbored somatic TSC1 alterations. Four patients subsequently were recruited onto an expansion cohort: 3 patients with TSC1 alterations and 1 patient with a PIK3CA-activating mutation. No patient achieved disease control at 8 weeks and accrual was halted. Of the 19 patients evaluable for toxicity, 17 demonstrated treatment-related toxicities, 2 of whom had to discontinue therapy. CONCLUSIONS: Buparlisib was found to demonstrate modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations; however, this was not a robust predictor of response to buparlisib. The pattern of genetic coalterations likely influences drug sensitivity. Given the modest clinical activity and substantial toxicity of buparlisib, future trials of PI3K inhibitors in patients with UC should focus on isoform-selective PI3K inhibitors in genomically selected patients. LAY SUMMARY: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway frequently is upregulated in patients with metastatic urothelial carcinoma (UC). This trial explored buparlisib, an inhibitor of the pathway, in patients with heavily pretreated metastatic UC. Although the drug was found to have modest efficacy, with 6 patients experiencing stable disease and 1 patient achieving a partial response at 8 weeks on therapy, significant side effects also were observed. Patients with specific genetic alterations responded to treatment. Further studies of PI3K pathway inhibition are warranted using newer agents that have superior toxicity profiles and are more selective inhibitors of the pathway.

Evaluating the association of multiple single nucleotide polymorphisms with response to gemcitabine and platinum combination chemotherapy in urothelial carcinoma of the bladder
.

OBJECTIVE: To examine germline single nucleotide polymorphisms (SNPs) as markers of response to gemcitabine platinum (GP) combination chemotherapy in urothelial carcinoma (UC). METHODS: Saliva or blood was prospectively collected from 216 patients treated with GP for UC of the bladder between 1991 and 2011. Based on reported associations with gemcitabine and cisplatin response or putative mechanisms of gemcitabine or cisplatin/carboplatin activity, we selected SNPs of interest and were able to genotype 59 SNPs (using the SequenomMass ARRAYiPLEX platform) in 261 patients randomly split 2/3 into a training set (n = 174) and 1/3 into a test set (n = 87). Logistic regression was used to test the association between response to GP and SNPs. RESULTS: The median age at diagnosis was 64 years (range: 28 - 85) for the discovery set and 67 years (range: 30 - 84) for the validation set. Males composed 76% and 69%, and white non-Hispanics composed 88% and 91% of the training and test validation sets, respectively. Three SNPs on GALNTL4 (rs7937567, rs12278731, and rs9988868) and one intergenic SNP (rs1321391) were significantly associated with response to GP in the training set and were used to build a SNP score. However, when assessed in the test set, the SNP score was not significantly associated with response. CONCLUSION: Multiple SNPs selected from previous studies failed to predict response to GP in this cohort. Larger studies capable of accounting for population-based allele frequency heterogeneity may be required for replication of genetic alterations important to pharmacogenomics.
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Outcome and Impact Evaluation of a Transgender Health Course for Health Profession Students.

PURPOSE: Being transgender is associated with numerous health disparities, and transgender individuals face mistreatment and discrimination in healthcare settings. At the same time, healthcare professionals report inadequate preparation to care for transgender people, and patients often have to teach their own medical providers about transgender care. Our study aimed to evaluate the impact of an elective course for health profession students in transgender health that was implemented to address these gaps in provider knowledge. METHODS: Students participated in a 10-session, lunch-hour elective course during the spring of 2015. To evaluate impact, course participants completed pre-, immediately post-, and 3-month postcourse questionnaires, including a previously validated nine-item transphobia scale, to determine the course's effect on knowledge, attitudes, and beliefs about transgender health. RESULTS: Forty-six students completed the pre- and immediately postelective questionnaire (74% response rate). Compared with pre-elective surveys, immediately postelective scores demonstrated increased knowledge in most domains and reduced transphobia. Specific knowledge domains with improvements included terminology, best practices for collecting gender identity, awareness of the DSM-V gender dysphoria diagnosis, medications used for gender affirmation, and relevant federal policies. A previously validated transphobia scale was found to have good reliability in the current sample. CONCLUSION: This elective course led to positive short-term changes in measures of multiple knowledge domains and reduced measures of transphobia among health profession students. Further study is needed to assess the long-term impact. Our methods and findings, including the demonstration of reliability of a previously validated nine-item transphobia scale, serve as formative data for the future development of theory-based transgender medicine curricula and measures.

Clinical Evaluation of Cisplatin Sensitivity of Germline Polymorphisms in Neoadjuvant Chemotherapy for Urothelial Cancer.

BACKGROUND: Level 1 evidence has demonstrated increased overall survival with cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive urothelial cancer. Usage remains low, however, in part because neoadjuvant chemotherapy will not be effective for every patient. To identify the patients most likely to benefit, we evaluated germline pharmacogenomic markers for association with neoadjuvant chemotherapy sensitivity in 2 large cohorts of patients with urothelial cancer. PATIENTS AND METHODS: Patients receiving neoadjuvant cisplatin-based chemotherapy for muscle-invasive urothelial cancer were eligible. Nine germline single nucleotide polymorphisms (SNPs) potentially conferring platinum sensitivity were tested for an association with a complete pathologic response to neoadjuvant chemotherapy (pT0) or elimination of muscle-invasive cancer (

The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced urothelial carcinoma: a large single-institution experience.

BACKGROUND: Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. PATIENTS AND METHODS: Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. RESULTS: One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. CONCLUSION: This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.

Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma.

