A comparison between phase-III trials and a phase-IV study of nalmefene in alcohol use disorder patients. Is there a difference? / Una comparación entre los estudios de fase 3 y un estudio de fase 4 de nalmefeno en el trastorno por uso de alcohol. ¿Existen diferencias?

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.

En muchas disciplinas médicas existen diferencias significativas entre las muestras procedentes de estudios experimentales y las muestras procedentes de ámbitos clínicos, como es por ejemplo el caso de la hipertensión. El objetivo del presente estudio fue comparar las muestras procedentes de los ensayos pivotales de fase 3 de nalmefeno con la muestra de un estudio de fase 4 realizado recientemente. Las características basales de las muestras se compararon mediante técnicas univariantes. Se encontraron diferencias significativas entre el porcentaje de los participantes consumidores de alcohol de bajo riesgo. También se encontraron diferencias en los patrones de prescripción y en la toma de nalmefeno, así como en el porcentaje de comorbilidades psiquiátricas y adictivas, que fueron muy superiores en el estudio de fase 4. En su conjunto, estos datos sugieren que en el campo del trastorno por uso de alcohol (TUA) existen también diferencias relevantes entre muestras procedentes de estudios experimentales y muestras procedentes de estudios clínico-observacionales. Este hecho refuerza la necesidad de que los estudios de fase 3 sean complementados con estudios observacionales de fase 4.

Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Most studies have focused on short-term prognosis, whereas factors associated with long-term survival are largely unknown. The aims of our study were to (1) determine the impact of complete abstinence from alcohol on long-term survival and (2) identify prognostic factors at admission capable of predicting abstinence during long-term follow-up in patients with AH. One hundred forty-two patients with biopsy-proven AH that survived the first episode were included. Demographic, psychiatric, and biochemical variables at admission and drinking status during follow-up were obtained. Cox regression, logistic regression, and classification and regression trees (CART) analyses were used for statistical analysis. Overall mortality was 38% with a median follow-up of 55 months. During follow-up, complete abstinence was reported in 39% and was associated with better long-term survival (hazard ratio, 0.53; P = 0.03). After adjustment for baseline prognostic scoring systems (Model for End-Stage Liver Disease and age, bilirubin, international normalized ratio, creatinine scores), complete abstinence was independently associated with survival (P < 0.05). Age and lack of past alcoholism treatments were independently associated with complete abstinence (P < 0.001 and P = 0.02, respectively) during follow-up. CART analysis generated a simple and practical algorithm based on the combination of past alcoholism treatments and age. Using CART analysis, we stratified 2 subgroups of patients with high (65%) and low (26%-29%) rates of complete abstinence after an episode of AH. CONCLUSION: Complete abstinence after an episode of AH positively impacts long-term survival. The combination of 2 variables easily obtained at admission might be useful to predict long-term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are necessary. (Hepatology 2017;66:1842-1853).

Remediation therapy in patients with alcohol use disorders and neurocognitive disorders: A Pilot Study. / Terapia de rehabilitación cognitiva en pacientes con trastorno por consumo de alcohol y trastorno neurocognitivo. Estudio piloto.

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.

El deterioro cognitivo es común en los pacientes alcohólicos. Éste se manifiesta por alteraciones en la memoria anterógrada y retrógrada, el procesamiento visual-espacial, y en las habilidades cognitivas y la atención, siendo algunas reversibles. Las terapias de rehabilitación cognitiva podrían mejorar el rendimiento de los pacientes, siendo una alternativa terapéutica de interés. El objetivo de este estudio piloto fue evaluar la implementación, viabilidad y efectividad de la terapia de rehabilitación cognitiva en pacientes con dependencia al alcohol y deterioro cognitivo asociado. Se trata de un estudio piloto con 16 pacientes (63% hombres, edad media de 59 años) seguidos en la Unidad de Conductas Adictivas de un hospital de tercer nivel. Siendo la abstinencia un requisito para la inclusión, durante 6 meses una enfermera realizó sesiones semanales de una hora (24 sesiones), realizándose ejercicios de psico-estimulación para la mejora del rendimiento cognitivo, funcional y social. Se evaluó a los pacientes al inicio, al final y pasados 6 meses, mediante las escalas MMSE (test Mini-mental de Lobo) y T@M (test de Alteración de Memoria). Sus puntuaciones medias respectivas fueron 26.4 (DE 3,16), 29 (DE 1,67) y 27 (DE 3,1) para MMSE y 38,7 (DE 6,81), 45,7 (DE 5,6) y 41,1 (DE 7,86) para T@M. Los datos se analizaron mediante la prueba de Friedman y se comparon los distintos periodos temporales mediante la prueba de rangos con signo de Wilcoxon, siendo la mayoría de comparaciones significativas (p < 0,05). La asistencia y la satisfacción fueron elevadas. Así pues, la terapia fue viable, ampliamente aceptada y mostró ser efectiva.

