Medicine and Health Sciences Commons^™

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …

Risk Factors For Wound Complications After Ankle Fracture Surgery., Adam G Miller, Andrew Margules, Steven M Raikin

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The overall rate of complications after ankle fracture fixation varies between 5% and 40% depending on the population investigated, and wound complications have been reported to occur in 1.4% to 18.8% of patients. Large studies have focused on complications in terms of readmission, but few studies have examined risk factors for wound-related issues in the outpatient setting in a large number of patients. A review was performed to identify risk factors for wound complications tracked in the hospital and outpatient setting.

METHODS: Four hundred and seventy-eight patients underwent open reduction and internal fixation of an ankle fracture between 2003 …

Predictive Value Of Alpha-Fetoprotein In The Long-Term Risk Of Developing Hepatocellular Carcinoma In Patients With Hepatitis B Virus Infection--Results From A Clinic-Based Longitudinal Cohort., Hie-Won Hann, Xiaoying Fu, Ronald E. Myers, Richard Hann, Shaogui Wan, Su Hee Kim, Natalie Au, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Although serum level of alpha-fetoprotein (AFP) has long been used to complement imaging tests in the screening and diagnosis of hepatocellular carcinoma (HCC), whether it can be used as a predictive marker of long-term risk for developing HCC in patients with hepatitis B virus (HBV) has not been extensively evaluated and thus remains controversial.

METHODS: We retrospectively conducted a clinic-based longitudinal cohort study including 617 Korean American patients with HBV who had been followed for up to 22 years (median follow-up time, 6.2 years) to evaluate the association between baseline serum AFP level and the long-term risk of HCC. …

Subjective Outcome Evaluation Of The Project P.A.T.H.S. In Different Cohorts Of Students, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

The project P.A.T.H.S. is an indigenously developed positive youth development program in Hong Kong. In the extension phase (2009/2010 school year), subjective outcome evaluation data were collected from 231 schools involving 89,068 participants after completion of the curricula-based Tier 1 Program. With schools as the units of analysis, results showed that participants generally had positive perceptions of the program content and implementers, with over four-fifth of the participants regarded the program as helpful to them. There were some significant grade differences in the subjective outcome evaluation findings, although the related effect size was not strong. Multiple regression analyses revealed that …

Process Evaluation Of A Positive Youth Development Program In Hong Kong Based On Different Cohorts, Ben M. F. Law, Daniel T. L. Shek

Pediatrics Faculty Publications

There are only a few process evaluation studies on positive youth development programs, particularly in the Chinese context. This study aims to examine the quality of implementation of a positive youth development program (the Project P.A.T.H.S.: Positive Adolescent Training through Holistic Social Programmes) and investigate the relationships among program adherence, process factors, implementation quality, and perceived program success. Process evaluation of 97 classroom-based teaching units was conducted in 62 schools from 2005 to 2009. Findings based on different cohorts generally showed that there were high overall program adherence and implementation quality. Program adherence and implementation process were highly correlated with …

Qualitative Evaluation Of Project P.A.T.H.S.: An Integration Of Findings Based On Program Participants, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by …

A Heuristic Solution Of The Identifiability Problem Of The Age-Period-Cohort Analysis Of Cancer Occurrence: Lung Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: The Age-Period-Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of …

Helping Adolescents With Greater Psychosocial Needs: Subjective Outcome Evaluation Based On Different Cohorts, Daniel T. L. Shek, Tak Yan Lee

Pediatrics Faculty Publications

The Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) is designed to help students with greater psychosocial needs. This paper examines nine sets of subjective outcome evaluation data collected from 2005 to 2009 (n = 60, 241 participants). Based on the consolidated data with schools as units, results showed that participants generally had positive perceptions of the program, implementers, and benefits of the program. The subjective outcome evaluation instrument was found to be internally consistent. Multiple regression analysis revealed that perceived qualities of the program and the program implementers predicted perceived effectiveness of the …

Evaluation Of The Training Program Of The Project P.A.T.H.S.: Findings Based On The Perspective Of The Participants From Different Cohorts, Daniel T. L. Shek, Yammy L. Y. Chak

Pediatrics Faculty Publications

Subjective outcome evaluation findings based on the perspective of the participants participating in a 3-day training program of the Project P.A.T.H.S. are reported in this paper. The findings were based on the data collected from the training workshops conducted between 2005 and 2009 (N = 4.167). Results showed that the respondents had good and positive perceptions of the training program and found it very valuable, particularly with respect to training instructors and familiarization with the project. Besides, the training participants were able to acquire attitude, knowledge and skills that are conducive to the successful implementation of the program. Based on …

A Placebo-Controlled, Double-Blind, Dose-Escalation Study To Assess The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Single And Multiple Intravenous Infusions Of Azd9773 In Patients With Severe Sepsis And Septic Shock, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Shampa Das, Timi Edeki, Steven G. Simonson, Gordon R. Bernard

Surgery Faculty Publications

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

METHODS: In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, …

Is There A Role For The Quantification Of Rrm1 And Ercc1 Expression In Pancreatic Ductal Adenocarcinoma?, Matias E Valsecchi, Thomas Holdbrook, Benjamin E Leiby, Edward Pequignot, Susan J Littman, Charles Yeo, Jonathan Brody, Angieszka Witkiewicz

Department of Medical Oncology Faculty Papers

BACKGROUND: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.

METHODS: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).

RESULTS: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …