[Infectious adverse events related to misuse of high-dose buprenorphine: a retrospective study of 42 cases]. / Complications infectieuses induites par le mésusage de la buprénorphine haut dosage (Subutex): analyse rétrospective de 42 observations.

PURPOSE: Misuse of high-dose buprenorphine (HDB), mainly by injection, is responsible of frequent infectious adverse events. METHODS: This is a retrospective study of infectious complications occurring in patients using HDB by injection. Forty-two cases were identified (29 men and ten women) and the data were collected between March 1999 and December 2008. RESULTS: The infectious complications included cutaneous infections (27 cases), endocarditis (nine cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis), and a vascular embolism with decrease in visual acuity. CONCLUSION: The results of HDB maintenance treatment must be improved, both from the point of view of substitution and to limit its misuse by intravenous route injection. Health professionals have to play an important role in drug addict patients' education and supervision, to prevent buprenorphine injection and related infectious complications.

[Impact of music therapy on anxiety and depression for patients with Alzheimer's disease and on the burden felt by the main caregiver (feasibility study)]. / Intérêts de la musicothérapie sur l'anxiété, la dépression des patients atteints de la maladie d'Alzheimer et sur la charge ressentie par l'accompagnant principal (étude de faisabilité).

INTRODUCTION: The impact of music therapy on dementia care for patients with Alzheimer's disease (AD) is well-recognized. Music alters the different components of the disease through sensory, cognitive, emotional, behavioral and social impacts. The academic aspect of music therapy in this area was based on the fact that music can alter the various components of the overall evolution of this disease. We found around 10 case studies presenting various results from receptive music therapy sessions on patients with Alzheimer's disease. The results of these studies point out the interest of music therapy in the multidisciplinary care of Alzheimer's disease and its related syndromes. It has been deemed useful for significantly reducing the medication given to AD patients. A music therapy protocol, specifically tailored to the patient's needs has been shown to significantly reduce anxiety, depression and aggressiveness in patients suffering from Alzheimer's disease. This technique has also demonstrated its impact on helping AD patients recall their previous life experience. OBJECTIVE: To demonstrate the feasibility and to evaluate the impact of music therapy on anxiety and depression at the early to moderate stage of Alzheimer's disease and on the main caregiver burden. METHOD: Five outpatients suffering from early stage of Alzheimer's disease (MMS: 18-26) were prospectively included. They were living in Montpellier with a reliable caregiver. A weekly receptive music therapy session was delivered to patients over a 10-week period, according to the U method standardized protocol. This technique was based on the recommendations made by Gardner and Good relating to the importance given to an individualized choice of music. Instrumental tracks were selected from various music styles (classic, jazz, world music...) and were tailored to the patient's requirements. This individual session was always followed by an interview with the music therapist in order to allow the patient to express the emotions felt during the session and to stimulate the patient's cognitive functions by recalling memories and images from his past life experience. The main evaluation criterion was regular session attendance at the hospital. Secondary criteria were: anxiety score (Hamilton scale), depression score (Cornell scale) and the burden score felt by the main caregiver (Zarit scale). Evaluations took place at W1, W4 and W10. The score evolution on the Hamilton, Cornell and Zarit scales were tested using the Wilcoxon test on paired data. The significance threshold has conventionally been set at 5% for all tests used. The statistical analysis was done using the SAS software (8th version) (SAS Institute, Cary, N.C.; proc npar1way, proc univariate, proc freq). Alzheimer's disease is a recognized indication for music therapy. A simple oral consent was collected prior to the study inclusion. RESULTS: Five patients were included for a total of 44 sessions. The patients' regular attendance at the music therapy sessions showed its feasibility. Thanks to oral feedback, we were able to see that music therapy was very well-accepted both by patients and caregivers. After the sessions, all patients expressed a sensation of well-being and pleasure, such as: "Music made me feel better, I feel more relaxed", "I feel better", "I didn't know that music could have such an impact on me"... Other verbal comments were collected regarding the patients' previous life experience: "This music reminds me of my childhood", "I imagined myself dancing just like I used to in the old days", "This reminds me of my trip to Italy with my children"... The level of anxiety (Hamilton scale) dropped significantly from 9.4 (+/-2.2) to 3.4 (+/-2.6) between the first session and the fourth session (P<0.004). The differences observed between W4-W10 and W1-W10 were close to the threshold of significance due to a major drop in the anxiety level starting at W4 (P=NS). On the Cornell scale, the depression level dropped significantly from 10.8 (+/-5.3) to 2.2 (+/-1.9) between the first session and the fourth session (P<0.01). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). The weight of the physical and emotional burden experienced by the main caregiver (Zarit scale) fell significantly from 30.2 (+/-11.7) to 15.6 (+/-10.4) between W1-W4 (P<0.002). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). DISCUSSION/CONCLUSION: This preliminary study demonstrates the feasibility as well as the initial efficacy of music therapy in terms of its impact on the overall care for patients suffering from Alzheimer's disease. This easily applicable technique can be useful in treating anxiety and depression in a patient with Alzheimer's disease and also in relieving the emotional and physical burden experienced by the main caregiver.

