Pharmacie française en ligne: Acheter des antibiotiques sans ordonnance en ligne prix bas et Livraison rapide.

Untitled

Alcohol and Alcoholism Advance Access published March 19, 2012
Alcohol and Alcoholism Vol. 0, No. 0, pp. 1–4, 2012 Abstinence and ‘Low-Risk’ Consumption 1 Year after the Initiation of High-Dose Baclofen: A Retrospective Study among ‘High-Risk’ Drinkers Laurent Rigal1,*, Constance Alexandre-Dubroeucq1, Renaud de Beaurepaire2, Claire Le Jeunne3 and Philippe Jaury1 1Département de Médecine Générale, Faculté de Médecine Paris Descartes—Site Cochin, Université Paris Descartes, 24, rue du Faubourg Saint-Jacques, Sorbonne Paris Cité, 75014 Paris, France, 2Centre Hospitalier Paul-Giraud, Service de Psychiatrie, Villejuif, France and 3Faculté de Médecine, Service de Médecine Interne Hôtel Dieu, Université Paris Descartes, Sorbonne Paris Cité, Paris, France *Corresponding author: Tel.: +33-6-25-72-62-84; E-mail: [email protected] (Received 30 September 2011; accepted 21 February 2012) Abstract — Aims: The aim of the study was to assess the proportions of ‘high-risk’ drinkers’ abstinent or with ‘low-risk’ consump-tion levels 1 year after the initiation of high-dose baclofen. Methods: This is a retrospective ‘open’ study; the outcome of this studywas to assess the level of alcohol consumption in the 12th month of treatment. Results: Of the 181 patients included, a follow-upevaluation was possible in 132 patients. The initial alcohol consumption of the 132 patients analysed averaged 182 ± 92 g/day. After 1 year, 80% of the 132 (i.e. 58% of 181) were either abstinent (n = 78) or drinking at low-risk levels (n = 28) in their 12th month oftreatment. The mean baclofen dose at 1 year was 129 ± 71 mg/day. Conclusion: High-dose baclofen should be tested in randomizedplacebo-controlled trials among high-risk drinkers.
Baclofen, a gamma-aminobutyric acid ‘B-receptor’ agonist, This retrospective study is based on two physicians’ study of has long been used to treat spasticity from neurological dis- the records of patients to whom they had prescribed baclo- eases, at a dose of 30–90 mg/day. It appears today to be a fen. Both worked in the Paris metropolitan area: one general promising but controversial candidate for treating alcoholic practitioner in private practice and one hospital-based psych- patients (by reducing or even suppressing iatrist, both of whom prescribed baclofen to outpatients with their craving (which we define here as an irrepressible sense drinking problems. Neither practitioner applied any absolute of needing) to drink. A few case reports ; contraindications to baclofen, except for allergies. Neither detoxification nor alcohol dependence was a necessary pre- might respond favourably to baclofen at doses >90 mg/day.
condition to treatment. No particular management ( pharma- Although no randomized controlled trial testing such doses has yet been conducted, some physicians are prescribing offered, and the physicians were free to prescribe as they high-dose baclofen off-label to informed patients in a com- thought appropriate. Patients systematically received com- passionate approach. To date, published randomized con- plete information about various characteristics of the treat- trolled trials have tested 30 mg/day dosage ment (off-label prescription, increasing dose potentially higher than for neurological indications, list of adverse This study presents two physicians’ clinical experience of effects and in particular the risk of hypersomnolence, espe- prescribing high-dose baclofen in patients with ‘high-risk’ cially if taken with alcohol, and the risk of withdrawal symp- consumption levels, as defined by the World Health toms if the medication were to be stopped suddenly).
Organization (WHO; i.e. >40 g/day for women and >60 g/ Patients eligible for this study were all ‘high-risk’ drinkers who had started baclofen more than a year before 1 their usual clinical practice, they prescribed baclofen at a November 2010, regardless of the length of their treatment progressively increasing dose (steps of 15 mg/week, then 30 or follow-up. Each physician kept an exhaustive list of if possible, according to tolerance) until it abolished craving, patients who had taken baclofen, and subjects were identified to the extent possible, thereby allowing patients to reduce their consumption to the WHO’s ‘low-risk’ level (i.e. ≤20 g/ Data for each eligible patient were collected first by exam- ining his or her medical record and then by an interview of the patient, either in the physician’s office during a regular The aim of the study was to assess the proportions of consultation or by telephone, by a physician–investigator.
‘high-risk’ drinkers who had either one of the two satisfac- The aim of the interview was to obtain all of the necessary tory alcohol consumption profiles (full abstinence or data (completing data for patients who had stopped treatment ‘low-risk’ consumption) during the 12th month of high-dose with the physician before a year had elapsed) and to obtain baclofen treatment. Our secondary objectives were to high-quality measurements of some patient characteristics examine the patient characteristics associated with these pro- (initial alcohol dependence, alcohol consumption during the files and to analyse the tolerance for and safety of high doses 12th month after the initiation of baclofen and adverse effects) about which they were systematically questioned.
