Alzheimer's disease and related syndromes and hospitalization: a nationwide 5-year longitudinal study.

BACKGROUND AND PURPOSE: To study the association between Alzheimer's disease and related syndromes (ADRS) and the incidence of short-stay hospitalizations from the year before (Y-1 ) to 4 years after (Y1 -Y4 ) ADRS identification in the healthcare system. METHODS: Among all beneficiaries of the French health insurance general scheme aged 40 years or more, those with an incident ADRS in 2011, identified through long-term disease registry, hospitalization diagnoses or ADRS-specific drug delivery, were matched with beneficiaries without ADRS of the same age, gender and residence area. The annual incidence rates of all-cause hospitalizations (excluding those with a diagnosis code of ADRS) were compared between individuals with or without ADRS using incidence ratios (IRs) globally and by age, gender, deprivation index and modified Charlson score. We also studied cause-specific hospitalizations using patients' diagnoses and procedure codes. RESULTS: A total of 90 871 subjects with and 90 871 subjects without ADRS were included (mean age 79.6 years, 66% females). From Y-1 to Y4 , incidence rates were significantly higher in subjects with ADRS than in those without for all-cause hospitalization [IR(Y-1 ) = 1.73; 95% confidence intervals, 1.71-1.75; IR(Y4 ) = 1.37; 95% confidence intervals, 1.35-1.39], hospitalizations for social reasons [IR(Y-1 ) = 4.28; IR(Y4 ) = 2.70], fall [IR(Y-1 ) = 5.36; IR(Y4 ) = 2.59], injury [IR(Y-1 ) = 2.71; IR(Y4 ) = 2.09] and infection [IR(Y-1 ) = 2.04; IR(Y4 ) = 2.07]. The inverse was observed for hospitalizations for cataract surgery [IR(Y-1 )=0.73; IR(Y4 ) = 0.51] or total hip prosthesis after 2 years [IR(Y4 ) = 0.72]. CONCLUSIONS: Incident ADRS cases were associated with a higher incidence of hospitalization, but these subjects underwent some common non-emergency surgeries less frequently. Future studies need to assess the clinical impact of these differences.

[Identification of neurodegenerative diseases in administrative databases in France: A systematic review of the literature]. / Identification des maladies neurodégénératives dans les bases de données médicoadministratives en France : revue systématique de la littérature.

BACKGROUND: Given the health, social and economic burden of neurodegenerative diseases (ND), the development of epidemiologic studies is required. Administrative databases, such as the French national health insurance database (SNIIRAM) could represent an opportunity for researchers. ND could be presumed from drug reimbursement data, hospital stays or registration of a chronic condition. The aim of this study was to describe, in French administrative databases, algorithms used to identify Alzheimer's disease and associated disorders (ADAD), Parkinson's disease and associated disorders (PDAD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). METHODS: A systematic literature review was performed in Medline and gray literature through December 31th, 2015. French studies focusing on ADAD, PDAD, MS or ALS as a primary health outcome, conducted among one of the SNIIRAM data sources (outpatient reimbursements, chronic condition registration, hospital discharge) were included. RESULTS: Thirty-four studies were included (ADAD, n=18, PDAD, n=9, MS, n=4, ALS, n=3), leading to 36 algorithms. For each studied ND, there was an important variability in the algorithms, concerning (i) the type of criteria used (administrative database versus multi-source systems); (ii) the number of criteria used; (iii) the definition used for each criteria. The extent and level of drug exposure highly varied. Identification through hospitalizations showed variations in terms of type of stay (short stay, long-term stay, psychiatric ward…), extent of diagnosis codes used, diagnosis type (principal, related, associated diagnosis) and period used. A validation study was conducted for 2 out of 36 algorithms (PDAD), and criteria completeness was estimated for 3 algorithms (MS, ALS). CONCLUSION: Despite the increase in ND identification among French administrative databases, few algorithms have been validated. Validation studies should be encouraged.

[Preventive staff meetings in maternity ward for women at high medico-psycho-social risk: Qualitative study between 2012 and 2018]. / Réunions pluridisciplinaires en maternité pour les femmes à haut risque médico-psycho-social : étude qualitative entre 2012­2018.

OBJECTIVE: To assess the effectiveness of a multidisciplinary consultation meeting created in collaboration between a perinatal psychiatry team and professionals from a level 3 maternity hospital, whose purpose is to prepare the delivery and postpartum of pregnant women at high medico-psycho-social risk. I) Study the functioning of these multidisciplinary meetings. II) Assess the concordance between the decisions made in antenatal care and the actual management of the delivery and postpartum care. METHODS: This is a retrospective study of 140 files for which the opinion of the multidisciplinary meeting was requested in the years 2012, 2014, 2016 and 2018. We looked at the psychiatric files of the patients, as well as the summary sheets written after staff meetings. RESULTS: The selection of files is compliant in 98% of cases and the traceability of information in the summary sheet is over 80% for half of the process indicators. The overall compliance rate between the decisions taken at meetings and their implementation in the post-partum period is 68%. Acute psychiatric episode and reporting could be anticipated. CONCLUSION: This multidisciplinary consultation meeting is efficient in the early detection of risk situations. The decisions taken during the multidisciplinary meetings in antenatal care are mostly applied postpartum in the Maternity Ward. In cases where they are not applied, the system offers great reactivity to postpartum professionals.