Inherited long QT syndrome revealed by antifungals drug-drug interaction.

A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest. Voriconazole plasma level measured 15 h after the last administration was 7 mg/L. Genotyping suggested that the patient was an extensive metabolizer with respect to CYP2C9 and CYP2C19. The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.

Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

OBJECTIVE: To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs. METHODS: Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985-2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature. RESULTS: Two hundred and sixteen patients with symptoms and signs consistent with cutaneous drug reactions with systemic symptoms were reported to the FPD during this period of time. Their pattern was similar to published data for these drugs, with fever, cutaneous eruption, hepatic abnormalities and eosinophilia being the most prominent but inconstant symptoms. There are clues suggesting that some particular lesional patterns may exist for some drugs. CONCLUSIONS: Although some trends emerge from these retrospective data, they suggest that no clear, unified outline can currently be defined for these multi-organ drug-induced reactions. Instead, a constellation of various symptoms and signs were recorded, that might be sorted in different patterns according to the causal drug, a finding that might indeed improve accurate identification of the causative drug in patients receiving several principal medications at a time. A national prospective study systematically collecting standardized data is required better to define the outlines of these severe adverse drug reactions and to evaluate prognostic data.

[Effect of music therapy among hospitalized patients with chronic low back pain: a controlled, randomized trial]. / Intérêt de la musicothérapie dans la prise en charge de la lombalgie chronique en milieu hospitalier (Etude contrôlée, randomisée sur 65 patients).

OBJECTIVE: To evaluate the influence of music therapy in hospitalized patients with chronic low back pain. METHODS: A controlled, randomized study (N = 65). During a stationary rehabilitation stay of 12 days, 65 patients with low back pain were randomized to receive on alternate months standardized physical therapy plus 4 music therapy sessions between day 1 and day 5 (intervention group; N = 33) or standardized physical therapy alone (control group; N =32). Scores for pain (as measured on a visual analogue scale [VAS]), disability (Oswestry index) and anxiety and depression (as measured on the hospital anxiety and depression scale [HAD]) were collected on day 1, 5 and 12. Pain intensity was also evaluated on a VAS just before and after music therapy sessions. RESULTS: Introduced music therapy sessions during a stationary rehabilitation stay in patients with chronic low back pain reduce pain (-2.0+/-2.7 vs -1.8+/-2.6) but not significantly. However, music therapy significantly (p < 0.01) reduced disability as measured on the Owestry index between day 1 and day 5 (-11.8+/-17.8 vs -2.5+/-9.4), anxiety (-3.5+/-3.7 vs -0.9+/-2.7) and depression (-2.1+/-3.0 vs 0.6+/-2.4). The immediate effect on pain intensity (VAS score) was confirmed (p < 0.001). CONCLUSION: Our results confirmed the effectiveness of music therapy for hospitalized patients with chronic low back pain. Music therapy can be a useful complementary treatment in chronic pain and associated anxiety-depression and behavioural consequences.

[Inter-regional differences in dysthyroidism due to amiodarone: comparison of spontaneous notifications in Aquitaine, Midi-Pyrenees and Languedoc-Roussillon]. / Différences inter-régionales des dysthyroïdies à l'amiodarone: comparaison des notifications spontanées en Aquitaine, Midi-Pyrénées et Languedoc-Roussillon.

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?]. / Toxicité neurologique induite par le Zelitrex (valaciclovir) chez trois patients insuffisants rénaux. Surdosage lié à l'amélioration de la biodisponibilité du produit?

INTRODUCTION: We report three cases of neurotoxicity in patients with renal failure, treated with Zelitrex (valacyclovir). EXEGESIS: The patients are two women and a man, aged 76 +/- 4.6 years, who presented acute mental confusion during a treatment with valacyclovir. In two cases, the patients previously had altered renal function and were under peritoneal dialysis. In the last case, the patient had simultaneous neurotoxicity and acute renal failure. After the discontinuation of the drug, the outcome was favourable in all cases. CONCLUSION: Our cases focus attention on the possible neurotoxicity of valacyclovir, which is an amino acid ester prodrug of acyclovir, rapidly and almost completely hydrolysed to acyclovir prior to systemic exposure. The bioavailability of valacyclovir is 54% compared to approximately 20% for oral acyclovir and may account for unexpected overdoses, which may lead to serious neurological toxicity.

