Impact of medical comorbidity and risk of death in 680 patients with alcohol use disorders.

BACKGROUND: The association between alcohol use disorders and increased risk of mortality is well known; however, there have been few systematic evaluations of alcohol-related organ damage and its impact on survival in younger alcoholics. Therefore, we assessed medical comorbidity with a clinical index to identify subgroups of alcoholic patients at high risk of premature death. METHODS: Hospital-based cohort of alcohol-dependent patients admitted for detoxification between 1999 and 2008 in Barcelona, Spain. At admission, sociodemographic characteristics and a history of alcohol dependence and abuse of illegal drugs were obtained through clinical interviews and questionnaires. Medical comorbidity was assessed with the Cumulative Illness Rating Scale (Substance Abuse) (CIRS-SA). Dates and causes of death were obtained from clinical records and death registers. Survival was analyzed using Kaplan-Meier methods, and Cox regression models were used to analyze the risk factors for premature death. RESULTS: Median age of the patients (686 total, 79.7% men) was 43.5 years (interquartile range [IQR], 37.8 to 50.4), average alcohol consumption was 200 g/d (IQR, 120 to 280 g/d), and duration of alcohol use disorder was 18 years (IQR, 11 to 24). Medical comorbidity by CIRS-SA at admission showed that the organs/systems most affected were liver (99%), respiratory (86%), and cardiovascular (58%). After median follow-up of 3.1 years (IQR, 1.5 to 5.1), 78 (11.4%) patients died with a mortality rate of 3.28 × 100 person-years; according to Kaplan-Meier estimates, 50% (95% confidence interval [95% CI], 24 to 69%) of patients with severe medical comorbidity died in the first decade after treatment. In multivariate analysis, severe medical comorbidity (hazard ratio [HR], 5.5; 95% CI, 3.02 to 10.07) and being treated with methadone at admission (HR, 2.60; 95% CI, 1.50 to 4.51) were independent risk factors for premature death. CONCLUSIONS: Systematic assessment of alcohol-related organ damage is relevant for the identification and treatment of those at increased risk of death.

[Gender and liver, nutritional and metabolic alterations of severe alcoholism: a study of 480 patients]. / Género y alteraciones hepáticas, nutricionales y metabólicas del alcoholismo grave: estudio de 480 pacientes.

BACKGROUND AND OBJECTIVE: To analyze gender differences in the hepatic, nutritional and metabolic complications associated with alcoholism. PATIENTS AND METHODS: Cross-sectional study in alcoholic patients admitted to detoxification in two university hospitals of Barcelona between 1999 and 2006. During admission, co-morbidity prior to admission was assessed and blood samples to analyze biological markers were collected. Demographic and anthropometric data, daily alcohol consumption and other drug use characteristics were also obtained at admission. RESULTS: There were 566 admissions in 480 patients (375 males). Age at admission was 43 years (IQR: 36.3-49.0 years). Overall, 68.4% showed macrocytosis (MCV > 95 fl), 81.7% GGT>40 U/L and 57.7% AST>37 U/L. Regarding liver function tests, frequency of alkaline phosphatase > 120 U/L was significantly higher in women (18.5 vs 10.5%, p=0.037). However, the prevalence of hyperferritinemia (> 90 ng/mL) was significantly higher in alcoholic men (85.7% vs 62.2%) (p=0.000). Having multiple liver function test alterations was significantly higher in men (OR: 1.64, 95% CI: 1.01-2.65) (p=0.043). Women showed significant differences regarding the prevalence of macrocytosis (77.5% vs 65.8%, p=0.026), low serum creatinine (< 0.7 mg/100mL) (28.2 vs 14.6%, p=0.001), low serum ferritin (< 30 ng/mL) (10.8 vs 3.9%, p=0.020), as well as of multiple nutritional alterations (OR: 1.59, 95% CI: 1.02-2.48) (p=0.040). However, men had higher prevalence of anemia than women (32.3 vs 21.4%, p=0.032). Prevalence of type I obesity (BMI>30 kg/m(2)) was significantly higher in alcoholic women (29.2 vs 7.9%, p=0.007). CONCLUSIONS: Hepatic, nutritional and metabolic complications of alcoholism in women are frequent, thus increasing the risk of developing adverse clinical outcomes.

