Cluster-randomized controlled trial of dissemination strategies of an online quality improvement programme for alcohol-related disorders.

AIMS: This project investigated different dissemination strategies of an online quality improvement programme for alcohol-related disorders into routine care in South Baden and South Württemberg in Germany. METHODS: In a cluster-randomized controlled trial, 112 general practices were randomized into three groups. The first group (n = 43) received access to the online system and a training programme for the general practitioners (GPs). The second group (n = 42) additionally received education for the whole practice team. The third group (n = 27) acted as control and received only access to the online system. RESULTS: Two thousand six hundred and forty-seven practitioners were asked to take part in the study, and it was possible to randomize 112 (4%) practices. There were no significant differences concerning the use of the system between the groups: 41.9% of the GPs in the first group, 42.9% in the second group and 44.4% in the control group used the system. In terms of only the system users, 55.6% of the GPs in the first group, 33.3% in the second group and 8.3% in the control group used the system six times or more (P = 0.019). Diagnostic assessments made by the GPs in the groups differed substantially: 72.2% of diagnoses in the first group were correct, while this figure lay at 69.7% in the second group and 36.4% in the control group (P = 0.034). CONCLUSIONS: No effect of the additional training on the primary outcome (acceptance) was identified, but on two of the secondary outcomes. Further cost-effectiveness studies should investigate whether the effort involved in providing training additionally to the system is justifiable. The study is registered at ClinicalTrials.gov: NCT00314067. This article conforms to the guidelines in the Consolidated Standards of Reporting Trials (CONSORT) statement (Moher et al., 2001; Campbell et al., 2004).

[Diagnostic and treatment approaches to alcohol-related disorders]. / Diagnostik und Behandlung alkoholbezogener Störungen -- Ergebnisse einer Umfrage in hausärztlichen Praxen.

BACKGROUND: Due to their high prevalence alcohol related disorders (dependent, harmful and at risk drinking) are of major importance for the general practitioner (GP). The aim of this study was to examine the diagnostic and treatment strategies employed by the general practitioners. METHODS: A standardized 10-page questionnaire was mailed to a representative sample (n = 1232) of the general practitioners in south-west Germany. They were asked about diagnostic and therapeutic procedures they had employed in the last patient seen. Further questions regarded patient-related and structural problems. The response rate was 24.3 %. RESULTS: The reported patients had a mean age of 49 +/- 10.3 years. 70.6 % were of male sex. The mean duration of the last patient contact was 18.7 minutes. The diagnosis originated more in clinical impression than in use of screening instruments (0.7 % of patients) or formal diagnostic criteria. 76.7 % fulfilled ICD-10 criteria for dependent drinking, 65.0 % were judged dependent drinkers by the GP's. In most cases the patient had been referred to inpatient services. The main intervention (97.3 % of cases) was disease related counseling. 69.4 % were judged to be quite ill and severely ill. In most cases an inpatient referral had taken place. Pharmacotherapeutic measures were relatively rarely employed (11.3 %). As the major impediments of treatment patient related factors were stated (lack of acceptance of diagnosis, resistance to treatment). DISCUSSION: The majority of patients described by the GP's were dependent drinkers. This indicates that many at risk drinkers might perhaps not be correctly identified. Concerning therapeutic competency patient-related factors are considered as the major impediments for the delivery of effective care. This reflects a view of GP's that patients with alcohol problems are being difficult and time consuming. This should be carefully addressed by future GP-education programs.

Galantamine: a cholinergic patch in the treatment of alcoholism: a randomized, placebo-controlled trial.

OBJECTIVES: The involvement of the central cholinergic system in alcohol abuse behavior is well known. It is possible that the reinforcing effects of ethanol are partially mediated by nicotinic receptors, which modulate neurotransmitter release. It was demonstrated that the application of a cholinesterase inhibitor reduces alcohol consumption in alcohol-preferring rats. This suggests that galantamine (GAL), a cholinesterase inhibitor, could be effective when seeking to prolong abstinence in recently detoxified alcoholics. This study represents the first reported clinical trial of a cholinergic drug in alcohol-relapse prevention. PATIENTS AND METHODS: We investigated the efficacy and safety of GAL by conducting a 24-week randomized, placebo-controlled, multicentric clinical trial on 149 recently detoxified alcoholics. Survival analyses (Kaplan-Meier) were performed to reveal evidence of prolonged abstinence periods in patients who received GAL. RESULTS: Our findings did not support our hypothesis. GAL did not extend the time to first severe relapse. However, additional post hoc analyses suggest that relapsed patients treated with GAL consume less ethanol per drinking day than patients treated with placebo. CONCLUSIONS: GAL seems to be ineffective when used in relapse prevention of detoxified alcoholics. It is possible that alcohol needs to be "on board" for GAL to be beneficial. This could explain why our post hoc analysis showed that GAL possibly reduces the alcohol consumption of relapsers. If confirmed, GAL could play a role in the reduction of harmful alcohol use and at-risk consumption.

