Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Ocio nocturno y consumo de sustancias en jóvenes universitarios

El principal objectiu del treball és conèixer la situació general del consum de drogues en una mostra d’estudiants de la Universitat de Girona i analitzar algunes de les variables relacionades amb el seu ús durant l’oci nocturn de cap de setmana

Effectiveness of interventions targeting frequent users of emergency departments: a systematic review.

STUDY OBJECTIVE: Frequent users of emergency departments (EDs) are a relatively small group of vulnerable patients accounting for a disproportionally high number of ED visits. Our objective is to perform a systematic review of the type and effectiveness of interventions to reduce the number of ED visits by frequent users. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsychINFO, the Cochrane Library, and ISI Web of Science for randomized controlled trials, nonrandomized controlled trials, interrupted time series, and controlled and noncontrolled before-and-after studies describing interventions targeting adult frequent users of EDs. Primary outcome of interest was the reduction in ED use. We also explored costs analyses and various clinical (alcohol and drug use, psychiatric symptoms, mortality) and social (homelessness, insurance status, social security support) outcomes. RESULTS: We included 11 studies (3 randomized controlled trials, 2 controlled and 6 noncontrolled before-and-after studies). Heterogeneity in both study designs and definitions of frequent users precluded meta-analyses of the results. The most studied intervention was case management (n=7). Only 1 of 3 randomized controlled trials showed a significant reduction in ED use compared with usual care. Six of the 8 before-and-after studies reported a significant reduction in ED use, and 1 study showed a significant increase. ED cost reductions were demonstrated in 3 studies. Social outcomes such as reduction of homelessness were favorable in 3 of 3 studies, and clinical outcomes trended toward positive results in 2 of 3 studies. CONCLUSION: Interventions targeting frequent users may reduce ED use. Case management, the most frequently described intervention, reduced ED costs and seemed to improve social and clinical outcomes. It appears to be beneficial to patients and justifiable for hospitals to implement case management for frequent users in the framework of a clear and consensual definition of frequent users and standardized outcome measures.

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study.

OBJECTIVES: To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study. METHODS: Two sub-populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment-naïve patients with CD4>or=200 cells/microL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/microL without ART despite cohort follow-up. RESULTS: Median initial CD4 cell count in group A was 331 cells/microL; 31% and 10% were <200 and <50 cells/microL, respectively. Risk factors for low CD4 count were age and non-White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4>or=200 cells/microL; 18% and 2% dropped to CD4 <200 and <50 cells/microL without ART, respectively. Sub-Saharan origin was associated with lower probability of CD4 <200 cells/microL without ART during follow-up. Median CD4 count at ART initiation was 207 and 253 cells/microL in groups A and B, respectively. CONCLUSIONS: CD4<200 cells/microL and, particularly, CD4<50 cells/microL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.

Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.

Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

Supervised injection services : what has been demonstrated? : a systematic literature review

BACKGROUND: Supervised injection services (SISs) have been developed to promote safer drug injection practices, enhance health-related behaviors among people who inject drugs (PWID), and connect PWID with external health and social services. Nevertheless, SISs have also been accused of fostering drug use and drug trafficking. AIMS: To systematically collect and synthesize the currently available evidence regarding SIS-induced benefits and harm. METHODS: A systematic review was performed via the PubMed, Web of Science, and ScienceDirect databases using the keyword algorithm [("SUPERVISED" OR "SAFER") AND ("INJECTION" OR "INJECTING" OR "SHOOTING" OR "CONSUMPTION") AND ("FACILITY" OR "FACILITIES" OR "ROOM" OR "GALLERY" OR "CENTRE" OR "SITE")]. RESULTS: Seventy-five relevant articles were found. All studies converged to find that SISs were efficacious in attracting the most marginalized PWID, promoting safer injection conditions, enhancing access to primary health care, and reducing the overdose frequency. SISs were not found to increase drug injecting, drug trafficking or crime in the surrounding environments. SISs were found to be associated with reduced levels of public drug injections and dropped syringes. Of the articles, 85% originated from Vancouver or Sydney. CONCLUSION: SISs have largely fulfilled their initial objectives without enhancing drug use or drug trafficking. Almost all of the studies found in this review were performed in Canada or Australia, whereas the majority of SISs are located in Europe. The implementation of new SISs in places with high rates of injection drug use and associated harms appears to be supported by evidence.

Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.

BACKGROUND: The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. OBJECTIVE: To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. DESIGN: Prospective cohort study. SETTING: 61 hospitals in 28 countries. PATIENTS: Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. MEASUREMENTS: Clinical and echocardiographic findings, microbiology, complications, and mortality. RESULTS: Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). LIMITATIONS: Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. CONCLUSION: More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. PRIMARY FUNDING SOURCE: None.

Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have an increased risk for several cancers, but the influences of behavioral risk factors, such as smoking and intravenous drug use, and highly active antiretroviral therapy (HAART) on cancer risk are not clear. METHODS: Patient records were linked between the Swiss HIV Cohort Study and Swiss cantonal cancer registries. Observed and expected numbers of incident cancers were assessed in 7304 persons infected with HIV followed for 28,836 person-years. Relative risks for cancer compared with those for the general population were determined by estimating cancer registry-, sex-, age-, and period-standardized incidence ratios (SIRs). RESULTS: Highly elevated SIRs were confirmed in persons infected with HIV for Kaposi sarcoma (KS) (SIR = 192, 95% confidence interval [CI] = 170 to 217) and non-Hodgkin lymphoma (SIR = 76.4, 95% CI = 66.5 to 87.4). Statistically significantly elevated SIRs were also observed for anal cancer (SIR = 33.4, 95% CI = 10.5 to 78.6); Hodgkin lymphoma (SIR = 17.3, 95% CI = 10.2 to 27.4); cancers of the cervix (SIR = 8.0, 95% CI = 2.9 to 17.4); liver (SIR = 7.0, 95% CI = 2.2 to 16.5); lip, mouth, and pharynx (SIR = 4.1, 95% CI = 2.1 to 7.4); trachea, lung, and bronchus (SIR = 3.2, 95% CI = 1.7 to 5.4); and skin, nonmelanomatous (SIR = 3.2, 95% CI = 2.2 to 4.5). In HAART users, SIRs for KS (SIR = 25.3, 95% CI = 10.8 to 50.1) and non-Hodgkin lymphoma (SIR = 24.2, 95% CI = 15.0 to 37.1) were lower than those for nonusers (KS SIR = 239, 95% CI = 211 to 270; non-Hodgkin lymphoma SIR = 99.3, 95% CI = 85.8 to 114). Among HAART users, however, the SIR (although not absolute numbers) for Hodgkin lymphoma (SIR = 36.2, 95% CI = 16.4 to 68.9) was comparable to that for KS and non-Hodgkin lymphoma. No clear impact of HAART on SIRs emerged for cervical cancer or non-acquired immunodeficiency syndrome-defining cancers. Cancers of the lung, lip, mouth, or pharynx were not observed among nonsmokers. CONCLUSION: In persons infected with HIV, HAART use may prevent most excess risk of KS and non-Hodgkin lymphoma, but not that of Hodgkin lymphoma and other non-acquired immunodeficiency syndrome-defining cancers. No cancers of the lip, mouth, pharynx, or lung were observed in nonsmokers.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Practices in primary health care oriented toward the harmful consumption of drugs

Objective To analyze the practices of primary care focused on the harmful consumption of drugs. Method This is a qualitative study, developed with a dialectical-critical approach. Data collection was carried out through semi-structured interviews with 10 employees of a basic health unit (UBS). Results The demands are not accepted, and if they go beyond the barriers shaped by the historical absence of health care practices for drug users and moralistic and preconceived ideologies, they are not reinterpreted as health needs; practices that meet these demands and go beyond the barriers are poor; the functionalist approach, which explains drug use as a disease and considers drug users as deviants, supports the few existing practices. Conclusion primary health care is mistakenly focused on addiction; it lacks structural elements of the production process in health and internal dynamics of the working processes that would foster the development of collective practices.