[Diversity of Legionella pneumophila in cooling towers: coculture kinetics and virulence studies]. / Diversidad de subtipos de Legionella pneumophila en torres de refrigeración: estudios de cinética de crecimiento y virulencia.

BACKGROUND: Legionella pneumophila (L. pneumophila) was isolated from three cooling towers involved in three community outbreaks of Legionnaires disease. Each cooling tower had two different chromosomal DNA subtypes. However, only one matched identically to the clinical strains. To try to understand why only one of the environmental strains caused clinical cases we investigated the intrinsic virulence of these strains. METHODS: We selected six strains of L. pneumophila sg.1: two strains (A1 and B1) from cooling tower 1, two strains (A2 and B2) from tower 2 and two strains (A3 and B3) from tower 3. One of the two subtypes (A) exhibited the same chromosomal DNA subtype as the strains isolated from the patients in each outbreak and the other exhibited a different subtype. The replication within macrophages, the presence of lipopolysaccharide epitope recognized by MAb 3/1 and the growth kinetics in BCYE broth were investigated. Isolates were typed by pulsed field electrophoresis. RESULTS: The A strains did not have a higher virulence level, but were able to grow and survive better than strains B in BCYE broth. CONCLUSIONS: These results suggest that the strains better adapted to the environment will manage to displace the others and will be able to spread and infect humans. The adaptation to the environmental conditions could play an important role in the pathogenesis of the strains.

Hepatitis B virus serum profiles in injection drug users and rates of immunization over time in Barcelona: 1987-2006.

UNLABELLED: Injection drug users are at increased risk for hepatitis B. Surveillance of the unexposed to infection and of the vaccinated is necessary to understand the impact of interventions. We aimed to analyze HBV serum profiles and rates of HBV vaccination over 20 years. METHODS: Cross-sectional study in IDUs admitted to detoxification between 1987 and 2006 in two hospitals in Barcelona, Spain. Clinical data and serum samples for HBV, HCV and HIV infections were collected. HBV serostatus was assessed with HBsAg, Anti-HBs and Anti-HBc. RESULTS: A total of 1223 IDUs were eligible; 80.3% were men; median age at admission was 28 years. Prevalence of HCV infection and HIV infection was 84.2% and 44.3%, respectively. There was a significant (p<0.001) increase of the rates of HBV vaccine-induced immunity from 3.7% in period 1987-1991 to 19.9% in period 2002-2006 and, a significant (p<0.001) decline of those with HBsAg from 9.3% in 1987-1991 to <2% after 1997. The rates of absence of HBV markers and of natural immunity remained stable from 1992 onwards. In multivariate logistic regression model, HBV vaccination was significantly (p<0.001) less frequent in older individuals (OR=0.61 [95% CI: 0.50-0.74] for a 5-year increase in age) and in HIV infected patients (p=0.014) (OR=0.51 [95% CI: 0.30-0.87]). CONCLUSIONS: In the 20-year period from 1987 to 2006, HBV vaccine-induced immunity in IDUs has shown an upward trend, although overall prevalence remained low. More effective interventions are needed to reduce high rates of HBV infection in this population.

Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus.

