Validation of a new patient-reported outcome instrument of health-related quality of life specific to patients with alcohol use disorder: the Alcohol Quality of Life Scale (AQoLS).

PURPOSE: The Alcohol Quality of Life Scale (AQoLS) is a new patient-reported outcome 34-item questionnaire measuring health-related quality of life (HRQOL), specific to patients with an alcohol use disorder, developed from the patients' perspective. This is the first report establishing evidence in support of measurement reliability and validity of the AQoLS. METHODS: A total of 285 randomly selected patients receiving interventions for alcohol use disorder in addiction specialised care settings in France were included in the study (response rate 80.1 %). Exploratory factor analysis was conducted to evaluate the hypothesised-during-development-stage dimensional structure of the AQoLS. Internal consistency of the total score and the dimensions subscores were assessed through Cronbach's alpha coefficients. Construct validity was tested through correlations with the Short-Form 36 Health Survey (SF-36) and EuroQol 5 dimensions (EQ-5D). RESULTS: Exploratory analysis indicated seven observed dimensions which differed slightly from the 7 dimensions defined a priori in the framework hypothesised during the scale development: activities, relationships, living conditions, negative emotions, self-esteem, control and sleep. A major common factor allows the summing of the 34 items to obtain a total score. All the 34 items were acceptable. Cronbach's alpha for the AQoLS total score was 0.96 and ranged from 0.8 to 0.9 for the dimensions subscores. Negative correlations between AQoLS and all dimensions of the SF-36, but general health and positive correlations between AQoLS and all items of the EQ-5D were shown. As expected, the correlations were mostly moderate in magnitude, low with scores referring to physical areas and the highest with the SF-36 MSC. CONCLUSION: This study provides evidence of the measure's psychometric properties in terms of construct validity and internal consistency. The "control" and "self-esteem" dimensions are of particular interest as these concepts are not captured in existing HRQOL. Further longitudinal validation of the scale is necessary to assess sensitivity to change.

[Cognitive impairment induced by digoxin intake in patients older than 65 years]. / Troubles cognitifs chez les sujets de plus de 65 ans induits par la prise de digoxine.

Cognitive impairment or clinical signs of dementia in an old patient who receives digoxin, should suggest a digitalis intoxication. Symptoms can be present although a normal digoxin serum concentration. It is recommended to stop the treatment to obtain a regression of dementia symptoms.

[Neurosyphilis: a rare cause of dementia]. / La neurosyphilis: une cause rare de démence.

INTRODUCTION: Neurosyphilis had to be evoked in the face of an atypical dementia. CASE RECORD: We describe the case of a 65-year-old man who presented with neurosyphilis suspected to precede behavioral and cognitive problems in the context of risky sexual behavior and was confirmed by serologic tests in the cerebrospinal fluid. DISCUSSION: This case proves the necessity to investigate the possibility of neurosyphilis in subjects with dementia syndrome which does not correspond to classic etiologies.

Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice. A general practitioner-based survey in France.