The Author 2012. Medical Council on Alcohol and Oxford University Press. All rights reserved The other characteristics collected came from the medical effects. We used χ2 tests (or Fisher’s exact tests if needed) and Student t-tests (or Kruskal–Wallis tests if needed) to We defined two satisfactory alcohol consumption profiles, based on the patient reports of their alcohol consumption All patients were informed about the study’s purpose and during the 12th month of baclofen treatment: design (and about our intention to publish the results) andgave their consent to participate. Patients seen in the physi- (1) full abstinence (vs any alcohol consumption) and cian’s office signed a consent form and those interviewed by (2) ‘low-risk’ consumption (vs more than low risk consump- telephone gave their consent verbally. This study was not tion), that is, which might include occasional periods of reviewed by a research ethics committee, because it is inher- abstinence, but had no days above 20 g (women) or 40 g ently an ‘audit’ of two physicians, which was not deemed within the purview of ethics committees.
Besides consumption levels during the 12th month of treatment, the following information was collected: Of the 181 patients eligible, 132 (73%) were included in the (1) sociodemographic data: age, sex, whether the patient analysis, while 49 were lost to follow-up. Complete informa- tion was available for all of the patients analysed: all their (2) history of their alcoholism: number of episodes of de- medical records were evaluated, and all were interviewed.
toxification, previous treatment with drugs approved for The 49 patients lost to follow-up had stopped seeing their physician regularly before a full year was completed; even though their files had been examined, their alcohol consump- (3) alcohol consumption and smoking at the beginning of tion during the 12th month of treatment could not be deter- mined because they could not be interviewed. Among this (4) initial alcohol dependence (diagnosed in accordance group, four patients had died; none from a cause attributable with DSM-IV, without using a questionnaire); (5) psychiatric disorders (diagnosed in accordance with Overall, 63% of the patients were men, 52% lived with a partner and only 9% were not alcohol dependent (these 12 anxiety, depression, bipolar disorder, psychosis or other patients nonetheless met at least the fourth DSM-IV criterion for alcohol dependence: uncontrolled use). The patients’ (6) addictive behaviour (food, i.e. binge eating, shopping, mean age was 47 ± 11 years. Their baseline alcohol con- gambling, work or sex, without using questionnaires); sumption averaged 182 ± 92 g/day (197 g/day in men vs 157 (7) treatment with psychotropic drugs: anxiolytics, antide- g/day in women, P = 0.04; 190 g/day in the alcohol- pressants, mood stabilizers and neuroleptics; dependent patients vs 120 g/day in those who were not (8) baclofen dosage: maximum and at 12 months; P = 0.04). Eighty per cent of the patients had psychiatric (9) perceived diminution in craving intensity: binary disorders (92% of the men vs 73% of the women, P = 0.02), measure corresponding to the patient’s perceived dim- detailed in Table . Most (85%) of the patients had already inution in craving between the beginning of treatment tried a drug approved for relapse prevention and 44% had undergone detoxification at least once. In addition to baclo- (10) adverse effects, both those reported spontaneously and fen, 77% of the patients took psychotropic drugs (90% of the men vs 70% of the women, P = 0.008; 75% of the alcohol-dependent vs 100% of those who were not, P = 0.048), alsolisted in Table The smokers (71%) consumed a mean of The patients included in the analysis were those who were eligible for the study and for whom the alcohol con- At 1 year, 78 patients (59% of those analysed and 43% of sumption during the 12th month of treatment could be those eligible) were abstinent, 28 (21% of those analysed determined, as opposed to the patients lost to follow-up. For and 15% of those eligible) were drinking but only below or the latter, alcohol consumption at their last visit, the number at the ‘low risk’ level and 26 (20% of those analysed and of visits and the length of the follow-up were extracted 14% of those eligible) were drinking above that level.