One Year Clinical Correlates of EtG Positive Urine Screening in Alcohol-Dependent Patients: A Survival Analysis.

AIMS: Little evidence exists supporting the efficacy of regular alcohol urine screening (RAUS) in the management of alcohol dependence, despite recent improvements in urine biomarkers. In this study, we aimed at investigating 1 year, differential clinical correlates between a positive and a negative baseline urine ethyl glucuronide (EtG) screening. METHODS: Alcohol-dependent outpatients participating in a previous cross-sectional study where EtG and ethanol diagnostic performances were compared in a double blind design were included. After 1 year, the presence of relapse, the number of hospitalizations and whether patients had abandoned treatment or not were assessed from electronic medical records. A survival analysis was conducted to compare time to relapse between EtG negative and positive subjects. 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. RESULTS: Of note, 152 patients (mean age 52, 67% males) were included. The mean time to relapse was of 163 days in EtG positive subjects, compared to 329 days in those with a negative result. In the Cox-regression model, only EtG positivity yielded significant results, with a hazard ratio of 5:3 (95% CI: 3.1-9.1). EtG positive was also the only significant predictor of a greater number of hospitalization days and treatment expenses. Younger age was the only variable predicting a greater risk of treatment abandonment. CONCLUSION: RAUS with sensible biomarkers could improve clinicians' ability to assess patients' relapse risk. Further prospective studies will have to determine if this can be translated into a better prevention capacity. SHORT SUMMARY: Positive urine screenings, when conducted with highly sensible alcohol biomarkers, significantly indicate a greater risk of relapse in alcohol-dependent patients and have the capacity to predict a greater risk of hospitalization and greater treatment expenses.

Self-management and Shared Decision-Making in Alcohol Dependence via a Mobile App: a Pilot Study.

PURPOSE: Mobile applications (apps) have created new opportunities in the field of alcohol dependence (AD) within new paradigms of shared decision-making and self-management. The aim of this study is to report the results of a pilot study testing the usability of and satisfaction with a mobile app (called SIDEAL) in AD patients. METHODS: Adult AD outpatients were included. SIDEAL was installed on patients' personal phones. The Timeline Followback (TLFB) method for the preceding 6 weeks was administered both at baseline and after 6 weeks (end of the study). Self-reports from the app were also assessed at the end of the study and compared to data provided by the TLFB. An online questionnaire about usability and satisfaction was administered to participants after completion of the study. Exploratory efficacy analyses were conducted. RESULTS: Twenty-four patients were included (mean age 48 years (SD 11.3), women 50%). Most patients (22/24) selected a goal to reduce their consumption. Patients used the self-register module of the app for an average of 80% of the study days. The consumption and medication self-register modules were the most valued, as along with the weekly feedback provided by the app about participants' weekly rate of usage. Participants' satisfaction with the app was high. Significant reductions were observed in alcohol consumption (binge drinking days in the last 6 weeks declined from 25 (SD 18.6) to 5.8 (SD 8), p < 0.001; mean daily alcohol consumption in standard units declined from 6.5 (SD 4.3) to 1.9 (SD 1.8), p < 0.001). On most days (88%), patients achieved their self-imposed objectives. CONCLUSION: SIDEAL is a well-accepted and highly used app by AD patients that could improve their efficacy in managing their AD. Further larger, randomized studies are warranted.

Urine Ethyl Glucuronide Unraveling the Reality of Abstinence Monitoring in a Routine Outpatient Setting: A Cross-Sectional Comparison with Ethanol, Self Report and Clinical Judgment.