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most frequently prescribed drugs. Gastrointestinal damage, the most common side effect of NSAIDs. can be limited by the prescription of cytoprotective agents. In order to assess determinants of NSAID-associated cytoprotective agent prescriptions in primary care practice, we performed a general practitioner (GP)-based study. METHODS: After a 2-month intensive information campaign, the participation of all GPs of the Côte d'Or (France) administrative area was requested. During a 2-month period, GPs had to return a mailed questionnaire on NSAID prescription for up to ten consecutive patients aged over 18 years who required NSAIDs. This 30-item questionnaire included questions about the patient, the type of NSAID and the GP. RESULTS: GP participation rate was 24%, and 791 prescriptions were provided. GPs who participated in the study were representative of GPs of the area in terms of sex, time elapsed since graduation and GP practice area. Around 80% of the patients included in the study were under the age of 65 years. The proportion of prescriptions combining NSAIDs and gastroprotective agents was 29.5%. Omeprazole accounted for 58% of the coprescriptions and misoprostol for 29%. Independent determinants associated with the co-prescription of a cytoprotective agent were age [odds ratio (OR) 4.1; confidence interval (CI) 95% 2.3 7.4], previous history of poor NSAID tolerance (OR 10.4; CI 95% 5.8-18.6), previous history of moderate to severe digestive disorders (OR 13.4; CI 95% 5.1 35.4) and indication for chronic illness (OR 1.8, CI 95% 1.1-3.1). Prescriptions of cytoprotective drugs were in conformity with official guidelines for 78.3% of the patients. Although around 60% of the patients with risk factors for poor tolerance received a gastroprotective drug, 50% of the patients over 65 years did not receive it. Conversely, nearly 12% of the patients with no risk factors were prescribed cytoprotective agents. Patient history was the main reason put forward by GPs for prescribing cytoprotective drugs. CONCLUSION: Although a large majority of GP prescriptions were in accordance with official recommendations, inadequate NSAID prescription practices remain relatively frequent especially with regard to the elderly.

Objetivos, indicaciones y modalidades de desintoxicación de los pacientes alcohólicos / Goals, indications and modalities of detoxification in alcholics

La desintoxicación del alcohólico sólo tiene sentido dentro de una estrategia que supone tres etapas: 1) diagnóstico: Es importante separar, aunque en la práctica a veces no es fácil, el abuso del alcohol de la dependencia del alcohol, sobre todo desde que desde 1994 los síntomas físicos de abstinencia no son necesarios para el diagnóstico. 2) Todo cuadro de dependencia alcohólica confirmado justifica una desintoxicación terapéutica completa y prolongada, integrada dentro de un proyecto de vida en que los objetivos deben ser precisados en colaboración con el paciente. La prescripción de medicamentos no siempre está indicada y su uso debe ser en general breve (de 5 a 7 días en una desintoxicación sin complicaciones) tanto ambulatoriamente como en hospitalización. La calidad de la relación médico-enfermo es esencial, así como establecer de entrada un apoyo psicoterapéutico o psicoterapias más estructuradas. 3) La calidad del seguimiento es el elemento esencial de la cura bio-psico-social (AU)

How useful is aminolevulinic acid dehydratase as a marker of recent alcohol intake?

Erythroycte delta aminolevulinic acid dehydratase (ALAD) has been suggested as a marker for detecting recent alcohol intake. Unlike other markers, ALAD activity decreases after alcohol intake. Review of the literature suggests that the main interest in this marker is because it increases rapidly after withdrawal. The present study investigated the changes in erythrocyte ALAD and serum gamma-glutamyltransferase activities after alcohol withdrawal in 120 alcoholics. Our data showed that ALAD is less sensitive than GGT as an indicator of recent alcohol intake (56% and 84% abnormal, respectively). The increase in ALAD activity was greater between day 12 and 18 after withdrawal (11%) than between day 1 and 12 after withdrawal (5%). There were as many patients returning to normal values 12 and 18 days after withdrawal, for GGT as for ALAD. Thus, our results contradict the claim that ALAD rises rapidly after withdrawal. ALAD shows no advantage over GGT as a marker of recent alcohol intake.

Changes in serum apolipoprotein and lipoprotein profile induced by chronic alcohol consumption and withdrawal: determinant effect on heart disease?

The effects of alcohol consumption on serum concentrations of apolipoproteins (apo) A-I, C-III, B, and E and of lipoproteins (Lp) A-I, A-I:A-II, C-III, C-III:B, and (a) were studied in 132 healthy subjects, including 55 low drinkers of alcohol (<20 g/day), 36 moderate drinkers (20-50 g/day), and 41 heavy drinkers (>50 g/day), and in 97 hospitalized alcoholic patients (> 100 g/day) without severe liver disease (especially functional insufficiency), before and after 21 days of withdrawal treatment. Serum concentrations of apo A-I, LpA-I, LpA-I:A-II, apo C-III, and LpC-III significantly (P

Opposite effects of cholesteryl ester transfer protein and phospholipid transfer protein on the size distribution of plasma high density lipoproteins. Physiological relevance in alcoholic patients.