UNLABELLED: Cisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, although molecular determinants of cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 patients with muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin-based chemotherapy followed by cystectomy (25 pT0/pTis "responders," 25 pT2+ "nonresponders") to identify somatic mutations that occurred preferentially in responders. ERCC2, a nucleotide excision repair gene, was the only significantly mutated gene enriched in the cisplatin responders compared with nonresponders (q < 0.01). Expression of representative ERCC2 mutants in an ERCC2-deficient cell line failed to rescue cisplatin and UV sensitivity compared with wild-type ERCC2. The lack of normal ERCC2 function may contribute to cisplatin sensitivity in urothelial cancer, and somatic ERCC2 mutation status may inform cisplatin-containing regimen usage in muscle-invasive urothelial carcinoma. SIGNIFICANCE: Somatic ERCC2 mutations correlate with complete response to cisplatin-based chemosensitivity in muscle-invasive urothelial carcinoma, and clinically identified mutations lead to cisplatin sensitivity in vitro. Nucleotide excision repair pathway defects may drive exceptional response to conventional chemotherapy.

Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer.

PURPOSE: We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with high-grade bladder cancer to serve as a platform for therapeutic drug discovery. PATIENTS AND METHODS: An integrative analysis of 97 high-grade bladder tumors was conducted to identify actionable drug targets, which are defined as genomic alterations that have been clinically validated in another cancer type (eg, BRAF mutation) or alterations for which a selective inhibitor of the target or pathway is under clinical investigation. DNA copy number alterations (CNAs) were defined by using array comparative genomic hybridization. Mutation profiling was performed by using both mass spectroscopy-based genotyping and Sanger sequencing. RESULTS: Sixty-one percent of tumors harbored potentially actionable genomic alterations. A core pathway analysis of the integrated data set revealed a nonoverlapping pattern of mutations in the RTK-RAS-RAF and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways and regulators of G1-S cell cycle progression. Unsupervised clustering of CNAs defined two distinct classes of bladder tumors that differed in the degree of their CNA burden. Integration of mutation and copy number analyses revealed that mutations in TP53 and RB1 were significantly more common in tumors with a high CNA burden (P < .001 and P < .003, respectively). CONCLUSION: High-grade bladder cancer possesses substantial genomic heterogeneity. The majority of tumors harbor potentially tractable genomic alterations that may predict for response to target-selective agents. Given the genomic diversity of bladder cancers, optimal development of target-specific agents will require pretreatment genomic characterization.

Phase II study of everolimus in metastatic urothelial cancer.

UNLABELLED: What's known on the subject? and what does the study add?: No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up-regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near-complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer. To maximize benefit from targeted agents such as everolimus, the preselection of patients based on molecular phenotype is required. OBJECTIVE: To assess the efficacy and tolerability of everolimus in advanced urothelial carcimoma (UC). PATIENTS AND METHODS: The present study comprised a single-arm, non-randomized study in which all patients received everolimus 10 mg orally once daily continuously (one cycle = 4 weeks). In total, 45 patients with metastatic UC progressing after one to four cytotoxic agents were enrolled between February 2009 and November 2010 at the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month progression-free survival (PFS) and the safety of everolimus, with the secondary endpoint being the response rate. A Simon minimax two-stage design tested the null hypothesis that the true two month PFS rate was ≤ 50%, as opposed to the alternative hypothesis of ≥ 70%. RESULTS: The most common grade 3/4 toxicities were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and hypophosphataemia. There were two partial responses in nodal metastases, with one patient achieving a 94% decrease in target lesions and remaining on drug at 26 months. An additional 12 patients exhibited minor tumour regression. There were 23 of 45 (51%) patients who were progression-free at 2 months with a median (95% CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3 (5.5-12.1) months. No clear association was observed between mammalian target of rapamycin pathway marker expression and 2-month PFS. CONCLUSIONS: Although everolimus did not meet its primary endpoint, one partial response, one near-complete response and twelve minor regressions were observed. Everolimus possesses meaningful anti-tumour activity in a subset of patients with advanced UC. Studies aiming to define the genetic basis of everolimus activity in individual responders are ongoing.

Phase II study of gemcitabine, carboplatin, and bevacizumab in patients with advanced unresectable or metastatic urothelial cancer.

PURPOSE: Although gemcitabine and carboplatin (GCa) is a standard option for patients with advanced urothelial cancer (UC) who are ineligible for cisplatin, outcomes remain poor. This trial evaluated the efficacy and safety of bevacizumab with GCa in advanced UC. PATIENTS AND METHODS: Patients with Karnofsky performance status of 60% to 70%, creatinine clearance less than 60 mL/min, visceral metastasis, or solitary kidney were eligible and received a lead-in dose of bevacizumab 10 mg/kg followed 2 weeks later by gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin at area under the [concentration-time] curve (AUC) 5.0 or 4.5 and bevacizumab 15 mg/kg on day 1 every 21 days for six cycles. Patients achieving at least stable disease (SD) continued bevacizumab 15 mg/kg every 21 days for 18 additional cycles. The study was powered to detect a 50% improvement in median progression-free survival (PFS) over a historical control. RESULTS: Fifty-one patients, median age 67 years (range, 42 to 83 years), were enrolled onto the study and were evaluable for toxicity. Twenty (39%) experienced grade 3 to 4 toxicity, and 10 (20%) had thromboembolic events (deep venous thrombosis or pulmonary embolism). Four received one or fewer cycles leaving 47 evaluable for outcomes. Twenty-three (49%) achieved response (three complete; 20 partial), and 11 had SD. Median PFS was 6.5 months (95% CI, 4.7 to 7.8 months); PFS was greater in the carboplatin AUC 5.0 group (P = .04). Median overall survival (OS) was 13.9 months. CONCLUSION: The 95% one-sided lower confidence bound of 4.77 months for median PFS did not meet the predesignated PFS of more than 4.8 months considered sufficient for further study. Median OS was greater than expected. An ongoing phase III trial in patients who are eligible for therapy with cisplatin will define the role of bevacizumab in UC.