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Background: The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment durations in cornerstone phase 3 clinical trials vary between a fixed 2-year duration and pursuit until disease progression. Clinical practices may thus differ according to the attending physician. Objectives: Here we provide real-world data about treatment decisions at 2 years, with subsequent clinical outcomes. Design and Methods: This multicentric observational study included patients with advanced NSCLC whose disease was controlled after 2 years of pembrolizumab or nivolumab. The primary outcome was the decision to discontinue ICI treatment or not, along with factors motivating this decision. Secondary outcomes included progression-free survival (PFS) (according to treatment continuation or not) and adverse events. Results: A total of 91 patients were included, of which 60 (66%) had been pre-treated. The programmed death-ligand 1 expression level was ⩾50% in 43 patients (47%). In 61 patients (67%), ICI was continued after 2 years of treatment. This decision was significantly associated with the care center (p < 0.001) but neither with the tumor response at 2 years, as evaluated by CT scan or PET scan, nor with clinical status, immune-related adverse events, or previous locally treated oligo-progressive disease under ICI. Two years after the 2-year decision, PFS was 68.5%, [95% confidence interval (CI) (53.3–88.0)] in the 'ICI discontinuation' group and 64.1% [95% CI (51.9–79.2)] in the 'ICI pursuit' group; hazard ratio for relapse was 1.14 [95% CI (0.54–2.30), p = 0.77]. The overall survival rate at 24 months after discontinuation was 89.2% [95% CI (78.4–100)] for the 'discontinuation' group and 93.1% [95% CI (85.8–100)] for the 'pursuit' group. Given insufficient power, overall survival could not be compared. Conclusion: The decision to continue ICI or not after 2 years of treatment depends mainly on the care center and does not seem to impact survival. Larger, randomized data sets are required to confirm this result. [ABSTRACT FROM AUTHOR]

Study objective: Different behaviors are considered important factors that may influence a healthy lifestyle. Given this fact, we aim to analyze the relationship between moderate-vigorous physical activity (MVPA), sleep time, and sedentary time, with cardiometabolic outcomes in adolescents. Methods: Cross-sectional study, with 152 eutrophic and healthy adolescents. The behavioral variables were collected objectively and the arterial thickness was measured through ultrasound. Blood variables (LDL, TG, HDL, glucose, and insulin) were collected in a private laboratory. To analyze the data, the Student t test and Kruskal-Wallis test were used to compare the groups. All analyses adopted p < 0.05. Results: Girls who demonstrated better combined behaviors, presented significant results for TG (p = 0.045), BP (p = 0.016), and cardiovascular score (p = 0.049) when compared to their peers. Furthermore, the practice of physical activity combined with sufficient sleep time was associated with lower values of arterial thickening (p = 0.017). Conclusions: In view of the results presented, it is possible to state that the aggregation of behaviors was more consistent in females and that the practice of physical activity and adequate sleep time can reflect on cardiovascular health. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. Methods: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2–4 (152), we estimated and compared the mean change in eGFR at 2 years after baseline under each intervention. We used the parametric g-formula to adjust our estimates for baseline and time-varying confounders. Results: First, among 1390 patients with normal kidney function at baseline the estimated 2-year risk difference (95% CI) of reaching Stage 3 CKD for DAA initiation versus no DAA was -1% (-3, 2). Second, among 733 patients with CKD Stage 2–4 at baseline the estimated 2-year mean difference in change in eGFR for DAA initiation versus no DAA therapy was -3 ml/min/1.73m2 (-8, 2). Conclusions: We found no effect of DAA initiation on kidney function, independent of baseline renal status. This suggests that DAAs may not be nephrotoxic; furthermore, in the short-term, HCV clearance may not improve CKD. [ABSTRACT FROM AUTHOR]