BACKGROUND & AIMS: We assessed the ability of 3 simple biochemical tests to stage liver fibrosis in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: We analyzed liver biopsy samples from 324 consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0, 22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses were used to predict the probability of significant (>or=F2) or advanced (>or=F3) fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and in combination). Area under the receiver operating characteristic curves were analyzed to assess diagnostic performance. RESULTS: Area under the receiver operating characteristic curves analyses indicated that the 3 tests had similar abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75, 0.73, and 0.78, respectively. The accuracy of each test in predicting which samples were F3 or greater was significantly higher than for F2 or greater (APRI, FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and 68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or greater was ruled out with sensitivity and negative predictive values of 79% to 94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver fibrosis (>or=F3) was identified using the highest cut-off value, with specificity and positive predictive values of 90% to 96% and 63% to 73%, respectively, and 75% to 77% accuracy. CONCLUSIONS: Simple biochemical tests accurately predicted liver fibrosis in more than half the HIV/HCV co-infected patients. The absence and presence of liver fibrosis are predicted fairly using the lowest and highest cut-off levels, respectively.

Fatal fast-evolution of nasopharyngeal squamous cell carcinoma in an HIV patient with EBV and HPV (-16 AND -33) in blood serum.

Our case illustrates the first report of an HIV-infected patient with a nasopharyngeal squamous cell carcinoma with viremia by one Epstein-Barr virus (EBV) and seropositivity by two high risk oncogenic human papilloma viruses (HPV)-types (HPV-16 and HPV-33), previous to his death. This patient presented a fatal fast-evolution.

[Asymmetric dimethylarginine as cardiovascular risk factor]. / Dimetilarginina asimétrica como marcador de riesgo cardiovascular.

The amino acid L-arginine is the substrate for endothelial nitric oxide synthesis. The endothelium is capable of producing asymmetric dimethylargine (ADMA) (L-arginine methylated). ADMA is able to compete with L-arginine in nitric oxide (NO) production and inhibits oxide nitric synthase activity. Elevated blood levels of ADMA can block the synthesis of NO, and induce endothelial dysfunction, which may lead to the initiation and progression of atherosclerosic vascular disease. Prospective clinical studies in different patients populations suggest that ADMA is a new marker in cardiovascular disease and is to able to predict new cardiovascular events. Recently, intraindividual variations of ADMA in healthy subjects have been described. This fact induces to continue studying the diagnosis and prognosis value of this potential and novel marker of cardiovascular risk.

Genotypic variability and persistence of Legionella pneumophila PFGE patterns in 34 cooling towers from two different areas.

Genotypic variability and clonal persistence are important concepts in molecular epidemiology as they facilitate the search for the source of sporadic cases or outbreaks of legionellosis. We studied the genotypic variability and persistence of Legionella pulsed-field gel electrophoresis (PFGE) patterns over time (period > 6 months) in 34 positive cooling towers from two different areas. In area A, radius of 70 km, 52 indistinguishable PFGE patterns were differentiated among the 27 cooling towers. In 13 cooling towers we observed >or= 2 PFGE patterns. Each cooling tower had its own indistinguishable Legionella PFGE pattern which was not shared with any other cooling tower. In area B, radius of 1 km, 10 indistinguishable PFGE patterns were obtained from the seven cooling towers. In four, we observed >or= 2 PFGE patterns. Three of these 10 indistinguishable PFGE patterns were shared by more than one cooling tower. In 27 of 34 cooling towers the same PFGE pattern was recovered after 6 months to up to 5 years of follow-up. The large genotypic diversity of Legionella observed in the cooling towers aids in the investigation of community outbreaks of Legionnaires' disease. However, shared patterns in small areas may confound the epidemiological investigation. The persistence of some PFGE patterns in cooling towers makes the recovery of the Legionella isolate causing the outbreak possible over time.

Liver enzyme alterations in HCV-monoinfected and HCV/HIV-coinfected patients.

