Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder.

BACKGROUND: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. METHODS: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. RESULTS: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (-0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42-20.56), 1.87 (1.11-3.16), 2.99 (1.79-5.01), 1.84 (1.11-3.16), and 2.13 (1.30-3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48-4.58), p < 0.01). CONCLUSION: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF.

Monitoring hepatitis C virus treatment rates in an Opioid Treatment Program: A longitudinal study.

BACKGROUND: Direct-acting antivirals (DAAs) are recommended for the treatment of hepatitis C virus (HCV) infection in patients treated with methadone or buprenorphine. AIM: To assess HCV treatment rates in an Opioid Treatment Program (OTP). METHODS: This longitudinal study included 501 patients (81.4% men, median age: 45 years; interquartile range: 39-50 years) enrolled in an OTP between October 2015 and September 2017. Patients were followed until September 2019. Data on socio-demographics, substance use, HCV infection, human immunodeficiency virus (HIV) infection and laboratory parameters were collected at entry. We analyzed medical records to evaluate HCV treatment. Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors. RESULTS: Prevalence of HCV and HIV infection was 70% and 34%, respectively. Among anti-HCV-positive (n = 336) patients, 47.2%, 41.3%, and 31.9% used alcohol, cannabis, and cocaine, respectively. HCV-RNA tests were positive in 233 (69.3%) patients. Twentyeight patients (8.3%) cleared the infection, and 59/308 (19.1%) had received interferon-based treatment regimens before 2015. Among 249 patients eligible, 111 (44.6%) received DAAs. Treatment rates significantly increased over time from 7.8/100 person-years (p-y) (95%CI: 5.0-12.3) in 2015 to 18.9/100 p-y (95%CI: 11.7-30.3) in 2019. In a multivariate analysis, patients with HIV co-infection were twice as likely to receive DAAs (HR = 1.94, 95%CI: 1.21-3.12) than patients with HCV mono-infection. Current drug use was an independent risk factor for not receiving treatment against infection (HR = 0.48, 95%CI: 0.29-0.80). CONCLUSION: HCV treatment is evolving in patients with HCV-HIV co-infection. Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.

Ultrasound findings of liver damage in a series of patients consecutively admitted for treatment of alcohol use disorder.

BACKGROUND: To analyze ultrasound findings of liver damage in alcohol use disorder (AUD) patients. METHODS: A cross-sectional analysis of detoxification patients. Clinical and laboratory parameters were obtained at admission. Analytical liver injury (ALI) was defined as at least two of the following: aspartate aminotransferase (AST) levels ≥74 < 300 U/L, AST/alanine aminotransferase (ALT) ratio >2, and total bilirubin >1.2 mg/dL. Advanced liver fibrosis (ALF) was defined as a FIB-4 score ≥3.25. Abdominal ultrasound was used to identify steatosis, hepatomegaly, heterogeneous liver, and portal hypertension. Predictors of these findings were determined by logistic regression. RESULTS: We included 301 patients (80% male) with a median age of 46 years (IQR: 39-51 years) and alcohol consumption of 180 g/day (IQR: 120-201 g). The prevalence of Hepatitis C virus (HCV) was 21.2%; AST and ALT serum levels were 42 U/L (IQR: 23-78 U/L) and 35 U/L (IQR: 19-60 U/L), respectively; 16% of patients had ALI and 24% ALF. Ultrasound findings were: 57.2% steatosis, 49.5% hepatomegaly, 17% heterogeneous liver, and 16% portal hypertension; 77% had at least one ultrasound abnormality, and 45% had ≥2. HCV infection was associated with heterogeneous liver (p = 0.046) and portal hypertension (p < 0.01). ALI and ALF were associated with steatosis (both p < 0.01) and hepatomegaly (both p < 0.01), ALI with portal hypertension (p = 0.08), and ALF with heterogeneous liver (p < 0.01). In logistic regression, ALI and ALF were associated with ≥2 abnormalities [OR (95%CI): 5.2 (2.1-12.8), p < 0.01 and 4.7 (2.2-9.7), p < 0.01; respectively]. CONCLUSIONS: Ultrasound findings of liver damage may facilitate clinical decisions and alcohol cessation in AUD patients.

Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study. / Pacientes con trastorno por uso de alcohol: resultados iniciales de un registro multicéntrico en la Red de Trastornos Adictivos-RTA. Estudio CohRTA.

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.

El Programa Alcohol de la Red de Trastornos Adictivos (RTA) requiere de un estudio clínico longitudinal para dar respuesta a preguntas de investigación en el trastorno por uso de alcohol. El proyecto CohRTA es un estudio multicéntrico de investigación cooperativa que se pone en marcha para mejorar la prevención secundaria y el diagnóstico precoz de los procesos patológicos asociados al trastorno por uso de alcohol. Método: estudio observacional en cohorte multicéntrica de pacientes mayores de 18 años que solicitan tratamiento del trastorno por primera vez y autorizan su participación. La información clínica se recoge en una plataforma online diseñada para el estudio y puede ir acompañada de una muestra biológica que se deposita en un biobanco. Se recogen datos basales y prospectivos, sociodemográficos, epidemiológicos, clínicos y de tratamiento. A diciembre de 2015 son 10 los centros proveedores de pacientes y se espera reclutar más de 1.000 pacientes en los próximos años. Resultados: se dispone de 344 pacientes (77% hombres) que cumplen los criterios de inclusión en el estudio y con una edad de 50 años (RIQ: 43-55 años). La edad de inicio de consumo de alcohol fue de 15 años (RIQ: 14-18 años) y un 61% tenían antecedente familiar de trastorno por uso de alcohol. Durante los 30 días previos al inicio del tratamiento los pacientes bebían 12.5 UBE/día (RIQ: 7.1-20 UBE/día), el 72% fumaba tabaco y el 30% consumía cocaína. Conclusiones: Disponer de una cohorte abierta y multicéntrica de pacientes con trastorno por uso de alcohol será útil para analizar las consecuencias del abuso de alcohol, potenciar la investigación traslacional y añadir valor a la investigación clínica y básica del Programa Alcohol dentro de RTA/RETICS. Con una cohorte bien establecida y representativa se espera aumentar la cantidad y calidad científica en relación a las complicaciones del trastorno por uso de alcohol y sus consecuencias clínicas y sociales en España.

Pacientes con trastorno por uso de alcohol: resultados iniciales de un registro multicéntrico en la Red de Trastornos Adictivos-RTA. Estudio CohRTA / Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study

El Programa Alcohol de la Red de Trastornos Adictivos (RTA) requiere de un estudio clínico longitudinal para dar respuesta a preguntas de investigación en el trastorno por uso de alcohol. El proyecto CohRTA es un estudio multicéntrico de investigación cooperativa que se pone en marcha para mejorar la prevención secundaria y el diagnóstico precoz de los procesos patológicos asociados al trastorno por uso de alcohol. Método: estudio observacional en cohorte multicéntrica de pacientes mayores de 18 años que solicitan tratamiento del trastorno por primera vez y autorizan su participación. La información clínica se recoge en una plataforma online diseñada para el estudio y puede ir acompañada de una muestra biológica que se deposita en un biobanco. Se recogen datos basales y prospectivos, sociodemográficos, epidemiológicos, clínicos y de tratamiento. A diciembre de 2015 son 10 los centros proveedores de pacientes y se espera reclutar más de 1.000 pacientes en los próximos años. Resultados: se dispone de 344 pacientes (77% hombres) que cumplen los criterios de inclusión en el estudio y con una edad de 50 años (RIQ: 43-55 años). La edad de inicio de consumo de alcohol fue de 15 años (RIQ: 14-18 años) y un 61% tenían antecedente familiar de trastorno por uso de alcohol. Durante los 30 días previos al inicio del tratamiento los pacientes bebían 12.5 UBE/día (RIQ: 7.1-20 UBE/día), el 72% fumaba tabaco y el 30% consumía cocaína. Conclusiones: Disponer de una cohorte abierta y multicéntrica de pacientes con trastorno por uso de alcohol será útil para analizar las consecuencias del abuso de alcohol, potenciar la investigación traslacional y añadir valor a la investigación clínica y básica del Programa Alcohol dentro de RTA/RETICS. Con una cohorte bien establecida y representativa se espera aumentar la cantidad y calidad científica en relación a las complicaciones del trastorno por uso de alcohol y sus consecuencias clínicas y sociales en España

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/ day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country

Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome.

