Nurturing diversity and inclusion in AI in Biomedicine through a virtual summer program for high school students.

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at the final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students' knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.

Limited English Proficiency Associated With Suboptimal Pain Assessment in Hospitalized Trauma Patients.

INTRODUCTION: Traumatic injury causes significant acute and chronic pain, and accurate pain assessment is foundational to optimal pain control. Prior literature has revealed disparities in the treatment of pain by race and ethnicity, but the effect of patient language on pain assessment remains unknown. We aimed to investigate the relationship between Limited English Proficiency (LEP) in pain assessment frequency and pain score magnitude for hospitalized trauma patients. METHODS: We conducted a cross-sectional, retrospective study including all hospitalized adult trauma patients from 2012 to 2018 at a single urban Level-1 trauma center. Patient language, 0-10 Numeric Rating Scale (NRS) pain scores, and demographic and clinical covariates were extracted from the electronic medical record. We used multivariable negative binomial regressions to compare NRS pain assessment frequency and multivariable linear regression to compare NRS pain score magnitude between LEP and English Proficient patients. RESULTS: Between 2012 and 2018, 9754 English proficient and 1878 LEP patients were hospitalized for traumatic injury. In multivariable models adjusted for demographic and injury characteristics, LEP patients had 2.4 fewer pain assessments per day compared to English proficient patients (7.21 versus 9.61, P = 0.001). Excluding days spent in the ICU, LEP patients had 2.6 fewer assessments per day (9.28 versus 11.88, P = 0.001). Median pain scores were lower in the LEP group (2.2 versus 3.61, P < 0.001), with a difference of 1.19 points in adjusted multivariable models. CONCLUSIONS: Compared to English Proficient patients, LEP patients had fewer pain assessments and lower NRS scores. Differences in pain assessment by patient language may be associated with disparities in pain management and morbidity.

Identification and Characterization of Circulating Tumor Cells in Men Who have Undergone Prostatectomy for Clinically Localized, High Risk Prostate Cancer.

PURPOSE: Approximately 15% of men with newly diagnosed prostate cancer have high risk features which increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence and change surveillance and adjuvant treatment paradigms. Circulating tumor cells are thought to represent the earliest form of metastases. However, their role as biomarkers in men with high risk, localized prostate cancer is not well defined. MATERIALS AND METHODS: Two to 5 months after prostatectomy we obtained blood samples from 37 patients with high risk, localized prostate cancer, defined as stage T3a or higher, Gleason score 8 or greater, or prostate specific antigen 20 ng/ml or greater. Circulating tumor cells were enumerated using a commercial platform. Matched tumor and single circulating tumor cell sequencing was performed. RESULTS: Circulating tumor cells were detected in 30 of 37 samples (81.1%) with a median of 2.4 circulating tumor cells per ml (range 0 to 22.9). Patients with detectable circulating tumor cells showed a trend toward shorter recurrence time (p=0.12). All patients with biochemical recurrence had detectable circulating tumor cells. Androgen receptor over expression was detected in 7 of 37 patients (18.9%). Patients with biochemical recurrence had more circulating tumor cell copy number aberrations (p=0.027). Matched tumor tissue and single circulating tumor cell sequencing revealed heterogeneity. CONCLUSIONS: We noted a high incidence of circulating tumor cell detection after radical prostatectomy and shorter time to biochemical recurrence in men with a higher circulating tumor cell burden and more circulating tumor cell copy number aberrations. Genomic alterations consistent with established copy number aberrations in prostate cancer were detectable in circulating tumor cells but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts early circulating tumor cell detection could be an informative biomarker to assist with adjuvant treatment decisions.

Validation of GEMCaP as a DNA Based Biomarker to Predict Prostate Cancer Recurrence after Radical Prostatectomy.

