Anna Lligoña

Prevalence and Mechanisms of Hyperhomocysteinemia in Chronic Alcoholics

BACKGROUND Homocysteine (Hcy) is formed as an intermediary in methionine metabolism. Impairment of Hcy remethylation or transulfuration leads to hyperhomocysteinemia, which is considered as a risk factor for atherosclerotic vascular disease and stroke in chronic alcoholics. The aim of the study was to investigate the prevalence of hyperhomocysteinemia in chronic alcoholics and the influence of alcohol consumption, vitamin deficiencies and liver damage on the plasma levels of Hcy. METHODS 228 chronic alcoholic patients consecutively admitted for detoxication, classified according to clinical and biochemical data in normal liver (n = 117), and in mild to moderate liver disease (n = 111), and 49 healthy controls were studied. Blood levels of Hcy, vitamin B6, vitamin B12 and folate were measured. RESULTS Plasma Hcy was significantly higher in chronic alcoholics than in controls (9.66 +/- 8.1 vs. 6.93 +/- 2.33 mumol/liter, p < 0.025). Furthermore, plasma Hcy levels were significantly higher in chronic alcoholics with liver injury (12.17 +/- 10.14 mumol/liter) than in those with normal liver and in controls (p < 0.001). The prevalence of hyperhomocysteinemia was also significantly higher in alcoholics with liver damage than in those with normal liver and in controls (29.7%, 5.1%, and 2%, respectively, p < 0.001). Serum folate values were lower in chronic alcoholics than in controls (4.7 +/- 2.6 vs. 7.6 +/- 2.4 nmol/liter, p < 0.001). The lowest values of folate were found in alcoholics with liver disease, especially in those with hyperhomocysteinemia, with a negative correlation between the two parameters. CONCLUSIONS Moderate hyperhomocysteinemia is common in chronic alcoholics, mainly in those with liver damage, suggesting that, although folate deficiencies may have a contributory role, liver impairment, through changes in methionine metabolism, is the most important mechanism for the elevated plasma Hcy found in these patients.

Treatment for alcohol dependence in Catalonia: health outcomes and stability of drinking patterns over 20 years in 850 patients.

AIMS The aim of this study was to evaluate long-term outcomes in alcohol-dependent patients following outpatient treatment and gender differences in drinking outcome and mortality. METHODS A 20-year longitudinal prospective study was done with interim analyses at 1, 5 and 10 years. Of the original sample of 850 patients, 767 (90%) were located 20 years later and 393 of these were interviewed. 273 (32%) patients died during the intervening period and 101 (12%) no longer wished to participate in the study. Drinking status was assigned based on the 12 months prior to the follow-up interview. RESULTS At the 20-year follow-up, 277 (32.6%) of the 393 patients for whom drinking status could be assigned were abstinent (defined never drinking or drinking on less than occasion per month and never more than four drinks/drinking occasion.), 29 (3.4%) were controlled drinkers and 87 (10.2%) were heavy drinkers. Controlled drinking was the least stable category, with 23% continuing from year 5 to year 10 in that category, and 10% continuing in that category from year 10 to year 20. Mortality was higher (39.1%) in those who had been categorized at year 5 as heavy drinkers compared to those who had been categorized as controlled drinkers or abstinent. Abstinent patients reported fewer alcohol-related problems and better psychosocial functioning than heavy drinkers. Women achieved higher abstinence rates (47.2% versus 29.0%, P = 0.005) and had lower mortality (22.4% versus 34.5%, P = 0.03) than men. CONCLUSIONS Over the long-term, abstinence is the most frequent and stable drinking outcome achieved and is associated with fewer problems and better psychosocial functioning. Controlled drinking is rarely achieved and sustained. Women appear to do better than men in the long term.

Adult ADHD screening in alcohol-dependent patients using the Wender-Utah Rating Scale and the adult ADHD Self-Report Scale.

Objective: The aim was to analyze the psychometric properties of two screening instruments, Wender-Utah Rating Scale (WURS) that evaluates childhood ADHD and Adult ADHD Self-Report Scales (ASRS) that assesses symptoms in adulthood, in alcohol-dependent patients. Method: A total of 355 outpatients were included. Conners’ adult ADHD diagnostic interview results were used as a gold standard in childhood and adulthood ADHD. Results: The WURS with a 41 cutoff had a sensitivity of 79.6% and a specificity of 60.3%. The ASRS with a 14 cutoff had a sensitivity of 86.7% and specificity of 66.1%. Analyzing both rating scales in combination, it was observed that patients with positive ASRS and WURS presented a sensitivity of 92.3%. Patients with positive ASRS, but negative WURS, presented a specificity of 73.6%. Conclusion: WURS and ASRS are useful tools in the diagnosis of adult ADHD in alcohol-dependent patients; with the use of both instruments, the psychometric properties are substantially improved.

Gender differences in the long-term outcome of alcohol dependence treatments: an analysis of twenty-year prospective follow up.