Background: Treatment eradication rates of Helicobacter pylori, a gastrointestinal infection, are 70% to 90% in clinical studies but lower in real-world settings. Potential barriers include multidrug regimen complexity or prescribing/administration errors. A pharmacist-managed H pylori treatment service was implemented to address these barriers and optimize treatment outcomes. The clinical pharmacist provided 2 services: (1) treatment education and monitoring for treatment-naïve patients and (2) treatment initiation, education, and monitoring for treatment-experienced patients. Objective: We aimed to evaluate the impact of a pharmacist-managed H pylori treatment service within a gastroenterology clinic. Methods: We conducted a retrospective observational cohort study of all patients referred to and seen in the pharmacist-managed H pylori treatment service from July 10, 2019, to December 31, 2020. Patient demographics, prior treatment history, course(s) of treatment prescribed, frequency of follow-ups, and outcomes posttreatment were collected. Results: The clinical pharmacist managed 60 referrals for 55 unique patients over a mean of 5 ± 2 visits. Five patients failed H pylori treatment and were re-referred. Identified barriers included prescribing/dispensing and administration errors. Posttreatment, 38 referrals tested for H pylori eradication, of which 100% of treatment-naïve patients and 69% of treatment-experienced patients were cured, and 13 (22%) referrals were lost to follow-up. Conclusion and Relevance: This study described and assessed the impact of a pharmacist-managed H pylori treatment service in a gastroenterology clinic, in which various barriers were effectively addressed to optimize treatment outcomes. Future studies should focus on long-term outcome, impact on health care costs, and patient satisfaction with this service. [ABSTRACT FROM AUTHOR]

Background: Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion.Methods: This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data.Results: The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer).Conclusions: Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series. [ABSTRACT FROM AUTHOR]

Background: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP).Aims: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP).Methods: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates.Results: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type.Conclusions: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. Experimental design: A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaffinized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. Results: PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen’s d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. Conclusions: High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha‐based therapies that were difficult to tolerate and were associated with adverse side‐effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side‐effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon‐based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct‐acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation. [ABSTRACT FROM AUTHOR]

Background: Salvador is the city with the highest number of HTLV-1 infected individuals in Brazil, yet the main route of HTLV-1 transmission is unknown. Objective: To investigate the association of syphilis infection as a proxy for sexual transmission of HTLV-1 infection in the general population of this city. Methods: A cross sectional population-based study was conducted with 3,451 serum samples obtained by a representative simple random sampling. Data on gender, age, income, and years of education were collected by questionnaire and the presence of HTLV, HIV and Treponema pallidum infection was determined by serology. Logistic regression analysis was used to evaluate the independent effect of the potential explanatory variables to HTLV-1 infection and Odds Ratios (OR) and 95% CI were calculated. Results: The majority of studied individuals were female (56.4%), had less than 7 years of education (55.3%) and earned two or less minimum wages (52.0%). The overall prevalence of HTLV-1 was 1.48% (51/3,451; 95% CI: 1.10%– 1.94%), which increased with age. Only three persons younger than 17 (3/958; 0.31%; CI 95% 0.06–0.91) years were infected by HTLV-1. Among the 45 syphilis positives, 12 (26.7%) were HTLV positive, while among 21 HIV positives, only one (4.8%) was HTLV positive. HTLV-1 infection was found to be associated with syphilis infection (ORADJUSTED 36.77; 95% CI 14.96–90.41). Conclusion: The data presented herein indicate that horizontal transmission between adults is the main route of HTLV-1 infection in the general population of Salvador and that this is likely to occur through sexual contact. [ABSTRACT FROM AUTHOR]

Aims To assess the association between hepatitis C virus ( HCV) infection and overall and liver-related death in human immunodeficiency virus ( HIV)-infected patients with alcohol problems. Design We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index. Setting and participants Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers and another cohort study with comparable recruitment sites. Measurements The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was hepatitis C virus ( HCV) RNA status (positive versus negative). Mortality rates and Kaplan- Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time. Findings A total of 397 adults (50% HCV-infected) were included. As of 31 December 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log-rank test P < 0.001), and 26 of those deaths were liver-related (21 HCV-infected, five HCV-uninfected; log-rank test P < 0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [hazard ratio ( HR) = 2.55, 95% confidence interval ( CI) = 1.50-4.33, P < 0.01], and liver-related mortality ( HR = 3.24, 95% CI = 1.18-8.94, P = 0.02]. Conclusion Hepatitis C virus infection is associated independently with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use. [ABSTRACT FROM AUTHOR]

Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products' most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background The effect of alcohol on liver disease in HIV infection has not been well characterized. Methods We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, ' FIB-4,' which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index (' APRI'), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). Results Subjects ( n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus ( HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm3. Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis ( FIB-4 <1.45) (adjusted odds ratio [ AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis ( FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. Conclusions In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population. [ABSTRACT FROM AUTHOR]

