Faculty Bibliography

PURPOSE/OBJECTIVE:Active surveillance (AS) for intermediate-risk prostate cancer (PCa) is controversial. Many AS programs are limited to grade group (GG) 1 (Gleason 6) and PSA<10 ng/ml. However, recent guidelines state that AS can be considered for limited GG2 (Gleason 3+4), despite limited data on outcomes. Our objective was to compare prostatectomy outcomes between subgroups of intermediate-risk versus low-risk PCa. METHODS:We performed an observational study in the National Prostate Cancer Register (NPCR) of Sweden, including 98% of PCa nationwide. From 2009-2012, 5087 men with low-risk (GG1, PSA<10, and ≤cT2) and intermediate-risk PCa (GG2 or PSA 10-20, or T2) underwent radical prostatectomy. We compared upgrading and upstaging between groups, based on the UCSF Cancer of the Prostate Risk Assessment (CAPRA) scores and published AS criteria. Results were validated in an independent dataset of cases diagnosed 2013-2016. RESULTS:Men with GG1, PSA 10-15ng/ml and PSA density <0.15 had no significant difference in upgrading and adverse pathology compared to low-risk PCa. PSA>15 or GG2 were associated with a significantly greater risk of aggressive PCa. Men with low-risk CAPRA scores (0-2) and GG2 had almost a 3-fold increased risk of upgrading and 2-fold increased risk of adverse pathology compared to low-risk CAPRA GG1. CONCLUSIONS:Expanding the PSA threshold to 15 ng/ml for GG1 PCa would allow more men to choose AS and is unlikely to compromise outcomes, particularly if PSA density is low. By contrast, caution should be exercised in offering AS to men with PSA>15 or GG2.

INTRODUCTION/BACKGROUND:This study assesses preventable hospitalization rates among New York City residents living in public housing developments compared with all New York City residents and residents in low-income areas. Additionally, preventable hospitalization rates by development (one or multiple buildings in close proximity and served by the same management office) were determined. METHODS:The 2010-2014 New York City hospital discharge data were geocoded and linked with New York City Housing Authority records using building-level identifiers. Preventable hospitalizations resulting from ambulatory care-sensitive conditions were identified for public housing residents, citywide, and residents of low-income areas. Age-adjusted overall and ambulatory care-sensitive, condition-specific preventable hospitalization rates (11 outcomes) were determined and compared across groups to assess potential disparities. Additionally, rates were ranked and compared among public housing developments by quartiles. The analysis was conducted in 2016 and 2017. RESULTS:The age-adjusted rate of preventable hospitalization was significantly higher among public housing residents than citywide (rate ratio [RR]=2.67, 95% CI=2.65, 2.69), with the greatest disparities in hospitalizations related to diabetes (RR=3.12, 95% CI=3.07, 3.18) and asthma (RR=4.14, 95% CI=4.07, 4.21). The preventable hospitalization rate was also higher among residents of public housing than low-income areas (RR=1.33, 95% CI=1.31, 1.35). There were large differences between developments ranked in the top and bottom quartiles of preventable hospitalization (RR=1.81, 95% CI=1.76, 1.85) with the largest difference related to chronic obstructive pulmonary disease (RR=3.38, 95% CI=3.08, 3.70). CONCLUSIONS:Preventable hospitalization rates are high among public housing residents, and vary significantly by development and condition. By providing geographically granular information, geocoded hospital discharge data can serve as a valuable tool for health assessment and engagement of the healthcare sector and other stakeholders in interventions that address health inequities.

BACKGROUND:Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials. METHODS:, or doubling of serum creatinine. We used a Bayesian mixed-effects meta-regression analysis to relate the treatment effects on albuminuria to those on the clinical endpoint across studies and developed a prediction model for the treatment effect on the clinical endpoint on the basis of the treatment effect on albuminuria. FINDINGS:0·72, 0·05-0·99]). For future trials, the model predicts that treatments that decrease the geometric mean albuminuria to 0·7 (ie, 30% decrease in albuminuria) relative to the control will provide an average hazard ratio (HR) for the clinical endpoint of 0·68, and 95% of sufficiently large studies would have HRs between 0·47 and 0·95. INTERPRETATION:Our results support a role for change in albuminuria as a surrogate endpoint for the progression of chronic kidney disease, particularly in patients with high baseline albuminuria; for patients with low baseline levels of albuminuria this association is less certain. FUNDING:US National Kidney Foundation.

BACKGROUND:Blood eosinophils are used to determine eligibility for agents targeting IL-5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation. OBJECTIVE:To characterize variability and patterns of variability of blood eosinophil levels in a real-world clinic for severe asthmatics. METHODS:Retrospective review of blood eosinophils measured over a 5-year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analyzed. RESULTS:Patients treated in the Bellevue Hospital Asthma Clinic within a 3-month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n= 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures. CONCLUSION/CONCLUSIONS:In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability. These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention.