AIMS: To test the screening performance of urinary ethyl glucuronide (EtG) under routine clinical conditions in a sample of alcohol-dependent outpatients, comparing it against urinary ethanol, self reports and clinical judgment. METHODS: A cross-sectional study under routine conditions was conducted in February 2015, where 613 consecutive urinary samples, provided by 188 outpatients with alcohol use disorders, were analyzed for ethanol and EtG (cut-off level = 500 ng/ml). Clinical variables such as the presence of aversive medication, comorbidities and clinician judgment were also collected. The discrepancy between the number of alcohol and EtG positives was recorded. A logistic regression analysis including clinical variables was conducted to assess for predictors of EtG positivity. RESULTS: Urinary alcohol yielded 9 positives (1.5% of all urine samples) belonging to 8 patients. EtG yielded 136 positives (22% of all urine samples) belonging to 74 patients. Of these, 93.4% (127 of 136) were negative for alcohol. All urinary alcohol positives resulted in EtG positives. The clinician judged 48 samples from 26 patients as belonging to not abstinent patients and 550 samples from 178 patients as belonging to abstinent patients. She was unsure in 15 samples from 15 patients. When comparing it against EtG as the gold standard, the area under the curve was 0.592. Self reports were extremely unreliable in this study, with only 5 patients reporting drinking in a total of 6 urine samples. In the logistic regression model, only aversive medications (OR 2.1, 95% CI 1.3-3.3) and clinician judgment (OR 2, 95% CI 1.4-2.9) resulted in significant effects. CONCLUSIONS: EtG performed largely better than ethanol for urine screening in alcohol outpatients, detecting an extra 20.4% (125 out of 613) of positives. It means that for each alcohol-positive sample, there were 15 EtG-positive samples. Although better than ethanol, clinician judgment was also not performed efficiently. If routinely implemented in the screening of alcohol outpatients, EtG might bring relevant changes that merit further research.

[Detection and prevalence of alcohol use disorders in primary health care in Catalonia]. / Detección y prevalencia del trastorno por uso de alcohol en los centros de atención primaria de Cataluña.

AIM: To describe the detection by general practitioners (GP) of alcohol use disorders (AUD) and alcohol dependence, and their prevalence in primary health settings. DESIGN: Cross-sectional study. SETTINGS: Twenty Catalan primary health care centres (Spain). PARTICIPANTS AND MEASUREMENTS: Twenty three randomly selected GP were surveyed about alcohol and other diseases of their patients. A total of 1,372 patient interviews were collected. Patients and GPs were asked about AUD and other mental and health conditions. The Composite International Diagnostic Interview (CIDI) as the gold standard was used, as well as other structured interviews (K10 screening and World Health Organization Disability Assessment Schedule 2.0). RESULTS: The CIDI diagnosed 9.6% of the total sample with an AUD, and 4.8% diagnosed by GPs. CIDI could detect more AUD in young adults, while GPs diagnosed more AUD and alcohol dependence in elderly people, who also had more health conditions. GPs recognised AUD in 28.8% of patients diagnosed with CIDI, but 42.4% of patients diagnosed by GPs were not detected with CIDI. Taking both into consideration, the gold standard and the GP clinical impression, 11.7% of patients had an AUD and 8.6% an AD. CONCLUSIONS: GP recognise AUD better in the elderly with worst health conditions than CIDI. AUD and alcohol dependence prevalence is high in primary health care centres.

Alcohol in Primary Care. Differential characteristics between alcohol-dependent patients who are receiving or not receiving treatment. / El Alcohol en Atención Primaria. Características diferenciales entre los pacientes dependientes del alcohol que han solicitado o no tratamiento.

primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD.