UNLABELLED: Hepatitis C virus (HCV) is the most common blood-borne infection in developed countries and co-infection with the Human Immunodeficiency Virus (HIV) is frequent in individuals with history of injecting drug use (IDU).We aimed to analyze liver transaminases in HCV monoinfected and HCV/HIV co-infected patients to assess the effect of HIV infection on liver enzyme elevations.We studied 429 current IDUs admitted to substance abuse treatment (82.5% males). Serum samples for liver tests, HIV infection and viral hepatitis serologies were obtained at admission. RESULTS: Median age was 30 years (IQR:27-34), median duration of IDU was 10 years (IQR:5-14), 52% of patients were HCV/HIV co-infected, 40.8% were HCV monoinfected, and 7.2% were HCV and HIV- seronegatives. Elevated AST was associated with male gender and lower CD8(+) cell count in the HCV monoinfected patients, and with age and lower cholesterol in the HCV/HIV coinfected subjects. ALT elevation was associated with younger age, higher body mass index and male gender in the monoinfected patients, and with higher CD4(+) cell counts and lower cholesterol in the co-infected group. Male sex was strongly associated with elevated ALT and AST transaminase in the monoinfected but not in dual-infected subjects.These data suggest that the effect of gender on liver enzymes may be lost in patients with HIV infection. The overall differences observed between groups regarding liver enzyme elevations are of clinical relevance in the management of IDUs with chronic hepatitis C.

Differences in virological response to pegylated interferon and ribavirin between hepatitis C virus (HCV)-monoinfected and HCV-HIV-coinfected patients.

BACKGROUND: Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS: A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n = 104) were compared. All patients received PEG-IFN-alpha2a 180 microg/week plus ribavirin 800-1,200 mg daily (HCV genotype 2/3 patients received 800 mg daily and those with genotype 1/4 received 1,000-1,200 mg daily) for 48 weeks (24 weeks for monoinfected patients with genotypes 2/3). HCV RNA levels were determined qualitatively at weeks 4, 12, 24, 48 and 72 and quantified monthly until week 12. RESULTS: The coinfected cohort had more advanced liver disease and lower body weight. HCV genotype 1 patients coinfected with HIV showed higher levels of HCV RNA than monoinfected patients. A significantly higher proportion of coinfected patients interrupted the prescribed treatment period prematurely (84% versus 98%). During the first 12 weeks, smaller decreases in HCV RNA levels were observed in coinfected patients. Among patients with HCV genotype 1, coinfected patients achieved lower rates of early virological response (64% versus 87%), end-of-treatment response (47.3% versus 80%) and sustained virological response (SVR; 27.3% versus 56.4%), but not rapid virological response (RVR). HCV-HIV-coinfected patients with HCV genotype 2/3 achieved significantly lower rates of RVR (52% versus 88%). Multivariate analysis identified RVR, gender and liver fibrosis as independent predictors of SVR. CONCLUSIONS: Differences in efficacy of PEG-IFN-alpha2a plus ribavirin treatment between HCV-HIV-coinfected and HCV-monoinfected patients were maintained despite optimized ribavirin dose.

Association between HIV replication and cholesterol in peripheral blood mononuclear cells in HIV-infected patients interrupting HAART.

BACKGROUND: Cellular cholesterol is essential for HIV replication and may control HIV spread. HIV, in turn, appears to control cholesterol metabolism. OBJECTIVES: To describe the relationships between serum lipids, cellular cholesterol and viral replication during highly active antiretroviral therapy (HAART) interruption. METHODS: We have correlated virological parameters with the level of circulating lipids in serum and the content of cellular cholesterol in peripheral blood mononuclear cells (PBMCs). The study included 33 patients interrupting HAART with (n = 23) or without (n = 10) atorvastatin treatment. RESULTS: Atorvastatin treatment did not modify PBMC cholesterol levels at week 4 after HAART interruption, although it significantly reduced serum cholesterol (total and LDL, where LDL stands for low density lipoprotein) (P < 0.05). Serum cholesterol or LDL marginally influenced PBMC cholesterol since no significant correlations were found between these parameters either at 0 or 4 weeks after HAART interruption. Analysis of virological data in all patients revealed a negative trend (P = 0.07) between baseline PBMC cholesterol and absolute CD4 T cell counts at baseline but a poor correlation (P = 0.18) with the viral load (VL) at week 4. Separate analysis of control patients showed a correlation between baseline PBMC cholesterol and VL at week 4 (P = 0.01). However, atorvastatin treatment abrogated this correlation by increasing viral replication in individuals with low cellular cholesterol. CONCLUSIONS: Our data underscore the potential relevance of PBMC cholesterol in in vivo HIV replication and the complex effects of atorvastatin that seem to be unrelated to PBMC cholesterol.

