Appropriateness of psychotropic drug prescriptions in the elderly: structuring tools based on data extracted from the hospital information system to understand physician practices.

BACKGROUND: The appropriateness of psychotropic prescriptions in the elderly is a major quality-of-care challenge at hospital. Quality indicators have been developed to prevent inappropriate psychotropic prescriptions. We aimed to select and automatically calculate such indicators, from the Bordeaux University Hospital information system, and to analyze the appropriateness of psychotropic prescription practices, in an observational study. METHODS: Experts selected indicators of the appropriateness of psychotropic prescriptions in hospitalized elderly patients, according to guidelines from the French High Authority for Health. The indicators were reformulated to focus on psychotropic administrations. The automated calculation of indicators was analyzed by comparing their measure to data collected from a clinical audit. In elderly patients hospitalized between 2014 and 2015, we then analyzed the evolution of the appropriateness of psychotropic prescription practices during hospital stay, using methods of visualization, and described practices by considering patients' characteristics. RESULTS: Two indicators were automated to detect overuse and misuse of psychotropic drugs. Indicators identified frequent inappropriate drug administrations, but practices tended to become more appropriate after quality-of-care improvement actions. In the majority of patients (85%), there was no inappropriate administration of psychotropic drugs during hospital stay; for the remaining 15% with at least one inappropriate administration, physicians tended to limit overuse or misuse during hospital stay. Inappropriate administrations were more frequent in patients suffering from psychiatric disorders, dependence and associated complications or morbidities. CONCLUSIONS: The automated indicators are structuring tools for the development of a drug prescription monitoring system. Inappropriate psychotropic administrations were limited by physicians during hospital stay; some inappropriate prescriptions might be explained by clinical characteristics of patients.

Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece.

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPSIII) is a lysosomal storage disease with predominant neurological manifestations in affected children. It is considered heterogeneous with respect to prevalence, clinical presentation, biochemistry (four biochemical forms of the disease referred to as MPSIIIA, B, C, and D are known), and causative mutations. The perspective of therapeutic options emphasizes the need for better knowledge of MPSIII incidence and natural history. We performed parallel retrospective epidemiological studies of patients diagnosed with MSPIII in France (n = 128), UK (n = 126), and Greece (n = 20) from 1990 to 2006. Incidences ranged from 0.68 per 100,000 live-births in France to 1.21 per 100,000 live-births in UK. MPSIIIA, which predominates in France and UK, was absent in Greece, where most patients have MPSIIIB. The study confirmed the large allelic heterogeneity of MPSIIIA and MPSIIIB and detected several yet undescribed mutations. Analysis of clinical manifestations at diagnosis and over a 6-7 years follow-up indicated that almost all patients, whatever the disease subtype, expressed neurological manifestations before the age of 5 years, including language acquisition delay, cognitive delay, and/or abnormal behavior. In contrast to relatively homogeneous early onset manifestations, disease progression showed significant variation depending on subtype and age at diagnosis. Different severities of disease progressions and different allele distribution between France and UK suggested that mutations are not equally deleterious, although genotype-phenotype correlation could not be established. Notwithstanding the rapidity of further clinical deterioration, all MPSIII patients suffer early onset devastating neurological manifestations that deserve early treatment when available.

School performance in a cohort of children with CNS inflammatory demyelination.

BACKGROUND: Acute CNS inflammatory demyelination in childhood may induce permanent cognitive impairment. However, there has been no epidemiological assessment of prognostic factors for school performance in a cohort of children with such a disease. METHODS: The cohort consisted of 344 children from the French "KIDSEP" neuropediatric cohort with at least one clinically defined attack of CNS inflammatory demyelination occurring before the age of 16 years, and with at least two years of follow-up (inclusion from 1990 to 2003, follow-up until June 2007). We used multivariate survival analysis (Cox model) to evaluate the prognostic value for grade retention between the start of elementary school ( approximately 6 years of age) and the end of high school ( approximately 17-18 years of age), of variables related to both the socioeconomic status of the parents and the characteristics of the disease at onset. RESULTS: The cohort was monitored for a mean of 8.0+/-3.4 years. Grade retention after disease onset was recorded for 151 patients (43.9%). The risk of grade retention was significantly higher for boys, children from families with lower social status and poorer housing conditions, children over the age of 11 years at disease onset and children suffering optic neuritis or brainstem dysfunction at the first attack or irreversible disability, even if only moderate, following the first attack. CONCLUSIONS: The risk factors for poor school performance are related to low socioeconomic status and to factors predictive of a relapsing severe course of the disease, leading to the diagnosis of multiple sclerosis.