A pesar de la elevada morbi-mortalidad de la dependencia del alcohol (DA), pocos pacientes afectos reciben tratamiento. Sin embargo, muchos de ellos son visitados en atención primaria por otras razones. El objetivo del presente estudio es describir las características diferenciales de los pacientes dependientes del alcohol atendidos en Atención Primaria, distinguiendo también entre aquellos que realizan tratamiento o no, y los motivos por los que no lo solicitan.Se trata de un estudio transversal en el que los pacientes fueron entrevistados tanto por sus médicos de atención primaria (MAP) como por un investigador del estudio. Se recabaron datos sociodemográficos, diagnósticos y clínicos.De 1372 entrevistados, 118 (8,6%) fueron diagnosticados de DA. Éstos presentaron un nivel socioeconómico más bajo (48.3% vs 33.3%, odds ratio 2.02), más desempleo (32.2% vs 19.2 %, odds ratio 2.11), y mayores niveles de malestar psicológico y de incapacidad. Los que recibían tratamiento (16,9%), tenían más edad (44 vs 36 años), mayores tasas de desempleo (66% vs 25.5%, odds ratio 6.18) y mayor consumo diario de alcohol (61.5 vs 23.7 gramos), sugiriendo una mayor evolución de la enfermedad. La mayoría de variables clínicas analizadas mostraron una mayor comorbilidad en los pacientes afectos de dependencia del alcohol, y dentro de éstos, una mayor gravedad en los que recibían tratamiento respecto a los que no lo hacían. Las principales razones esgrimidas para no acudir a tratamiento fueron la vergüenza, el miedo a dejar de beber y las barreras para acceder al tratamiento. Estos datos sugieren pues la necesidad de implementar estrategias de detección y tratamiento precoces de la DA.

[Alcoholic patients hospitalized in a psychiatry unit: mortality at 14 years]. / Alcohólicos ingresados en una sala de psiquiatría: mortalidad a los 14 años.

INTRODUCTION: Alcoholic patients show a high mortality rate. We know about the increased mortality of outpatients following specialized treatment for alcohol abuse and inpatients with organic diseases related to alcohol, but it is not clear whether alcoholics with a comorbid psychiatric profile also die prematurely. OBJECTIVE: To investigate clinical characteristics, therapeutic evolution, survival, and factors that can better predict mortality. MATERIALS: 14-year longitudinal monitoring of 91 patients hospitalized in 1993 for detoxification in a psychiatric unit and who subsequently received outpatient treatment. RESULTS: Patients show a high prevalence of psychiatric disorders (40.6%) and multiple periods of previous treatment (78%). After 14 years the mortality rate was 34.1%. Deceased patients more often presented cognitive decline and were more often on pensions. They were also taking more antidepressants, had less family support and were more likely to have relapsed into alcohol use. DISCUSSION: Many of the factors that predict higher mortality are age-related. In younger patients, the presence of neuropsychological deterioration symptoms may indicate a premature organic disorder and probably greater risk of treatment failure, poor physical care and traumatic physical and mental situations, all of which would also increase the likelihood of premature mortality.

Attentional Bias, Alcohol Craving, and Anxiety Implications of the Virtual Reality Cue-Exposure Therapy in Severe Alcohol Use Disorder: A Case Report.

Aims: Attentional bias (AB), alcohol craving, and anxiety have important implications in the development and maintenance of alcohol use disorder (AUD). The current study aims to test the effectiveness of a Virtual Reality Cue-Exposure Therapy (VR-CET) to reduce levels of alcohol craving and anxiety and prompt changes in AB toward alcohol content. Method: A 49-year-old male participated in this study, diagnosed with severe AUD, who also used tobacco and illicit substances on an occasional basis and who made several failed attempts to cease substance misuse. The protocol consisted of six VR-CET booster sessions and two assessment sessions (pre- and post-VR-CET) over the course of 5 weeks. The VR-CET program consisted of booster therapy sessions based on virtual reality (VR) exposure to preferred alcohol-related cues and contexts. The initial and final assessment sessions were focused on exploring AB, alcohol craving, and anxiety using paper-and-pencil instruments and the eye-tracking (ET) and VR technologies at different time points. Results: Pre and post assessment sessions indicated falls on the scores of all instruments assessing alcohol craving, anxiety, and AB. Conclusions: This case report, part of a larger project, demonstrates the effectiveness of the VR-CET booster sessions in AUD. In the post-treatment measurements, a variety of instruments showed a change in the AB pattern and an improvement in craving and anxiety responses. As a result of the systematic desensitization, virtual exposure gradually reduced the responses to significant alcohol-related cues and contexts. The implications for AB, anxiety and craving are discussed.

Predictors of Changes in Alcohol Craving Levels during a Virtual Reality Cue Exposure Treatment among Patients with Alcohol Use Disorder.