Neuroimaging of gender differences in alcohol dependence: are women more vulnerable?

BACKGROUND: Alcoholic brain damage has been demonstrated in numerous studies using neuropathology and brain imaging techniques. However, gender differences were addressed only in a few studies. Recent research has shown that development, course, and consequences of alcohol dependence may differ between female and male patients. Our investigation was built upon earlier research where we hypothesized that women develop alcoholic brain damage more readily than men do. To further compare the impact of alcohol dependence between men and women, we examined brain atrophy in female and male alcoholics by means of computed tomography (CT). METHODS: The study group consisted of a total of 158 subjects (76 women: 42 patients, 34 healthy controls; 82 age-matched men: 34 patients, 48 healthy controls). All patients had a DSM-IV and ICD-10 diagnosis of alcohol dependence. CT with digital volumetry was performed twice in patients (at the beginning and end of the 6-week inpatient treatment program) and once in controls. RESULTS: Patients of both genders had consumed alcohol very heavily. Although the average alcohol consumption in the year before the study was significantly lower in female alcoholics, this gender difference disappeared when controlled for weight. However, women had a significantly shorter duration of alcohol dependence. Despite this fact, both genders developed brain atrophy to a comparable extent. Brain atrophy was reversible in part after 6 weeks of treatment; it did not reach the level in the control groups. CONCLUSIONS: Gender-specific differences in the onset of alcohol dependence were confirmed. This is in line with the telescoping effect, where a later onset and a more rapid development of dependence in women were described. Under the assumption of a gradual development of consequential organ damage, brain atrophy seems to develop faster in women. As shown in other organs (i.e., heart, muscle, liver), this may confirm a higher vulnerability to alcohol among women.

[Short- and medium-term outcome of outpatient treatment of alcohol dependent patients. A 6-, 18- and 36-month follow-up]. / Kurz- und mittelfristige Erfolgsraten ambulanter Entwöhnungsbehandlungen für alkoholabhängige Patienten. Eine 6-, 18- und 36-Monats-Katamnese.

The aim of this study was to investigate the short- and medium-term outcome of alcohol dependent patients in Germany after a one-year outpatient treatment. For this purpose, a 6-, 18- and 36-month follow-up of 97 socially well adapted alcohol dependent patients treated between 1992 and 1997 at three "psychosocial advice center" run by the Diakonie Württemberg, Germany, was carried out. Based on the time period between treatment and follow-up, all 97 patients could be followed up for 6 months, 71 for 18 months, and 33 for 36 months. 83% of patients could be interviewed at 6 months, 80% at 18 months, and 78% at 36 months. The statistical analyses were based on the "intention to treat" model. All patients treated between 1992 and 1997 were included. Patients for whom no information was available were classified as relapsers. 6 months after the outpatient treatment 59% of patients were abstinent, 4% had lapsed and 37% were relapsers. At the 18- and 36-month follow-ups 61% of patients had been abstinent in the 6 months before the interview. 53% and 39% of patients respectively were continuously abstinent over the entire follow-up period of 18 and 36 months. Prognostic criteria for a relapse were regular completion of treatment (p < 0.001) and no prior detoxification or abstinence oriented treatment (p < 0.01). Patients without a partner showed a tendency towards higher relapse rates (p < 0.10). The results of this study indicate that an outpatient treatment program can be as effective as inpatient or combined inpatient/outpatient treatments, at least for some patients with good social integration.