Clinically observed chickenpox and the risk of childhood-onset multiple sclerosis.

The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population.

Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood.

BACKGROUND: The risk of CNS inflammatory demyelination associated with hepatitis B (HB) vaccine is debated, with studies reporting conflicting findings. METHODS: We conducted a population-based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France (1994-2003). Each case was matched on age, sex, and geographic location to up to 12 controls, randomly selected from the general population. Information on vaccinations was confirmed by a copy of the vaccination certificate. The odds ratios (ORs) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression. RESULTS: The rates of HB vaccination in the 3 years before the index date were 24.4% for the 349 cases and 27.3% for their 2,941 matched controls. HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination (adjusted OR, 0.74; 0.54-1.02), neither >3 years nor as a function of the number of injections or brand type. When the analysis was restricted to subjects compliant with vaccination, HB vaccine exposure >3 years before index date was associated with an increased trend (1.50; 0.93-2.43), essentially from the Engerix B vaccine (1.74; 1.03-2.95). The OR was particularly elevated for this brand in patients with confirmed multiple sclerosis (2.77; 1.23-6.24). CONCLUSIONS: Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood. However, the Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term. Our results require confirmation in future studies.

Effectiveness of early beta interferon on the first attack after confirmed multiple sclerosis: a comparative cohort study.

BACKGROUND: In the absence of randomized controlled trials to support therapeutic decisions in pediatric MS (multiple sclerosis), comparative observational studies based on the real practice of physicians are important tools. AIM: To assess the effectiveness of beta interferon (ssIFN) in preventing the first attack and severe disability after confirmed MS diagnosis in a pediatric cohort. METHODS: A cohort of 197 relapsing-remitting pediatric MS patients was studied (1990-2005). Patients were followed from MS diagnosis until the first subsequent attack or severe disability occurrence (DSS score of >or=4) or were censored. The Cox model, with time-dependent ssIFN exposure to account for the varying times of starting this treatment, was used to estimate the effect of ssIFN on the risk of this attack or severe disability, adjusting for potential confounding factors. RESULTS: During cohort follow-up (mean 5.5 years), 70.5% of the 197 children had a first attack (80% within the first 2 years) and 24 started ssIFN (mean delay 3.6 months; mean duration 17.1 months). The use of ssIFN was associated with a significant reduction in the rate of the first attack during the first year of treatment (hazard ratio: 0.31, 95% confidence interval: 0.13-0.72) as well as the first 2 years (0.40, 0.20-0.83). This effect was less significant over the entire follow-up of up to 4 years of treatment (0.57, 0.30-1.10). The use of ssIFN suggests a reduction on the occurrence of severe disability, although not statistically significant (HR 0.78; 95% CI: 0.25-2.42). CONCLUSIONS: The use of ssIFN, given after the diagnosis of MS, significantly reduces the risk of relapse during the first 2 years.

Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis.

OBJECTIVE: To investigate whether vaccination against hepatitis B (HB) increases the risk of incident multiple sclerosis (MS) in childhood in the short and long terms. DESIGN: Case-control study. SETTING: Population-based study conducted in France from January 1, 1994, to December 31, 2003. PARTICIPANTS: The case patients had incident MS with onset before age 16 years. Each case was individually matched for age, sex, and geographic location (current place of residence) to 12 control participants randomly selected from the general population of France. EXPOSURE: Hepatitis B vaccine. MAIN OUTCOME MEASURE: The risk of MS associated with HB vaccine exposure. RESULTS: One hundred forty-three case patients with MS were matched to 1122 control participants. The rate of HB vaccination in the 3 years before the index date was approximately 32% for both cases and controls. Vaccination against HB within the 3-year study period was not associated with an increased rate of a first episode of MS (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.69). The rate was also not increased for HB vaccination within 6 months of the index date or at any time since birth or as a function of the number of injections or the brand of HB vaccine. CONCLUSION: Vaccination against HB does not seem to increase the risk of a first episode of MS in childhood.

Parental smoking at home and the risk of childhood-onset multiple sclerosis in children.

The possibility of a link between active smoking and incident multiple sclerosis (MS) has been raised. However, possible links between incidence of MS and passive smoking, particularly in children, have not been analysed. We conducted a population-based, case-control study. The cases were patients with incident MS occurring between 1994 and 2003, before the age of 16 years, in France. Each case was matched for age, sex and geographic origin with 12 controls, randomly selected from the French general population. Information about the smoking history of the parents of the cases and controls was collected with a standardized questionnaire. Conditional logistic regression was used to estimate the rate ratio (RR) of MS associated with parental smoking at home. The 129 cases of MS were matched with 1038 controls. Information about parental smoking was obtained for all these cases and controls. Exposure to parental smoking was noted in 62.0% of cases and 45.1% of controls. The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 (95% confidence interval: 1.43-3.15). Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases (over 10 years of age at the time of the index episode)-RR 2.49 (1.53-4.08)-than in younger cases. Children exposed to parent smoking have a higher MS risk. The duration of exposure also affects the level of risk.

Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination.

Public concern about possible increases in the risk of multiple sclerosis associated with hepatitis B vaccination has led to low vaccination coverage. We investigated whether this vaccination after a first episode of acute CNS inflammatory demyelination in childhood increased the risk of conversion to multiple sclerosis. We studied the French Kid Sclérose en Plaques (KIDSEP) neuropaediatric cohort of patients enrolled between 1994 and 2003 from their first episode of acute CNS inflammatory demyelination (inclusion in the cohort) until the occurrence of a second episode, up to 2005. A Cox proportional hazards model of time-dependent vaccine exposure was used to evaluate the effect of vaccination (hepatitis B, tetanus) during follow-up on the risk of second episode occurrence (conversion to multiple sclerosis). The cohort included 356 subjects with a mean follow-up of 5.8 years (SD 2.7). Relapse occurred in 146 (41%) subjects during follow-up; 33 subjects were exposed to hepatitis B vaccine and 28 to tetanus vaccine at some time during follow-up. The adjusted hazard ratio (HR) for relapse occurring within 3 years of hepatitis B vaccination was 0.78 (0.32-1.89) and during any time period was 1.09 (0.53-2.24). The adjusted HR for relapse occurring within 3 years of tetanus vaccination was 0.99 (0.58-1.67) and during any time period was 1.08 (0.63-1.83). We conclude that vaccination against hepatitis B or tetanus after a first episode of CNS inflammatory demyelination in childhood does not appear to increase the risk of conversion to multiple sclerosis, although the possibility of a small increase in risk cannot be excluded.

Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse.

To date, there is no available epidemiological study about prognostic factors of acute disseminated encephalomyelitis (ADEM) in children, using a cohort of patients with homogenous inclusion criteria. We aimed to evaluate prognostic factors for relapse after ADEM in children. A total of 132 children from the French National KIDSEP Neuropediatric Cohort (mean age at onset: 6+/-3.3 years; mean follow-up: 5.4+/-3.3 years; lost to follow-up: 10%). ADEM diagnosis was considered in a previously healthy patient acutely presenting more than one neurological deficit, change in mental state and MRI alterations including white matter changes. We used multivariate survival analysis (Cox model) evaluating the prognostic value of baseline clinical, biological and MRI covariates, for the occurrence of a second attack. Twenty-four (18%) of included patients had a second attack. An increased risk of relapse was associated with optic neuritis (hazard ratio, 5.23; 95% CI, 2-13.65), familial history of central nervous system inflammatory demyelination (7.79; 1.54-39.5), Barkhof multiple sclerosis (MS) criteria on MRI (2.52; 1.04-6.12) and no neurological sequelae after first attack (3.79; 1.12-12.85). Clinical and MRI prognostic factors for relapse in ADEM may contribute to an early distinction between monophasic and relapsing disease, which may be related to MS.

Prognostic factors for early severity in a childhood multiple sclerosis cohort.

OBJECTIVE: The goal was to identify prognostic factors for an early severe course in a cohort of patients with childhood-onset multiple sclerosis, for the construction of a predictive tool. METHODS: The cohort consisted of 197 children from the French Kid Sclérose en Plaques neuropediatric cohort with relapsing/remitting multiple sclerosis beginning before the age of 16 years. Patients were included from 1990 to 2003. We used multivariate survival analysis (Cox model) to evaluate the prognostic value of clinical, MRI, and biological covariates at onset for the occurrence of a third attack or severe disability ("severity" outcome). RESULTS: The cohort was monitored for a mean of 5.5 +/- 3.6 years. The "severity" outcome was recorded for 144 patients (73%). The risk of severity was higher for girls, for a time between the first and second attacks of < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an absence of severe mental state changes at onset, and for a progressive course. A derived childhood-onset multiple sclerosis potential index for early severity was found to have a positive predictive value for severity of > 35% for the upper 2 quartiles. CONCLUSIONS: The clinical and MRI prognostic factors for early severity that were identified were used as the basis of a predictive tool, which will be validated in another cohort. This tool should make it possible to identify subgroups at risk of early severe disease and should facilitate therapeutic studies.