Attrition in geriatric research: how important is it and how should it be dealt with?

Attrition, defined as a total loss to follow-up of participants, is a potential major bias in clinical trials. Participants can be lost for many reasons (death, illness, worsened health, refusal, withdrawal, lost to follow up). Attrition may be higher in older populations, so geriatric researchers should pay particular attention to the difficulties it raises. For a proper interpretation of research findings, a detailed analysis of the type of attrition observed and its possible determinants is essential, to determine if attrition has occurred at random or if it is associated to certain patient or treatment characteristics. This paper aims to review different causes of attrition, its prevalence among studies in different elderly populations, and its consequences on research findings. In addition, strategies used to minimise attrition (tracking, bonding, incentives) are discussed, and methods proposed to take this phenomenon into account are proposed.

Drug-induced myoclonus: a French pharmacovigilance database study.

Various drugs have been reported to induce myoclonus. However, this adverse event is not well known because of the difficult diagnosis and the lack of pharmaco-epidemiological or controlled studies. As far as we know, there are only case reports. In the literature, antiparkinsonian medications, antipsychotics, antidepressants, anesthetics, opiates and anti-infectious drugs have been reported in the occurrence of myoclonus. In a French pharmacovigilance database study, only 423 reports (0.2%) involved drug-induced myoclonus. The median age of patients was 55 years and 10% of these patients had a concomitant neurological disease. Only 16% of these reports had a strong imputability score (likely). The most frequently involved drugs were anti-infectious (15%), antidepressants (15%), anxiolytics (14%), and opiates agents (12%). Fifty-six percent of these reports were classified as serious adverse event. Concerning outcome, most patients (84%) recovered without sequels.

Representations and practices of prevention in elderly populations: investigating acceptance to participate in and adhesion to an intervention study for the prevention of Alzheimer's disease (ACCEPT study)--the need for a multidisciplinary approach.

BACKGROUND: In the domain of Alzheimer's disease (AD) prevention, various potentially protective factors have been identified in epidemiological studies. Although the results of these observational studies have been relatively consistent, the results of intervention studies remain disappointing. Methodological problems could explain these negative results, like the selection of the population; a plausible assumption is that the older people who agree to take part in these intervention studies differ from those who refuse, and are those that are least likely to benefit from such programs. The aim of this study was (i) to study the determinants of participation in and adhesion to a prevention trial in a population of older individuals via a quantitative approach using a questionnaire, (ii) to study the representations and practices of prevention in this population using a qualitative approach using semi-structured interviews and focus groups. METHOD: The study population for the ACCEPT study was recruited at the time of inclusion of subjects in a prevention trial. The population was made up of persons aged 70 years or older, living at home and demonstrating some form of frailty, defined as a spontaneous memory complaint to their general practitioner or difficulties in carrying out instrumental activities of daily living. We used a quantitative approach based on the administration of a self-completed questionnaire sent to 1680 subjects having accepted to take part in the prevention trial, and to the sample of subjects meeting the inclusion criteria but having refused to take part. The qualitative approach, carried out at the moment of inclusion, involved subjects that having accepted to take part and subjects that having refused. Semi-structured interviews were carried out in order to understand the logic leading to refusal or acceptance. CONCLUSION: The analysis of the results will combine the viewpoints of the different disciplines. It will allow us to better understand the logic at work, to characterise the populations at risk of refusal, and perhaps to remove some of the barriers to participation in prevention programs. The identification of such barriers will provide feedback in terms of the conception and management of prevention measures.

Progression of Alzheimer disease in Europe: data from the European ICTUS study.

The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts/first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems. Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p < 0.001) and admission to nursing home (2.97, 95%CI: 1.83-4.11, p < 0.001) were lowest in Southern Europe. In general cognitive and functional decline was slower than in former cohorts. European geographical location reflecting differences in culture and in health care system does not impact on the progression of AD but does influence the management of AD subjects and caregiver burden.

How should we deal with missing data in clinical trials involving Alzheimer's disease patients?