The aim of the present study was to investigate the role of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) in determining the size distribution of high density lipoproteins (HDL) in human plasma. Whereas both purified CETP and PLTP preparations were able to promote the size redistribution of isolated HDL3, CETP favored the emergence of small HDL, while PLTP induced the formation of both small and large conversion products. When the total plasma lipoprotein fractions isolated from nine distinct subjects were incubated for 24 h at 37 degrees C with either purified PLTP or purified CETP, significant alterations in the relative proportions of the five distinct plasma HDL subpopulations, i.e., HDL2b (9.71-12.90 nm), HDL2a (8.77-9.71 nm), HDL3a (8.17-8.77 nm), HDL3b (7.76-8.17 nm), and HDL3c (7.21-7. 76 nm) were also observed. PLTP induced a significant increase in the relative abundance of HDL2b (8.66 +/- 2.34% versus 7.87 +/- 1. 83% in controls; p < 0.01) and a significant decrease in the relative abundance of HDL3a (32.76 +/- 3.42% versus 37.87 +/- 2.62% in controls; p < 0.05). In contrast, CETP significantly reduced the relative proportion of HDL2a (33.03 +/- 2.53% versus 37.56 +/- 6.43% in controls; p < 0.01) but significantly increased the relative proportion of both HDL3b (21.36 +/- 6.97% versus 15.58 +/- 7.75% in controls; p < 0.01) and HDL3c (3.21 +/- 4.84% versus 1.13 +/- 0.56% in controls; p < 0.05). Finally, in order to assess further the physiological relevance of in vitro observations, CETP activity, PLTP activity, and HDL size distribution were determined in plasmas from 33 alcoholic patients entering a cessation program. Alcohol withdrawal was associated with (i) a significant increase in plasma CETP activity (173.5 +/- 70.5%/h/ml before versus 223.2 +/- 69. 3%/h/ml after alcohol withdrawal, p = 0.0007), (ii) a significant reduction in plasma PLTP activity (473.9 +/- 203.7%/h/ml before versus 312.7 +/- 148.4%/h/ml after alcohol withdrawal, p = 0.0001), and (iii) a significant shift of large HDL2b and HDL2a toward small HDL3b and HDL3c. On the one hand, changes in plasma CETP activity correlated negatively with changes in the proportion of HDL2a (r = -0.597, p = 0.0002) and positively with changes in the proportion of HDL3b (r = 0.457, p = 0.0075). On the other hand, changes in plasma PLTP activity correlated positively with changes in the proportion of HDL2b (r = 0.482, p = 0.0045) and negatively with changes in the proportion of HDL3a (r = -0.418, p = 0.0154). Taken together, data of the present study revealed that plasma PLTP and CETP can exert opposite effects on the size distribution of plasma HDL. PLTP can promote the formation of HDL2b particles at the expense of HDL3a, while CETP can promote the formation of HDL3b particles at the expense of HDL2a.

[The prescription and drug interactions: prospective study in 896 patients treated for arterial hypertension in general medicine]. / L'ordonnance et les interactions médicamenteuses: étude prospective chez 896 patients traités pour hypertension artérielle en médecine générale.

