RESUMO
BACKGROUND AND AIM: Recreational use of nitrous oxide (N2O) has been associated with the development of severe nitrous oxide-induced neuropathy (N2On). Follow-up of these patients poses challenges, and their clinical progression remains largely unknown. The identification of prognostic factors is made difficult by the lack of standardized longitudinal assessments in most studies. The objective was to document the course of neuropathy through systematic follow-up assessments in N2On patients to identify prognostic factors for persistent disability after 6 months. METHODS: We gathered demographic, clinical, biological, and electrophysiological data from N2On patients hospitalized in the Referral center in Marseille, both at baseline and during a standardized follow-up assessment at 6 months. RESULTS: We retrospectively included 26 N2On patients (mean age 22.6 ± 4.4). Significant improvements were observed in all main clinical scores including Rankin, ONLS, and MRC testing (p < .01). Electrophysiological studies (EDX) revealed a predominantly motor neuropathy with marked reduction in CMAP in the lower limbs at baseline, and no significant improvement in motor parameters (p = .543). Rankin score at 6 months correlated with the initial weekly N2O consumption (r = .43, p = .03) and the CMAP sum score in the lower limbs at the first EDX (r = -.47, p = .02). Patients with and without myelitis showed similar Rankin and ONLS score after 6 months. INTERPRETATION: The clinical course generally improved favorably at 6 months with notable amelioration in the primary disability scores, sensory deficits, and ataxia. However, distal motor impairment associated with peripheral neuropathy persisted, with distal axonal loss emerging as the main prognostic factor for long-term disability in these young patients.
Assuntos
Óxido Nitroso , Doenças do Sistema Nervoso Periférico , Humanos , Óxido Nitroso/efeitos adversos , Óxido Nitroso/administração & dosagem , Masculino , Feminino , Adulto , Adulto Jovem , Estudos Retrospectivos , Prognóstico , Estudos Longitudinais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Seguimentos , Adolescente , Condução Nervosa/fisiologia , Condução Nervosa/efeitos dos fármacosRESUMO
BACKGROUND: Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. METHODS: A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. RESULTS: The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05-1.49]; aHR time-varying 8.74 [5.21-14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22-2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26-3.63]). The relative incidence (RI) for all events was 2.13 [1.76-2.58] in the SCCS, for cardiac (RI: 1.67 [1.23-2.27]) and for cerebral events (RI: 3.20, [2.30-4.45]). CONCLUSION: The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.
Assuntos
Hospitalização , Triptaminas , Humanos , Idoso , Feminino , Masculino , Hospitalização/estatística & dados numéricos , Triptaminas/efeitos adversos , Triptaminas/uso terapêutico , Estudos de Coortes , Idoso de 80 Anos ou mais , Pontuação de Propensão , França/epidemiologiaRESUMO
AIMS: The aim of this paper is to assess recent developments in non-medical tramadol use, tramadol use disorder, illegal procurement and deaths. METHODS: This study used repeated cross-sectional analysis of data collected nationwide from 2013 to 2018. Analysis was conducted through multisource monitoring of the French Addictovigilance Network of: (1) validated reports of high-risk tramadol use, (2) record systems collecting information from toxicology experts investigating analgesic-related deaths (DTA) and deaths related to substance abuse (DRAMES), and pharmacists for forged prescriptions (OSIAP), and (3) survey of drug users, with investigation of patterns of use while visiting addiction-specialised institutions (OPPIDUM). RESULTS: Despite a plateauing level of tramadol exposure in the French population, the proportion of tramadol reports increased 1.7-fold (187 cases in 2018, 3.2% (95% confidence interval [CI]: 2.74-3.63%), versus 1.9% (95% CI: 1.49-2.42% in 2013). Trends were similar in OSIAP: 11.9% of forged prescriptions in 2018 (95% CI: 10.56-13.45%); 1.7-fold increase; in OPPIDUM: 0.76% (95% CI: 0.55-1.02); 2.2-fold increase; and DRAMES: 3.2% of drug abuse-related deaths in 2018 (95% CI: 1.89-5.16) versus 1.7% in 2013 (95% CI: 0.65-3.84). Tramadol was the primary opioid in analgesic-related deaths in DTA (45% in 2018). Two profiles of high-risk tramadol users were identified: (1) patients treated for pain or with tramadol persistence when pain disappeared (mainly women; mean age 44 years), and (2) individuals with non-medical use for psychoactive effects (mainly men; mean age 36 years). CONCLUSION: The triangulation of the data obtained through addictovigilance monitoring evidenced a recent increase in high-risk tramadol use. These findings have a practical impact on the limitation of the maximal duration of tramadol prescriptions.
