Management and monitoring of patients treated with zonisamide: the OZONE study.

AIM: To characterise patients treated with zonisamide in everyday practice and describe the effectiveness and tolerability of treatment. METHODS: This was an observational, longitudinal, naturalistic study, conducted by neurologists in France. Patients who had started zonisamide treatment at least three months prior to inclusion were eligible. Data were collected at routine consultations at inclusion (Visit 1) and three to six months later (Visit 2). At Visit 1, investigators documented epilepsy-related variables based on patient records before initiation of zonisamide and at inclusion. At Visit 2, the investigators re-evaluated seizure activity and rated effectiveness. Adverse events were also documented. RESULTS: A total of 428 patients were included in the study based on evaluation by 132 neurologists. Zonisamide was initiated at a daily dose of 50 mg and 25 mg in 61% and 31.8% of patients, respectively. The median maintenance dose was 300 mg/day. Prior to initiation of zonisamide, the mean seizure frequency was 16.0 seizures/month. This was reduced to 8.7 seizures/month at Visit 1 and to 7.1 seizures/month at Visit 2. The response rate and proportion of seizure-free patients was 61.9 and 31.1% at Visit 1 and 65.9 and 25.6% at Visit 2, respectively. The frequency of seizures at Visit 2 decreased significantly (p<0.05) for all seizure type subgroups, except for simple partial seizures. Responder rates were >60% for all analysed subgroups. The proportion of seizure-free patients was significantly higher in patients receiving bitherapy, compared to the others (p=0.007). The most frequently reported adverse event was somnolence (5.1%); three serious adverse events were reported. CONCLUSION: In everyday practice, zonisamide is principally used in association with other antiepileptic drugs for the treatment of focal epilepsy in adults. It is effective in improving seizure control and quality of life, and is generally well-tolerated.

Paediatric drug development and evaluation: Existing challenges and recommendations.

Despite various international regulatory initiatives over the last 20 years, many challenges remain in the field of paediatric drug development and evaluation. Indeed, drug research and development is still focused essentially on adult indications, thereby excluding many paediatric patients, limiting the feasibility of trials and favouring competing developments. Off-label prescribing persists and the development of age-appropriate dosage forms for children remains limited. Against this background, the members of this panel (TR) recommend the launch of multi-partner exchange forums on specific topics in order to focus new drug research and development on the real, unmet medical needs of children and adolescents, and in keeping with the underlying mechanisms of action. Scientific information sharing and cooperation between stakeholders are also essential for defining reference evaluation methods in each medical field. These forums can be organised through existing paediatric facilities and research networks at the French and European level. The latter are specifically dedicated to paediatric research and can facilitate clinical trial implementation and patient enrolment. Moreover, specific grants and public/private partnerships are still needed to support studies on the repositioning of drugs in paediatric indications, and pharmacokinetic studies aimed at defining appropriate dosages. The development of new pharmaceutical forms, better suited for paediatric use, and the promotion of resulting innovations will stimulate future investments. Initiatives to gather observational safety and efficacy data following off-label and/or derogatory early access should also be encouraged to compensate for the lack of information available in these situations. Finally, the creation of Ethics Committees (EC) with a specific "mother-child" advisory expertise should be promoted to ensure that the current regulation (Jardé law in France) is implemented whilst also taking into account the paediatric specificities in medical trials.

[Polycystic kidney disease: An analysis of e-patients exchanges in the public blogosphere]. / Polykystose rénale : analyse des discussions des e-patients sur la blogosphère publique.

The goal this study was to understand the preoccupations of e-patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD), through their discussions on social networks, and to compare them with those of members of a specialized association. We collected and analyzed all messages containing an unequivocal expression of the pathology (polycystic kidney disease, PKD, ADPKD, etc.) available on public forums on the French Internet and all french-language messages posted on the forum of the patient group Association Polykystose-France (PKD-France) during 2 years. The automated processing of messages (extraction of themes), using a referential associating each theme with a variety of expressions, allowed classification in different thematic families. 8494themes were extracted from 764 messages sent by 329 different users on 68 public forum websites. The main thematic families were treatments (17%), pathology (16%), signs and symptoms (13%), feelings (11%), healthcare system (7%) and patient life (7%). On the association's forum, 345 messages were sent by 57 different members. The thematic richness was equivalent (number of themes per message: 10.2 versus 11.1 respectively), with 3517 themes, but the thematic families corresponded more to the emotional aspects and daily problems: Feelings (15.5%) came before treatment (14.5%), then anatomy (9%) before the healthcare system (8%) and pathology (7%). Knowing the e-patients' views expressed on the internet will enable physicians to respond to patients real expectations and correct erroneous perceptions. As for the patients, they will know the leading sites of opinion, shared by their peers.

Appropriate medication use in individuals aged 80 or more years.

Over the last few years, there has been a rapid and steadily expanding demographic explosion in the elderly population in France. When the most dynamic segment of this growth is considered, i.e. patients aged 80 years or more (who, moreover, usually have several diseases), under- or over-prescribing and/or inappropriate prescribing are identified. Three short- and medium-term recommendations are proposed: to quickly get expert consensus on the theme of prescribing for the aged patient; to integrate systematic drug re-evaluation into annual consultations for people aged 80 years or more; and to better coordinate actions and communication between institutions, health professionals and the pharmaceutical industry.

Apathy and depression in mild Alzheimer's disease: a cross-sectional study using diagnostic criteria.

Apathy and depression are the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). In a cross-sectional observational study of 734 subjects with probable mild AD, we evaluated the prevalence of apathy and depression. After the use of specific diagnostic criteria, we tested the interaction between the two syndromes and their relation with specific comorbidities, and different functional outcomes. Depression was diagnosed using the diagnostic criteria for depression in AD, and apathy with the diagnostic criteria for apathy in neuropsychiatric disorders. According to the specific diagnostic criteria, depression had a 47.9% prevalence, while apathy prevalence was 41.6%. Apathy and depression were associated in 32.4% of patients (n = 225). 9.4% (n = 65) had only apathy, 15.4% (n = 107) had only depression, and 42.9% had no apathy and no depression (n = 298). The three most frequent depressive symptoms were fatigue or loss of energy (59.4%), decreased positive affect or pleasure in response to social contacts and activities (46.2%), and psychomotor agitation or retardation (36.9%). Concerning apathy, loss of goal-directed cognition was the most frequently altered (63.6%), followed by loss of goal-directed action (60.6%) and loss of goal-directed emotion (43.8%). Patients with both apathy and depression more frequently required a resource allowance for dependency. Neurological comorbidities were more frequent in the "apathy and depression" and "depression alone" groups (p < 0.001). Apathy and depression overlap considerably, and this might be explained by the presence of some non-specific symptoms in both diagnostic criteria. The need for social support is higher when a patient fulfills the two diagnostic criteria.