from the files. We also asked the physicians for their The proportion of psychiatric disorders (and especially of opinion about the principal reason that the patient stopped anxiety disorders) was significantly lower among patients The patients analysed were first described, and the varia- (Table ). The patients with eating disorders or who took tions in their characteristics according to sex and alcohol de- psychotropic drugs (anxiolytics and anti-depressants in par- pendence were examined. The two satisfactory profiles were ticular) were significantly less frequent among abstinent than then described, and their variations according to characteris- among non-abstinent patients. Among patients with either tics tested. The same analysis was conducted for the satisfactory profile, a perceived diminution in craving was maximum baclofen doses and the doses at 1 year. Next, significantly more frequent. No satisfactory profile varied the adverse effects were described. Finally, we described the significantly by initial alcohol consumption, alcohol depend- patients lost to follow-up and compared them with the patients analysed as a function of age, sex, alcohol depend- One year after the initiation of baclofen, 83% of the ence, initial alcohol consumption and proportion of adverse patients were still taking it. The maximum dose averaged Table 1. Patient characteristics and their associations with outcome measures Association with no or ‘low-risk’ consumption *Only the figures related to a significant association are presented.
145 ± 75 mg/day (min = 30, max = 400, median 145, first quartile = 85, third quartile = 200; 150 in the alcohol-dependent patients vs 93 in those who were not, P = 0.01) Our observational study has some limitations. First of all, it and the dose taken at 1 year averaged 129 + 71 mg/day (min had no control group. Some of the satisfactory responses = 20, max = 300, median = 120, first quartile = 65, third quar- might therefore have been due to regression towards the tile = 180; 134 in the alcohol-dependent patients vs 76 in mean, to a classification (memory or social desirability) bias, those who were not, P = 0.006). No dose was associated with or to the other medications they received, as well as to the sex, initial alcohol consumption, psychiatric disorders or ad- physicians’ support. Next, some patients had expressed the desire to be treated with baclofen even before the physician Overall, 86% of the patients (69% of the men vs 84% of suggested this medication, which might have accentuated the the women, P = 0.04) had experienced adverse effects. Most placebo effect. Another limitation is that we cannot present of them were transient, during dose increases, and some oc- corroborative evidence, by family reports or biological curred while drinking alcohol. The physicians reported that baclofen seemed to potentiate somnolence and probably also This study is innovative in several ways: its length, its the mental confusion induced by alcohol. In the order of de- large number of patients from only two centres, the dosage creasing frequency, the principal adverse effects were fatigue or somnolence, insomnia, vertigo and digestive disorders.
None required hospitalization. Because of intolerance, six patients (<5%) stopped their treatment and four had to inter- atypical compared with the studies that most often target only rupt a dosage increase (although all four maintained their alcohol-dependent patients. These doctors also treated several ‘low-risk’ consumption level, although the craving had not ‘high-risk’ drinkers who were not alcohol dependent. Indeed, the majority of patients with alcohol use disorders are not The patients lost to follow-up had seen the physician for alcohol dependent (), and the benefit–risk an average of 6.2 ± 5.9 consultations over an average follow- ratio may be favourable for some of them (especially those up period of 5.6 ± 5.2 months. During their last contact with who cannot control their ‘high-risk’ consumption).
the physician, 36% of them were abstinent, 22% were drink- This study also renews the questions about abstinence. A ing but only below or at the ‘low risk’ level and 42% were reduction in craving allowed some patients to advance drinking above that level. They had significantly fewer (P = towards abstinence and to maintain this state without having 0.01) adverse effects (69%) than the patients analysed (86%).
to experience the personal hardships of detoxification The physicians considered that an adverse effect was respon- (This change is likely to modify the indivi- sible for only three of the patients’ stopping treatment, one dual’s experience of treatment by limiting the usual feelings because of mental confusion that occurred when he drank.
of guilt and failure. Abstinence is neither a preliminary re- The most frequent reason for stopping (n = 10) was a lack of quirement nor an objective that can be met only in pain.
motivation. The patients analysed and those lost to follow-up And, if some patients succeed in maintaining moderate con- did not differ significantly by age, sex, initial alcohol con- sumption, should we not prefer consumption at low risk to sumption levels, alcohol dependence, psychiatric disorders or abstinence as the principal endpoint of trials The larger doses taken by alcohol-dependent patients com- pared with their non-dependent counterparts might be inter-preted as the adaptation of dosage to disease severity.