Missing data are frequent in Alzheimer's disease (AD) trials due to the age of participants and the nature of the disease. This can lead to bias and decreased statistical power. We assessed the level and causes of missing data in a 2-year randomised trial of an AD patient management program (PLASA study), and conducted sensitivity analyses on the primary endpoint (functional decline), using various methods for handling missing data: complete case, LOCF, Z-score LOCF, longitudinal mixed effects model, multiple imputation. By 2 years, 32% of the 1131 subjects had dropped out, with the commonest reasons being death (28% of dropouts) and refusal (22%). Baseline cognitive and functional status were predictive of dropout. All sensitivity analyses led to the same conclusion: no effect of the intervention on the rate of functional decline. All analyses demonstrated significant functional decline over time in both groups, but the magnitude of decline and between-group (intervention versus usual care) differences varied across methods. In particular, the LOCF analysis substantially underestimated 2-year decline in both groups compared to other methods. Our results suggest that data were not "missing completely at random", meaning that the complete case method was unsuitable. The LOCF method was also unsuitable since it assumes no decline after dropout. Methods based on the more plausible "missing at random" hypothesis (multiple imputation, longitudinal mixed effects models, z-score LOCF) appeared more appropriate. This work highlights the importance of considering the validity of the underlying hypotheses of methods used for handling missing data in AD trials.

Incidence and predictive factors of depressive symptoms in Alzheimer's disease: the REAL.FR study.

BACKGROUND: Many patients develop psychiatric and behavioral disturbances in the course of Alzheimer's disease (AD). Among these disturbances, depressive symptoms are frequent and affect nearly 40% of patients. The natural history and course of such symptoms in AD, and in particular the predictive factors, are little known. We studied the incidence and risk factors for the development of the first depressive symptoms in AD. DESIGN: Multicenter prospective study. PARTICIPANTS: Three hundred twelve AD patients from the French Network on AD (REAL.FR) without depression and without antidepressant treatment at baseline were followed up and assessed every 6 months for 4 years. During follow-up, all events occurring between two visits were carefully recorded. MEASUREMENTS: We used the Neuropsychiatric Inventory (NPI) for comprehensive evaluation of behavioral and psychological symptoms and depressive symptoms in particular. A multivariate analysis was performed using a backward stepwise Cox proportional hazards model. RESULTS: The incidence of depressive symptoms was 17.45% person/years, 95%CI (13.88-21.02). Among non-time dependent variables, duration of disease (RR=0.51; 95%CI: 0.30-0.85, p=0.0102) and the number of comorbid conditions (RR=0.45; 95%CI: 0.24-0.83, p=0.0115) were protective factors against the development of depressive symptoms. Agitation/aggression (RR=1.96; 95%CI: 1.19-3.23, p=0.0078) and sleep disturbances (RR=2.65; 95%CI: 1.40-5.00, p=0.0026) were time-dependent variables predictive of depressive symptoms. CONCLUSION: Better knowledge of predictive factors of mood disturbances in AD will enable clinicians to set up appropriate management of their patients. As published longitudinal studies are few, further works should be carried out to improve knowledge of the pattern and course of depression and depressive symptoms in AD.

Predictors of symptoms of post-traumatic stress disorder after the AZF chemical factory explosion on 21 September 2001, in Toulouse, France.

OBJECTIVE: To analyse in the general population the prevalence and predictors of symptomatology consistent with post-traumatic stress disorder (S-PTSD) 18 months after an industrial explosion. DESIGN: Cross-sectional survey. PARTICIPANTS AND OUTCOME MEASURES: A random sample of 1191 city inhabitants, including an oversample of the immediate area (<3 km). S-PTSD was measured by the self-administered Impact of Event Scale-Revised. The relation between S-PTSD and individual vulnerability factors, immediate exposure and post-trauma factors was analysed by gender. RESULTS: S-PTSD was more prevalent in the immediate area than in the peripheral area (women 19% vs 8%; men 8% vs 2%, p<0.01). In the immediate area, S-PTSD was independently associated with birth outside France (men: OR(a) = 13.9, 95% CI 3.7 to 52.8; women: OR(a) = 2.1, 95% CI 1.0 to 4.2), age more than 40 years (men: OR(a) = 4.3, 95% CI 1.01 to 18.2; women: OR(a) = 2.3, 95% CI 1.1 to 4.5), previous psychotropic treatment (men: OR(a) = 11.5, 95% CI 2.4 to 53.6), proximity to the explosion (less educated men only) (OR(a) = 9.3, 95% CI 1.9 to 44.7), rescue efforts (men: OR(a) = 5.2, 95% CI 1.5 to 18.2), temporarily uninhabitable home (men: OR(a) = 5.8, 95% CI 1.9 to 18.1), personal injury (women: OR(a) = 3.7, 95% CI 1.7 to 8.4), financial difficulties (men: OR(a) = 17.4, 95% CI 4.2 to 72.1; women: OR(a) = 3.4, 95% CI 1.7 to 7.1) and inconvenience due to closure of public services (women: OR(a) = 4.1, 95% CI 1.6 to 9.9). CONCLUSIONS: Individual vulnerability, exposure and post-trauma factors were associated with S-PTSD. Vulnerable subgroups, defined by low socioeconomic characteristics may warrant focused screening after such disasters.