Highly active antiretroviral therapy and incidence of cervical squamous intraepithelial lesions among HIV-infected women with normal cytology and CD4 counts above 350 cells/mm3.

OBJECTIVES: To provide evidence for the long-term effect of highly active antiretroviral therapy (HAART) on the incidence of cervical squamous intraepithelial lesions (SILs) among HIV-positive women with normal cytology test and CD4 count above 350 cells/mm(3). PATIENTS AND METHODS: A retrospective cohort study was carried out in HIV-positive women with two consecutive normal cervical cytological tests (Papanicolaou test) and at least one subsequent test, without previous cervical history of SIL or cancer diagnosis, and with an immunological status >350 CD4 cells/mm(3). The patients were divided into two groups: treated with HAART (HAART group) or not treated with HAART (NO-HAART group), during the period of time between cytology tests included in the survival analysis and time until SIL. RESULTS: Between January 1997 and December 2006, 127 women were included: 90 in the HAART group and 37 in the NO-HAART group. Both groups of patients were similar with respect to demographic data, except for HIV viral load and previous HAART inclusion (P < 0.001). SIL was diagnosed in 27 of 90 (30%) patients in the HAART group and in 7 of 37 (19%) patients in the NO-HAART group (OR = 1.84, 95% CI: 0.72-4.69, P = 0.202). The actuarial probability of remaining free of SIL at 3 years was 70% in the HAART group and 78% in the NO-HAART group. No variable was associated with an increased risk of developing SILs. CONCLUSIONS: These results suggest that when the patients' immunological status is above 350 CD4 cells/mm(3), the HIV-infected women treated with HAART present a similar cervical SIL incidence to women not on HAART.

[Clinical, echocardiographic and prognostic evaluation of atrial fibrillation in patients with heart failure]. / Valoración clínica, ecocardiográfica y pronóstica de la fibrilación auricular en pacientes con insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: We aimed to assess the prevalence of atrial fibrillation (AF) in a general heart failure (HF) population admitted to a HF unit, analyze the parameters associated with AF, and evaluate its prognostic significance. PATIENTS AND METHOD: 389 patients, 64 with AF at the first visit. Mean (SD) age was 65.38 (10.77) years and 72.5% were men. The main etiology was ischemic heart disease (59.9%). Mean ejection fraction (EF) was 32.25% (13%). Vital status at 2 years was available in 377 patients (97%), 314 in sinus rhythm (SR) and 63 in AF. RESULTS: The prevalence of AF was 15.8%. AF was associated with: older age, female gender, valvular and hypertensive etiology, longer time since the onset of HF symptoms, higher EF, higher left atrium diameter, degree of mitral regurgitation, and lower quality of life, but not with the NYHA functional class. The 2-years mortality (16.7%) was significantly higher in patients with AF (33.3% vs 18.4%; OR = 2.20; 95% confidence interval, 1.21-4). However, when adjusted for other relevant variables such as age, NYHA functional class, ejection fraction, sex and etiology, AF did not remain as an independent prognostic factor. The strongest mortality differences between patients with AF and those with SR where observed in ischemic heart disease and dilated cardiomyopathy. CONCLUSIONS: AF was associated mainly with age, valvular and hypertensive etiology, higher left atrium diameter and lower end-systolic left ventricular diameter. Two years mortality was significantly higher in patients with AF, although other parameters such as age and NYHA functional class had a higher prognostic value.

Evolution of cervical cytologic changes among HIV-infected women with normal cytology in the HAART era.