Wireless sensor networks have been more and more deployed for monitoring and controlling real environments. However, because of sensor nodes' limitations, their radios are more susceptible to noise and interference than in other wireless technologies. These are critical factors in the rigorous industrial environment, whose effects may not be the same on all channels of a sensor network. In this paper, we present some experimental studies about the characteristics of IEEE 802.15.4 channels in ISM band. We are particularly interested in the differences of implementing wireless sensor networks in academic and industrial environments. A common problem of wireless sensor network implementations is that most of them are purely academic or initially prepared in laboratory. Our study shows that it is very difficult to predict the quality and stability of the different channels in sensor networks, as the environment conditions greatly influence the network performance. Empirical approaches are suitable methods for choosing the appropriate channels to deploy WSNs in noisy environments. We conduct several tests in both laboratory and in a real world environment, particularly in an oil refinery as this is our case study in the context of the FP7 GINSENG project (Ginseng ). [ABSTRACT FROM AUTHOR]

The article presents the RESTful Web Service-based model for people-centric sensing frameworks. It discusses the application of the framework model to online social networking. It explores the utilization of sensors and mobile phones by the model to detect activities and locations to users of social networking sites. It also provides some screenshot results of the experimental prototype.

OBJECTIVES:Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality.METHODS:We assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child–Pugh–Turcotte (CPT) and model of end-stage liver disease (MELD) scores.RESULTS:A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86–0.96), CPT 0.91 (0.79–0.96), APRI 0.88 (0.80–0.93), Fib-4 0.87 (0.77–0.92), MELD 0.84 (71–0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT.CONCLUSION:Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD. [ABSTRACT FROM AUTHOR]

Background: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS). Methods: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019. Results: There was not a prevalence of either sex in any age group. Most reports (n = 1120, 55.0%) belonged to patients in the age group 19–64 years old. Hepatitis (n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity (n = 362, 15.5%) and hepatitis (n = 333, 14.2%) were more frequent in age group 19–64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs (n = 1867, 92%). Most patients in our study evolved to "cure" (n = 796; 39%). Hepatotoxicity (n = 23; 13.8%) and hepatitis (n = 610; 25.9%) had a female predominancy while choluria (n = 8; 4.8%) and splenomegaly (n = 8; 4.8%) were of male predominance. Conclusions: DILI is rare but can be fatal. As such, an active search of DILI is necessary. [ABSTRACT FROM AUTHOR]

Aims To examine the impact of alcohol use on depressive symptoms in human immunodeficiency virus (HIV)-infected patients. Design Data were collected at 6-month intervals and analyzed to evaluate the association between alcohol dependence and consumption on depressive symptoms using longitudinal mixed-effects regression models controlling for specified covariates. Measurements The two independent variables were current alcohol dependence assessed using the Composite International Diagnostic Interview (CIDI) and past month consumption (heavy versus not heavy drinking) using a validated calendar-based method. The primary outcome was depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Participants HIV-infected adults with current or past alcohol problems. Findings Alcohol dependence and heavy alcohol use were significantly associated with higher CES-D scores in unadjusted models. In adjusted analyses, the association of current alcohol dependence persisted [mean difference in CES-D was 3.49 for dependence versus non-dependence; 95% confidence interval (CI): 1.76–5.22]; however, the effect of heavy drinking was no longer statistically significant (mean difference in CES-D was 1.04 for heavy versus not heavy drinking; 95% CI: −0.24–2.32). Conclusions Alcohol use is associated with more depressive symptoms in HIV-infected patients with alcohol problems. This association remains significant after adjusting for potential confounders only when alcohol use meets the criteria for alcohol dependence. [ABSTRACT FROM AUTHOR]

Background and Objective: It is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told.Design, Participants, and Measurements: Data from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests.Results: Participants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR = 1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR = 1.46; 95% CI: 1.01 to 2.11).Conclusions: Among patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking. [ABSTRACT FROM AUTHOR]

Background: Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. Methods: This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Results: Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference −46.0 cells/ μL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Conclusions: Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population. [ABSTRACT FROM AUTHOR]