The aim of this study was to investigate the occurrence of potential drug interactions in primary health care. It reports the analysis of 896 prescriptions for hypertensive patients collected from 237 general practitioners. The mean number of prescribed drugs was 4.55 +/- 2.14, and each patient received, on average, 1.92 +/- 0.92 antihypertensive drugs. All prescriptions were compared with a French computerized database of drug interactions (Micro-Vidal). A total of 1324 cases of potential drug interactions were found related to 552 patients (61.6 pour cent). Among the most dangerous interactions, there were 26 contra-indications and 168 unsuitable drug pairs. As reported in previous studies, there was a strong correlation between the number of prescribed drugs and the number of interactions. All in all, more than 16 per cent of prescriptions contained a contra-indication or unsuitable drug association. Potential drug interactions occur at a high rate in general practice. This raises questions about the best way to improve general practitioner training and to introduce preventive measures to reduce adverse drug effects.

Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.

A prospective placebo-controlled, randomized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed. After detoxification, each of the 538 patients included was randomly assigned to one of three groups: 177 patients received placebo, 188 received Acamprosate at 1.3 g/day (low dose group) and 173 received 2.0 g/day (high dose group) for 12 months. This was followed by a single blind 6 month period on placebo. The patients' mean age was 43.2 +/- 8.6 years. Their mean daily alcohol intake was high (nearly 200 g/day) and of long duration (9.5 +/- 7.1 years). Abstinence figures followed the order high dose > low dose > placebo. The difference was significant at 6 months (P < or = 0.02) but not at 12 months (P = 0.096). The number of days of continuous abstinence after detoxification was 153 +/- 197 for the high-dose group versus 102 +/- 165 for the placebo group (P = 0.005), with the lose-dose group reporting 135 +/- 189 days. Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months (P = 0.002) and 12 months (P = 0.005). During the 6-month post-treatment period, no increased relapse rate or residual drug effect was observed. The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently (P < 0.01). This study confirms the pharmacological efficacy of Acamprosate and its good acceptability. As an adjunct to psychotherapy, this study supports the inclusion of Acamprosate in a strategy for treating alcoholism.

Serial evaluation of dilated cardiomyopathy with exercise thallium-201 tomography: correlation with the evolution of left ventricular parameters.

The purpose of this prospective study was to correlate (1) the initial findings of exercise thallium-201 tomography with the evolution of left ventricular parameters at long term follow-up in patients with dilated cardiomyopathy and (2) the changes of exercise thallium-201 tomography repeated 1 year later. We studied 19 men with dilated cardiomyopathy and normal coronary angiogram. Two patients died and three patients had heart transplantation during follow-up. The other 14 patients were assessed at baseline and 1-year follow-up. Thallium-201 tomograms were divided into 20 segments for each patient. Two groups were defined according to the evolution of left ventricular ejection fraction: group 1 (n = 7) had unchanged or decreased ejection fraction at follow-up (24 +/- 11% at baseline versus 22 +/- 11% at follow-up, ns) and group 2 (n = 7) had improved ejection fraction at follow-up (25 +/- 9% at baseline versus 49 +/- 8% at follow-up, P < 0.03). The number of total abnormal segments at stress were not statistically different at baseline between groups 1 and 2, and in group 1 between baseline and follow-up. Group 2 at follow-up had a reduced number of total abnormal segments (P < 0.03). The percentage of reversibility was similar in both groups at baseline and follow-up. On exercise thallium-201 tomography, neither the presence nor the reversibility of stress myocardial perfusion abnormalities can predict improvement of left ventricular ejection fraction in dilated cardiomyopathy. However, regression of dilated cardiomyopathy is accompanied by a reduction of stress myocardial perfusion abnormalities.

Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress indicators.

The effects of alcohol consumption on plasma concentrations of antioxidant vitamins (alpha-tocopherol and ascorbic acid), selenium, and markers of oxidative stress, especially malondialdehyde (MDA) and autoantibodies directed to MDA adducts to proteins (Ig-NH2-MDA) were investigated in a large population of 417 supposedly healthy men who consumed only low or moderate amounts of alcohol as compared with 102 alcoholic patients without severe liver disease, who were studied both before and after 21 d of withdrawal treatment. Plasma concentrations of alpha-tocopherol, ascorbic acid, and selenium were lower in alcoholics than in men who drank low amounts of alcohol (P < or = 0.001), whereas MDA and Ig-NH2-MDA were higher (P < or = 0.001). Plasma concentrations of alpha-tocopherol and selenium remained unchanged after the withdrawal period, whereas ascorbic acid (P < or = 0.01), MDA, and Ig-NH2-MDA concentrations decreased (P < or = 0.001). Adjustment of data for circulating lipids and nutritional intake suggests a specific effect of alcohol on antioxidant vitamins, independent of nutritional status.