AIMS: To characterize a series of contemporary patients with alcohol-related Wernicke's encephalopathy (WE) or Korsakoff's syndrome (KS) and to update the current prognosis of disease. METHODS: Retrospective and prospective study of patients diagnosed with an alcohol-related WE or KS between 2002 and 2011 in a tertiary hospital. Socio-demographic, alcohol use characteristics, signs and symptoms, co-morbidity and blood parameters were obtained at admission. Patients were followed up until 2013 and causes of death were ascertained through the review of charts. RESULTS: Sixty-one patients were included (51 with WE and 10 with KS). Among patients with WE, 78% were men and age at diagnosis was 57 years (interquartile range (IQR): 49-66). Twenty-three percent fulfilled the classic WE triad. Regarding Caine's criteria for WE, 70.6% presented with at least two out of four signs or symptoms. Median follow-up of patients with WE syndrome was 5.3 years (IQR: 2.6-8.8), the cumulated mortality was 45% and death rate of 7.4 × 100 person-years (95% confidence interval (CI): 4.8-10.9). Overall, 50% of patients would be expected to die within 8 years of WE episode and main causes of death included serious bacterial infections (44.5%) and cancer (33.3%). CONCLUSIONS: Survival of patients with an alcohol-related Wernicke-Korsakoff syndrome is poor; pursuing treatment of alcohol use disorder and early diagnosis of thiamine deficiency is a priority for improving clinical outcomes.

Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence.

BACKGROUND: The health burden of cannabis use in patients with other substance dependencies is not fully understood. OBJECTIVE: To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders. PARTICIPANTS: Patients with opiate, cocaine, or alcohol dependence admitted to detoxification from 2001 to 2010 at a teaching hospital in Badalona, Spain. MAIN MEASUREMENTS: Sociodemographic characteristics, drug use, medical comorbidities, and urine drug screens were obtained at admission. Deaths were ascertained through clinical records and a death registry. Mortality rates and Cox regression models were used to analyze the association between urinary cannabis and mortality. RESULTS: A total of 474 patients (20% women) were admitted with a median age of 38 years (interquartile range: 32-44 years). The main substances that motivated admissions were opiates (27%), cocaine (24%), and alcohol (49%). Positive urinary cannabis was detected in 168 patients (35%). Prevalence of cannabis use among patients with opiate, cocaine, or alcohol dependence was 46.5%, 42.9%, and 25.5%, respectively. At admission, 110 (23.7%) patients had human immunodeficiency virus infection and 217 (46.5%) had hepatitis C virus infection. Patients were studied for a median of 5.6 years (interquartile range: 2.6-7.7 years) (2454.7 person-years), and at the end of the study, 50 patients (10.5%) had died, yielding a mortality rate of 2.04 × 100 patient-years (95% confidence interval: 1.53-2.66). There was no association between cannabis detection and overall mortality in the adjusted regression models [hazard ratio (95% confidence interval): 1.12 (0.60-2.00), P = 0.73], but acquired immune deficiency syndrome-related deaths were more frequent in those positive for cannabis (26% vs 2%, P = 0.03). CONCLUSION: Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections.

Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

Hepatitis C associated to substance abuse: ever closer to a treatment without Interferon.

With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of the new HCV infections are associated with injection drug use. The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA) that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection. The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders.