Assuntos
Transtornos Relacionados ao Uso de Substâncias , Tramadol , Adulto , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Dor/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tramadol/efeitos adversosRESUMO
The study aim was to assess the abuse/misuse potential of second-generation antipsychotics (SGAPs) using VigiBase data. We extracted individual case safety reports of "Drug abuse, dependence and withdrawal" involving SGAPs up to June 2018. We assessed disproportionate reporting by calculating the information component, considering the lower end of the 95% credibility interval for the information component (IC025 ), and the proportional reporting ratio. We identified 1683 individual case safety reports recorded as "abuse, dependence and withdrawal" involving SGAPs, mainly quetiapine (n = 1089) and olanzapine (n = 209). The disproportional reporting indicators highlighted an association between "Drug abuse and dependence", and quetiapine, olanzapine and ziprasidone, as indicated by the IC025 (2.263, 0.259 and 1.051, respectively) and proportional reporting ratio values (3.929, 1.020 and 1.334, respectively). The abuse/misuse potential is confirmed for quetiapine and olanzapine and highlighted for the first time for ziprasidone. Physicians should consider these risks when prescribing these antipsychotics, especially to patients with history of drug abuse.
Assuntos
Antipsicóticos , Transtornos Relacionados ao Uso de Substâncias , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Humanos , Olanzapina/efeitos adversos , Farmacovigilância , Fumarato de Quetiapina/efeitos adversos , Organização Mundial da SaúdeRESUMO
AIMS: Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence. METHODS: A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed. RESULTS: The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly. CONCLUSION: The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.
Assuntos
Analgésicos não Narcóticos , Transtornos Relacionados ao Uso de Opioides , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológicoRESUMO
PURPOSE/BACKGROUND: Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. Therefore, we implemented a 24-hour sleep deprivation (SD) design on healthy volunteers in a randomized, double-blind, placebo-controlled, crossover study on 36 healthy volunteers. METHODS/PROCEDURE: To validate the SD model, cognitive tests were chosen to assess a transient worsening of cognitive functions after SD and a restoration under modafinil as positive control (one dose of 200 mg). Then, the same evaluations were replicated after 15 days of donepezil (5 mg/d) or memantine (10 mg/d). The working memory (WM) function was assessed by the N-back task and the rapid visual processing (RVP) task. FINDINGS/RESULTS: The accuracy of the N-back task and the reaction time of the RVP revealed the alteration of the WM with SD and its restoration with modafinil (changes in score after SD compared with baseline before SD), respectively, in the placebo group and in the modafinil group (-0.2% and +1.0% of satisfactory answers, P = 0.022; +21.3 and +1.9 milliseconds of reaction time, P = 0.025). Alzheimer disease drugs also tended to reverse this deterioration: the accuracy of the N-back task was more stable through SD (compared with -3.0% in the placebo group, respectively, in the memantine group and in the donepezil group: -1.4% and -1.6%, P = 0.027 and P = 0.092) and RVP reaction time was less impacted (compared with +41.3 milliseconds in the placebo group, respectively, in the memantine group and in the donepezil group: +16.1 and +29.3 milliseconds, P = 0.034 and P = 0.459). IMPLICATIONS/CONCLUSIONS: Our SD challenge model actually led to a worsening of WM that was moderated by both modafinil and AD drugs. To use this approach, the cognitive battery, the vulnerability of the subjects to SD, and the expected drug effect should be carefully considered.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Voluntários Saudáveis/psicologia , Memantina/uso terapêutico , Memória de Curto Prazo/efeitos dos fármacos , Privação do Sono/psicologia , Adulto , Doença de Alzheimer/psicologia , Estudos Cross-Over , Donepezila/uso terapêutico , Método Duplo-Cego , Humanos , Masculino , Modafinila/uso terapêutico , Modelos Psicológicos , Testes Neuropsicológicos , Nootrópicos/uso terapêutico , Tempo de Reação/efeitos dos fármacosRESUMO