A timely determination of the risk of post-traumatic stress disorder (PTSD) is a prerequisite for efficient service delivery and prevention. We provide a risk estimate tool allowing a calculation of individuals' PTSD likelihood from early predictors. Members of the International Consortium to Predict PTSD (ICPP) shared individual participants' item-level data from ten longitudinal studies of civilian trauma survivors admitted to acute care centers in six countries. Eligible participants (N=2,473) completed an initial clinical assessment within 60 days of trauma exposure, and at least one follow-up assessment 4-15 months later. The Clinician-Administered PTSD Scale for DSM-IV (CAPS) evaluated PTSD symptom severity and diagnostic status at each assessment. Participants' education, prior lifetime trauma exposure, marital status and socio-economic status were assessed and harmonized across studies. The study's main outcome was the likelihood of a follow-up PTSD given early predictors. The prevalence of follow-up PTSD was 11.8% (9.2% for male participants and 16.4% for females). A logistic model using early PTSD symptom severity (initial CAPS total score) as a predictor produced remarkably accurate estimates of follow-up PTSD (predicted vs. raw probabilities: r=0.976). Adding respondents' female gender, lower education, and exposure to prior interpersonal trauma to the model yielded higher PTSD likelihood estimates, with similar model accuracy (predicted vs. raw probabilities: r=0.941). The current model could be adjusted for other traumatic circumstances and accommodate risk factors not captured by the ICPP (e.g., biological, social). In line with their use in general medicine, risk estimate models can inform clinical choices in psychiatry. It is hoped that quantifying individuals' PTSD risk will be a first step towards systematic prevention of the disorder.

INTRODUCTION:After the 2004 FDA box warning raised concerns about increased suicidal ideation among youth taking antidepressants, antidepressant use decreased for White youth but slightly increased for Black and Latino youth. Better understanding of patient and provider factors contributing to these differences is needed to improve future risk warning dissemination. METHODS:We analyzed antidepressant prescriptions for youth aged 5-17 in 2002-2006 Medicaid claims data from four states (CA, FL, NC, and NY). In multilevel models, we assessed provider- and patient-level contributions to changes in antidepressant use by race/ethnicity and compared responses to the box warning between providers with large (>2/3) and small (<1/3) proportions of minority patients. RESULTS:A significant amount of variance in overall prescribing patterns (calculated by the ICC) was explained at the provider level. Significant provider-level variation was also identified in the differential effect of the box warning by racial/ethnic group. In a test of the influence of provider panel mix, we found that providers with large proportions of minority patients reduced antidepressant prescribing more slowly after the box warning than other providers. DISCUSSION:This study is the first to assess provider- and patient-level variation in the impact of a health care policy change on treatment disparities. Black and Latino youth Medicaid beneficiaries were seen by largely different providers than their White counterparts, and these distinct providers were influential in driving antidepressant prescription patterns following the box warning. Concerted outreach to providers of minority beneficiaries is needed to ensure that risk warnings and clinical innovations diffuse swiftly across racial/ethnic minority groups.

Air pollution poses a great environmental risk to health. Outdoor fine particulate matter (PM_2.5) exposure is the fifth leading risk factor for death in the world, accounting for 4.2 million deaths and more than a hundred million disability-adjusted-life-years lost according to the Global Burden of Disease Report. The World Health Organization attributes 3.8 million additional deaths to Indoor air pollution. Air pollution can harm acutely, usually manifested by respiratory or cardiac symptoms, as well as chronically, potentially affecting every organ in the body. It can cause, complicate, or exacerbate many adverse health conditions. Tissue damage may result directly from pollutant toxicity, because fine and ultrafine particles can gain access to organs, or indirectly through systemic inflammatory processes. Susceptibility is partly under genetic and epigenetic regulation. Although air pollution affects people of all regions, ages, and social groups, it is likely to cause greater illness in those with heavy exposure and greater susceptibility. Persons are more vulnerable to air pollution if they have other illnesses or less social support. Harmful effects occur on a continuum of dosage and even at levels below air quality standards previously considered to be safe.

Changing weather patterns, droughts and competing water demands are dramatically altering the landscape and creating conditions conducive to the production of wind-blown dust and dust storms. In California, such factors are leading to the rapid shrinking of the Salton Sea, a 345 mile² land-locked "sea" situated near the southeastern rural border region known as the Imperial Valley. The region is anticipated to experience a dramatic increase in wind-blown dust and existing studies suggest a significant impact on the health and quality of life for nearby residents of this predominantly low-income, Mexican-American community. The discussion calls attention to the public health dimensions of the Salton Sea crisis. We know little about the possible long-term health effects of exposure to mobilized lakebed sediments or the numerous toxic contaminants that may become respirable on entrained particles. We draw on existing epidemiological literature of other known sources of wind-blown dust, such as desert dust storms, and related health effects to begin to understand the potential public health impact of wind-blown dust exposure. The increased production of wind-blown dust and environmental exposures to such non-combustion related sources of particulate matter are a growing health threat, due in part to drought coupled with increasing pressures on limited water resources. Recent population-based studies have linked dust storms with cardiovascular mortality, asthma hospitalization and decrease in pulmonary function in both adults and children. A growing number of studies provide evidence of the acute health effects of wind-blown dust exposures among children, which with repeated insults have the potential to influence respiratory health over time. The shrinking of the Salton Sea illustrates a public health and environmental justice crisis that requires action and attention to protect the health and well-being of local communities.