Phosphorus magnetic resonance spectroscopy: a noninvasive technique for the study of occlusive arterial leg disease and peripheral vasodilator therapy.

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intracellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index ([PCr]/([PCr] + [Pi])) at rest was correlated with blood flow measured by plethysmography. During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 +/- 3.04 J vs 58.89 +/- 8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 +/- 3.04 J vs 38.85 +/- 3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

The relation of alcohol consumption to serum carotenoid and retinol levels. Effects of withdrawal.

The effects of alcohol consumption on plasma concentrations of retinol and various carotenoids (beta-carotene, alpha-carotene, zeaxanthin-lutein, lycopene and beta-cryptoxanthin) were studied in a control population of 118 supposedly healthy men consuming low or moderate amounts of alcohol, and 95 alcoholic patients without severe liver disease before and after a withdrawal treatment of 21 days. There was no significant difference between alcoholics and controls regarding plasma retinol level. Conversely, plasma concentrations of all the carotenoid fractions were significantly lower in the alcoholic group than in the low drinker group. After withdrawal, plasma levels of all the carotenoids increased whereas retinol concentration diminished. Adjustment of data for various potential confounding factors especially including nutritional intake suggests an effect of alcohol on plasma carotenoids and a specific effect of withdrawal on plasma retinol, both of them being not only related to nutritional status.

[Physiopathology of acute alcoholic intoxication and alcoholic withdrawal]. / Physiopathologie de l'alcoolisation aiguë et du sevrage alcoolique.

Ethanol blood levels are the result of alcohol absorption and the process of its distribution, metabolism and excretion. Kinetics are complex and not yet well known. They can be influenced by acquired factors (type of alcohol ingested, association with fasting or eating, induction or inhibition of ethanol metabolism) or by genetically determined differences in the activity of alcohol and of acetaldehyde dehydrogenase. The presence of ethanol in the organism leads to various consequences. On the one hand, hydropic changes on membranes modify their function and thus that of membrane proteins (particularly receptors); on the other, ethanol can affect neurotransmitter metabolism. Such modification of the major neurotransmitter systems (cholinergic, aminergic and GABA) in some cerebral regions explains the pharmacologic consequences of acute alcohol ingestion. In chronic alcohol dependence, adaptation phenomena occur, in both the membranes (increased rigidity) and the neurotransmitter systems. They are reflected by the hyperexcitability (catecholaminergic hyperactivity and GABA hypoactivity) observed after disappearance of the tranquilizing effect of ethanol and are clinically expressed by the withdrawal syndrome.

[Acute alcoholic intoxication and drugs]. / Alcoolisation aiguë et médicaments.

Acute alcohol ingestion can induce drug interactions, either pharmacokinetic or pharmacodynamic. Metabolically, they especially result from interference in the enzymatic systems which catalyse ethanol oxidation, the blocking of alcohol dehydrogenase, blocking of the microsomal oxidation system of ethanol with accumulation of the xenobiotic and risk of overdose, and blocking of acetaldehyde dehydrogenase with an antabuse effect. Pharmacodynamically, the main interactions result from the action of drugs having a sedative effect, such as tranquilizers but also antidepressants, neuroleptics, analgesics, H1 antihistamines, central antihypertensive drugs (CNS depressant?), etc. This sedative effect is increased by ethanol, which can be dangerous in at-risk situations.

Radionuclide assessment of regional differences in left ventricular wall motion and myocardial perfusion in idiopathic dilated cardiomyopathy.

Regional variations in left ventricular contractility and myocardial perfusion are frequent in idiopathic dilated cardiomyopathy and might result from an increase in left ventricular wall stress responsible for regional wall motion abnormalities. The aim of the study was to perform radionuclide studies in patients with idiopathic dilated cardiomyopathy to assess regional left ventricular wall motion and myocardial perfusion abnormalities in this myocardial disease. We studied 29 men referred with idiopathic dilated cardiomyopathy and normal coronary angiograms. Rest radionuclide left ventriculography and exercise thallium-201 tomography were performed in all patients. The thallium-201 tomograms were divided into 20 segments for each patient. Mean left ventricular ejection fraction was 27 +/- 11%; 17 patients had diffuse hypokinesia (mean left ventricular ejection fraction: 24 +/- 9%) and 12 patients had predominant regional hypokinesia (mean left ventricular ejection fraction: 32 +/- 12%). Of all 580 tomographic segments, 186 had a reduction of thallium-201 uptake at exercise. Among them, reversibility was found in 53%. On the whole, 68% (158/232) of anterior, inferior and apical segments had a perfusion abnormality, compared with 8% (28/348) of septal and lateral segments (P < 0.0001). Left ventricular wall motion and myocardial perfusion abnormalities are heterogeneous and not evenly distributed in dilated cardiomyopathy. The alterations are predominant on the myocardial regions delineating the antero-posterior axis of the left ventricle. These findings suggest the possible role of increased left ventricular wall stress on this axis.

Blood activities of antioxidant enzymes in alcoholics before and after withdrawal.

Since free radicals and peroxides seem to be involved in the toxicity of alcohol, several authors have examined the variations of blood activities of antioxidant enzymes in alcoholics, but published results are somewhat conflicting. In this study, erythrocyte (E) activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT), and plasma (P) activities of SOD and GPX were measured in 58 male alcoholics without evidence of severe liver disease before and after a 21-day weaning period, and in a control group of 78 healthy men. Before abstinence, E-SOD and E-GPX activities were, respectively, 6.8% and 13.0% lower in alcoholics than in controls (p < or = .05 and p < or = .01, respectively), whereas the slight increases of E-CAT, P-SOD and P-GPX were not statistically significant. After 21 days of abstinence, no change in activities of the erythrocyte enzymes was noticed; conversely, P-SOD activity was reduced by 8.3% (p < or = .01) and P-GPX by 23.3% (p < or = .001). Variations of blood antioxidant enzymes observed in patients were of limited amplitude and do not allow the use of either of them as markers of alcohol abuse.

Concentration and hydroxyapatite binding capacity of plasma osteocalcin in chronic alcoholic men: effect of a three-week withdrawal therapy.

Plasma concentrations of osteocalcin (OC) were studied in 40 chronic alcoholic men (age range: 21-56 years) before and after 3 weeks of ethanol withdrawal therapy and in 50 non-alcoholic controls selected in respect to age and sex. Plasma OC level in alcoholic subjects was significantly lower than in the controls (3.0 +/- 2.6 micrograms/l and 4.7 +/- 2.8 micrograms/l, respectively). After 21 days of withdrawal therapy, plasma OC level was significantly higher than at the day of admission (5.8 +/- 3.5 micrograms/l, P < 0.001). This level was not statistically different from that of the controls. We also demonstrated that the hydroxyapatite binding capacity of plasma OC before as well as after the withdrawal period was not different from that of the controls. The acetaldehyde adduction of purified bovine OC in vitro did not change any of its immunoactivity and hydroxyapatite binding capacity. The results emphasize the fact that the decrease of plasma osteocalcin in chronic alcoholics is reversible within 3 weeks of alcohol withdrawal and that the circulating protein seems to be similar to that present in controls.