La infección por el virus de la hepatitis C (VHC) es un problema de Salud Pública de primera magnitud; cada año ocurren entre 3 y 4 millones de nuevas infecciones y de hecho, la hepatitis crónica C es una de las principales causas de enfermedad hepática en el mundo. Usar drogas por vía parenteral está en el origen de dos de cada tres nuevas infecciones por VHC en el mundo occidental.El tratamiento de la hepatitis C va a cambiar en los próximos años. El cambio es debido a la aparición de los llamados Antivirales de Acción Directa (AAD), unos fármacos que actúan contra proteínas clave del ciclo vital del VHC y que serán más eficaces, mejor tolerados y se administrarán durante menos tiempo. En este sentido, la nueva guía de tratamiento de la OMS en 2014 ya incluye alguno de ellos en sus recomendaciones; los nuevos fármacos se utilizarán en combinación y probablemente se podrá prescindir del Interferón.Con la aparición de más y mejores antivirales contra el VHC es probable que debamos revisar el modelo asistencial vigente y orientarlo hacia uno más ágil e integrador, que trate al mayor número posible de pacientes, incluyendo a aquellos con abuso de sustancias.

Markers of inflammation and mortality in a cohort of patients with alcohol dependence.

Inflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence. This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models. We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV). We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38-50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120-265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8-6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11-2.52, P < 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels. A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41-7.26; P < 0.01) and 3.39 (95% CI: 1.86-6.43; P < 0.01), respectively. Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia was present at admission. More accurate markers of systemic inflammation are needed to serve as prognostic factors for poor outcomes in this subset of patients.

Hepatitis C asociada al abuso de sustancias: nunca tan cerca de un tratamiento sin Interferón / Hepatitis C associated with substance abuse: ever closer to a treatment without Interferon

La infección por el virus de la hepatitis C (VHC) es un problema de Salud Pública de primera magnitud; cada año ocurren entre 3 y 4 millones de nuevas infecciones y de hecho, la hepatitis crónica C es una de las principales causas de enfermedad hepática en el mundo. Usar drogas por vía parenteral está en el origen de dos de cada tres nuevas infecciones por VHC en el mundo occidental.El tratamiento de la hepatitis C va a cambiar en los próximos años. El cambio es debido a la aparición de los llamados Antivirales de Acción Directa (AAD), unos fármacos que actúan contra proteínas clave del ciclo vital del VHC y que serán más eficaces, mejor tolerados y se administrarán durante menos tiempo. En este sentido, la nueva guía de tratamiento de la OMS en 2014 ya incluye alguno de ellos en sus recomendaciones; los nuevos fármacos se utilizarán en combinación y probablemente se podrá prescindir del Interferón. Con la aparición de más y mejores antivirales contra el VHC es probable que debamos revisar el modelo asistencial vigente y orientarlo hacia uno más ágil e integrador, que trate al mayor número posible de pacientes, incluyendo a aquellos con abuso de sustancias

With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of the new HCV infections are associated with injection drug use. The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA) that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection.The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders

Sex-specific disease outcomes of HIV-positive and HIV-negative drug users admitted to an opioid substitution therapy program in Spain: a cohort study.

BACKGROUND: Opioid substitution therapy has improved the survival of heroin users with and without HIV infection. We aimed to analyze sex differences in mortality rates and predictors of death among those admitted to a methadone treatment program (MTP). METHODS: Longitudinal study of patients enrolled in a MTP from 1992 to 2010. Socio-demographic and drug use characteristics, and markers of viral infections were assessed at entry. Vital status was ascertained by clinical charts and the mortality register. Four calendar periods were defined according to the introduction of preventive and treatment interventions in Spain. Predictors of death were analyzed by Cox regression models. RESULTS: 1,678 patients (82.8% men) were included; age at first heroin use was 18.6 years (IQR: 16-23 years), and age at first entry into a MTP was 30.7 years (IQR: 26-36 years). A total of 441 (26.3%) deaths occurred during 15,124 person-years (p-y) of follow-up (median: 9.2 years, IQR: 4-13 years). HIV infection was the main predictor of death in men (HR = 3.5, 95% CI: 2.1-5.7) and women (HR = 3.2, 95% CI: 1.2-8.7 ) and main cause of death was HIV/AIDS. Overall mortality rate was 2.9 per 100 p-y (95% CI: 2.7-3.2 per 100 p-y) and death rates decreased over time: 7.4 per 100 p-y (95% CI: 6.3-8.8 per 100 p-y) for the 1992-1996 period to 1.9 per 100 p-y (95% CI: 1.6-2.4 per 100 p-y) for the 2007-2010 period. In women, a slightly increase in mortality was observed in recent periods specifically among HIV-positive women (3.7 per 100 p-y in period 2002-2006 and 4.5 per 100 p-y in 2007-2010). CONCLUSIONS: Significant reductions in mortality of patients in MTP are observed after nineteen years of observation. However, HIV infection shows a great impact on survival, particularly among HIV-infected women.

