Publications

Large (>or=45 transplants per year) North American liver transplant centres were surveyed regarding management of hepatitis C virus (HCV). A total of 25/41 (59%) and 28/48 (58%) of centres responded to the surveys in 1998 and 2003, respectively, with 17 centres participating in both surveys. HCV was the most common indication for transplantation. Use of protocol liver biopsies was higher in 2003 and 60% used them to monitor HCV disease. Fewer centres reported modifying primary immunosuppression (IMS) for HCV-positive (vs. non-HCV) patients in 2003 (26%) vs. 1998 (56%). IMS was most frequently tacrolimus-based, but mycophenolate mofetil use increased in 2003 (52% vs. 23% in 1998). In both years, approximately 40% treated allograft rejection differently in HCV-positive recipients, with less use of OKT3 in 2003. Combination anti-HCV therapy for 12 months or more was the treatment of choice and growth factor use was common (68%). HCV-positive recipients were considered candidates for retransplantation but HCV-specific criteria were used in decision-making. Practice of centres changed over time with an increase in HCV transplantation and use of protocol liver biopsies, and a trend towards lesser modification of IMS in HCV-positive recipients. We conclude that there is considerable variability in the management of HCV among transplant programs and over time.

BACKGROUND

Homelessness and hunger are associated with poor health outcomes. Housing instability and food insecurity describe less severe problems securing housing and food.

OBJECTIVE

To determine the association between housing instability and food insecurity and access to ambulatory health care and rates of acute health care utilization.

DESIGN

Secondary data analysis of the National Survey of American Families.

PARTICIPANTS

16,651 low-income adults.

MEASUREMENT

Self-reported measures of past-year access: (1) not having a usual source of care, (2) postponing needed medical care, or (3) postponing medication; and past-year utilization: (1) not having an ambulatory care visit, (2) having emergency department (ED) visits, or (3) inpatient hospitalization.

RESULTS

23.6% of subjects had housing instability and 42.7% had food insecurity. In multivariate logistic regression models, housing instability was independently associated with not having a usual source of care (adjusted odds ratio [AOR] 1.31, 95% confidence interval [CI] 1.08 to 1.59), postponing needed medical care (AOR 1.84, 95% CI 1.46 to 2.31) and postponing medications (AOR 2.16, 95% CI 1.70 to 2.74), increased ED use (AOR: 1.43, 95% CI 1.20 to 1.70), and hospitalizations (AOR 1.30, 95% CI 1.01 to 1.67). Food insecurity was independently associated with postponing needed medical care (AOR 1.74, 95% CI 1.38 to 2.21) and postponing medications (AOR 2.15, 95% CI 1.62 to 2.85), increased ED use (AOR 1.39, 95% CI 1.17 to 1.66), and hospitalizations (AOR 1.42, 95% CI 1.09 to 1.85).

CONCLUSIONS

Housing instability and food insecurity are associated with poor access to ambulatory care and high rates of acute care. These competing life demands may lead to delays in seeking care and predispose to acute care.

RuleEd is a web-based editing environment which enables clinical trial eligibility rules entered as free text to be represented as a series of terms mapped to unique concepts in a controlled vocabulary. RuleEd provides interfaces for creating and refining concept mappings for terms within rules and disambiguating multiply-mapped terms. A combination of inter-active and non-interactive methods enable authors to specify eligibility rule representations with a fine level of control.

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease.

Knee injuries are common in sports activities. Understanding the mechanisms of injury allows for better treatment of these injuries and for the development of effective prevention programmes. Tibial torque and knee flexion angle have been associated with several mechanisms of injury in the knee. This article focuses on the injury to the anterior cruciate ligament (ACL), the posterior cruciate ligament (PCL) and the meniscus of the knee as they relate to knee flexion angle and tibial torque. Hyperflexion and hyperextension with the application of tibial torque have both been implicated in the mechanism of ACL injury. A combination of anterior tibial force and internal tibial torque near full extension puts the ACL at high risk for injury. Hyperflexion also increases ACL force; however, in this position, internal and external tibial torque only minimally increase ACL force. Several successful prevention programmes have been based on these biomechanical factors. Injury to the PCL typically occurs in a flexed or hyperflexed knee position. The effects of application of a tibial torque, both internally and externally, remains controversial. Biomechanical studies have shown an increase in PCL force with knee flexion and the application of internal tibial torque, while others have shown that PCL-deficient knees have greater external tibial rotation. The meniscus must endure greater compressive loads at higher flexion angles of the knee and, as a result, are more prone to injury in these positions. In addition, ACL deficiency puts the meniscus at greater risk for injury. Reducing the forces on the ACL, PCL and meniscus during athletic activity through training, the use of appropriate equipment and safe surfaces will help to reduce injury to these structures.