PURPOSE: We aimed to validate GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate) as a novel copy number signature predictive of prostate cancer recurrence. MATERIALS AND METHODS: We randomly selected patients who underwent radical prostatectomy at Cleveland Clinic or University of Rochester from 2000 to 2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization. A high GEMCaP score was defined as 20% or greater of genomic loci showing copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and the risk of biochemical recurrence. RESULTS: We report results in 140 patients. Overall 38% of patients experienced recurrence with a median time to recurrence of 45 months. Based on the CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score 39% of the patients were at low risk, 42% were at intermediate risk and 19% were at high risk. The GEMCaP score was high (20% or greater) in 31% of the cohort. A high GEMCaP score was associated with a higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51-4.77) and it remained associated after adjusting for CAPRA-S score and age (HR 1.94, 95% CI 1.06-3.56). The C-index of GEMCaP alone was 0.64, which improved when combined with the CAPRA-S score and patient age (C-index = 0.75). CONCLUSIONS: A high GEMCaP score was associated with biochemical recurrence in 2 external cohorts. This remained true after adjusting for clinical and pathological factors. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify patients with prostate cancer for early adjuvant therapy.

Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients.

BACKGROUND: While programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity in a proportion of patients with advanced bladder cancer, strongly predictive and prognostic biomarkers are still lacking. In this study, we evaluated PD-L1 protein expression on circulating tumor cells (CTCs) isolated from patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer and explore the prognostic value of CTC PD-L1 expression on clinical outcomes. METHODS: Blood samples from 25 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK)+ and (CK)-CTCs (CD45-, intact nuclei, morphologically distinct from WBCs) were enumerated. A subset of patient samples underwent genetic characterization by fluorescence in situ hybridization (FISH) and copy number variation (CNV) analysis. RESULTS: CTCs were detected in 20/25 (80 %) patients, inclusive of CK+ CTCs (13/25, 52 %), CK-CTCs (14/25, 56 %), CK+ CTC Clusters (6/25, 24 %), and apoptotic CTCs (13/25, 52 %). Seven of 25 (28 %) patients had PD-L1+ CTCs; 4 of these patients had exclusively CK-/CD45-/PD-L1+ CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH and CNV analysis, which revealed marked genomic instability. Although this study was not powered to evaluate survival, exploratory analyses demonstrated that patients with high PD-L1+/CD45-CTC burden and low burden of apoptotic CTCs had worse overall survival. CONCLUSIONS: CTCs are detectable in both MIBC and mBCa patients. PD-L1 expression is demonstrated in both CK+ and CK-CTCs in patients with mBCa, and genomic analysis of these cells supports their tumor origin. Here we demonstrate the ability to identify CTCs in patients with advanced bladder cancer through a minimally invasive process. This may have the potential to guide checkpoint inhibitor immune therapies that have been established to have activity, often with durable responses, in a proportion of these patients.

The impact of improved microarray coverage and larger sample sizes on future genome-wide association studies.

Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with complex traits. However, the genetic heritability of most of these traits remains unexplained. To help guide future studies, we address the crucial question of whether future GWAS can detect new SNP associations and explain additional heritability given the new availability of larger GWAS SNP arrays, imputation, and reduced genotyping costs. We first describe the pairwise and imputation coverage of all SNPs in the human genome by commercially available GWAS SNP arrays, using the 1000 Genomes Project as a reference. Next, we describe the findings from 6 years of GWAS of 172 chronic diseases, calculating the power to detect each of them while taking array coverage and sample size into account. We then calculate the power to detect these SNP associations under different conditions using improved coverage and/or sample sizes. Finally, we estimate the percentages of SNP associations and heritability previously detected and detectable by future GWAS under each condition. Overall, we estimated that previous GWAS have detected less than one-fifth of all GWAS-detectable SNPs underlying chronic disease. Furthermore, increasing sample size has a much larger impact than increasing coverage on the potential of future GWAS to detect additional SNP-disease associations and heritability.

Probing versus primary nasal endoscopy for the treatment of congenital dacryocystoceles.

PURPOSE: To compare outcomes and complications of three surgical techniques for the treatment of congenital dacryocystoceles: nasolacrimal probing and irrigation (P+I), P+I plus nasal endoscopy (NE) with intranasal cyst marsupialization, and primary NE with intranasal cyst marsupialization. METHODS: The medical records of children ≤2 years of age at a single academic center with a diagnosis of dacryocystocele from 2012 to 2022 were retrospectively identified and reviewed. The primary outcome was resolution of the dacryocystocele (ie, elimination of the medial canthal mass and resolution of tearing or discharge) after a single procedure ("primary success"). Surgical techniques were compared using exact logistic regression. RESULTS: Of 54 patients, 21 (39%) underwent P+I, 23 (43%) underwent P+I plus nasal endoscopy, and 10 (18%) underwent primary NE. Primary success was 76% for P+I and 100% for the other two cohorts. Most patients (89%) who underwent P+I received general anesthesia compared with none who underwent primary nasal endoscopy. Most complications were related to the use of general anesthesia, with a complication rate of 10% for P+I, 48% for P+I plus NE, and 0% for primary NE. Most P+I procedures required hospital admission compared to half of primary NE procedures. CONCLUSIONS: In our study cohort, primary NE provided good outcomes and was associated with a lower complication rate than P+I with or without NE.

In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months.

Importance: Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking. Objective: To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age. Design, Setting, and Participants: This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely. Exposure: In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed. Main Outcomes and Measures: Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay. Results: A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07). Conclusions and Relevance: Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

Prevalence and incidence of comorbidities in elderly women with ovarian cancer.

OBJECTIVE: Studies suggest comorbidity plays an important role in ovarian cancer. We characterized the epidemiology of comorbid conditions in elderly U.S. women with ovarian cancer. METHODS: Women with ovarian cancer age ≥66 years, and matched cancer-free women, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Prevalence before diagnosis/index date and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis/index date were estimated for 34 chronic and acute conditions across a broad range of diagnostic categories. RESULTS: There were 5087 each of women with ovarian cancer and cancer-free women. The prevalence of most conditions was similar between cancer and cancer-free patients, but exceptions included hypertension (51.8% and 43.5%, respectively), osteoarthritis (13.4% and 17.3%, respectively), and cerebrovascular disease (8.0% and 9.8%, respectively). In contrast, 3- and 12-month incidence rates (per 1000 person years) of most conditions were significantly higher in cancer than in cancer-free patients: hypertension (177.3 and 47.4, respectively); thromboembolic event (145.3 and 5.5, respectively); congestive heart failure (113.3 and 28.6, respectively); infection (664.4 and 55.2, respectively); and anemia (408.3 and 33.1, respectively) at 12 months. CONCLUSIONS: Comorbidities were common among elderly women. After cancer diagnosis, women with ovarian cancer had a much higher incidence of comorbidities than cancer-free women. The high incidence of some of these comorbidities may be related to the cancer or its treatment, but others may have been prevalent but undiagnosed until the cancer diagnosis. The presence of comorbidities may affect treatment decisions.

Trends in the likelihood of receiving percutaneous coronary intervention in a low-volume hospital and disparities by sociodemographic communities.

INTRODUCTION: Over the past two decades, percutaneous coronary intervention (PCI) capacity has increased while coronary artery disease has decreased, potentially lowering per-hospital PCI volumes, which is associated with less favorable patient outcomes. Trends in the likelihood of receiving PCI in a low-volume center have not been well-documented, and it is unknown whether certain socioeconomic factors are associated with a greater risk of PCI in a low-volume facility. Our study aims to determine the likelihood of being treated in a low-volume PCI center over time and if this likelihood differs by sociodemographic factors. METHODS: We conducted a retrospective cohort study of 374,066 hospitalized patients in California receiving PCI from January 1, 2010, to December 31, 2018. Our primary outcome was the likelihood of PCI discharges at a low-volume hospital (<150 PCI/year), and secondary outcomes included whether this likelihood varied across different sociodemographic groups and across low-volume hospitals stratified by high or low ZIP code median income. RESULTS: The proportion of PCI discharges from low-volume hospitals increased from 5.4% to 11.0% over the study period. Patients of all sociodemographic groups considered were more likely to visit low-volume hospitals over time (P<0.001). Latinx patients were more likely to receive PCI at a low-volume hospital compared with non-Latinx White in 2010 with a 166% higher gap in 2018 (unadjusted proportions). The gaps in relative risk (RR) between Black, Latinx and Asian patients versus non-Latinx white increased over time, whereas the gap between private versus public/no insurance, and high versus low income decreased (interaction P<0.001). In low-income ZIP codes, patients with Medicaid were less likely to visit low-volume hospitals than patients with private insurance in 2010; however, this gap reversed and increased by 500% in 2018. Patients with low income were more likely to receive PCI at low-volume hospitals relative to patients with high income in all study years. CONCLUSIONS: The likelihood of receiving PCI at low-volume hospitals has increased across all race/ethnicity, insurance, and income groups over time; however, this increase has not occurred evenly across all sociodemographic groups.

