Perelman School of Medicine
Perelman School of Medicine's mission is to advance knowledge and improve health through research, patient care, and the education of trainees in an inclusive culture that embraces diversity, fosters innovation, stimulates critical thinking, supports lifelong learning, and sustains our legacy of excellence.
- Center for Public Health Initiatives
- Department of Biostatistics, Epidemiology and Informatics
- Department of Family Medicine and Community Health
- Department of Medical Ethics and Health Policy
- Department of Microbiology Papers
- Department of Obstetrics and Gynecology
- Department of Psychiatry
- Department of Systems Pharmacology and Translational Therapeutics
- Botswana-UPenn Partnership
- Center for Cognitive Neuroscience
- Global Health Programs
- Medical Physics Programs
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Publication 2014-2015 Annual Report(2015-01-01) Center for Public Health InitiativesPublication Experience Based Quality Control in IMRT Treatment Planning of High Risk Post-Prostatectomy Prostate Cancer with RapidPlan(2017-01-01) O'Grady, Fionnbarr T; Geng, Huaizhi; Huang, Mi; Giaddui, Tawfik; Zong, Haoyu; Xiao, YingPurpose: To develop a knowledge based planning (KBP) model with RapidPlan (Varian Medical Systems, Palo Alto, USA) for the treatment of high risk post-prostatectomy prostate cancer. The model was trained on a knowledge database of high quality treatment plans from the national clinical trial RTOG 0621, then tested as a QA tool. Methods: An initial dosimetric analysis was carried out to identify high quality plans from clinical trial RTOG 0621. Treatment plans for patients enrolled in the trial were scored according to the system used by the Imaging and Radiation Oncology Core (IROC) of the National Clinical Trials Network (NCTN) of the NCI to assess adherence to the trial protocol. Of the 80 plans enrolled in the trial 39 were chosen for the training sample. Another subset of 8 plans, orthogonal to the training sample, was chosen for the validation sample to ensure that the model accurately predicts dose volume histograms (DVHs) for all critical structures. The validation plans were then re-optimized with the model in order to test its effectiveness as a tool for planning QA. DVHs of the re-optimized plans were compared with those of the original clinical plans. Normal tissue complication probabilities and tumor control probabilities were calculated with the Lyman-Kutcher-Burman (LKB) model before and after re-optimization to determine the effect on patient outcome. Results: The RapidPlan prostate model was shown to accurately predict estimated DVH bands for all plans in the validation sample that matched the geometry of the training sample. Three treatment plans in the validation sample were geometric outliers with respect to the training sample leading to inaccuracies in the model predictions for the cone down phase of these treatment plans. All of the re-optimized plans showed increased dose sparring to the bladder and rectum respectively without lose of target coverage. The average reduction in NTCP was 0.34 ± 0.21 % for the bladder and 0.11 ± 0.25 % for the rectum with corresponding p-values of 0.116 and 0.668. The average TCP for the prostate bed decreased slightly from 97.05 % to 96.54 % with a p-value of 0.149. Due to limited statistics the changes reported in these numbers are not statistically significant as indicated by the p-values. Although the average values are inconclusive the model was effectively used to identify sub-optimal treatment plans which were improved through re-optimization with the model. For treatment plan 0621c0027 the NTCP decreased from 0.35 % to 0.06 % for the bladder and from 0.10 % to 0.06 % for the rectum while the TCP increased from 96.78 % to 96.87 %. Conclusions: The RapidPlan prostate model developed in this study is an effective tool for monitoring the quality of IMRT treatment plans for high-risk post prostatectomy prostate cancer.Publication Bartonella Infection in Immunocompromised Hosts: Immunology of Vascular Infection and Vasoproliferation(2012-01-01) Mosepele, Mosepele; Mazo, Dana; Cohn, JenniferMost infections by genus Bartonella in immunocompromised patients are caused by B. henselae and B. quintana. Unlike immunocompetent hosts who usually develop milder diseases such as cat scratch disease and trench fever, immunocompromised patients, including those living with HIV/AIDS and posttransplant patients, are more likely to develop different and severe life-threatening disease. This paper will discuss Bartonella's manifestations in immunosuppressed patients and will examine Bartonella's interaction with the immune system including its mechanisms of establishing infection and immune escape. Gaps in current understanding of the immunology of Bartonella infection in immunocompromised hosts will be highlighted.Publication Patterns of Cost for Patients Dying in the Intensive Care Unit and Implications for Cost Savings of Palliative Care Interventions.