Temporal trends in the survival of drug and alcohol abusers according to the primary drug of admission to treatment in Spain.

BACKGROUND: Mortality of alcohol and drug abusers is much higher than the general population. We aimed to characterize the role of the primary substance of abuse on the survival of patients admitted to treatment and to analyze changes in mortality over time. METHODS: Longitudinal study analyzing demographic, drug use, and biological data of 5023 patients admitted to three hospital-based treatment units in Barcelona, Spain, between 1985 and 2006. Vital status and causes of death were ascertained from clinical charts and the mortality register. Piecewise regression models were used to analyze changes in mortality. RESULTS: The primary substances of dependence were heroin, cocaine, and alcohol in 3388 (67.5%), 945 (18.8%), and 690 patients (13.7%), respectively. The median follow-up after admission to treatment was 11.6 years (IQR: 6.6-16.1), 6.5 years (IQR: 3.9-10.6), and 4.8 years (IQR: 3.1-7.8) for the heroin-, cocaine-, and alcohol-dependent patients, respectively. For heroin-dependent patients, mortality rate decreased from 7.3×100person-years (p-y) in 1985 to 1.8×100p-y in 2008. For cocaine-dependent patients, mortality rate decreased from 10.7×100p-y in 1985 to <2.5×100p-y after 2004. The annual average decrease was 2% for alcohol-dependent patients, with the lowest mortality rate (3.3×100p-y) in 2008. CONCLUSIONS: Significant reductions in mortality of alcohol and drug dependent patients are observed in recent years in Spain. Preventive interventions, treatment of substance dependence and antiretroviral therapy may have contributed to improve survival in this population.

Características de los pacientes adictos a la heroína admitidos en un programa de tratamiento con metadona / Characteristics of heroin dependent patients admitted to a methadone treatment program

Fundamento y objetivo: La metadona es uno de los fármacos más utilizados en el tratamiento de la adicción a la heroína. El objetivo del estudio es analizar la experiencia de un programa de tratamiento de metadona desde su introducción en el área de Barcelona. Método: Estudio transversal en adictos a la heroína incluidos en tratamiento sustitutivo de metadona entre 1992 y 2010. Se analizan características sociodemográficas, de la drogadicción, prevalencia de infecciones por el virus de la inmunodeficiencia humana (VIH) y hepatitis B (VHB) y C (VHC), y comorbilidad psiquiátrica, según período de inclusión en el tratamiento. Resultados: Se incluyeron 1.678 pacientes (82,8% varones). En el período 1992-1996 fueron incluidos 608 pacientes (36,2%), 566 (33,7%) entre 1997-2001, 305 (18,2%) entre 2002-2006 y 199 (11,9%) en el último período. La edad a la entrada en tratamiento aumentó de forma significativa (28 años en el 1992-1996 frente a 37 años en el último período [p < 0,005]). El porcentaje de pacientes con historia de drogadicción intravenosa decreció significativamente (89,5% en el primer período frente a 56,4% en el último, p < 0,05). La prevalencia de infección por el VIH, VHC y VHB (positividad para anticuerpos anti-core del VHB [HBcAc+]) fue del 53,7, 73,6 y 61,3%, respectivamente. En el análisis por períodos se observa una significativa disminución de la prevalencia de VIH (66,2% en el primer período y 43,5% en el último, p < 0,05) y de VHC (82,8% en el primer período y 69,8% en el último, p < 0,05). Un 25% de los pacientes tenían trastorno psiquiátrico; se observó un significativo aumento de la prevalencia de trastorno según el período analizado (21% en el primer período y 32% en el último, p < 0,05). Conclusión: Los pacientes que inician un tratamiento sustitutivo de la heroína son cada vez de mayor edad y muestran mayor frecuencia de comorbilidad psiquiátrica. Sin embargo, se demuestra un marcado descenso de las infecciones por el VIH y las hepatitis (AU)