Background. Ongoing substance use is a potential confounder for immunological studies on hepatitis C virus (HCV), but there is little in the literature regarding the effects of injection drug use (IDU) or alcohol on HCV-specific immune responses. We wanted to determine whether IDU or alcohol affected immune responses in HCV-infected and human immunodeficiency virus (HIV)/HCV coinfected subjects. Methods. Eight-four subjects with HIV/HCV and 57 with HCV were classified as either injection drug users, drinkers, or nonusers based on questionnaire results. Immune responses were studied with enzyme-linked immunosorbent spot assay for interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α against HCV proteins Core, NS3, and NS5 and recall antigens. Results. Subjects with HIV/HCV, in aggregate, had significantly lower HCV-specific IFN-g and TNF-aresponses than subjects with HCV. However, HIV/HCV injection drug users had HCV specific IFN-γ and IL-10 responses that were similar to those of HCV injection drug users and were significantly higher than in nonusers with HIV/HCV. Conversely, subjects who drank alcohol had similar immune responses to those who were abstinent, among both subjects with HIV/HCV and subjects with HCV. Conclusions. Studies that examine IFN-γ or IL-10 immune responses in HIV/HCV-coinfected or HCV-infected persons need to consider current IDU. Alcohol, at levels consumed in this cohort, does not appear to have as much of an effect on antigen-specific immune responses. [ABSTRACT FROM AUTHOR]

Background: Alcohol use and human immune deficiency virus (HIV) infection are both associated with accelerated progression of hepatitis C virus (HCV) disease and reduced response rates to interferon therapy. In this study, we assessed the prevalence of barriers to interferon treatment in a population of HIV/HCV-coinfected patients with current or past alcohol problems and the extent to which they received treatment to address the barriers. Methods: This is a cross-sectional, descriptive analysis of baseline data from a prospective study assessing the impact of HCV and alcohol use on HIV disease progression. Using consensus guidelines, subjects were categorized as having absolute, relative, or no contraindications to interferon therapy for HCV. Absolute contraindications to treatment included heavy alcohol use, decompensated liver disease, CD4 cell count <100 cells/ μL, recent needle sharing, and suicidal ideation. Relative contraindications included moderate alcohol use, recent injection drug use, depressive symptoms, and CD4 cell count from 100 to 199 cells/ μL. Results: Of 401 HIV-infected subjects, 200 were HCV RNA-positive. Fifty-three percent had an absolute contraindication to interferon therapy, 35% a relative but no absolute contraindication, and only 12% had no contraindication. Of those with an absolute contraindication, 61% reported heavy drinking and the majority (88%) had multiple contraindications. These contraindications were present despite the fact that over 50% were in receipt of substance abuse and mental health treatment. Conclusions: Continued alcohol and drug use as well as depressive symptoms are the major barriers to interferon therapy in HCV/HIV-coinfected subjects and these barriers persist despite high treatment rates for these problems. Therefore, more intensive treatments of alcohol, drug, and mental health issues are needed to improve HCV treatment eligibility in HCV/HIV-coinfected persons. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Depression is common in persons with HIV infection and with alcohol problems, and it has important prognostic implications. Neurocognitive dysfunction has been reported with chronic hepatitis C virus (HCV) infection. We hypothesized that HCV infection is associated with more depressive symptoms in HIV-infected persons with a history of alcohol problems. METHODS: We performed a cross-sectional analysis of baseline data from a prospective cohort study of 391 HIV-infected subjects with a history of alcohol problems, of whom 59% were HCV antibody (Ab) positive and 49% were HCV RNA-positive. We assessed depressive symptoms (Center for Epidemiologic Studies Depression [CES-D]) and past month alcohol consumption. In the primary analysis, we evaluated whether there were more depressive symptoms in HCV Ab-positive and RNA-positive subjects in unadjusted analyses and adjusting for alcohol consumption, gender, age, race, CD4 count, homelessness, drug dependence, and medical comorbidity. RESULTS: Mean CES-D scores were higher in subjects who were HCV Ab-positive compared with those who were HCV Ab-negative (24.3 vs 19.0; p < 0.001). In adjusted analyses, the difference in CES-D scores between HCV Ab-positive and Ab-negative subjects persisted (24.0 vs 19.0; p < 0.001). Unadjusted mean CES-D scores were also significantly higher in HCV RNA-positive subjects compared with those who were RNA-negative, and the difference remained significant (24.6 vs 19.3; p < 0.001) in adjusted analyses. CONCLUSIONS: HCV/HIV coinfected persons with a history of alcohol problems have more depressive symptoms than those without HCV, and this association is unexplained by a variety of population characteristics. These data suggest that HCV may have a direct effect on neuropsychiatric function. [ABSTRACT FROM AUTHOR]

