Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the veterans health administration.

Background & Aims: The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the United States. We analyzed the cost effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection.

Methods: We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment.

β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.

Background: The use of β-blockers for the management of hypertension has been recently associated with significant clinical benefits in cancer patients. Herein, we investigated whether β-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma.

Methods: Seven β-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma.

Central implementation strategies outperform local ones in improving HIV testing in Veterans Healthcare Administration facilities.

Background: Pilot data suggest that a multifaceted approach may increase HIV testing rates, but the scalability of this approach and the level of support needed for successful implementation remain unknown.

Objective: To evaluate the effectiveness of a scaled-up multi-component intervention in increasing the rate of risk-based and routine HIV diagnostic testing in primary care clinics and the impact of differing levels of program support.

Design: Three arm, quasi-experimental implementation research study.

A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P).

Canine body composition quantification using 3 tesla fat-water MRI.

Purpose: To test the hypothesis that a whole-body fat-water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet.

Materials And Methods: Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach.

Histologic markers of inflammation in patients with ulcerative colitis in clinical remission.

Background & Aims: Mucosal healing, based on histologic analysis, is an end point of maintenance therapy for patients with ulcerative colitis (UC). There are few data on how histologic signs of inflammation correlate with endoscopic and peripheral blood measures of inflammation in these patients. We investigated patterns of histologic features of inflammation in patients with UC in clinical remission, and correlated these with endoscopic and biochemical measures of inflammation.

Systematic review: the quality of the scientific evidence and conflicts of interest in international inflammatory bowel disease practice guidelines.

Background: Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes.

Aim: We examined inflammatory bowel disease guidelines (IBD) for quality of evidence, methods of grading evidence and conflicts of interest (COI).

Methods: All 182 guidelines published by the American College of Gastroenterology, American Gastroenterological Association, British Society of Gastroenterology, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of America and European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed.

Development and evaluation of an internet and personal health record training program for low-income patients with HIV or hepatitis C.

Background: Vulnerable populations face difficulties accessing and using the internet and personal health record (PHR) systems for health-related purposes. Populations disconnected from the internet also tend to be disconnected from health care services.

Objectives: To develop and evaluate an intervention to increase skills in health-related internet and PHR use for vulnerable populations with limited computer and internet experience.

Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission.

Background: Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of active endoscopic disease, and factors associated with it, in patients with UC who are in clinical remission.

Methods: Prospective observational study in a single center.

The hepatitis C self-management program: sustainability of primary outcomes at 1 year.

Objective: Chronic hepatitis C infection afflicts millions of people worldwide. Although antiviral treatments are increasingly effective, many hepatitis C virus (HCV) patients avoid treatment, do not complete or respond to treatment, or have contraindications. Self-management interventions are one option for promoting behavioral changes leading to liver wellness and improved quality of life.

HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.

Melanoma is a highly lethal malignancy notorious for its aggressive clinical course and eventual resistance to existing therapies. Currently, we possess a limited understanding of the genetic events driving melanoma progression, and much effort is focused on identifying pro-metastatic aberrations or perturbed signaling networks that constitute new therapeutic targets. In this study, we validate and assess the mechanism by which homeobox transcription factor A1 (HOXA1), a pro-invasion oncogene previously identified in a metastasis screen by our group, contributes to melanoma progression.

Personal health record use and its association with antiretroviral adherence: survey and medical record data from 1871 US veterans infected with HIV.

Patient electronic personal health record (PHR) use has been associated with improved patient outcomes in diabetes and depression care. Little is known about the effect of PHR use on HIV care processes and outcomes. We evaluated whether there was an association between patient PHR use and antiretroviral adherence.

A random urine test can identify patients at risk of mesalamine non-adherence: a prospective study.

Objectives: Mesalamine non-adherence is common among patients with ulcerative colitis (UC), and can be difficult to identify in practice. We sought to determine whether a random urine test for salicylates could be used as a marker of 5-aminosalicylic acid (5-ASA) ingestion and identify patients at risk of non-adherence. Our aim is to determine whether measurement of salicylates in a random urine sample correlates with 5-ASA levels, and predicts an individual's risk of mesalamine non-adherence.

Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus® dry powder inhaler.

Background: Patients who exhibit a suboptimal peak inspiratory flow rate (PIFR) against the resistance (resist) of a dry powder inhaler (DPI) may not be able to effectively inhale the medication into their lower respiratory tract. PIFRresist was measured using the In-Check DIAL(®) to simulate the resistance of the Diskus(®) DPI in patients with chronic obstructive pulmonary disease (COPD) who were ≥ 60 years of age and had forced expiratory volume in 1 sec (FEV1) of ≤ 50% predicted. Our objectives were to: establish the prevalence of a suboptimal PIFRresist (< 60 L/min) in this population; identify a phenotype of patients with COPD who exhibit a suboptimal PIFRresist; and assess test-retest reliability of PIFRresist.

Development and field testing of an HIV medication touch screen computer patient adherence tool with telephone-based, targeted adherence counseling.

Background: HIV medication nonadherence is a major problem, yet many providers lack the time and training to carefully ask patients about their adherence.

Objective: To design and pilot a technology-assisted intervention, for use in clinical settings, to identify nonadherent patients.

Methods: The intervention uses audio computer-assisted self-interview (ACASI) to improve the assessment of adherence and medication-related problems.

Remote frozen section examination of breast sentinel lymph nodes by telepathology.

Background: Intraoperative sentinel lymph node (SLN) examination during breast cancer surgery guides the need for immediate axillary clearance. This may be difficult to implement when surgery is performed distant to the centres where pathological examination is undertaken. We aimed to implement and validate a telepathology service for the remote examination of breast SLN by frozen section (FS).

Iron homeostasis during cystic fibrosis pulmonary exacerbation.

Background: Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease.

Chronic inflammation and lung fibrosis: pleotropic syndromes but limited distinct phenotypes.

Experimental models of lung fibrosis have been disappointing in predicting therapeutic responses to a wide variety of interventions in clinical fibrosing lung diseases. There are multiple potential reasons, but this fundamentally calls into question the validity of the models and their fidelity to clinical syndromes. We propose that the clinical diseases associated with pulmonary fibrosis, although manifesting a broad array of widely different clinical presentations and features, result in essentially two distinct phenotypes of fibrosis that we will describe.

Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability.

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing.

Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics.

National patterns and predictors of liver biopsy use for management of hepatitis C.

Background & Aims: Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample.

Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk.

Background: An estimated 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.

Living with HIV: responses to a mantram intervention using the critical incident research method.

Objectives: The objective of this study was to identify and describe ways that a spiritually based intervention of silently repeating a mantram-sacred word or phrase-was used as a coping strategy for managing human immunodeficiency virus (HIV) disease.

Design: The design was a qualitative research method, the critical incident technique.

Settings/location: The study was conducted at an academically affiliated Veterans Affairs Hospital in southern California.

Exportability of an intervention to increase HIV testing in the Veterans Health Administration.

Background: Exportability, or the dissemination of successful health services interventions from one site to another, must be demonstrated before systemwide implementation.

Methods: The effectiveness of a previously successful multicomponent intervention to increase rates of HIV testing in Veterans Health Administration (VHA) health care facilities among those without records of previous testing was evaluated in two other VHA facilities. Whereas the principle responsibility for the provider-activation component of the intervention was previously borne by research staff, nonresearch staff now took on these responsibilities.