Background and objetive: Methadone is largely used as the primary opioid substitution therapy for the treatment of heroin addiction; the objective of the study was to describe the clinical characteristics of heroin abusers admitted into a methadone maintenance program (MMP) in metropolitan Barcelona. Method: Cross-sectional study in patients enrolled in MMP since its introduction in 1992 through December 2010. Socio-demographic data, drug use characteristics, prevalence of blood-borne infections (human immunodeficiency virus [HIV], and hepatitis B [HBV] and C [HCV]) and psychiatric co-morbidity were assessed at entry. Results: One thousand and six hundred seventy eight patients (82.8% male). A total of 608 (36.2%) patients were admitted during 1992-1996, 566 (33.7%) between 1997-2001, 305 (18.2%) between 2002-2006 and 199 (11.9%) in the last period. Age at admission to methadone increased significantly (28 years in period 1992-1996 vs. 37 years in the last period [P < .005]). The percentage of patients with a history of intravenous drug use decreased significantly (89.5% in first period vs. 56.4% in period 2007-2010 [P < .05]). Prevalence of HIV, HCV and HBV (HBcAb+) was 53.7, 73.6 and 61.3%, respectively. The prevalence of HIV decreased over time from 66.2% in first period to 43.5% in 2007-2010 (P < .05); the prevalence of HCV decreased significantly from 82.8% in 1992-1996 to 69.8% in last period (P < .05). Twenty five percent of patients had psychiatric co-morbidity at admission and the prevalence of psychiatric co-morbidity increased over time (21% in 1992-1996 and 32% in 2007-2010; P < .05). Conclusion: Age at first opioid substitution therapy is increasing over time, as well as the proportion of patients with psychiatric co-morbidity. There were significant reductions in blood-borne infections (AU)

[Characteristics of heroin dependent patients admitted to a methadone treatment program]. / Características de los pacientes adictos a la heroína admitidos en un programa de tratamiento con metadona.

BACKGROUND AND OBJETIVE: Methadone is largely used as the primary opioid substitution therapy for the treatment of heroin addiction; the objective of the study was to describe the clinical characteristics of heroin abusers admitted into a methadone maintenance program (MMP) in metropolitan Barcelona. METHOD: Cross-sectional study in patients enrolled in MMP since its introduction in 1992 through December 2010. Socio-demographic data, drug use characteristics, prevalence of blood-borne infections (human immunodeficiency virus [HIV], and hepatitis B [HBV] and C [HCV]) and psychiatric co-morbidity were assessed at entry. RESULTS: One thousand and six hundred seventy eight patients (82.8% male). A total of 608 (36.2%) patients were admitted during 1992-1996, 566 (33.7%) between 1997-2001, 305 (18.2%) between 2002-2006 and 199 (11.9%) in the last period. Age at admission to methadone increased significantly (28 years in period 1992-1996 vs. 37 years in the last period [P<.005]). The percentage of patients with a history of intravenous drug use decreased significantly (89.5% in first period vs. 56.4% in period 2007-2010 [P<.05]). Prevalence of HIV, HCV and HBV (HBcAb+) was 53.7, 73.6 and 61.3%, respectively. The prevalence of HIV decreased over time from 66.2% in first period to 43.5% in 2007-2010 (P<.05); the prevalence of HCV decreased significantly from 82.8% in 1992-1996 to 69.8% in last period (P<.05). Twenty five percent of patients had psychiatric co-morbidity at admission and the prevalence of psychiatric co-morbidity increased over time (21% in 1992-1996 and 32% in 2007-2010; P<.05). CONCLUSION: Age at first opioid substitution therapy is increasing over time, as well as the proportion of patients with psychiatric co-morbidity. There were significant reductions in blood-borne infections.

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.