After the publication of an article discussing the methodological options to detect the diversion potential of prescription drugs, this letter presents the multidimensional functioning of the French Addictovigilance System. This system aims at monitoring all substances with abuse potential, relying on a network of experts specialized in clinical and fundamental pharmacology. For more than 25 years, we have created collaborations with partners at the interface with field data related to substance use and the potential related disorders. When relevant depending on the context, these data sources are explored and crossed to analyze the abuse potential of one given substance. This organizational approach is useful to detect early Addictovigilance warning signals and to take appropriate measures. Generalizing such a multidimensional approach outside France appears an appealing option to move towards more effective Addictovigilance systems at the international level.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transtornos Relacionados ao Uso de Substâncias , Bases de Dados Factuais , França , Humanos , FarmacovigilânciaRESUMO
AIMS: Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA). METHODS: From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. RESULTS: G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m-2 . Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. CONCLUSION: This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Neoplasias/tratamento farmacológico , Farmacovigilância , Microangiopatias Trombóticas/epidemiologia , Idoso , Desoxicitidina/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microangiopatias Trombóticas/induzido quimicamente , GencitabinaRESUMO
AIM: The aim of the present study was to characterize patterns of use of methylphenidate (MPH), a prescription stimulant medication recommended in the treatment of attention deficit hyperactivity disorder (ADHD) and of narcolepsy, in France, both in children and adults, over a 3-year period. METHODS: Using the French General Health Insurance database, limited to two areas covering approximately 4 million individuals, we made up a cohort of incident MPH users between July 2010 and June 2013. Splitting them into distinct age groups (18-24, 25-49 and ≥50 years of age for adults and <6, 6-11 and 12-17 years of age for children), we established the characteristics of these populations at MPH initiation and during follow-up according to the duration of treatment, quantities dispensed and coprescription with central nervous system (CNS) drugs. RESULTS: We included a cohort of 3534 incident users, involving 30 238 dispensings of MPH, leading to an annual rate of 29 incident users per 100 000 in 2013. Children (66% of new users) were characterized by long-term use of MPH with few comedications. The group of 25-49-year-old patients were dispensed MPH more frequently than other groups, had the highest mean dose and were more often coprescribed other CNS drugs. The ≥50 year-old group was more often coprescribed antidepressants and antiparkinsonian drugs. CONCLUSIONS: Our pharmacoepidemiological study involving incident MPH users with a large number of characteristics showed different patterns of MPH use among children and adults. The results from the 25-49-year-old group suggested that MPH might be being used for medical conditions other than ADHD or narcolepsy in adults, and that it might be subject to misuse and/or abuse.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Narcolepsia/tratamento farmacológico , Padrões de Prática Médica/tendências , Adolescente , Adulto , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Bases de Dados Factuais , Prescrições de Medicamentos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Narcolepsia/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer's disease, the analysis of networks altered by medication would be particularly interesting. Eleven healthy subjects were recruited in the context of the European Innovative Medicines Initiative 'PharmaCog'. Each underwent five sessions of simultaneous EEG-fMRI in order to investigate the effects of donepezil and memantine before and after sleep deprivation (SD). The SD approach has been previously proposed as a model for cognitive impairment in healthy subjects. By applying network based statistics (NBS), we observed altered brain networks significantly linked to donepezil intake and sleep deprivation. Taking into account the sleep stages extracted from the EEG data we revealed that a network linked to sleep is interacting with sleep deprivation but not with medication intake. We successfully extracted the functional resting-state networks modified by donepezil intake, sleep and SD. We observed donepezil induced whole brain connectivity alterations forming a network separated from the changes induced by sleep and SD, a result which shows the utility of this approach to check for the validity of pharmacological resting-state analysis of the tested medications without the need of taking into account the subject specific vigilance.