INTRODUCTION AND AIMS Women are underrepresented in long-term studies of alcohol dependence. While gender differences in drinking behaviour have been observed when starting treatment, very few studies have investigated gender differences in long-term drinking outcomes. This paper evaluates gender differences in the long-term outcome of patients treated for alcohol dependence. DESIGN AND METHODS A cohort of 850 outpatients (19% women, age 39 ± 9 years) treated for alcohol dependence in specialist centres of Catalonia (Spain) were followed up prospectively for 20 years. Covariance analysis was used to assess gender differences at 1, 5, 10 and 20 years in drinking behaviour, psychosocial stress and social functioning (Axes 4 and 5 of Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised). We evaluated gender differences in drinking trajectories using a multilevel model controlling for basal differences. RESULTS Women started treatment earlier in their drinking career, with more symptoms of dependence. In the first year they remained in treatment longer and had more clinic visits. Women presented lower alcohol consumption than men at baseline, 5 and 10 years, and similar levels of stress and psychosocial functioning. When basal alcohol consumption, length of treatment and employment were controlled, female gender predicted less drinking at year 1 and a drinking trajectory closer to abstinence between 1 and 20 years. DISCUSSION AND CONCLUSIONS Increased severity of alcohol dependence in women starting treatment was not associated with a worse prognosis. Women did better while under treatment and achieved a better long-term drinking outcome. Gender differences were not relevant concerning psychosocial stress and social functioning.

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.

Guía clínica de evaluación de pacientes con conductas adictivas para trasplante hepático

Liver transplantation is the only effective treatment for advanced cirrhosis. Nevertheless, the number of potential recipients far exceeds that of available donors. Therefore, liver transplant candidates must be carefully selected to optimize donor utilization. Candidate selection is complex in patients with addictive and/or psychopathological disorders. Alcohol consumption causes one-third of advanced liver disease in our environment and comorbid consumption of other addictive substances is frequent in these patients. The use or abuse of these substances in transplant recipients can be associated with graft loss. Despite the importance of this subject, there is no well established protocol in our environment for the evaluation and selection of candidates with addictive and/or psychopathological disorders. Therefore, a specific diagnostic and therapeutic strategy must be established for these patients. Hospital Clínic in Barcelona has an active liver transplantation program (90 transplantations in 2007). Since the start of this program in 1988, candidates with addictive and/or psychopathological disorders have been evaluated jointly by the Hepatology Service and Alcohol Unit, including psychiatrists, psychologists and social workers. We present the protocol approved by the Committee for Liver Transplantation and the Ethics Committee of Hospital Clínic in 2007 for the evaluation, selection and follow-up of transplant candidates with addictive and/or psychopathological disorders. This protocol includes a description of the evaluation process and defines the inclusion and exclusion criteria with respect to consumption of toxic substances, the social and family situation and psychiatric disorders. In addition, recommendations for the follow-up of these patients are provided.

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)

Alcohol Consumption and Inpatient Health Service Utilization in a Cohort of Patients With Alcohol Dependence After 20 Years of Follow-up

Aims To examine the association between drinking levels and inpatient health service utilization in people with a lifetime diagnosis of alcohol dependence. Methods A longitudinal prospective study was conducted in a cohort of patients with alcohol dependence who had undergone treatment in 1987. Current results refer to the association between drinking patterns at 20-year follow-up and subsequent inpatient health service utilization. At 20 years after baseline, 530 of 850 patients were alive with administrative data available. Follow-up interview was conducted on 378 patients. There were 88 refusals and 64 could not be traced. Three categories of alcohol consumption were established (abstainers, moderate drinkers and heavy drinkers) depending on the pattern of alcohol use during the last year prior to the evaluation. Health service utilization was based on official statistics, including admissions to general, rehabilitation and psychiatric hospitals. The time period analysed was 5 years after the assessment of drinking patterns. Results Admission rates were lowest for abstainers compared to people with moderate and heavy drinking. With respect to hospital days, heavy drinking was associated with significantly higher adjusted rates than both abstainers and moderate drinkers. Alcohol-related diagnoses in hospital admissions were more frequent for both moderate and heavy drinkers. Conclusion Abstinence and moderate alcohol consumption were both associated with lower hospitalization in people with a lifetime diagnosis of alcohol dependence. Thus, not only abstinence-oriented treatment strategies but also those to reduce alcohol intake would reduce inpatient hospitalizations. Short Summary Abstention and reduced drinking in lifetime alcohol-dependent patients were associated with lower health care utilization compared to heavy drinking. Alcohol treatment strategies for alcohol-dependent patients have a positive impact on the reduction in health care utilization. An increase in treatment rate for alcohol use disorders will consequently have marked population health improvements.

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.

Heavy prescription over time leading to opioid dependence

ABSTRACT Introduction: Opioid prescription (OP) is a widespread practice, which raises concerns for the risks involved. In the present study, we aimed to retrospectively evaluate risk factors for prescription opioid (PO) addiction in a sample of patients attended in a pain clinic in a big urban hospital. Methods: We conducted a case–control study to evaluate risk factors for OP addiction. We selected 20 patients referred to an addictions unit from the pain clinic for opioid use disorder and matched with 40 controls attending to the pain clinic who were not. Results: High dosage (OR = 1,023, P = 0,046) and long-lasting (OR = 1,023, P = 0,046) use of opioids are among the most important risk factors for a future referral to an addictions unit. Every 10 mg of equivalent dose of morphine escalation increases the probability for a future referral by 23%. Each month appears to increase the risk for a future referral to the addiction unit by 2.4%. Depressive and anxious symptomatology and concomitant benzodiazepine use showed a tendency, however nonsignificant. Conclusions: Although it may seem obvious, the greater and longer the use of opioids higher is the risk of opioid misuse. A multidisciplinary approach is needed to improve these patients’ prognosis.