(2016-11-01) Khandelwal, Nita; Benkeser, David; Coe, Norma B; Engelberg, Ruth A; Teno, Joan M; Curtis, J RandallBACKGROUND: Terminal intensive care unit (ICU) stays represent an important target to increase value of care. OBJECTIVE: To characterize patterns of daily costs of ICU care at the end of life and, based on these patterns, examine the role for palliative care interventions in enhancing value. DESIGN: Secondary analysis of an intervention study to improve quality of care for critically ill patients. SETTING/PATIENTS: 572 patients who died in the ICU between 2003 and 2005 at a Level-1 trauma center. METHODS: Data were linked with hospital financial records. Costs were categorized into direct fixed, direct variable, and indirect costs. Patterns of daily costs were explored using generalized estimating equations stratified by length of stay, cause of death, ICU type, and insurance status. Estimates from the literature of effects of palliative care interventions on ICU utilization were used to simulate potential cost savings under different time horizons and reimbursement models. MAIN RESULTS: Mean cost for a terminal ICU stay was 39.3K ± 45.1K. Direct fixed costs represented 45% of total hospital costs, direct variable costs 20%, and indirect costs 34%. Day of admission was most expensive (mean 9.6K ± 7.6K); average cost for subsequent days was 4.8K ± 3.4K and stable over time and patient characteristics. CONCLUSIONS: Terminal ICU stays display consistent cost patterns across patient characteristics. Savings can be realized with interventions that align care with patient preferences, helping to prevent unwanted ICU utilization at end of life. Cost modeling suggests that implications vary depending on time horizon and reimbursement models.Publication Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila(2008-11-28) Shin, Sunny; Case, Christopher L; Archer, Kristina A; Nogueira, Catarina V; Kobayashi, Koichi S; Flavell, Richard A; Roy, Craig R; Zamboni, Dario SThe immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.Publication Isoniazid Resistance and Death in Patients With Tuberculous Meningitis: Retrospective Cohort Study(2010-07-12) Vinnard, Christopher; Wileyto, E. Paul; MacGregor, Rob Roy; Bisson, Gregory P; Winston, Carla AObjective To determine whether initial isoniazid resistance is associated with death during the treatment of tuberculous meningitis. Design Retrospective cohort study. Setting National Tuberculosis Surveillance System at the Centers for Disease Control in the United States. Participants Patients with a clinical diagnosis of tuberculous meningitis, reported to the National Tuberculosis Surveillance System between 1 January 1993 and 31 December 2005. Main outcome measure All cause mortality during antituberculous treatment. Results Between 1993 and 2005, 1896 patients had a clinical diagnosis of tuberculous meningitis and positive cultures from any site. In 123 (6%) of these patients, isoniazid resistance was present on initial susceptibility testing. The unadjusted association between initial isoniazid resistance and subsequent death among these 1896 patients did not reach statistical significance (odds ratio 1.38, 95% confidence interval 0.94 to 2.02). However, among 1614 patients with positive cerebrospinal fluid cultures, a significant unadjusted association was found between initial isoniazid resistance and subsequent death (odds ratio 1.61, 1.08 to 2.40). This association increased after adjustment for age, race, sex, and HIV status (odds ratio 2.07, 1.30 to 3.29). Conclusions Isoniazid resistance on initial susceptibility testing was associated with subsequent death among cases of tuberculous meningitis with positive cerebrospinal fluid cultures. Randomised controlled trials are needed to evaluate the optimal empirical regimen for treating patients with tuberculous meningitis who are at high risk for both initial isoniazid resistance and poor clinical outcomes.Publication Leveraging a Rapid, Round-the-Clock HIV Testing System to Screen for Acute HIV Infection in a Large Urban Public Medical Center(2013-02-01) Christopoulos, Katerina A; Zetola, Nicola M; Klausner, Jeffrey D; Haller, Barbara; Louie, Brian; Hare, Bradley; Pandori, Mark; Nassos, Patricia; Roemer, Marguerite; Pilcher, Christopher DMethods The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department. For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as one outpatient HIV-related visit. Results Among 7,927 patients, 8,550 rapid tests resulted in 137 cases of HIV infection (1.7%, 95% CI 1.5%–2.0%), of whom 46 were new HIV diagnoses (0.58%, 95% CI 0.43%–0.77%). Pooled HIV RNA testing of 6,704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI 0.01%–0.14) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and 