BACKGROUND/OBJECTIVE: Determining the predictive variables associated with levels of alcohol craving can ease the identification of patients who can benefit from treatments. This study aimed to describe changes (improvement or no change/deterioration) in alcohol craving levels and explore the predictors of these changes from admission to discharge in outpatients with alcohol use disorder (AUD) undergoing treatment-as-usual (TAU), or treatment-as-usual supplemented with virtual reality cue-exposure therapy (TAU + VR-CET). METHOD: A prospective cohort study was conducted amongst 42 outpatients with AUD (n = 15 TAU + VR-CET and n = 27 TAU) from a clinical setting. Changes in the levels of alcohol craving between admission and discharge were assessed with the Multidimensional Alcohol Craving Scale. Sociodemographic characteristics (age, gender, education, and socioeconomic and civil status), cognitive-affective behavioral patterns (AUD severity, abstinence duration, psychiatric comorbidity, state anxiety, attentional bias, and substance use), and type of treatment (TAU + VR-CET and only TAU) were also evaluated. RESULTS: The TAU + VR-CET group showed greater changes of improvement in the levels of alcohol craving than the TAU group (χ2 = 10.996; p = 0.001). Intragroup changes in alcohol craving from pre to post-treatment were significant in the TAU + VR-CET group (χ2 = 13.818; p = 0.003) but not within the TAU group (χ2 = 2.349; p = 0.503). The odds of an improvement in any of the craving levels between pre- and post-test was 18.18 (1/0.055) times higher in the TAU + VR-CET group with respect to the TAU group. The use of illicit drugs in the month prior to the test increased the odds of having a positive change by 18.18 (1/0.055) with respect to not having consumed. CONCLUSIONS: Including VR-CET in TAU programs may provide benefits in the treatment of AUDs mainly among patients with intense alcohol craving and individuals having used illicit substances prior to treatment.

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.

Treatment retention in a specialized alcohol programme after an episode of alcoholic hepatitis: Impact on alcohol relapse.

AIMS: Alcoholic hepatitis (AH) is a life-threatening complication of alcohol use disorder (AUD). Alcohol abstinence is the main predictor of the long-term prognosis of AH. It is unknown whether AUD treatment retention (TR) after an AH episode impacts alcohol relapse and mortality or what baseline factors influence TR. METHODS: Design: case-control study; Study population: hospitalized patients (1999-2012) with an episode of biopsy-proven AH were included (n = 120); Assessment: demographic and clinical data, the High-Risk Alcoholism Relapse (HRAR) scale, mortality and alcohol relapse were assessed through clinical records and telephone or personal interviews; Follow-up period: short-term and long-term TRs were assessed at 12 and 24 months, respectively. RESULTS: The overall short-term and long-term TRs were 37% and 27.8%, respectively. The severity of liver disease at baseline predicted both short-term and long-term TR (OR 3.7 and 3.3, respectively), whereas HRAR >3 and a history of psychiatric disorders predicted long-term TR (OR 2.9 and 2.6, respectively). Moreover, HRAR >3 (OR 3.0) and previous treatment for AUD (OR 2.9) increased the risk of relapse in the short term. Importantly, receiving alcohol therapy in a centre different from the hospital where the patient was admitted was associated with increased risk of alcohol relapse over the long term (OR 5.4). CONCLUSION: Experiencing an alcohol-related life-threatening complication is insufficient motivation to seek treatment for AUD. AUD treatment after an episode of AH is suboptimal, with a low TR rate, high risk of alcohol relapse and poor impact of treatment on alcohol relapse.

Cue-Elicited Anxiety and Alcohol Craving as Indicators of the Validity of ALCO-VR Software: A Virtual Reality Study.

BACKGROUND: This study is part of a larger project aiming to develop a virtual reality (VR) software to be implemented as a clinical tool for patients diagnosed with alcohol use disorder (AUD). The study is based on previous research in which we identified factors that elicit craving for alcohol in a sample of AUD patients, and which led to the development of a virtual reality software to be used in cue exposure treatments of alcohol use disorder (ALCO-VR). The main objective of this study was to test the effectiveness of ALCO-VR to elicit cue-induced craving and anxiety responses among social drinkers (SD) and AUD patients. Our secondary objective was to explore which responses (cue-induced craving or anxiety) can best differentiate between AUD patients and the SD group. METHOD: Twenty-seven individuals (13 AUD patients and 14 SD) participated in this study after giving written informed consent. Their anxiety and alcohol craving levels were measured by different instruments at different stages of the procedure. The VR equipment consisted of Oculus Rift technology, and the software consisted of the ALCO-VR platform. RESULTS: Our data indicate that the ALCO-VR software can elicit responses of anxiety and alcohol craving, especially in the group of AUD patients. The cue-induced anxiety response differentiated AUD patients and the SD group better than the cue-induced craving response. CONCLUSIONS: The general interest in applying new technologies to the assessment and treatment of mental health disorders has led to the development of immersive real-life simulations based on the advantages of VR technology. Our study concluded that the ALCO-VR software can elicit anxiety and craving responses and that cue-induced anxiety responses can distinguish between AUD and SD groups better than cue-induced craving. The data on craving and anxiety were assessed consistently by different instruments. In addition, we consider that ALCO-VR is able to ecologically assess cue-induced anxiety and alcohol craving levels during exposure to VR alcohol-related environments.