Neuroimaging in alcoholism: ethanol and brain damage.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The co-chairs were Karl Mann and Ingrid Agartz. The presentations were (1) Neuropathological changes in alcohol-related brain damage, by Clive Harper; (2) Regional brain volumes including the hippocampus and monoamine metabolites in alcohol dependence, by Ingrid Agartz, Susan Shoaf, Robert R, Rawlings, Reza Momenan, and Daniel W Hommer; (3) Diffusion tensor abnormalities in imaging of white matter alcoholism, by Adolf Pfefferbaum and Edith V. Sullivan; (4) Use of functional MRI to evaluate brain activity during alcohol cue exposure in alcoholics: Relationship to craving, by Raymond F. Anton, David J. Drobes, and Mark S. George; and (5) mu-Opiate receptor availability in alcoholism: First results from a positron emission tomography study, by Karl Mann, Roland Bares, Hans-Juergen Machulla, Goetz Mundle, Matthias Reimold, and Andreas Heinz.

Fetal alcohol syndrome: an international perspective.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Kenneth R. Warren and Faye J. Calhoun. The presentations were (1) Epidemiological research on fetal alcohol syndrome (FAS) in the United States, by Philip A. May; (2) An overview of fetal alcohol syndrome in the Western Cape Province of South Africa, by Denis L. Viljoen and Ting-Kai Li; (3) Diagnostic perspectives of fetal alcohol and tobacco syndromes, by Harumi Tanaka; (4) FAS among pupils of special boarding schools and orphanages in Moscow, Russia, by Galina S. Marinicheva and Luther K. Robinson; and (5) Research on FAS and FAE in Germany: Update and perspectives, by Goetz Mundle.

Appetitve effects of drug cues modelled by pictures of the intake ritual: generality of cue-modulated startle examined with inpatient alcoholics.

RATIONALE: A cue-modulated startle test recently confirmed that smoking cues in smokers may not be withdrawal-like and aversive as traditionally believed. OBJECTIVE: Analogous tests were applied to alcohol cues in inpatient alcoholics. METHODS: Twenty-six withdrawn alcoholics (18 men) were examined. Alcohol-related pictures were compared to standardised pleasant, neutral or unpleasant control scenes using an acoustic startle test and measures of pleasure, arousal and desire for alcohol. RESULTS: Pictures depicting preparation for drinking (cues) were different from unpleasant control pictures and similar to pleasant pictures but only on the startle test; no differential effects were found for alcohol craving and mixed motivational effects were reported subjectively. The effects were not due to arousal and control pictures depicting post-drinking events showed less effect than the alcohol cues. CONCLUSIONS: New techniques of measuring drug cue motivation indicate that drug cues may have incentive properties in individuals in treatment for alcoholism.

Sex differences of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume in alcohol-dependent patients.

BACKGROUND: Biological markers like carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) are used widely to screen for alcoholism. Most research has focused on male alcoholics, and there are few studies on female patients. The results are inconsistent; in general, they show lower sensitivities for all markers for women. METHODS: We compared the diagnostic value of CDT, GGT, and MCV in 126 alcohol-dependent patients (91 men, 35 women) who entered an inpatient treatment program. For the receiver operating characteristic (ROC) analyses, we investigated a control group of 112 patients (64 men, 38 women) from the Department of Psychiatry at the University of Tübingen with no diagnosis of substance abuse or substance dependency. RESULTS: Mean levels of CDT and MCV were significantly different in male and female patients. CDT showed higher test results in men (4.4% vs. 2.8%, p < 0.05), whereas mean levels of MCV were higher in women (99.7 fl vs. 96.4 fl,p < 0.01). The sensitivities of CDT and GGT were higher in men than in women (CDT: 76% vs. 54%,p < 0.1; GGT: 68% vs. 43%,p < 0.05), and the sensitivity of MCV was significantly higher in women (71% vs. 41%,p < 0.01). The superiority of MCV in women also was supported by ROC analyses (p < 0.01). The combined use of markers showed satisfactory sensitivity rates of > or = 80% not only in men but also in women. Yet, the specificity rates were partly below the recommended 90% for identifying alcohol abuse; therefore, these markers must be combined with caution. CONCLUSIONS: If combined, the biological markers CDT and GGT are useful diagnostic instruments for both alcohol-dependent men and women. According to our results, the "forgotten" marker MCV is superior in women and is a marker of second choice in men. The combination GGT and MCV is the most cost-effective choice for men and women.