Addolorato G, Caputo F, Capristo E et al. (2002) Baclofen efficacy Proposals for modifying the fifth revision of the DSM elim- in reducing alcohol craving and intake: a preliminary double- inate the abuse/dependence dichotomy and suggest a dimen- blind randomized controlled study. Alcohol Alcohol 37:504–8.
Addolorato G, Leggio L, Ferrulli A et al. (2007) Effectiveness and sional approach to ‘alcohol use disorders’ (): safety of baclofen for maintenance of alcohol abstinence in using such a diagnostic approach, we suggest that perhaps alcohol-dependent patients with liver cirrhosis: randomised, the more severe the use disorder, the higher the dose of double-blind controlled study. Lancet 370:1915–22.
Addolorato G, Leggio L, Cardone S et al.
GABA(B) receptor system in alcoholism and stress: focus on clinical studies and treatment perspectives. Alcohol 43:559–63.
that high levels of alcohol dependence or anxiety may be Agabio R, Marras P, Addolorato G et al.
predictive of a favourable response to baclofen. We did not presses alcohol intake and craving for alcohol in a schizophrenic find evidence that alcohol dependence was a good prognostic alcohol-dependent patient: a case report. Alcohol Alcohol factor in our study, but this finding might have differed had Ameisen O. (2005) Complete and prolonged suppression of symp- we used a criterion of dependence severity, for example, toms and consequences of alcohol-dependence using high-dose based on the number of DSM-IV criteria met or the severity baclofen: a self-case report of a physician. Alcohol Alcohol of alcohol withdrawal symptoms. Moreover, although several studies have consistently reported that baclofen is effective in Ameisen O. (2008) The End of My Addiction. New York: S Bucknam W. (2007) Suppression of symptoms of alcohol depend- ), we found a negative association between the existence ence and craving using high-dose baclofen. Alcohol Alcohol of an anxiety disorder and a satisfactory profile at 1 year.
However, no causal relation could be deduced from our Dore GM, Lo K, Juckes L et al. (2011) Clinical experience with finding, unlike, for example, the studies by baclofen in the management of alcohol-dependent patients withpsychiatric comorbidity: a selected case series. Alcohol Alcohol were prospective and used a placebo control group.
Enserink M. (2011) Addiction research. Anonymous alcoholic Finally, we found that baclofen, including at a high dose bankrolls trial of controversial therapy. Science 332:653.
and in patients with psychiatric disorders, appears to be well European Medicines Agency. (2010) Guidelines for the develop- ment of medicinal products for the treatment of alcohol depend- tolerated and manageable, thus confirming other reports Garbutt JC, Flannery B. (2007) Baclofen for alcoholism. Lancet Garbutt JC, Kampov-Polevoy AB, Gallop R et al. (2010) Efficacy and safety of baclofen for alcohol dependence: a randomized,double-blind, placebo-controlled trial. Alcohol Clin Exp Res34:1849–57.
Our encouraging results must be interpreted in the light of O’Brien C. (2011) Addiction and dependence in DSM-V. Addiction the finding that psychiatric diseases, frequent ) among alcoholics, might modulate the efficacy of baclofen and that tolerance to it at high doses and over the mental disorders with alcohol and other drug abuse. Resultsfrom the epidemiologic catchment area (ECA) Study. J Am Med long-term is not known with any certainty ). These must be confirmed by randomized placebo- Reid MC, Fiellin DA, O’Connor PG. (1999) Hazardous and harmful alcohol consumption in primary care. Arch Intern Med159:1681–9.
Smith CR, LaRocca NG, Giesser BS et al. (1991) High-dose oral Acknowledgements — The authors thank the patients who agreed to participate in this survey. They also thank Virginie Ringa for her reading of a previous version of this World Health Organization, Department of Mental Health and Substance Dependence, Noncommunicable Diseases and MentalHealth Cluster. (2000) International Guide for Monitoring Conflict of interest statement. No conflict of interest declared.
Alcohol Consumption and Related Harm. Geneva: WHO.

Source: http://www.apima.org/img_bronner/high_dose_baclofen_Rigal_Jaury.pdf

Microsoft word - wacv2012 program v4

WACV 2012 Organizing Committee General Chairs Terry Boult, Univ. Colorado at Colorado Springs Walter Scheirer, Univ. Colorado at Colorado Springs Program Chairs Michael Brown, National University of Singapore Ram Nevatia, University of Southern California Luc Vincent, Google Publications Chair Anderson Rocha, UNICAMP Registration Chair Ginger Boult Program C

Pulmonary alveolar microlithiasis in childhood: clinical and radiological follow-up

Pediatric Pulmonology 34:384–387 (2002)Pulmonary Alveolar Microlithiasis in Childhood:Stipan Jankovic, MD, PhD,1* Neven Pavlov, MD, PhD,2 Ante Ivkosic, MD,3 Ivana Erceg, MD,3Meri Glavina-Durdov, MD, PhD,4 Jadranka Tocilj, MD, PhD,5 Slavica Dragisic-Ivulic, MD,2Summary. This report describes a case of pulmonary alveolar microlithiasis that was diagnosed inan 8.5-year-old girl by high-resoluti

Copyright © 2010-2018 Pharmacy Drugs Pdf