Identifying Triggers of Alcohol Craving to Develop Effective Virtual Environments for Cue Exposure Therapy.

Background: Many studies have indicated that alcohol craving is a core mechanism in the acquisition, maintenance, and precipitation of relapse in alcohol use disorder (AUD). A common treatment approach in AUD is cue exposure therapy (CET). New technologies like virtual reality (VR) have the potential to enhance the effectiveness of CET by creating realistic scenarios in naturalistic environments. In this study, we aimed to determine relevant triggers of alcohol craving in patients with AUD. Methods: We enrolled 75 outpatients diagnosed with AUD according to the DSM-5 criteria Participants completed the Alcohol Use Disorder Identification Test and a self-administered questionnaire to assess alcohol craving. The variables included in the craving questionnaire were as follows: presence of others, situations, time of the day, day of the week, mood, and type of alcoholic beverage. Results: Greater levels of alcohol craving were seen in many situations, including being at a party, in a restaurant, in a bar or pub, and at home. Drinking alone and drinking with two or more friends were equally associated with higher levels of craving. Drinking at night and drinking at weekends also emerged as triggers for alcohol craving. Emotional states like anxiety or tension, sadness, stress, frustration, or irritability were highly associated with urges to drink alcohol. The alcoholic drinks most highly associated with increased levels of craving were beer, wine, and whisky. Gender and age implications were discussed. Conclusion: This study is part of a larger project aiming to develop and validate CET based on VR technology for patients with AUD who are resistant to classical treatment. The identified triggers have been used to develop relevant VR environments for CET, and further research is ongoing to implement our findings.

Psychiatric Comorbidity in Treatment-Seeking Alcohol Dependence Patients With and Without ADHD.

Objective: To estimate the prevalence of ADHD in adult patients treated for alcohol dependence and to analyze the characteristics of consumption and psychiatric comorbidity, in function of a possible ADHD in adulthood. Method: We administered the Adult ADHD Self-Report Scale (ASRS) to 726 alcohol-dependent patients. Clinical diagnosis, following Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria was made in the first four weeks of treatment. A subsample of 297 patients was evaluated using Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID-II) to test the psychometric properties of ASRS. Results: After analyzing the properties of the ASRS (sensitivity: 83.3%; specificity: 66.1%), the prevalence of ADHD, in the whole sample, was estimated to be 16.2%. Being younger, lifetime history of cocaine dependence and the presence of an affective, anxiety or personality disorder were associated with a possible ADHD. Conclusion: The estimated prevalence of ADHD in patients being treated for alcohol dependence is high, and the presence of a possible ADHD in adulthood is associated with an increase in psychiatric comorbidity.

Who Receives Nalmefene and How Does It Work in the Real World? A Single-Arm, Phase IV Study of Nalmefene in Alcohol Dependent Outpatients: Baseline and 1-Month Results.