Assuntos
Encéfalo/efeitos dos fármacos , Donepezila/farmacologia , Rede Nervosa/efeitos dos fármacos , Nootrópicos/farmacologia , Privação do Sono/fisiopatologia , Sono/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Privação do Sono/diagnóstico por imagemRESUMO
Ketamine is frequently used in the management of refractory chronic pain. To date, the level of proof in the literature on ketamine in this type of indication is generally poor and physicians have no consensus or recommendation to support their practice. This narrative review is an update on literature data assessing the efficacy and safety of ketamine in chronic pain. The electronic search of the Medline, PubMed, Google Scholar and Cochrane databases identified a total of 61 articles including randomized and non-randomized trials and 14 international reviews. In view of these data, it is difficult to conclude on the effectiveness of ketamine in this type of indication and on its safety due to the heterogeneity of practice in terms of doses, routes, duration and frequency of administration and especially a lack of clinical trials with a high level of evidence.
Assuntos
Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Ketamina/uso terapêutico , Analgésicos/efeitos adversos , Analgésicos/farmacocinética , Dor Crônica/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Ketamina/efeitos adversos , Ketamina/farmacocinética , Manejo da Dor/efeitos adversos , Manejo da Dor/métodos , Resultado do TratamentoRESUMO
Because national data on proton pump inbibitors (PPIs) consumption in France are scarce and because there is a growing literature on potential adverse drug reaction induced by this pharmacological class, we would like to more describe the main evolution of PPI use and the main characteristics of its users in France. We used a 1/97th representative sample of beneï¬ciaries of the French health insurance called "échantillon généraliste des bénéficiaires" (EGB) to describe PPIs' use over time (duration of use by year) from 2006 to 2016. In 2016, 108,249 patients had at least 1 dispensing of PPI (i.e. 19.5% of EGB versus 16.5% in 2006). The part of patients with only 1 reimbursement of PPI by years decreased from 43.9% in 2006 to 39.0% in 2016. Among the patient with at least 2 PPI dispensing/years, the mean number of dispensing increased from 6.2±4.2 in 2006 to 6.9 in 2016. The over 75 year's old group is particularly concerned by the increase in both duration and dosage over the period of study, as mean DDD per year increased by 31% and mean number of dispensing per year by 17% from 2006 to 2016. Based on these results, PPI users could almost represent 11 million peoples in France (13 million on a whole population) in 2016. Initiatives to assess the appropriateness of use of these drugs might be warranted.
Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Uso de Medicamentos , Feminino , França/epidemiologia , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Programas Nacionais de SaúdeRESUMO
Over the course of these last decades, we observed a change on opioid use with the marketing of opiate maintenance treatment, an increase of opioids used for pain management and recent concerns have arisen around the use of synthetic opioid. The World Health Organization (WHO) reports around 70,000 people opioid overdose death each year. In France, according to the DRAMES program (fatalities in relation with abuse of licit or illicit drugs) of the French addictovigilance network, most of deaths are related to opioids overdose (especially methadone, following by heroin, buprenorphine and opioid used for pain management). Opioid overdose is treatable with naloxone, an opioid antagonist which rapidly reverses the effects of opioids. In recent years, a number of programs around the world have shown that it is feasible to provide naloxone to people likely to witness an opioid overdose. In 2014, the WHO published recommendations for this provision and the need to train users and their entourage in the management of opioid overdose. In this context, in July 2016, French drug agency has granted a temporary authorization for use of a naloxone nasal spray Nalscue®. Because different opioids can be used and because each opioid has specific characteristics (pharmacodynamics, pharmacokinetics, galenic form ), the risk of overdose may differ from one opioid to another and it may be necessary, depending on the clinical context, to use larger and repeated doses of naloxone.
Assuntos
Overdose de Drogas/tratamento farmacológico , Serviços de Assistência Domiciliar , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Medicina do Vício/métodos , Medicina do Vício/organização & administração , Medicina do Vício/normas , França , Serviços de Assistência Domiciliar/organização & administração , Serviços de Assistência Domiciliar/normas , Humanos , Erros de Medicação/efeitos adversos , Erros de Medicação/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/diagnósticoRESUMO
Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship. Several mechanisms have been suggested through in vitro studies (endothelial dysfunction, endothelial senescence, hypomagnesemia, increase of chromogranin A levels, decrease of nitric oxide in endothelial cells) leading to the impairment of vascular homesostasis, paving the way to these complications. Evidence that PPIs may have off-targets and pleiotropic effects are mounting and may impose a cautious attitude in the prescription of PPI's, especially in elderly and/or in the context of chronic use.
Assuntos
Inibidores da Bomba de Prótons/efeitos adversos , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Segurança , Pesquisa Translacional BiomédicaRESUMO
The constant development of health technologies, combined with the increase in the cost of treatment, means that States must continually make choices about the introduction of new technologies into their healthcare system and how they are to be funded. In France, the systematic participation of patients in these processes is one of the targets to be met in terms of healthcare democracy. Although, on an international level, patient involvement in these assessments is constantly growing, it is difficult to define due to the presence of unstabilised elements in terms of both terminology and assessment methods. As a result, patient and public involvement in health technology assessments varies considerably from one country to the next, from one field to the next and even from one type of technology to the next. Several types of involvement exist, ranging from studies conducted to collect patient "insight" (experience, perception, needs, preferences, attitudes to treatment and health, etc.) to processes aimed at including patients in assessments (as individuals, as representatives of associations, etc.). Given the scope and complexity of the subject, and the difficulty involved in understanding all the different aspects of health technologies and innovations, the members of the Round Table chose to concentrate on health technology assessments (medicinal products and medical devices) to develop national recommendations on all possible types of patient involvement in the health technology assessment processes conducted by the health authorities in France.
Assuntos
Participação da Comunidade , Avaliação da Tecnologia Biomédica , HumanosRESUMO
AIMS: Acute kidney injury (AKI) is associated with a high hospitalization rate, accelerated long-term decline in kidney function and a high mortality rate. Adverse drug reactions (ADRs) constitute one of the most important modifiable factors in the context of AKI. Most studies of drug-induced AKI have focused on a sole drug class. The objective of the present study was to establish a comprehensive overview of drug-induced AKI on the basis of spontaneously reported ADRs in the French national pharmacovigilance database (FPVD). METHODS: We performed a case-noncase study of drug-induced AKI. Cases corresponded to the reports of AKI recorded in the FPVD between 1 January 2015 and 31 December 2015. The noncases corresponded to all other spontaneously reported ADRs (excluding AKI) recorded in the FPVD during the same period. Data were expressed as the reporting odds ratio (ROR) and the 95% confidence interval. RESULTS: Of the 38 782 ADRs recorded in the FPVD during the study period, 3.2% were classified as cases of AKI. A total of 1254 patients experienced AKI (males: 55%; mean age ± standard deviation: 68.7 ± 15.0 years). Overall, 15.2% of the patients required renal replacement therapy. Two or more concomitantly administered drugs were involved in 66% of the cases of AKI. The most frequently implicated drug classes were antibacterial agents for systemic use (29.5%), diuretics (18.5%), agents acting on the renin-angiotensin system (16.3%), antineoplastic agents (10.2%) and anti-inflammatory agents (5.4%). Gentamicin, eplerenone, spironolactone, candesartan, cisplatin and acyclovir had the highest RORs (>10). CONCLUSION: A comprehensive study of a national pharmacovigilance database enabled us to identify the drug classes that most frequently induced AKI. Even though most of the identified drugs were already known to induce AKI, the present work should raise physicians' awareness of the compounds responsible for triggering this potentially life-threatening condition.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Farmacovigilância , Injúria Renal Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , França/epidemiologia , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Terapia de Substituição Renal/estatística & dados numéricos , Adulto JovemRESUMO
In France, most cases of opioid use disorder are treated with buprenorphine by general practitioners in private practice. Using reimbursement data of a representative sample of the French population, Echantillon Généraliste des Bénéficiaires, we investigated mortality during periods when patients were in and out of treatment in a cohort of 713 new users of buprenorphine having a mean (SD) follow-up of 4.5 (1.5) years. The mortality rate was 0.63 per 100 person-years (95% CI, 0.40-0.85) overall. In a multivariate Cox regression model, compared with being in treatment, being out of treatment was associated with a markedly increased risk of death (hazard ratio = 29.04; 95% CI, 10.04-83.99). Buprenorphine appears to be a strong protective factor against mortality.
Assuntos
Buprenorfina/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/mortalidade , Adulto , Estudos de Coortes , Feminino , França/epidemiologia , Medicina Geral , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
PURPOSE: Drugs administered to hospitalized patients are not available within almost all health insurance databases. However, this unobservable exposure time bias is very rarely taken into account in pharmacoepidemiology. The objective was to model unobservable periods due to hospitalization and to assess their impact on risk estimates in the context of the association between benzodiazepines and mortality. METHODS: A cohort study was identified using the General Sample of Beneficiaries in France for the period 2006-2012. Benzodiazepines incident users were matched to incident users of antidepressants/non-benzodiazepine sedatives and to controls (non-users) according to age and gender. All-cause mortality at 1 year (Cox regression model) was studied using time-dependent variables (exposed/unexposed or under two hypotheses, inpatients are exposed or inpatients are unexposed), complemented with a multistate model based on observable/unobservable/death status. RESULTS: In each group, 57 242 patients were included. All-cause mortality was significantly higher among those exposed to benzodiazepines (adjusted hazard ratio (aHR) = 1.17, 95% confidence interval (CI) = 1.04, 1.32), as compared with controls. Use of benzodiazepines exposure as a time-dependent variable resulted in significant results after adjustment (aHR = 1.45, 95%CI = 1.16, 1.80). When inpatients were considered as unexposed, all-cause mortality was not significantly increased (aHR = 0.85, 95%CI = 0.76, 1.10), but was significantly augmented when inpatients were considered as exposed (aHR = 2.93, 95%CI = 2.46, 3.48). CONCLUSIONS: This study highlights the need to take account of the impact of unobservable exposure periods on risk estimates. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Benzodiazepinas/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Farmacoepidemiologia/métodos , Adulto , Idoso , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Benzodiazepinas/efeitos adversos , Viés , Estudos de Coortes , Feminino , França , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de TempoRESUMO
INTRODUCTION: Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. AIM: We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. MATERIAL AND METHODS: We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. RESULTS: Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. CONCLUSION: Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hemorragia Gengival/induzido quimicamente , Farmacovigilância , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , FarmacoepidemiologiaRESUMO
We report the case of a 32-year-old man who developed acute psychiatric disorders after repeated intravenous injections of methylphenidate. The behavioural disorders with extreme psychomotor restlessness and delirious syndrome have resolved within 24hours. The available data highlight the fact that the prescriptions of methylphenidate, an amphetamine-like substance, are constantly increasing in Europe and Northern America. The potential of abuse and addiction to this drug, which is growingly misused, is now clearly established. The medical professionals should be cautious and attentive to the risk of misuse of this drug.