Ethylglucuronide replacing ethanol in the routine screening of alcohol dependent outpatients: clinical implications

[eng] BACKGROUND: The development of an alcohol biomarker is a long process where different stages take place over time. From discovery to full clinical use and implementation, each accomplished stage increases the confidence in and the relevance of such biomarkers. In recent years, new biomarkers have been discovered, with outstanding improvements in the sensibility and specificity for the detection of recent drinking. However, the clinical, therapeutic and economical consequences of such biochemical improvements remain to be determined. With the present thesis we expect to investigate the clinical implications of such new biomarkers, with a special focus on urine ethyl glucuronide (EtG), in order to fully establish its contribution to the field of alcohol use disorders. It comprises three articles: the first (Study 1) compares the screening performance of ethyl glucuronide versus ethanol, clinical judgment and self report, under routine, real circumstances in alcohol dependent outpatients. The second one (Study 2) investigates the differential, one-year clinical evolution of patients screening positive and negative in Study 1, taking into account both clinical and economic consequences. Finally, Study 3 evaluates patients’ knowledge and attitudes towards regular alcohol urine screening. METHODS: Study 1 consisted of a cross-sectional comparison aiming at clinically validating EtG under real, routinely clinical conditions. For that purpose, 613 consecutive urinary samples, provided by 188 outpatients with alcohol dependence were analyzed for ethanol and EtG. Study 2 retrospectively assessed the clinical evolution of patients participating in Study 1. A survival analysis was conducted in order to compare the rate of relapse between EtG positive and negative patients. Regression models were performed to compare the mean number of days hospitalized between groups, the risk of being lost to follow-up and treatment expenses. In Study 3 a cross-sectional survey among alcohol dependent outpatients was conducted. In consonance with the principles of patient centered care, it aimed at investigating patients’ attitudes and beliefs towards regular alcohol urine screening. For attitudes’ assessment, we adapted the Drug Attitude Inventory (DAI-10) to the field of alcohol urine screening. Internal consistency, test-retest reliability and concurrent validity were evaluated for the adapted questionnaire. RESULTS: Study 1 showed an overriding superiority of EtG over ethanol, clinical judgment and self report, detecting a significant greater number of positive samples in routine, real circumstances. Study 2 revealed a clearly different clinical evolution between EtG positive and negative patients during the following 12 months, with EtG positive patients being at greater risk of relapse, hospitalization and incurring in more treatment expenses. Study 3 suggested that regular alcohol screening is highly valued by alcohol outpatients. It also showed that besides relapse prevention, other functions related to therapeutic alliance building, social desirability and impression management play a key role as well. CONCLUSIONS: Regular alcohol urine screening with ethyl glucuronide seems to have an impact on the clinical management of alcohol dependent outpatients, offering a better detection of recent drinking and the possibility of an improved relapse prevention strategy.[spa] INTRODUCCIÓN: El desarrollo de biomarcadores para el consumo de alcohol es un proceso largo y laborioso, donde múltiples etapas se suceden en el tiempo. Desde su descubrimiento en el laboratorio hasta su total implementación clínica, cada etapa superada incrementa la confianza y la relevancia de dicho marcador. En los últimos años se han descubierto marcadores que cuentan con una notable sensibilidad y especificidad en cuanto a la detección de consumo reciente se refiere. Sin embargo, las implicaciones clínicas, terapéuticas y económicas de dichos marcadores todavía no han sido esclarecidas con total claridad. Con la presente tesis se pretende investigar las implicaciones clínicas de dichos nuevos marcadores, específicamente del etilglucurónido (EtG), con el objetivo de determinar su verdadera aportación al campo de los trastornos por uso de alcohol. Esta tesis está compuesta de tres artículos. El primero (Estudio 1) compara el rendimiento en el cribado de consumo de alcohol del etilglucurónido frente al etanol, el juicio clínico y el autoinforme, bajo condiciones rutinarias y reales en pacientes dependientes del alcohol ambulatorios. El segundo artículo (Estudio 2) investiga la evolución clínica diferencial entre los pacientes que obtuvieron un resultado positivo y uno negativo en el Estudio 1, durante los siguientes 12 meses. Finalmente, el tercer artículo (Estudio 3) evalúa los conocimientos y la actitud que los pacientes presentan ante el cribado rutinario de alcohol. MÉTODOS: El Estudio 1 consistió en una comparación transversal cuya finalidad fue la de evaluar el uso de EtG bajo condiciones clínicas rutinarias de elevada validez externa. Para ello 613 muestras de orina consecutivas, proporcionadas por 188 pacientes ambulatorios con dependencia al alcohol, fueron analizadas para etanol y etilglucurónido. El Estudio 2 evaluó retrospectivamente la evolución clínica de los participantes del Estudio 1. Se llevó a cabo un análisis de supervivencia con el fin de comparar la tasa de recaída entre pacientes con un resultado positivo y negativo a etilglucurónido. Se realizaron análisis de regresión para comparar entre grupos el número medio de días hospitalizados, el riesgo de abandonar tratamiento y los costes medios del tratamiento. En el Estudio 3, en consonancia con los principios de la medicina centrada en el paciente, se realizó una encuesta a pacientes con dependencia del alcohol ambulatorios con la finalidad de evaluar sus actitudes, creencias y conocimientos en relación al cribado rutinario de alcohol en orina. Para la evaluación de sus actitudes se adaptó la escala Drug Attitude Inventory (DAI-10), analizándose su consistencia interna, su fiabilidad test-retest y su validez concurrente. RESULTADOS: El Estudio 1 mostró una clara superioridad del EtG sobre el etanol, el juicio clínico y el autoinforme, detectando un mayor número de positivos en condiciones reales de elevada validez externa. El Estudio 2 demostró una clara y diferente evolución clínica entre los pacientes que fueron EtG positivo y EtG negativo durante los siguientes 12 meses, presentando los pacientes EtG positivo un mayor riesgo de recaída, de hospitalización así como mayores costes de tratamiento. El Estudio 3 sugirió que el cribado rutinario de alcohol en orina es percibido por los pacientes dependientes al alcohol como un elemento valioso de su tratamiento. Se observó también que, además de cumplir una función de prevención de recaídas, otras funciones relacionadas con el vínculo terapéutico, la conveniencia social y la gestión de impresiones juegan también un papel clave. CONCLUSIONES: El cribado rutinario de alcohol mediante EtG parece tener un impacto en el manejo de los pacientes dependientes al alcohol ambulatorios, ofreciendo una mejor detección del consumo reciente de alcohol así como la posibilidad de una mejor prevención de recaídas