Influence of age, alcohol consumption and abstinence on the sensitivity of carbohydrate-deficient transferrin, gamma-glutamyltransferase and mean corpuscular volume.

Duration of abstinence before blood test, alcohol consumption and age was examined in 177 male alcohol-dependent patients as factors influencing serum carbohydrate-deficient transferrin (CDT), serum gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV). The strongest influence on all markers was the factor 'duration of abstinence before blood test'. In patients who had been abstinent for >4 days before the blood test, the markers had low sensitivities (GGT, 33%; CDT, 14%; MCV, 42%), whereas in patients with < or = 4 days of abstinence the markers had reasonably good sensitivities (GGT, 72%; CDT, 56%; MCV, 48%). GGT was more sensitive than CDT (P < 0.05) and MCV (P < 0.001). The combined use of CDT and GGT had sensitivity of over 90%. Mean alcohol consumption in the 30 days prior to the blood test had a significant effect on CDT and GGT, but not on MCV. Age did not have a clear effect on CDT and GGT. For MCV, a significant and linear increase with age was shown. We conclude that GGT is the most sensitive of these three markers. Using GGT and CDT combined, sensitivity can be enhanced to over 90%. The period of abstinence before the blood test has a strong influence on CDT and GGT. If a longer period of abstinence is suspected, MCV should also be measured, in order to detect evidence of earlier heavy drinking.

Treatment outcome in alcoholism - a comparison of self-report and the biological markers carbohydrate-deficient transferrin and gamma-glutamyl transferase.

The primary source for evaluating treatment outcome in alcoholism is usually verbal self-report. Because the validity of self-report is often doubted, more objective markers for treatment outcome are needed. In this study, we compared self-report data from 238 male alcohol-dependent patients participating in a combined 6-week inpatient followed by a 1-year outpatient treatment program with the biological markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT). According to self-report, over 70% of the patients had a positive treatment outcome (57% abstinence, 16% intermediate relapse). These results are supported by the general reduction of CDT and GGT during the treatment period (p < 0. 001). When we performed a cross-sectional analysis at 6 months during the outpatient program, there was a high consistency of self-report data with the biological markers (CDT 93%, GGT 91%, CDT/GGT 85%). Our results support the hypothesis that in abstinence- oriented treatment programs, self-reports are valid and can be used as the basis of measurement for treatment outcome.

Biological markers as indicators for relapse in alcohol-dependent patients.

Although biological markers such as carbohydrate-deficient transferrin (CDT), γ-glutamyl transferase (GGT) and mean corpuscular volume (MCV) have been used as indicators for heavy alcohol consumption and alcoholism little information is available on the utitlity of these markers in detecting relapses. In this study the value of the biological markers CDT, GGT and MCV was examined in monitoring an outpatient treatment programme for alcohol-dependent patients. In 163 male alcoholic patients CDT, GGT and mean corpuscular volume (MCV) were assayed at the beginning and after 6 months during the outpatient programme. All markers distingushed between relapsers and abstainers (p<0.01). The sensitivity for relapses was 55% for CDT, 50% for GGT and 20% for MCV. Combining all markers the sensitivity could be enhanced to 85%, with only a little loss of specificity (85%). The highest positive predictive value was 73% for CDT used as a single marker. The negative predictive value (CDT 93%, GGT 92%, MCV 88%) and the diagnostic efficiency (CDT 91%, GGT 87%, MCV 85%) of all markers were very high. These results indicate that CDT is the most efficient marker for alcohol relapses, followed by GGT. MCV seems to be a marker of second choice.

Central pontine myelinolysis in a normonatraemic alcoholic patient.

Central pontine myelinolysis (CPM) is a rare disease which has been associated with hyponatraemia and its rapid correction. We describe a malnourished 32-year-old alcohol-dependent woman suffering from an infection who had developed CPM without any known prior derangement in serum electrolytes or its iatrogenic correction. Computerized tomography (CT) and magnetic resonance imaging (MRI) played an important role in the diagnosis. Even when an electrolyte derangement is absent, alcoholism, malnourishment and infection should be considered as important possible aetiological factors of CPM.

Aggressiveness, onset of dependence, and treatment outcome in socially well-adapted alcoholics.