The influence of HAART on the evolution to cervical squamous intraepithelial lesions (SIL) among HIV(+) women with a normal cytological test in the HAART era was studied. A retrospective cohort study (1997-2005) of HIV-infected women treated with HAART was conducted. Those with a normal cervical cytology (Papanicolaou test) and at least one subsequent test were included. Survival (time until diagnosis of SIL), univariate, and multivariate analyses were performed. A total of 133 HIV-infected patients treated with HAART were included. The incidence of SIL was 35% (47 patients). SIL was diagnosed in 36 of 110 (33%) patients with a baseline and final immunological status of >200 CD4 cells/microl and in 6 of 9 (67%) patients with a baseline and final immunological status of < or =200 CD4 (OR: 0.24, 95% CI: 0.06-1.03, p = 0.041). SIL was diagnosed in 10 of 60 (17%) patients with an undetectable baseline and final HIV viral load and in 36 of 70 (51%) patients with a detectable HIV viral load (OR: 0.19, 95% CI: 0.07-0.46, p < 0.001). A high incidence of SIL (cancer precursor lesions) was observed among HIV(+) women without a background of cervical pathology. The effect of HAART on the control of HIV replication and of immunological status (>200 CD4) through the follow-up was associated with a reduction of SIL.

Survival of HIV-infected injection drug users (IDUs) in the highly active antiretroviral therapy era, relative to sex- and age-specific survival of HIV-uninfected IDUs.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART), it remains unclear whether human immunodeficiency virus (HIV)-infected injection drug users (IDUs) have durations of survival similar to those for comparable HIV-uninfected IDUs. The goal of this study was to compare survival durations of HIV-infected and HIV-uninfected IDUs for the period 1987-2004.Methods. Demographic data, drug use characteristics, and biological markers were obtained at the time of admission to a substance abuse treatment program. The outcome of interest was the duration of survival after admission, and the primary exposure was HIV infection. Vital status was ascertained by means of the mortality register by the end of 2004. Three calendar periods, which were defined on the basis of use of specific therapies, were considered: 1987-1991 (the antiretroviral monotherapy era), 1992-1996 (the dual combination therapy era and the era when methadone was introduced in Spain), and 1997-2004 (the era of HAART and of established methadone programs). We used Cox regression methods allowing for late entries to handle the contribution of persons who survived a given period and entered the following period with nonzero time. We compared HIV-uninfected and HIV-infected IDUs with adjustments for age, sex, and duration of follow-up after admission. RESULTS: A total of 1209 IDUs were admitted to the hospital during the period from January 1987 through December 2004, and 1181 were eligible for the study. The majority (81.3%) of patients were men. The mean age (+/- standard deviation) at admission was 27.8+/-5.6 years, and the mean duration of injection drug use (+/- standard deviation) was 7.6+/-5.0 years. The prevalences of HIV and hepatitis C virus infections were 59.0% and 92.3%, respectively, and the total duration of follow-up was 10.116 person-years. Although survival duration for HIV-uninfected IDUs in 1997-2004 was similar to the duration in earlier periods, the duration for HIV-infected IDUs improved significantly since 1997 (P<.01). Furthermore, among patients admitted in the last period, the survival durations for HIV-uninfected and HIV-infected IDUs was virtually the same (relative hazard, 0.89; 95% confidence interval, 0.44-1.81). CONCLUSIONS: The duration of survival of HIV-infected IDUs has improved substantially since 1997, reaching rates similar to the rates for HIV-seronegative IDUs who accessed the health care system in the era of HAART.

Impact of copper and silver ionization on fungal colonization of the water supply in health care centers: implications for immunocompromised patients.

Copper and silver ionization is a well-recognized disinfection method to control Legionella species in water distribution systems in hospitals. These systems may also serve as a potential indoor reservoir for fungi. The prevalence of fungi was significantly lower in ionized than in nonionized water samples from health care facilities. The clinical consequences of this finding require further investigation.