Determination of 67Zn distribution in navy bean (Phaseolus vulgaris L.) after foliar application of 67Zn-lignosulfonates using isotope pattern deconvolution.

The improvement of Zn fertilizers requires new techniques to evaluate their efficacy. In this paper, the (67)Zn stable isotope was used as tracer of several Zn-lignosulfonate complexes to study the foliar-applied Zn uptake and distribution behavior in the plant, compared with ZnEDTA. Navy bean plants ( Phaseolus vulgaris L.) were grown hydroponically in a Zn-free nutrient solution, and six modified lignosulfonates and EDTA complexed with (67)Zn were used in foliar application in the young leaves as Zn sources. Zinc isotopes in roots, stems, and sprayed and unsprayed leaves were determined by ICP-MS, and signal interferences caused by the compounds of the digested vegetal samples were corrected. The mathematical procedure of isotope pattern deconvolution allowed the minimization of the uncertainty in the measured molar fractions of Zn from fertilizer or from natural sources. Significant differences in Zn use and distribution were observed among the fertilizers when the calculated concentrations of Zn from the fertilizer were compared, whereas they were unnoticeable attending to the total Zn in plant tissues, usually determined at the conventional studies. By foliar spray, higher Zn uptake and mobilization to leaves and stems were achieved with (67)ZnEDTA than with (67)Zn-LS complexes. The ultrafiltered LS and phenolated LS showed slightly better ability to provide Zn to the bean plants than the other LS. The foliar-applied Zn use and distribution in the plant were related with the stability of the Zn-lignosulfonates complexes. Those presenting the lower stability versus pH, but the highest complexing capacity, were slightly more suitable to supply foliar-applied Zn to navy beans.

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

Fundamento y objetivo: Analizar diferencias de género en alteraciones hepáticas, nutricionales y metabólicas asociadas al alcoholismo.Pacientes y método: Estudio transversal en pacientes ingresados para desintoxicación de alcohol entre 1999 y 2006 en dos hospitales del área de Barcelona. Durante el ingreso se evaluó la comorbilidad previa y se obtuvieron muestras de sangre para hemograma, bioquímica y serologías además de datos sociodemográficos, antropométricos y del consumo de alcohol y drogas. Resultados: 566 ingresos consecutivos en 480 pacientes (375 hombres). La edad al ingreso fue 43 años (Rango Intercuartil [RIQ]: 36,3-49,0). Globalmente, el 68,4% presentaba macrocitosis (VCM>95 fl.), 81,7% GGT>40U/L y 57,7% AST > 37U/L. En las alteraciones hepáticas, la frecuencia de fosfatasa alcalina>120 U/L fue significativamente superior en mujeres que en hombres (18,5 vs. 10,5%, p=0,037). Sin embargo, los hombres mostraban más frecuencia de hiperferritinemia (>90ng/mL) que las mujeres (85,7 vs. 62,2%) (p=0,000). La probabilidad de presentar dos o más alteraciones hepáticas fue significativamente mayor en los hombres (OR: 1,64, IC 95%: 1,01-2,65) (p=0,043). En las alteraciones nutricionales, las mujeres presentaron mayor frecuencia de macrocitosis (77,5 vs. 65,8%, p=0,026), de creatinina sérica baja (<0,7mg/100mL) (28,2 vs. 14,6%, p=0,001) y ferritina sérica baja (<30ng/mL) (10,8 vs. 3,9%, p=0,020), así como mayor probabilidad de tener múltiples alteraciones nutricionales (OR: 1,59, IC 95%: 1,02-2,48) (p=0,040). Por otro lado, los hombres presentaron mayor frecuencia de anemia (32,3 vs. 21,4%, p=0,032). La obesidad tipo I (IMC>30 kg/m2 fue significativamente más frecuente en mujeres (29,2%) que en hombres (7,9%) (p=0,007) alcohólicos. Conclusiones: Las mujeres con dependencia alcohólica muestran elevada comorbilidad médica que las expone a desarrollar complicaciones orgánicas graves (AU)

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 43years (IQR: 36.3-49.0years). 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 (< 0.7mg/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>30kg/m2) 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 (AU)

[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.

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.