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Françoise Haramburu

Publications and source records attributed to Françoise Haramburu.

14 recordsLinked to original sources
PubMed2007

Peripheral neuropathy associated with leflunomide: is there a risk patient profile?

PURPOSE: (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. METHOD: All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. RESULTS: One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). CONCLUSION: Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory.

Adult↗
PubMed2006

A new method for assessing drug causation provided agreement with experts' judgment.

BACKGROUND AND OBJECTIVE: The many methods proposed for causality assessment of adverse drug reaction (ADR) generally rely on algorithms. They have no clear relationship to probabilities, however, a situation we attempted to improve. STUDY DESIGN AND SETTING: Thirty ADR cases corresponding to 32 suspect drugs were randomly selected from the French pharmacovigilance database. The statistical weighting was performed by using a multilinear regression with logit(p) as the dependent variable and seven judgment criteria as independent variables. The best model (i.e., giving the best correlation with the gold standard) was retained for the new causality assessment method. RESULTS: The weights [logit(p)] for the 21 choices, on average three for each of the seven criteria, ranged from -3.95 to 0.86, secondarily rounded to multiples of 0.5. The correlation between the probability obtained from the final method and the gold standard was quite good (R(2) = .92). CONCLUSION: This method based on the rational weighting of seven causality criteria is straightforward to use and provides very good agreement with experts' judgment. Moreover, unlike most classical algorithms, it respects one basic rule of probabilities-namely, a symmetrical probability distribution for drug causation around the .5 neutral position (maximum uncertainty).

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Surveillance of adverse effects during a vaccination campaign against meningitis C.

OBJECTIVE: To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. METHODS: A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. RESULTS: The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. CONCLUSIONS: This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Adolescent↗
PubMed2005

Agreement of expert judgment in causality assessment of adverse drug reactions.

BACKGROUND: Global introspection is, with operational algorithms and Bayes' theorem, one of the three main approaches used to assess the causal relationship between a drug treatment and the occurrence of an adverse event. OBJECTIVE: To analyze and compare the judgments of five senior experts using global introspection about drug causation on a random set of putative adverse drug reactions. METHODS: A random sample of 150 drug-effect pairs was constituted. For each pair, five senior experts had to independently assess the probability of drug causation from 0 to 1 by using a 100 mm visual analog scale (VAS). For analysis, those probabilities were secondarily split into seven levels of causality: excluded (0-0.05); unlikely (0.06-0.25); doubtful (0.26-0.45); unassessable/unclassifiable (0.46-0.55); plausible (0.56-0.75); likely (0.75-0.95); and certain (0.95-1). Agreement among the five experts was assessed using kappa coefficients (kappa). RESULTS: The overall agreement between experts was poor (kappa=0.20), although significantly different from chance, and varied according to the level of causality. It was lower for the unlikely, doubtful, unassessable/unclassifiable, and plausible categories (kappa=0.03, 0.03, -0.01, and 0.13, respectively) than for VAS extremes: excluded, likely, and certain (kappa=0.40, 0.32, and 0.30, respectively). CONCLUSION: This study confirms that experts express marked disagreements when assessing drug causality independently. The agreement rate was lower for intermediate levels of causality, especially when strong evidence was lacking for confirming or ruling out drug causality. Therefore, in a decision-making context, a step-by-step consensual approach such as the Delphi method seems necessary to make the assessment of such cases more reliable.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

[Medical and socio-economical impact of drug-induced adverse reactions].

OBJECTIVE: To analyse the nature of adverse drug reactions, their frequency, the drugs incriminated, their outcome, the different ways to treat them and their cost. METHODS: Descriptive, prospective and non-comparative study, based on spontaneous reporting. Each patient was followed-up over a 6-month period. RESULTS: One hundred and fifteen adverse events were reported in 113 patients (58 men and 55 women), with a mean age of 59.5 years. Cutaneous and haematological reactions predominated, with a majority of cardiovascular and psychotropic agents incriminated. Sixty-three percent of adverse reactions were serious: 49% led to (or prolonged) hospitalisation, 6% led to death, 4% to after effects, 3% were life-threatening and 1% led to congenital malformation. The mean duration of an adverse reaction was of 37.4 days. The total cost of these 115 adverse reactions was an estimated 610.110 Euros, with a mean global cost of 5.305 Euros per event. CONCLUSION: This study shows the individual and collective extent of the impact of adverse individual and collective reactions.

Adolescent↗
PubMed2005

Trends in spontaneous adverse drug reaction reports to the French pharmacovigilance system (1986-2001).

BACKGROUND: The French pharmacovigilance system is based on a network of 31 regional centres located in teaching hospitals and coordinated by the French Medicines Agency ("Agence Française de Sécurité Sanitaire des Produits de Santé" [Afssaps]). Since 1984, they have shared a common database of adverse drug reactions (ADRs) that are spontaneously reported by healthcare professionals. The objective of this study is to describe the characteristics of the reports and the reporting trends in the French pharmacovigilance spontaneous reporting database from 1986 to 2001. METHODS: All the reports from January 1986 to December 2001 were included. Drugs and ADRs were translated to anatomical therapeutic chemical (ATC) codes and MedDRA classifications, respectively. RESULTS: The total number of reports was 197 580 over the 16-year period, with linearly increase over time. The median (interquartile range [IQR]) age of the patients was 53 (34-70) and the male/female ratio was 0.82. The median (IQR) time between the date of occurrence of the ADR and the date of report was 73 days (34-166). The reporter was a specialist in 74% of the reports and a general practitioner in 17%. The annual rate of reporting according to medical demography strongly increased for the specialists, especially since 1994. At least one ADR was considered as serious in 44.8% of the reports. The ADRs were most frequently related to nervous system drugs (23%), followed by cardiovascular drugs (19%) and systemic anti-infectives (17%). The latter class had the fastest progression mostly due to antiretroviral therapy since 1996. According to the Medical Dictionary for Regulatory Activities (MedDRA) coding, the system organ most often reported was skin and subcutaneous tissue disorders (29%), followed by nervous system disorders (19%), gastrointestinal disorders (12%), blood and lymphatic system disorders (12%), vascular disorders (12%) and general disorders and administration site conditions (12%). DISCUSSION: All spontaneous reporting systems are affected by under-reporting. One of their goals is to generate early signals, which might be more affected by reporting bias than by under-reporting. Some improvements should be made in the design of the French database, but data collected since 1986 constitute an essential tool for the routine work of the 31 pharmacovigilance centres. CONCLUSION: This first description of the data of the French pharmacovigilance database involving all drugs and ADRs shows an increasing tendency to reporting over time, especially in specialists and for systemic anti-infective drugs. The database that uses hierarchical international classifications for drugs and adverse reactions may be used for further studies and could be the basis for an automatic signal generation system.

Adult↗
PubMedDate not supplied

[Some questions about statins].

More than ten years after the statins became available in therapeutics, some questions remain unanswered. What would be the populational impact if the results of clinical trials were applied to a country such as France? Is the extrapolation licit? Does the benefit of the statins actually exceed the risk? What is the relevant target population? Are statins more effective than agents acting on other cardiovascular risk factors? How efficient are the statins really? Are the statins effective in non-hypercholesterolaemic patients? What is the overall cost of the statins? Despite the fact that the statins are the drug of choice in many situations, it is still important for these questions to be answered before we accept the widespread use of statins in the general population, such as the large numbers of patients that the drug may be prescribed for in France.

Cardiovascular Diseases↗
PubMedDate not supplied

[Pharmacologic criteria for medical substitution in opiate dependence].

Our goal was to establish new pharmacological criteria for a drug to be used in the treatment of opioid dependence. We propose the following six pharmacodynamic and pharmacokinetic criteria: (i) the same pharmacodynamic properties as the drug being substituted; (ii) a long duration of action (minimum 24 hours, not requiring several daily doses) in order to prevent fluctuations in effect and especially withdrawal symptoms; (iii) few euphoric effects together with a minimal reinforcing effect for the drug itself and other drugs; (iv) oral or sublingual administration without any special affinity for other routes, especially the intravenous; (v) a New Drug Application (NDA) in this indication, after submission of a dossier including both clinical randomised comparative trials and security data; and (vi) compatibility with a socially satisfying quality of life. These criteria were applied to methadone, buprenorphine and other drugs that were proposed in the treatment of opioid dependence (such as morphine or codeine).

Codeine↗
PubMedDate not supplied

[Validation of a measurement scale: example of a French Adverse Drug Reactions Preventability Scale].

Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts' judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs ("preventable", "potentially preventable", "unclassable", "not preventable" ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient interclass = 0.491). Classification of ADRs in the four categories by the experts showed discrepancies (Kappa = 0.1136). The preventability assessment using this scale was feasible, although poor concordance between the judges has raised some questions. Several experts found use of this scale difficult in terms of a clear understanding of the items, and found that two of them were redundant. We have oversimplified some items and revision of their formulation will be necessary. Moreover, most of ADR notifications were poorly documented, resulting in a frequent choice of an "unevaluable" item. This represented an important bias in the calculation of the global score. This experience suggests the need for further studies to improve this French ADR preventability scale and validate it in differing circumstances, in order to provide a useful tool to enhance the rational use of drugs.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

[Antidepressant adverse effects in the elderly: analysis of spontaneous reports in France].

The prescription of antidepressants in the elderly has changed since the marketing of new antidepressants such as selective serotonin reuptake inhibitors (SSRIs). We analysed the adverse effects associated with antidepressants in subjects aged > or =75 years reported to the pharmacovigilance centres in France. Among the 2381 cases recorded between 1985 and 2001, the distribution of adverse effects may reflect sales figures: 1040 for SSRIs (44%), 586 for tricyclic and related antidepressants (25%), 46 for monoamine oxidase inhibitors (2%) and 654 for other antidepressants (27%). Adverse effect patterns differed according to antidepressant class. For SSRIs, hyponatraemia was predominant (30%), followed by psychiatric (13%) and nervous system (10%) effects. For tricyclic antidepressants, psychiatric effects (confusion, agitation) [21%] were the most frequent followed by cardiovascular effects (15%). However, the consequences of adverse effects such as hyponatraemia are far from negligible in the elderly.

Adverse Drug Reaction Reporting Systems↗