2/3 of acute infections were detected in the emergency department and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI 93.8%– 99.8%); specificity was 99.9% (95% CI 99.7%–99.9%). Over 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care. Conclusions Patients undergoing HIV testing in emergency departments and urgent care clinics may benefit from being simultaneously screened for acute HIV infection.Publication Retirement Effects on Health in Europe(2011-01-01) Coe, Norma B; Zamarro, GemaWhat are the health impacts of retirement? As talk of raising retirement ages in pensions and social security schemes continues around the world, it is important to know both the costs and benefits for the individual, as well as the governments' budgets. In this paper we use the Survey of Health, Ageing and Retirement in Europe (SHARE) dataset to address this question in a multi-country setting. We use country-specific early and full retirement ages as instruments for retirement behavior. These statutory retirement ages clearly induce retirement, but are not related to an individual's health. Exploiting the discontinuities in retirement behavior across countries, we find significant evidence that retirement has a health-preserving effect on overall general health. Our estimates indicate that retirement leads to a 35 percent decrease in the probability of reporting to be in fair, bad, or very bad health, and an almost one standard deviation improvement in the health index. While the self-reported health seems to be a temporary impact, the health index indicates there are long-lasting health differences.Publication Evaluating the Economic Impact of Palliative and End-of-Life Care Interventions on Intensive Care Unit Utilization and Costs from the Hospital and Healthcare System Perspective.(2017-12-01) Khandelwal, Nita; Brumback, Lyndia C; Halpern, Scott D; Coe, Norma B; Brumback, Babette; Curtis, J RandallPurpose of report: Understanding the impact of palliative care interventions on intensive care unit (ICU) costs and utilization is critical for demonstrating the value of palliative care. Performing these economic assessments, however, can be challenging. The purpose of this special report is to highlight and discuss important considerations when assessing ICU utilization and costs from the hospital perspective, with the goal of providing recommendations on methods to consider for future analyses. FINDINGS: ICU length of stay (LOS) and associated costs of care are common and important outcome measures, but must be analyzed properly to yield valid conclusions. There is significant variation in costs by day of stay in the ICU with only modest differences between an ICU day at the end of a stay and the first day on the acute care floor; this variation must be appropriately accounted for analytically. Furthermore, reporting direct variable costs, in addition to total ICU costs, is needed to understand short-term and long-term impact of a reduction in LOS. Importantly, incentives for the hospital to realize savings vary depending on reimbursement policies. SUMMARY: ICU utilization and costs are common outcomes in studies evaluating palliative care interventions. Accurate estimation and interpretation are key to understanding the economic implications of palliative care interventions.Publication A Little Bit Pregnant: Modeling How the Accurate Detection of Pregnancy Can Improve HIV Prevention Trials(2008-01-01) Schreiber, Courtney A; Sammel, Mary; Hillier, Sharon L; Barnhart, Kurt TThe prevalence of unplanned pregnancies contributes to the methodological challenges of human immunodeficiency virus (HIV) prevention trials. In this paper, the authors discuss the incidence of pregnancy, including chemical pregnancy, and how the different methods of pregnancy diagnosis could affect the statistical power and calculated outcomes of HIV prevention trials. Study sample size inflation factors are estimated to aid in the design of clinical trials.The authors used published data of women attempting pregnancy as well as data from HPTN 055 (www.HPTN.org/research_studies/hptn055.asp) to estimate the percentage of early study discontinuation that would be associated with 3 diagnostic methods for pregnancy in a hypothetical clinical trial. They classified chemical pregnancies as false-positive pregnancy tests and showed the sample size adjustment that would be necessary in clinical trial design because of the early discontinuations associated with pregnancy. There is a greater than 3-fold difference in the number of falsely positive pregnancy tests that will be detected, depending upon the diagnostic method used. The number of incident pregnancies may render HIV prevention trial sample sizes inadequate by as much as 50%. Pregnancy prevention and precise pregnancy diagnosis are critical to the statistical power and integrity of HIV prevention trials.