Current typologies of alcoholism derive from the whole spectrum of afflicted persons. One type is characterized by variables such as early onset of dependence, violence, and aggressiveness. In previous research, this has been shown to be correlated with poorer prognosis. We tested this association in a fairly homogeneous subgroup of 258 socially rather well-adjusted male inpatients. Aggressiveness was assessed psychometrically. As a group, patients did not differ from general population norms. However, age was negatively correlated with aggressiveness. Even after taking patients' age and duration of dependence into account, aggressiveness was associated with an early onset of dependence and further aspects of drinking history, thus confirming results from previous typology research. Overall treatment outcome after 6 and 12 months was quite good, but was not influenced by aggression.

[Is the new guardianship law regarding alcoholic patients therapeutically useful? A case example]. / Ist das neue Betreuungsrecht bei Alkoholabhängigen therapeutisch nutzbar? Ein Fallbeispiel.

Although treatment outcome in alcoholism is good and well documented, many patients are not sufficiently motivated for participating in a treatment program. The following case-report illustrates the example of a young male alcoholic suffering from decompensated liver cirrhoses without motivation for a long-term treatment. The positive effects of the new guidelines of the laws regulating custody and civil commitment are shown and discussed.

[Changes in the self-concept of alcohol dependent women and men during inpatient psychotherapy]. / Veränderungen des Selbstbilds alkoholabhängiger Frauen und Männer während stationärer Psychotherapie.

At the beginning and at the end of a six week treatment programme, the self-concepts of 82 male and 31 female alcoholic inpatients were assessed. The Giessen test (a 40 item questionnaire comprising six scales oriented towards psychosocial aspects of personality) was applied. Compared to normative data from the general population, patients described themselves as being more depressed, less controlled, less socially responsive and more reserved. During inpatient treatment, patients approached the levels of the general population. With regard to control and depressiveness, however, there were still significant differences at the end of inpatients treatment. Changes on scales relating to interpersonal contact (social responsiveness, openess) are discussed as specific effects of group psychotherapy. Social potency showed a significant interaction effect, with women responding better to treatment than men.

Elevated norharman plasma levels in alcoholic patients and controls resulting from tobacco smoking.

Plasma norharman and harman levels were measured by solvent extraction and HPLC with fluorescence detection in alcohol-dependent patients undergoing in-patient abstinence treatment and in control subjects. In both groups, randomly collected samples from smokers contained higher mean norharman levels than those from non-smokers. In three volunteers norharman concentrations rose sharply after smoking of one or two cigarettes and declined to near-basal levels within one hour after one cigarette. When 12 patients kept a smoking-free interval of at least 6 h, they had similarly low plasma norharman concentrations (20 +/- 8 pg/ml) as 18 non-smoking control subjects (17 +/- 8 pg/ml) or as 13 smoking controls who had abstained from smoking (20 +/- 6 pg/ml). Ten of the patients smoked one cigarette and within 5-10 min attained norharman levels of 177 +/- 147 pg/ml plasma. The high prevalence of smokers among chronic alcoholics probably explains the previous finding of elevated norharman plasma levels in these patients.

Neuroimaging in alcoholism: CT and MRI results and clinical correlates.

For more than a century we have known the deleterious effects of alcohol on the brain regions surrounding the third ventricle and on the cerebellum. But it was only recently that we gained clearer evidence that the cortex is affected as well. Our imaging studies show that brain shrinkage is at least partially reversible once abstinence is maintained. They confirm results obtained in different laboratories from all over the world. Although our data contradict the rehydration hypothesis and thus lend credence to the idea of regeneration and neuroplasticity, the nature of reversibility is still a matter of debate.

The reversibility of alcoholic brain damage is not due to rehydration: a CT study.

Alcoholic brain damage is reversible when the patients are continually abstinent. An increase of brain water content was the putative explanation for this phenomenon. We tested the rehydration hypothesis using CT density measurements in 29 alcohol-dependent male inpatients. During a 5-week period of controlled abstinence, CT density measures did not decrease in any of the investigated regions of the brain as one would expect with an increase in brain water. Although the volumetry of the ventricular system and the subarachnoidal spaces revealed a significant reduction of CSF volume, we found a slight increase in CT density measures. Thus, our results are in contradiction to the rehydration hypothesis. Under discussion is whether neuronal plasticity might be the explanation of the reversibility of alcoholic brain damage in abstinent patients.