The more you take it, the better it works: six-month results of a nalmefene phase-IV trial

Background: Alcohol use disorders remain a major health problem. Reduced drinking has been increasingly recognized as a valuable alternative to abstinence. Nalmefene has shown in previous, experimental studies to be a useful tool to aid reduced drinking. However, more data from routine practice settings are needed in order to obtain evidence with high external validity. The aim of this study was to conduct a single-arm phase-IV study with alcohol-dependent outpatients starting with nalmefene for the first time. Here, we present the main effectiveness analysis, scheduled at six months. Methods: This was an observational, multisite, single-arm, phase-IV study conducted among adult alcohol-dependent outpatients who received nalmefene for the first time. The study consisted of four visits: Baseline, 1 month, 6 months, and 12 months. At each visit, drinking variables were obtained from the time-line follow-back regarding the previous month. Satisfaction with medication was also assessed from both patients and professionals with the Medication Satisfaction Questionnaire. A repeated measures mixed model was performed for effective analysis regarding drinking outcomes (reduction in total alcohol consumption and the number of heavy drinking days). Regression analyses were performed in order to find predictors of responses to nalmefene. Results: From a total of 110 patients included, 63 reported data at the six-month visit. On average, patients took nalmefene 69% of days during the month previous to the 6-month assessment. Compared to the one month results, the number of heavy drinking days and total alcohol consumption increased. Still, they were significantly lower than baseline values (outcome evolution over time was from 13.5 to 6.8 to 9.4 days/month, and from 169 to 79 to 116 units/month). A total of 23 patients were considered medication responders. The number of days of taking nalmefene was significantly associated in the regression analysis. Satisfaction was globally high for both professionals and patients and, overall, nalmefene was well-tolerated with no serious adverse events reported. Conclusion: The data provided by this phase-IV study suggest that nalmefene is an effective, well-tolerated treatment for alcohol-dependence in real world, clinical settings

A comparison between phase-III trials and a phase-IV study of nalmefene in alcohol use disorder patients. Is there a difference?

Concerns regarding the external validity of phase-III trials are common to many medical disciplines, with relevant discrepancies found between experimental and clinical samples in some diseases such as hypertension. The aim of this study was to compare the samples included in the pivotal, phase-III clinical trials of nalmefene with that of a recently conducted phase-IV trial. Baseline characteristics of the studies were compared through univariate analysis. Significant differences were found in the percentage of low-risk drinkers included. Differences were also found in the prescription and intake pattern of nalmefene, as well as in the rate of psychiatric and addictive comorbidities, which were much higher in the phase-IV study. These data suggest that in the field of alcohol use disorders there are also relevant differences between experimental and clinical samples, a fact that reinforces the need for phase-III trials to be balanced with observational, phase-IV trials

Remediation therapy in patients with alcohol use disorders and neurocognitive disorders: A Pilot Study.