Fatal systemic reaction after multiple doses of intravesical bacillus Calmette-Guérin for polyposis.

OBJECTIVE: To report a case of fatal systemic reaction after intravesical administrations of bacillus Calmette-Guérin (BCG) for polyposis. CASE SUMMARY: A 72-year-old white man was treated by monthly injections of intravesical BCG immunotherapy for polyposis of the urinary bladder. He received a total of eight injections; four hours after the seventh injection, he presented with pyrexia associated with chills, sweating, headache, and vomiting, which quickly resolved. Four hours after the eighth injection, the patient presented with the same symptoms plus a left-hemisphere deficiency. Results of a cerebral scan performed at this time were normal. The clinical status of the patient quickly worsened, with the appearance of disseminated intravascular coagulation, acute anuric renal insufficiency, rhabdomyolysis, hemolysis, and cytolytic and cholestatic hepatitis. The patient required hemodialysis and symptomatic treatment. Lactic acidosis with hemolytic-uremic syndrome appeared, and he died as the result of a multivisceral (respiratory, renal, hepatic) deficiency. DISCUSSION: The patient presented with symptoms compatible with a severe systemic reaction to BCG therapy, a rare but possible adverse effect. CONCLUSIONS: BCG instillation is a valuable tool in the therapy of bladder carcinoma, but increasing reports of severe adverse reactions should continue to remind practicing urologists to be alert to the possibility of common and uncommon reactions after its use.

[Drug allergies: a public health problem]. / Les allergies médicamenteuses: un problème de santé publique.

Adverse drug reactions occur in 10 to 20% of hospitalized patients and up to one third are due to allergic and pseudoallergic reactions. Allergic reactions are unpredictable reactions related to immunologic mechanisms. Pseudo-allergic reactions mimic allergic reactions but no drug specific antibody or T cell proliferation can be demonstrated. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

[Immunoallergic reactions of drug origin: epidemiologic and clinical data]. / Les réactions immuno-allergiques d'origine médicamenteuse: données épidémiologiques et cliniques.

Allergic and pseudoallergic reactions frequently occur in hospitalized patients and represent up to one-third of adverse drug reactions. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T-cell proliferation can be demonstrated. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

[Venlafaxine withdrawal syndrome: report of six cases and review of the literature]. / Syndrome de sevrage à l'arrêt de la venlafaxine: à propos de six cas et revue de la littérature.

INTRODUCTION: Venlafaxine is an antidepressant that selectively inhibits serotonin reuptake and is a norepinephrine inhibitor. Withdrawal syndromes can occur after abrupt drug discontinuation of long-term regimens. EXEGESIS: We report six cases of withdrawal symptoms after venlafaxine discontinuation. CONCLUSION: Physicians must be aware of the frequency, rapidity and potent severity of these withdrawal syndromes.

Carboxypeptidase G2 rescue in delayed methotrexate elimination in renal failure.

We report here the case of a 68-year-old woman who presented severe renal failure following the first cycle of high dose methotrexate (HDMTX) for the treatment of a cerebral malignant lymphoma. Before HDMTX administration, serum creatinine value was normal and three days after HDMTX, it reached 457 micromol/L. Leucovorin rescue, hemodialysis and cholestyramine did not increase MTX clearance. Because of the persistence of renal failure, and the high risk of important hematological side-effects associated with high MTX plasma levels, the patient received carboxypeptidase G2 (CPDG2). This allowed MTX plasma levels to decrease by 80% in 15 minutes. No side effects were observed and renal function normalized rapidly. In some patients, when high-dose leucovorin associated with hemodialysis and cholestyramine are unable to restore normal MTX clearance, CPDG2 should be considered because it may represent a safe and efficient alternative for the management of MTX intoxication.

[Incidence and prevalence of adverse drug reactions]. / Incidence et prévalence des effets indésirables des médicaments.