Interplay of demographics, geography and COVID-19 pandemic responses in the Puget Sound region: The Vashon, Washington Medical Reserve Corps experience.

BACKGROUND: Rural U.S. communities are at risk from COVID-19 due to advanced age and limited access to acute care. Recognizing this, the Vashon Medical Reserve Corps (VMRC) in King County, Washington, implemented an all-volunteer, community-based COVID-19 response program. This program integrated public engagement, SARS-CoV-2 testing, contact tracing, vaccination, and material community support, and was associated with the lowest cumulative COVID-19 case rate in King County. This study aimed to investigate the contributions of demographics, geography and public health interventions to Vashon's low COVID-19 rates. METHODS: This observational cross-sectional study compares cumulative COVID-19 rates and success of public health interventions from February 2020 through November 2021 for Vashon Island with King County (including metropolitan Seattle) and Whidbey Island, located ~50 km north of Vashon. To evaluate the role of demography, we developed multiple linear regression models of COVID-19 rates using metrics of age, race/ethnicity, wealth and educational attainment across 77 King County zip codes. To investigate the role of remote geography we expanded the regression models to include North, Central and South Whidbey, similarly remote island communities with varying demographic features. To evaluate the effectiveness of VMRC's community-based public health measures, we directly compared Vashon's success of vaccination and contact tracing with that of King County and South Whidbey, the Whidbey community most similar to Vashon. RESULTS: Vashon's cumulative COVID-19 case rate was 29% that of King County overall (22.2 vs 76.8 cases/K). A multiple linear regression model based on King County demographics found educational attainment to be a major correlate of COVID-19 rates, and Vashon's cumulative case rate was just 38% of predicted (p < .05), so demographics alone do not explain Vashon's low COVID-19 case rate. Inclusion of Whidbey communities in the model identified a major effect of remote geography (-49 cases/K, p < .001), such that observed COVID-19 rates for all remote communities fell within the model's 95% prediction interval. VMRC's vaccination effort was highly effective, reaching a vaccination rate of 1500 doses/K four months before South Whidbey and King County and maintaining a cumulative vaccination rate 200 doses/K higher throughout the latter half of 2021 (p < .001). Including vaccination rates in the model reduced the effect of remote geography to -41 cases/K (p < .001). VMRC case investigation was also highly effective, interviewing 96% of referred cases in an average of 1.7 days compared with 69% in 3.7 days for Washington Department of Health investigating South Whidbey cases and 80% in 3.4 days for Public Health-Seattle & King County (both p<0.001). VMRC's public health interventions were associated with a 30% lower case rate (p<0.001) and 55% lower hospitalization rate (p = 0.056) than South Whidbey. CONCLUSIONS: While the overall magnitude of the pre-Omicron COVID-19 pandemic in rural and urban U.S. communities was similar, we show that island communities in the Puget Sound region were substantially protected from COVID-19 by their geography. We further show that a volunteer community-based COVID-19 response program was highly effective in the Vashon community, augmenting the protective effect of geography. We suggest that Medical Reserve Corps should be an important element of future pandemic planning.

Fentanyl epidemic hits the U.S. West Coast: Opioid-related deaths in San Francisco from 2009-2019.

BACKGROUND: Opioid-use disorders have led to a nationwide epidemic of accidental overdoses in the United States. In recent years this opioid epidemic has worsened due to the increased availability of fentanyl in the illicit drug market. The increase in fentanyl-related deaths is well known on the U.S. East Coast, however, limited comprehensive information of mortality data exists from major West Coast cities. METHODS: Following comprehensive medico-legal death and toxicological investigations, a retrospective cohort study was performed on all accidental opioid overdose deaths (AOOD) from 2009 - 2019 in San Francisco. The sex, age and race of decedents, location, and date and time of death were described and statistically compared by the type of opioid(s) causing death. RESULTS: Since 2016, fentanyl deaths started to replace heroin deaths leading to a sharp increase in fatal overdoses involving fentanyl, surpassing heroin and/or medicinal opioids by 2018. Fentanyl contributed to between 3% and 12% of deaths per year from 2009 to 2015, and between 20% and 73% per year from 2016 to 2019. White and Black males represented 91.5% of all AOOD. Age groups younger than 45 died using fentanyl and heroin significantly more often than older populations (60.7% of ≤45 vs. 40.7% of >45 year-olds, χ2p<0.001). CONCLUSIONS: This study shows an upward trend in fentanyl fatal accidental overdoses in recent years in a major West Coast U.S. city. These patterns appear to follow patterns seen in eastern states, albeit with an approximate 3-year delay, and may be indicative of other western populations. The described observations provide detailed demographic, chronological and toxicological information to public health and policy-making agencies for drug harm reduction measures.