BACKGROUND

This paper evaluates the replicability of an NCI-funded didactic/experiential program to increase the diversity of doctorally-prepared cancer disparities investigators.

METHODS

The program was developed and operated successfully for three years in Northern California when a replication was established at UCLA. Feasibility, process, impact, and outcome measures on UCSF and UCLA summer-institute participants were compared.

RESULTS

Average participant rankings of the influence of the program on intention to apply for a doctorate were 9.1/10 (UCSF) and 8.6/10 (UCLA). A total of 22.5% of UCSF and 10% of UCLA participants have enrolled in, been accepted by, or completed doctoral programs. Among these alumni, 68% (21/31) of UCSF and 60% (3/5) of UCLA participants plan to conduct their doctoral research in cancer control.

CONCLUSIONS

This program has been successfully replicated and has met its objective to increase the pipeline of ethnically diverse doctoral-level public health researchers. Expansion of the program to other regions of the US is feasible and indicated.

An abnormal mammography finding constitutes a stressful event that may increase vulnerability by developing or intensifying pre-existing psychological morbidity. We evaluated depressive symptoms using the Composite International Diagnostic Interview among women of four ethnic groups who had an abnormal mammography result controlling for the effect of demographic, psychosocial and medical factors on recent onset of depressive symptoms. Telephone surveys were conducted among women aged 40-80 years recruited from four clinical sites in the San Francisco Bay Area after receiving a screening mammography result that was classified as abnormal but probably benign, suspicious or highly suspicious, or indeterminate using standard criteria. Among the 910 women who completed the interview, mean age was 56 (S.D.=10), 42% were White, 19% Latina, 25% African American, and 14% Asian. Prevalence of lifetime depressive symptoms was 44%, and 11% of women had symptoms in the previous month. Multivariate logistic regression models showed that Asian ethnicity, annual income >$10 000 and weekly attendance at religious services were significantly associated with decreased depressive symptoms. Having an indeterminate result on mammography and being on disability were significantly associated with more depressive symptoms. Reporting a first episode of depression more than a year before the interview was associated with significant increase in depressive symptoms in the month prior to the interview regardless of mammography result. Women with an indeterminate interpretation on mammography were at greater risk of depressive episode in the month prior to the interview compared to women with probably benign results (odds ratio=2.41; 95% CI=1.09-5.31) or with a suspicious finding. Clinicians need to consider depression as a possible consequence after an abnormal mammography result.

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

Reductive prodrugs, mitomycin C and 5-aziridinyl-2,4-dinitrobenzamide (CB 1954), are nontoxic in their native form but become highly toxic upon reduction. Their effectiveness in cancer chemotherapy can be enhanced by delivering to tumors enzymes with improved prodrug reduction kinetics. We report the discovery of a new prodrug-reducing enzyme, YieF, from Escherichia coli, and the improvement of its kinetics for reducing mitomycin C and CB 1954. A YieF-derived enzyme, Y6, killed HeLa spinner cells with >or=5-fold efficiency than the wild-type enzymes, YieF and NfsA, at a variety of drug and enzyme concentrations and incubation times. With adhered HeLa cells and Salmonella typhimurium SL 7838 bacteria as enzyme delivery vehicle, at least an order of magnitude less of Y6-producing bacteria were required to kill >90% of tumor cells compared with bacteria expressing the wild-type enzymes, which at a comparable level killed < 5% of the cells. Thus, Y6 is a promising enzyme for use in cancer chemotherapy, and Salmonella strain SL 7838, which specifically targets tumors, may be used to deliver the prodrug-activating enzymes to tumors.