FUNDAMENTAL DATA: Estimation of incidence and prevalence rates of adverse drug reactions are necessary to assess the consequences and impact of these effects in a population. HOSPITAL STUDIES: During the last 20 years, several studies conducted in one or more departments of a single hospital have found incidence of hospitalizations induced by adverse drug reactions between 2 and 8%. Three meta-analyses confirm these reports with incidence varying from 4.4 to 5.8% in different countries and from 5.2 to 8.2% and from 2.37 to 3.6% in the United States and Australia respectively. Two recent studies conducted by the French pharmacovigilance regional centers on a representative sample of medical departments in public hospitals found a prevalence of adverse drug reactions between 4.2 and 22.1% (according to the type of department and hospital) and a hospitalization incidence due to adverse drug reaction between 2.37 and 4.01%. COMMUNITY STUDIES: In community medicine, few data are available. In general medicine, the incidence would be 1.99 adverse effects per general practitioner per day. The number of serious adverse drug reactions has been estimated at 0.01 per general practitioner per day. These numbers show the magnitude of adverse drug reactions in terms of morbidity and mortality.

[Drug information and prescription guidance: role of regional centers of pharmacovigilance]. / Information du prescripteur et aide à la prescription: rôle des centres régionaux de pharmacovigilance.

MISSIONS: Drug information is one of the missions of the French Regional Pharmaco-Vigilance Centers together with the evaluation of adverse drug reaction (ADR) reports, expertise, teaching and research. SERVICES: Physicians and other health professionals call their regional center (the address and phone numbers are on the first pages of the Vidal, the French national drug compendium) for any kind of information pertaining to adverse drug reactions or proper use of drugs such as drug use in pregnancy or lactation. RELIABILITY: This information activity is successful because of the competence and impartiality of the regional centers which are based in university hospitals under an agreement signed with the French Medicines Agency.

Chronic constrictive pericarditis induced by long-term bromocriptine therapy: report of two cases.

OBJECTIVE: To report two cases of chronic constrictive pericarditis that appear to be related to the intake of bromocriptine for Parkinson's disease. CASE SUMMARY: Two white men (aged 63 and 69 y) were treated with bromocriptine for four (40 mg/d) and two years (30 mg/d), respectively, with a cumulative dose intake of 58.4 and 21.9 g, respectively. The patients experienced dyspnea with bilateral lower-limb edema and pleural effusion, suggesting right cardiac dysfunction. Echocardiography, computed tomography, and cardiac catheterization results were compatible with a diagnosis of constrictive pericarditis, so pericardectomy was performed on both patients. The anatomic pathology examination showed a fibrous pericardium; cultures were sterile. In the first case, pleural effusion recurred seven months after the pericarditis; bromocriptine was suspected and treatment was discontinued. In the second case, just prior to the pericardectomy, an episode of mental confusion occurred and prompted the cessation of bromocriptine therapy. DISCUSSION: To the best of our knowledge, only one case of constrictive pericarditis induced by bromocriptine therapy has previously been described in the literature. CONCLUSIONS: Our cases call attention to a possible association between bromocriptine use in patients who have Parkinson's disease and constrictive pericarditis.

[Iatrogenic medication: estimation of its prevalence in French public hospitals. Regional Centers of Pharmacovigilance]. / Iatrogénie médicamenteuse: estimation de sa prévalence dans les hôpitaux publics français. Centres régonaux de pharmacovigilance.

The French network of Regional Centres of Pharmacovigilance has made an estimation of the occurrence of adverse drug reactions in a representative sample of patients in French public hospitals (departments of medicine, of surgery and of geriatrics). The study looked at one specific day in the spring of 1997. Each observed case of adverse drug reaction was validated. The total sample comprised 2132 patients of whom 969 were in a university hospital and 1163 in a general hospital. The hospitals and units concerned are representative of the country as a whole. One adverse drug reaction at least was present for 221 patients on the day of the investigation. This means a prevalence rate of 10.3 per cent (95 per cent CI: 8.7 to 11.9 per cent). In 33 per cent of cases (95 per cent CI: 26 to 42 per cent), the observed effects were rated as serious. From an incidence rate of 1.8 per cent (95 per cent CI: 1.0 to 25 per cent) on one specified day it can be estimated that in France an adverse drug reaction will occur in about 1,300,000 patients per year during a stay in hospital.

[Drug allergies: management and current aspects]. / Allergies médicamenteuses: prise en charge et actualités.

UNLABELLED: ALLERGIC AND PSEUDOALLERGIC REACTIONS: Adverse drug reactions occur in 1 to 3% of hospitalized patients and 10% are due to allergic and pseudoallergic reactions. Allergic reactions are unpredictable reactions related to immunologic mechanism. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T cell proliferation can be demonstrated. PREVENTION: We are lacking clinical and biological tools and the available ones still need to be validated. However, a precise diagnosis is required in order to set up prevention measures. We focus here on some basic and new data concerning these reactions, in particular epidemiological studies, mechanisms and diagnostic methods.