Multiple Tissue Biomarkers Independently and Additively Predict Prostate Cancer Pathology Outcomes.

BACKGROUND: Distinguishing indolent from aggressive prostate cancer remains a key challenge for decision making regarding prostate cancer management. A growing number of biomarkers are now available to help address this need, but these have rarely been examined together in the same patients to determine their potentially additive value. OBJECTIVE: To determine whether two previously validated plasma markers (transforming growth factor ß1 [TGFß1] and interleukin-6 soluble receptor [IL6-SR]) and two validated tissue scores (the Genomic Evaluators of Metastatic Prostate Cancer [GEMCaP] and cell cycle progression [CCP] scores) can improve on clinical parameters in predicting adverse pathology after prostatectomy, and how much they vary within tumors with heterogeneous Gleason grade. DESIGN, SETTING, AND PARTICIPANTS: A case-control study was conducted among men with low-risk cancers defined by biopsy grade group (GG) 1, prostate-specific antigen (PSA) ≤10 ng/mL, and clinical stage ≤ T2 who underwent immediate prostatectomy. We collected paraffin-fixed prostatectomy tissue and presurgical plasma samples from 381 cases from the University of California, San Francisco, and 260 cases from the University of Washington. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathologic outcomes were minor upgrading/upstaging (GG 2 or pT3a) or major upgrading/upstaging (GG ≥ 3 or ≥ pT3b), and multinomial regression was performed to determine putative markers' ability to predict these outcomes, controlling for PSA, percent of positive biopsy cores, age, and clinical site. For upgraded tumors, a secondary analysis of the GEMCaP and CCP scores from the higher-grade tumor was also performed to evaluate for heterogeneity. RESULTS AND LIMITATIONS: Overall, 357 men had no upgrading/upstaging event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFß1 nor IL6-SR was statistically significantly associated with any upgrading/upstaging. On the contrary, both the CCP and the GEMCaP score obtained from Gleason pattern 3 tissue were directly associated with minor and major upgrading/upstaging on univariate analysis. The two scores correlated with each other, but weakly. On multinomial analysis including both scores in the model, the CCP score predicted minor upgrading/upstaging (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.05-2.49) and major upgrading/upstaging (OR 2.26, 95% CI 1.05-4.90), p =  0.04), and the GEMCaP score also predicted minor upgrading/upstaging (OR 1.05, 95% CI 1.03-1.08) and major upgrading/upstaging (OR 1.07, 95% CI 1.04-1.11), p <  0.01). The other clinical parameters were not significant in this model. Among upgraded tumors including both Gleason patterns 3 and 4, both the GEMCaP and the CCP score tended to be higher from the higher-grade tumor. The main limitation was the use of virtual biopsies from prostatectomy tissue as surrogates for prostate biopsies. CONCLUSIONS: Biomarker signatures based on analyses of both DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy. PATIENT SUMMARY: Validated biomarker scores derived from both prostate cancer DNA and prostate cancer RNA can add independent information to help predict outcomes after prostatectomy.

Medication prescribing practices for older prisoners in the Texas prison system.

OBJECTIVES: We sought to assess appropriateness of medication prescribing for older Texas prisoners. METHODS: In this 12-month cross-sectional study of 13 117 prisoners (aged > or = 55 years), we assessed medication use with Zhan criteria and compared our results to prior studies of community prescribing. We assessed use of indicated medications with 6 Assessing Care of Vulnerable Elders indicators. RESULTS: Inappropriate medications were prescribed to a third of older prisoners; half of inappropriate use was attributable to over-the-counter antihistamines. When these antihistamines were excluded, inappropriate use dropped to 14% (> or = 55 years) and 17% (> or = 65 years), equivalent to rates in a Department of Veterans Affairs study (17%) and lower than rates in a health maintenance organization study (26%). Median rate of indicated medication use for the 6 indicators was 80% (range = 12%-95%); gastrointestinal prophylaxis for patients on nonsteroidal anti-inflammatories at high risk for gastrointestinal bleed constituted the lowest rate. CONCLUSIONS: Medication prescribing for older prisoners in Texas was similar to that for older community adults. However, overuse of antihistamines and underuse of gastrointestinal prophylaxis suggests a need for education of prison health care providers in appropriate prescribing practices for older adults.

Impact of age and comorbidity on colorectal cancer screening among older veterans.

BACKGROUND: The Veterans Health Administration, the American Cancer Society, and the American Geriatrics Society recommend colorectal cancer screening for older adults unless they are unlikely to live 5 years or have significant comorbidity that would preclude treatment. OBJECTIVE: To determine whether colorectal cancer screening is targeted to healthy older patients and is avoided in older patients with severe comorbidity who have life expectancies of 5 years or less. DESIGN: Cohort study. SETTING: Veterans Affairs (VA) medical centers in Minneapolis, Minnesota; Durham, North Carolina; Portland, Oregon; and West Los Angeles, California, with linked national VA and Medicare administrative claims. PATIENTS: 27 068 patients 70 years or older who had an outpatient visit at 1 of 4 VA medical centers in 2001 or 2002 and were due for screening. MEASUREMENTS: The main outcome was receipt of fecal occult blood testing (FOBT), colonoscopy, sigmoidoscopy, or barium enema in 2001 or 2002, on the basis of national VA and Medicare claims. Charlson-Deyo comorbidity scores at the start of 2001 were used to stratify patients into 3 groups ranging from no comorbidity (score of 0) to severe comorbidity (score > or =4), and 5-year mortality was determined for each group. RESULTS: 46% of patients were screened from 2001 through 2002. Only 47% of patients with no comorbidity were screened despite having life expectancies greater than 5 years (5-year mortality, 19%). Although the incidence of screening decreased with age and worsening comorbidity, it was still 41% for patients with severe comorbidity who had life expectancies less than 5 years (5-year mortality, 55%). The number of VA outpatient visits predicted screening independent of comorbidity, such that patients with severe comorbidity and 4 or more visits had screening rates similar to or higher than those of healthier patients with fewer visits. LIMITATIONS: Some tests may have been performed for nonscreening reasons. The generalizability of findings to persons who do not use the VA system is uncertain. CONCLUSION: Advancing age was inversely associated with colorectal cancer screening, whereas comorbidity was a weaker predictor. More attention to comorbidity is needed to better target screening to older patients with substantial life expectancies and avoid screening older patients with limited life expectancies. primary funding source: VA Health Services Research and Development.

Factors associated with delays in discharge for trauma patients at an urban county hospital.

BACKGROUND: Discharge delays for non-medical reasons put patients at unnecessary risk for hospital-acquired infections, lead to loss of revenue for hospitals and reduce hospital capacity to treat other patients. The objective of this study was to determine prevalence of, and patient characteristics associated with, delays in discharge at an urban county trauma service. METHODS: We performed a retrospective cohort study with data from Zuckerberg San Francisco General Hospital (ZSFGH), a level-1 trauma center and safety net hospital in San Francisco, California. The study included 1720 patients from the trauma surgery service at ZSFGH. A 'delay in discharge' was defined as days in the hospital, including an initial overnight stay, after all medical needs had been met. We used logistic and zero-inflated negative binomial regression models to test whether the following factors were associated with prolonged, non-medical length of stay: age, gender, race/ethnicity, housing, disposition location, type of insurance, having a primary care provider, primary language and zip code. RESULTS: Of the 1720 patients, 15% experienced a delay in discharge, for a total of 1147 days (median 1.5 days/patient). The following were statistically significant (p<0.05) predictors of delays in discharge in a multivariable logistic regression model: older age, unhoused status or disposition to home health or postacute care (compared with home discharge) were associated with increased likelihood of delays. Having private insurance or Medicare (compared with public insurance) and discharge against medical advice or absent without leave (compared with home discharge) were associated with reduced likelihood of delays in discharge after all medical needs were met. DISCUSSION: These results suggest that policymakers interested in reducing non-medical hospital stays should focus on addressing structural determinants of health, such as lack of housing, bottlenecks at postacute care disposition destinations and lack of adequate insurance. LEVEL OF EVIDENCE: Epidemiological, Level III.

