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Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.Results: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.Conclusions: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported. [ABSTRACT FROM AUTHOR]

Background Despite the increasing annual incidence of hepatocellular carcinoma ( HCC) in the USA, now estimated at 2.7 cases per 100 000 population, only a small proportion of patients receive treatment and 5-year survival rates range from 9% to 17%. Objectives The present study examines the effects of multimodal treatment on survival in a mixed-stage HCC cohort, focusing on the impact of radical therapy in patients with Barcelona Clinic Liver Cancer ( BCLC) stage B disease. Methods A retrospective review of the medical records of 254 patients considered for HCC treatment between 2003 and 2011 at a large tertiary referral centre was conducted. Results A total of 195 (76.8%) patients were treated with a median of two liver-directed interventions. Median survival time was 16 months. In proportional hazards analysis, radiofrequency ablation ( RFA) and resection were associated with significantly improved 1- and 5-year survival among patients with BCLC stage 0-A disease. In patients with BCLC stage B disease, RFA conferred a survival benefit at 1 year and resection was associated with significantly improved survival at 5 years. Conclusions As one of few studies to track the complete course of sequential HCC therapies, the findings of the present study suggest that HCC patients with intermediate-stage ( BCLC stage B) disease may benefit from aggressive interventions not currently included in societal guidelines. [ABSTRACT FROM AUTHOR]

Background: The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored. Methods and Findings: We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis and of dying during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained virological response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in both cohorts had a statistically significantly increased hazard of cirrhosis compared to never treated patients, as stratified by pretreatment liver fibrosis stage and adjusted for clinical and psychosocial risk factors that disproportionately affect patients who were ineligible for treatment (Veterans Affairs HR = 2.35, CI 1.18–4.69, mean follow-up 10 years, and University Hospital HR = 5.90, CI 1.50–23.24, mean follow-up 7.7 years). Despite their increased risk for liver disease progression, the overall survival of nonresponders in both cohorts was not significantly different from that of never treated patients. Conclusion: These unexpected findings suggest that patients who receive interferon-α based therapies but fail to clear the hepatitis C virus may have an increased hazard of cirrhosis compared to untreated patients. [ABSTRACT FROM AUTHOR]

We assessed associations between indicators for moisture in office buildings and weekly, building-related lower respiratory and mucous membrane symptoms in office workers, using the U.S. EPA BASE data, collected in a representative sample of 100 U.S. office buildings. We estimated the strength of associations between the symptom outcomes and moisture indicators in multivariate logistic regression models as odds ratios (ORs) and 95% confidence intervals (CI), controlling for potential confounding factors and adjusting for correlation among workers in buildings. This analysis identified associations between building-related symptoms and several indicators of moisture or contamination in office buildings. One set of models showed almost a tripling of weekly building-related lower respiratory symptoms in association with lack of cleaning of the drip pans under air-conditioning cooling coils (OR [CI] = 2.8 (1.2-6.5)). Other models found that lack of cleaning of either drip pans or cooling coils was associated with increased mucous membrane symptoms (OR [CI] = 1.4 (1.1-1.9)). Slightly increased symptoms were also associated with other moisture indicators, especially mucous membrane symptoms and past water damage to building mechanical rooms (OR [CI] = 1.3 (1.0-1.7)). Overall, these findings suggest that the presence of moisture or contamination in ventilation systems or occupied spaces in office buildings may have adverse respiratory or irritant effects on workers. The analysis, however, failed to confirm several risks identified in a previous study, such as condition of drain pans or outdoor air intakes, and other hypothesized moisture risks. Studies with more rigorous measurement of environmental risks and health outcomes will be necessary to define moisture-related risks in buildings. [ABSTRACT FROM AUTHOR]

Investigates the reasons why African Americans are not using HIV/AIDS pharmaceuticals at the same rate as non-Latino whites. Effects of race or ethnicity on the use of HIV medication; Policy barriers and facilitators to access to HIV drugs; Programs designed for HIV medication.

Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues. To assess the role of macrophages and CCR2 in TBI, we determined outcomes in CCR2-deficient ( Ccr2−/−) mice in a controlled cortical impact model. We quantified brain myeloid cell numbers post-TBI by flow cytometry and found that Ccr2−/− mice had greatly reduced macrophage numbers (∼80-90% reduction) early post-TBI, compared with wild-type mice. Motor, locomotor, and cognitive outcomes were assessed. Lack of Ccr2 improved locomotor activity with less hyperactivity in open field testing, but did not affect anxiety levels or motor coordination on the rotarod three weeks after TBI. Importantly, Ccr2−/− mice demonstrated greater spatial learning and memory, compared with wild-type mice eight weeks after TBI. Although there was no difference in the volume of tissue loss, Ccr2−/− mice had significantly increased neuronal density in the CA1-CA3 regions of the hippocampus after TBI, compared with wild-type mice. These data demonstrate that Ccr2 directs the majority of macrophage homing to the brain early after TBI and indicates that Ccr2 may facilitate harmful responses. Lack of Ccr2 improves functional recovery and neuronal survival. These results suggest that therapeutic blockade of CCR2-dependent responses may improve outcomes following TBI. [ABSTRACT FROM AUTHOR]

Background. Interferon α (IFN-α) and ribavirin can induce a sustained virologic response (SVR) in some but not all hepatitis C virus (HCV)–infected patients. The mechanism of effective treatment is unclear. One possibility is that IFN-α differentially improves the functional capacity of classic myeloid dendritic cells (mDCs) by altering expression of surface molecules or cytokines. Others have proposed that antigen-presenting cell activation could be paradoxically detrimental during HCV infection because of the production by monocytes of substances inhibitory or toxic to plasmacytoid dendritic cells.Methods. We examined responses to in vitro IFN-α treatment of peripheral blood leukocyte samples from a retrospective treatment cohort of nearly 200 HCV-seropositive patients who had undergone antiviral therapy with ribavirin and pegylated IFN. We analyzed the variable responses of antigen-presenting cell subsets to drug.Results. We found that patients achieving SVR were no more likely to have robust mDC activation in response to IFN-α than those who did not achieve SVR. Rather, patients achieving SVR were distinguished by restrained monocyte activation in the presence of IFN-α, a factor that was second in importance only to IL28B genotype in its association with SVR.Conclusions. These results suggest that interindividual variability in the response of monocytes to IFN-α is an important determinant of treatment success with IFN-α–based regimens. [ABSTRACT FROM PUBLISHER]

Background: Studies of the retreatment with consensus interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.Aims: The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006.Results: A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P<0.0001). A 2-log10 or greater drop in HCV RNA after 24 weeks of PEG-IFN/RBV was a predictor of subsequent SVR to CIFN/RBV.Conclusions: CIFN/RBV was used frequently in clinical practice for retreatment of PEG-IFN/RBV. In this setting, early treatment discontinuation was common. Overall SVR was low, although response was significantly better in prior PEG-IFN/RBV relapsers and those who had a 2-log(10) or greater decline than in nonresponders. [ABSTRACT FROM AUTHOR]

BACKGROUND: We hoped to determine the attitudes and practices of primary care physicians regarding the use of opioids to treat chronic nonmalignant pain (CNMP). We also examined the factors associated with the willingness to prescribe opioids for CNMP. METHODS: A survey was mailed to primary care physicians in the University of California, San Francisco/Stanford Collaborative Research Net- work. This survey contained questions regarding treatment in response to 3 case vignettes, the use of opioids for CNMP in general, and the demographic characteristics of the physicians. RESULTS: Among 230 physicians surveyed, 161 (70%) responded. Two percent of the respondents were never willing to prescribe schedule III opioids (eg, acetaminophen with codeine) as needed for patients with CNMP that persisted unchanged after exhaustive evaluation and attempts at treatment. Thirty-five percent were never willing to prescribe schedule II opioids (eg, sustained-release morphine) on an around-the-clock schedule for these patients. The most significant predictor of willingness to prescribe opioids for patients with CNMP was a lower level of concern about physical dependence, tolerance, and addiction. CONCLUSIONS: Primary care physicians are willing to prescribe schedule III opioids as needed, but many are unwilling to use schedule II opioids around the clock for CNMP. Individual prescribing practices vary widely among primary care physicians. Concerns about physical dependence, tolerance, and addiction are barriers to the prescription of opioids by primary care physicians for patients with CNMP. [ABSTRACT FROM AUTHOR]