Many alcohol-dependent patients suffer from cognitive impairment of variable severity, manifested by alterations in retrograde and anterograde memory, visuospatial processing, cognitive abilities and attention, some of which are reversible. In this context, cognitive remediation therapies could significantly improve patients' performance; therefore, these are considered a valuable alternative. The aim of this study was to implement cognitive remediation therapy in patients with alcohol dependence and cognitive impairment and evaluate its viability and effectiveness. The participants were sixteen abstinent, alcohol-dependent patients (mean age of 59 years, 63% males) from the Addictive Behaviours Unit of a tertiary hospital. Over 6 months, a nurse led 1-hour weekly sessions (24 sessions in total) during which exercises for improving functional, social and cognitive performance were completed. Patients were assessed at baseline, at the end of the study and 6 months later, using the Mini-Mental State Examination (MMSE) and the Memory Alteration Test (M@T). Their respective scores were 26.4 (SD 3.16), 29 (SD 1.67) and 27 (SD 3.1) for the MMSE and 38.7 (SD 6.81), 45.7 (SD 5.6) and 41.1 (SD 7.86) for the M@T. Changes were assessed with both Friedman and Wilcoxon signed-rank tests, with mostly statistically significant differences (p < 0.05). Assistance and satisfaction were high. Therefore, the therapy was viable, widely accepted and effective

Detección y registro del consumo de alcohol en urgencias

Fundamentos: El consumo excesivo de alcohol es uno de los factores de riesgo de morbimortalidad más im-portantes en nuestro entorno, por lo que en los últimos años se han desarrollado múltiples programas para la de-tección e intervención sobre los consumidores de riesgo en los centros de atención primaria y de Urgencias. El ob-jetivo de este estudio fue analizar la tasa de detección y registro del consumo excesivo de los pacientes atendidos en un servicio de Urgencias.Métodos: Se incluyeron todos los pacientes con un consumo de riesgo de alcohol, mayores de 18 años, aten-didos en un servicio de Urgencias del Hospital Clínic de Barcelona. Se realizó un análisis descriptivo de los datos, tras evaluar los informes de alta de los pacientes.Resultados: Se evaluaron 2.047 pacientes median-te la escala AUDIT, detectándose 247 consumidores de riesgo, de lo que 200 aceptaron participar. De estos, sola-mente se realizó una adecuada detección y registro en el 32,5%. En 122 historias clínicas no había ninguna refe-rencia sobre el consumo de alcohol, y en 13 la referencia era inexacta y no informaba sobre si la cantidad de alcohol consumida era excesiva.Conclusiones: El consumo de riesgo de alcohol se registra de manera adecuada en menos del 35% de los pa-cientes. Es necesario evaluar las barreras que están obsta-culizando la detección y registro para una mejor identifi-cación de estos pacientes

Remediation therapy in patients with alcohol use disorders and neurocognitive disorders: A Pilot Study.

Many alcohol-dependent patients suffer from cognitive impairment of variable severity, manifested by alterations in retrograde and anterograde memory, visuospatial processing, cognitive abilities and attention, some of which are reversible. In this context, cognitive remediation therapies could significantly improve patients' performance; therefore, these are considered a valuable alternative. The aim of this study was to implement cognitive remediation therapy in patients with alcohol dependence and cognitive impairment and evaluate its viability and effectiveness. The participants were sixteen abstinent, alcohol-dependent patients (mean age of 59 years, 63% males) from the Addictive Behaviours Unit of a tertiary hospital. Over 6 months, a nurse led 1-hour weekly sessions (24 sessions in total) during which exercises for improving functional, social and cognitive performance were completed. Patients were assessed at baseline, at the end of the study and 6 months later, using the Mini-Mental State Examination (MMSE) and the Memory Alteration Test (M@T). Their respective scores were 26.4 (SD 3.16), 29 (SD 1.67) and 27 (SD 3.1) for the MMSE and 38.7 (SD 6.81), 45.7 (SD 5.6) and 41.1 (SD 7.86) for the M@T. Changes were assessed with both Friedman and Wilcoxon signed-rank tests, with mostly statistically significant differences (p < 0.05). Assistance and satisfaction were high. Therefore, the therapy was viable, widely accepted and effective

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial

Background: up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: a pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: this trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial

Background: up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: a pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: this trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial

Background: up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: a pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: this trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial

Background: up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. Methods: a pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, β = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. Discussion: this trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System