BACKGROUND: Alcohol dependence remains a major health problem from both a public health and clinical perspective. Harm reduction strategies have been increasingly recognized as suitable treatment goals. Nalmefene has been recently approved for this precise therapeutic indication after completion of phase III trials. 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 nalmefene for the first time. METHODS: An observational, multisite, single-arm, phase IV study was conducted among adult alcohol-dependent outpatients who received nalmefene for the first time. The study consisted of four visits: baseline, 4 weeks (referred to as 1 month hereafter), 6 and 12 months. At each visit, drinking variables were obtained from the Timeline Followback regarding the previous month. Satisfaction with medication was also assessed for both patients and professionals, with the Medication Satisfaction Questionnaire. A repeated measures mixed model was performed for effectiveness analysis regarding drinking outcomes (reduction in total alcohol consumption and number of heavy drinking days). Regression analyses were performed in order to find predictors of response to nalmefene. RESULTS: A total of 110 patients were included, with 88 reporting data at the 1-month visit. On average, patients took nalmefene 68% of the days. The number of heavy drinking days decreased from 13.5 to 6.8 days/month, and total alcohol consumption decreased from 169 to 79 units. For both outcomes, significant reductions at 1 month were found, with no other significant variables reaching significance. Thirty-seven patients were considered medication responders, but given the high presence of low-risk drinkers in our sample, no significant predictors could be found. 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 nalmefene is an effective, well-tolerated treatment for alcohol dependence in real-world, clinical settings.

Filling the gap between lab and clinical impact: An open randomized diagnostic trial comparing urinary ethylglucuronide and ethanol in alcohol dependent outpatients.

BACKGROUND: Efforts aimed at reducing alcohol-related harm include early detection of risky drinkers as well as detection of early relapse in patients with alcohol dependence. Ethyl glucuronide (EtG) has been proven to be a reliable biomarker for the detection of recent drinking; however, no randomized, diagnostic trial to date has tested its impact on drinking outcomes. The aim of this study was to assess, in a randomized design, the implications of EtG screening on alcohol outcomes, compared to screening with a low sensitivity biomarker such as ethanol. METHODS: Alcohol dependent outpatients were randomized to either 24 weeks of continuous screening with EtG or ethanol. Patients were aware of screening methods and results. After 24 weeks, all participants were screened with EtG. Self-reports were also gathered. A logistic regression compared the rate of EtG positive results at study end between groups. Generalized estimating equations evaluated the descending monthly rate of EtG positive patients in the EtG group. RESULTS: A total of 162 patients were randomized. During the study period, the ethanol group showed less patients with positive screens (19/64 (29.7%) vs 58/98 (59%)). After 24 weeks, the EtG group showed a greater number of patients having a negative screening test compared to ethanol subjects when they were all screened with EtG (5/62 (8.1%) vs 13/39 (33.3%)). A significant decrease in the rate of EtG positive patients was found for the first three months of the study. CONCLUSIONS: Routine screening with EtG seems to reduce drinking and improve abstinence rates in alcohol dependent outpatients.

Effectiveness of a Specialized Brief Intervention for At-risk Drinkers in an Emergency Department: Short-term Results of a Randomized Controlled Trial.

BACKGROUND: Screening, Brief Intervention, and Referral to Treatment (SBIRT) programs have been developed, evaluated, and shown to be effective, particularly in primary care and general practice. Nevertheless, effectiveness of SBIRT in emergency departments (EDs) has not been clearly established. OBJECTIVE: We aimed to evaluate the feasibility and efficacy of an SBIRT program conducted by highly specialized professionals in the ED of a tertiary hospital. METHODS: We conducted a randomized controlled trial to study the feasibility and efficacy of an SBIRT program conducted by alcohol specialists for at-risk drinkers presenting to the ED, measured with the three-item version of the Alcohol Use Disorder Identification Test (AUDIT-C). Patients were randomized to two groups, with the control group receiving two leaflets-one regarding alcohol use and the other giving information about the study protocol. The intervention group received the same leaflets as well as a brief motivational intervention on alcohol use and, where appropriate, a referral to specialized treatment. The primary outcomes were the proportion of at-risk alcohol use measured by AUDIT-C scale and the proportion of patients attending specialized treatment at 1.5 months. RESULTS: Of 3,027 patients presenting to the ED, 2,044 (67%) were potentially eligible to participate, 247 (12%) screened positive for at-risk drinking, and 200 agreed to participate. Seventy-two percent of the participating sample were men, and the mean (±SD) age was 43 (±16.7) years. Follow-up rates were 76.5%. At 1.5 months, the intervention group showed greater reductions in alcohol consumption and fewer patients continuing with at-risk alcohol use (27.8% vs. 48.1%; p = 0.01). The SBIRT program also increased the probability of attending specialized treatment, compared to the control condition (23% vs. 9.8%, p = 0.0119) CONCLUSION: The SBIRT program in the ED was found to be feasible and effective in identifying at-risk drinkers, reducing at-risk alcohol use, and increasing treatment for alcohol problems.