We estimate that only one-third of patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are eligible for therapy for HCV with interferon (IFN) and ribavirin, and, of those who are eligible, two-thirds decline treatment. To date we have initiated treatment with IFN and ribavirin for 8% of coinfected patients evaluated, and <1% of patients have had a sustained virological response. During this process, we have identified many problems that significantly limit our ability to initiate and complete treatment with IFN in this population and have categorized these difficulties into 4 main challenges. They include access to care, contraindications or barriers to treatment, patients' reluctance to start treatment with IFN, and the low tolerability of treatment. If patients coinfected with HCV and HIV are to be treated for hepatitis C in greater numbers, these issues will need to be addressed. [ABSTRACT FROM AUTHOR]

The diagnosis of liver fibrosis has traditionally relied on liver biopsy. However, recent studies have suggested that there can be up to a 33 % error in the diagnosis of cirrhosis. In this article, we review the current status of liver biopsy as a gold standard for the diagnosis of liver fibrosis and discuss the radiological and serum tests that have been proposed as potential adjuncts or alternatives to biopsies. Indirect markers of liver fibrosis which reflect alterations in liver function and or inflammation are discussed as well as more direct markers of liver fibrosis. The limitations of utilization of these markers for both cross-sectional diagnosis of fibrosis and monitoring disease progression or regression are discussed. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations. [ABSTRACT FROM AUTHOR]

Reports that hepatitis C virus and human immunodeficiency virus coinfected people in an urban population in the U.S. had low eligibility for interferon and ribavirin treatment. Percentage of people eligible and ineligible for treatment out of the total number of people evaluated Barriers in treatment eligibility.

The prevalence of clinical celiac disease has been shown to vary both across time and between genetically similar populations. Differences in wheat antigenicity and transglutaminase substrate properties are a possible explanation for these differences. This study assessed the antigenicity and transglutaminase substrate specificities of gliadins from regions of high and low celiac disease prevalence. Gliadin was extracted from three commercial US wheat sources and two Irish sources. SDS-PAGE and western blotting revealed minor, but significant variations in the gliadin extracts. However, ELISA showed no difference in the antigenicity of these gliadins. Transglutaminase pretreatment of gliadin resulted in no significant change in gliadin antigenicity and kinetic studies showed that the Kms of the various gliadins were very similar. Purified IgA and IgG had no effect on transglutaminase activity. In summary, minor variations in wheat gliadins are unlikely to explain the observed differences in disease expression across genetically similar populations. [ABSTRACT FROM AUTHOR]

Background: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited. Methods: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels. Results: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [β (95%CI): −0.04 (−0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (−0.24, 0.38), p = 0.66). Conclusions: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients. [ABSTRACT FROM AUTHOR]

Human submandibular/sublingual gland secretions contain a multimeric high molecular weight mucin (MG1) and a monomeric low molecular weight mucin (MG2). MG2 is the product of the MUC7 gene, whereas the gene for MG1 has not been identified. Previously, we isolated a clone (pSM2–1) from a human sublingual gland cDNA expression library using an antibody against deglycosylated MG1 (Troxler et al., Biochem. Biophys. Res Commun., 217, 1112–1119, 1995). In order to identify the mucin gene from which pPM2–1 was derived, Northern blots of human submandibular and sublingual gland RNA were hybridized with a series of probes for tandem repeats found in the high molecular weight secreted mucins MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6. The only known mucin expressed at high levels in sublingual gland was MUC5B, and no known mucin was expressed at high levels in submandibular gland. A series of overlapping clones was obtained by rescreening the sublingual gland cDNA library and by reverse transcriptase-polymerase chain reaction. The resulting clones connected pSM2–1 to a series of MUC5B tandem repeats at the 3′ end of the repeat domain and provided the complete nucleotide and deduced amino sequence of the carboxyl terminal region of MG1. This region is enriched with respect to cysteine (∼10 mol %) and contained a D domain and a carboxyl terminal domain that could be aligned with the corresponding domains in human intestinal MUC2, human tracheobronchial MUC5AC, and human von Willebrand factor. The limited expression of known mucin genes, together with the considerable mucin synthesizing capacity of submandibular gland, suggests that a novel (previously not described) mucin gene is expressed in this gland and constitutes a portion of MG1 in salivary secretions. [ABSTRACT FROM PUBLISHER]