Intimate partner violence against pregnant women: the environment according to Levine's nursing theory

Abstract OBJECTIVE Analyzing the elements that compose the environment of pregnant women who have experienced intimate partner violence in the light of Levine's Nursing Theory. METHOD A qualitative, descriptive study conducted from September to January 2012, with nine pregnant women in a Municipal Health Center in Rio de Janeiro. The interviews were semi-structured and individual. The theoretical framework was based on Levine's Nursing Theory. RESULTS Thematic analysis evidenced the elements that composed the external environment, such as violence perpetrated by intimate partners before and during pregnancy, violence in childhood and adolescence, alcohol consumption and drug use by the partner, unemployment, low education and economic dependency, which affected health and posed risks to the pregnancy. CONCLUSION Violence perpetrated by an intimate partner was the main external factor that influenced the internal environment with repercussions on health. This theory represents a tool in nursing care which will aid in detecting cases and the fight against violence.

Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand [Antiepileptics in women of childbearing age and during pregnancy : Comparison of specialized information with the current state of knowledge in Germany and Switzerland].

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.

The impact of generic reference pricing interventions in the statin market

The objective of this study was to evaluate the intended and unintended impact on pharmaceutical use and sales of three public financing reforms applied to the prescription of statins: a Spanish generic reference pricing (RP) system for lovastatin and simvastatin, and two competing policies introduced by the Andalusian Public Health Service (APHS) for all statins, first a maximum consumer price (MCP) and then a so called quality prescribing incentive for general practitioners (MCP plus PI).This study is designed as an observational, retrospective, interrupted time series analysis with comparison series (APHS and the rest of Spain) of 46 monthly drug use and sales ratios from January 2001 to October 2004 for each active ingredient in the group of statins.RP has been effective at reducing the volume of sales growth of the off-patent statins, yet its overall impact on sales of all statins has been relatively modest. The quantity and volume of sales impact heavily depends on regulatory RP details such as when the system is introduced, how often it is updated, and how the reference price is calculated.

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen.

OBJECTIVE: To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc). METHODS: HIV-positive patients with isolated anti-HBc and CD4 counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination. RESULTS: 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders. CONCLUSIONS: 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1-3 vaccine doses. However, duration of this immune response was short-lived (

Long term global evaluation of a national AIDS prevention strategy: the case of Switzerland.

OBJECTIVES: The Swiss Aids prevention strategy has been subject to a continuous process of evaluation for the past 12 years. This paper describes the conceptual approach, methodology, results obtained and contribution to policy-making of that evaluation.¦DESIGN: The evaluation is on-going, global with respect to all components of the strategy, and utilization-focused. Each successive phase of the evaluation has included 10-20 studies centred either on aspects of process, of outcome or of environmental context. Findings are synthesized at the end of each phase. METHODS: Both quantitative and qualitative methods are used. Studies generally have one of three functions within the overall evaluation: assessment of trends through surveys or other types of repeated studies; evaluation of specific areas through a series of studies from different viewpoints; in-depth investigation or rapid assessment through one-off studies. Various methods of triangulation are used to validate findings. RESULTS: The evaluation has allowed for: the observation of behavioural change in different populations; the availability of scientific data in controversial fields such as drug-use policy; an understanding of the diversity of public appropriation of prevention messages. Recommendations are regularly formulated and have been used by policy-makers and field workers for strategy development. CONCLUSIONS: The global approach adopted corresponds well to the evaluation requirements of an integrated long-term prevention strategy. Cost is low relative to the extent of information provided. Such an evaluation cannot however address the question of causal relationship between the strategy and observed changes. The evaluation has contributed to the development of a culture of evaluation in Swiss AIDS prevention more generally.