Cystatin C as a marker of cognitive function in elders: findings from the health ABC study.

We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).

Cost and mortality associated with hospitalizations in patients with immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is associated with low platelet counts and, consequently, a high risk of adverse events leading to hospitalization. However, there are few data on the clinical and economic burden of hospitalizations for ITP. The Nationwide Inpatient Sample (NIS) database of discharges, a stratified 20% sample of all United States (US) community hospitals across all payers, was used to evaluate discharges in ITP patients. We developed nationally representative numbers of discharges in ITP patients from 2003 to 2006 based on diagnosis codes. Using appropriate weights for each NIS discharge, we created national estimates of average cost, length of stay, and in-hospital mortality for specific groups of ITP-related hospitalizations. Approximately 129,000 discharges occurred between 2003 and 2006 in ITP patients. The average cost associated with all discharges in 2008 dollars was 16,476, with a 6.4-day length of stay and in-hospital mortality of 3.8%. In contrast, the average cost of all hospitalizations in the US population during the same period was 10,039, the average length of stay was 4.8 days, and in-hospital mortality was 2.5%. Mortality risk was higher for ITP patients than for the standard US population adjusted for age and gender, with a relative mortality ratio of 1.5 (95% CI: 1.4-1.6). On the basis of a nationally representative sample of US discharge records from 2003 to 2006, hospitalization with ITP represents an economically and clinically important event. ITP was associated with higher costs, longer stays, and more in-hospital deaths on average than all other hospitalized patients combined.

Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: a systematic review.

Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short-term surgical non-response rate and the long-term relapse rate after laparoscopic splenectomy. A systematic review was conducted of articles published between January 1, 1991 and January 1, 2008. Selection criteria included: chronic ITP, study enrollment in 1990 or later, > or =12 months of follow-up, > or =15 patients with ITP, > or =75% of patients at least 14 years of age, not HIV positive, not undergoing a second splenectomy, and type of performed splenectomy clearly reported. Data were pooled across studies to estimate rates. We identified 170 articles, of which 23 met our inclusion criteria (all observational studies). These studies represent 1,223 laparoscopic splenectomies (71 or 5.6% were converted to open splenectomy during surgery). The pooled short-term surgical non-response rate among the 18 studies reporting data was 8.2% (95% CI 5.4-11.0). The pooled long-term relapse rate across all 23 studies was 43.6 per 1,000 patient years (95% CI 28.2-67.2). This translates to an approximate failure rate of 28% at 5 years for all patients undergoing splenectomy. Studies with shorter durations of follow-up had significantly higher pooled relapse rates than studies with longer follow-up (P = 0.04). Laparoscopicsplenectomy is effective for most patients. Splenectomy may have higher initial relapse rates, particularly, in the first 2 years after surgery, and the rate may decline over time. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

Screening mammography in older women. Effect of wealth and prognosis.

BACKGROUND: Wealthy women have higher rates of screening mammography than poor women do. Screening mammography is beneficial for women with substantial life expectancies, but women with limited life expectancies are unlikely to benefit. It is unknown whether higher screening rates in wealthy women are due to increased screening in women with substantial life expectancies, limited life expectancies, or both. This study examines the relationship between wealth and screening mammography use in older women according to life expectancy. METHODS: A cohort study was performed of 4222 women 65 years or older with Medicare participating in the 2002 and 2004 Health and Retirement Survey. Women were categorized according to wealth and life expectancy (based on 5-year prognosis from a validated prognostic index). The outcome was self-reported receipt of screening mammography within 2 years. RESULTS: Overall, within 2 years, 68% of women (2871 of 4222) received a screening mammogram. Screening was associated with wealth (net worth, > $100 000) and good prognosis (< or = 10% probability of dying in 5 years). Screening mammography was more common among wealthy women than among poor women (net worth, < $10 000) both for women with good prognosis (82% vs 68%; P < .001) and for women with limited prognoses (> or = 50% probability of dying in 5 years) (48% vs 32%; P = .02). These associations remained after multivariate analysis accounting for age, race, education, proxy report, and rural residence. CONCLUSIONS: Poorer older women with favorable prognoses are at risk of not receiving screening mammography when they are likely to benefit. Wealthier older women with limited prognoses are often screened when they are unlikely to benefit.