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Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest.We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy.We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status.Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD).We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background The fear of contracting coronavirus disease 2019 (COVID-19) and the preventive measures taken during the health crisis affected both people’s lifestyles and the health system. This nationwide study aimed to investigate the impact of the first wave of the COVID-19 pandemic on hospitalizations and mortality related to geriatric syndromes (GS) in older adults in France. Methods The French National Health Data System was used to compare hospital admissions (excluding the main diagnosis of COVID-19) and mortality rates (using multiple-cause and initial-cause analyses, and both including or excluding confirmed/probable COVID-19) related to 10 different GS (dementia, other cognitive disorders and symptoms, delirium/disorientation, depression, undernutrition/malnutrition, dehydration, pressure ulcer, incontinence, fall/injury and femoral neck fracture) from January to September 2020 to rates observed in previous years. Analyses were stratified by age, sex, place of residence or place of death, and region. Results Hospitalization rates for all GS decreased during the first lockdown compared to the same periods in 2017-19 (from −59% for incontinence to −13% for femoral neck fractures). A dose–response relationship was observed between reduced hospitalizations and COVID-19-related mortality rates. Conversely, for almost all GS studied, excess mortality without COVID-19 was observed during this lockdown compared to 2015-17 (from +74% for delirium/disorientation to +8% for fall/injury), especially in nursing homes and at home. Conclusions In France, during the first lockdown, a substantial decrease in hospitalizations for GS was accompanied by excess mortality. This decline in the use of services, which persisted beyond lockdown, may have a mid- and long-term impact on older adults’ health.

ImportanceNursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented.ObjectivesThe primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present.DesignWe studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System).Main outcome and measuresThe main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated.ResultThere were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563).ConclusionNH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.Key pointsDuring the first wave of the COVID-19 pandemic in France, the mortality among nursing home residents increased by 43%.Nursing home residents accounted for 51% of the total excess deaths in France.The excess mortality was higher among younger residents than among older residents.The excess mortality was higher among males than among females.We did not observe a harvesting effect during the study period (ending on August 30th, 2020, i.e., three months after the end of the first wave).

Background Robust public health and health system response to the increasing burden of multimorbidity worldwide requires detailed epidemiological examination of its key sociodemographic and geographic determinants. We investigated the role of gender, age and socioeconomic and geographic factors on multimorbidity (i.e., having two or more conditions) in the adult population in France and examined implications for surveillance and prevention. Methods We used data from two large nationwide representative surveys with cross-sectional and longitudinal health and socio-demographic indicators, conducted in France between 2008 and 2014. Morbidity counts and frequent dyads/triads of conditions independently impacting mortality, activity limitations, and perceived health were investigated with regard to differences in gender, age, socioeconomic (education, occupation and income) and geography (size of the urban unit and region). Results The component conditions of multimorbidity varied with gender and age. Women experienced multimorbidity 23–31% more frequently and at a younger age (5–15 years earlier) than men. Multimorbidity increased with age while its associations with most health indicators weakened with it. Multimorbidity was strongly and independently associated with socioeconomic indicators, with a strong inverse dose-response relationship with education, but less consistently with geographic factors. Conclusions Multimorbidity has diverse and variable components and impacts across gender and age. It is strongly associated with socioeconomic factors, notably educational level, for which causality appears likely. Consideration of this diversity and variability, its common occurrence in dyads and triads, and its impact on health outcomes according to age and gender may contribute to efficient surveillance and support the identification of prevention strategies targeting middle-aged men and women.

Background Dementia onset in those aged, In an observational study, Laure Carcaillon-Bentata and colleagues investigate the prevalence and incidence of dementia onset among adults younger than 65 years of age using data from the French national health data system from 2016., Author summary Why was this study done? Dementia onset in people aged 55% of the sex difference in YOD incidence. What do these findings mean? We extrapolate that there were approximately 24,000 and approximately 5,300 persons with prevalent and incident YOD, respectively, in France in 2016. YOD incidence is higher in men than women, and this could possibly be due, at least in part, to the higher prevalence of cardiovascular and neurovascular diseases and substance abuse disorders in men.

Falls in older people are a major public health problem due to associated morbidity and mortality. Their origin is most often multifactorial.The objective of the present study, called ChuPaDom, was to identify patterns or profiles of home fallers (HF) - understood here as people who fall in their place of residence - among a sample of persons aged 65 and over who were hospitalized after a fall, and to study their association with falling-induced injuries using data from the ChuPAdom study.Multiple correspondence analysis and Hierarchical Clustering on Principal Components were performed. Multivariate logistic regression was used to test for associations between HF profiles and injuries.The sample comprised 1467 patients (69% female, average age = 84.5 years). Five profiles were identified: youngest seniors who took risks and fell from a raised height, youngest seniors with specific health problems who fell down a stairs, autonomous seniors who fell because they lost their balance or fell from their own height, dependent seniors who fell during low-intensity activities, very old seniors for whom missing data were frequent. Fractures were more frequent among the first profile than the last two profiles constituted with more dependent individuals (p 0.001).These results highlight the heterogeneity of the circumstances in which older people fall. A greater understanding of these circumstances is needed to implement targeted prevention actions.

Summary Background The coronavirus disease 2019 (COVID-19) pandemic and the national lockdown have led to significant changes in the use of emergency care by the French population. Aims To describe the national and regional temporal trends in emergency department (ED) admissions for myocardial infarction (MI) and stroke, before, during and after the first national lockdown. Methods The weekly numbers of ED admissions for MI and stroke were collected from the OSCOUR® network, which covers 93.3% of all ED admissions in France. National and regional incidence rate ratios from 02 February until 31 May (2020 versus 2017–2019) were estimated using Poisson regression for MI and stroke, before, during and after lockdown. Results A decrease in ED admissions was observed for MI (–20% for ST-segment elevation MI and–25% for non-ST-segment elevation MI) and stroke (–18% for ischaemic and–22% for haemorrhagic) during the lockdown. The decrease became significant earlier for stroke than for MI. No compensatory increase in ED admissions was observed at the end of the lockdown for these diseases. Important regional disparities in ED admissions were observed, without correlation with the regional levels of COVID-19 cases. The impact of lockdown on ED admissions was particularly significant in six regions (Ile-de France, Occitanie, Provence-Alpes-Cote d’Azur, Nouvelle Aquitaine, Hauts-de-France and Bretagne). Conclusions The decrease in ED admissions for MI and stroke observed during the lockdown was probably caused by fear of COVID-19 and augmented by the lockdown, and was heterogeneous across the French territory. ED admissions were slow to return to the usual levels from previous years, without a compensatory increase. These results underline the need to reinforce messages directed at the population to encourage them to seek care without delay in case of cardiovascular symptoms.

ObjectiveTo examine the relation of age with male-to-female (M/F) ratios and incidence rates of motor neuron disease (MND) in a French nationwide study and meta-analysis of incidence studies.MethodsWe used data from the French National Health Insurance databases. Patients with incident MND (2010–2014) were identified based on drug claims (riluzole), hospitalization records, death records, and long-term chronic disease benefits. We estimated age-specific M/F incidence ratios using Poisson regression. Poisson, Gompertz, and multistep models were used to model the relation between age and incidence. We performed a meta-analysis (n = 28 studies) and used meta-regression to examine the relation of age with incidence rates and ratios.ResultsIn France, we identified 10,848 patients with incident MND (6,021 men, 4,827 women). Incidence was higher in men than in women in all age groups. M/F ratios were significantly different across age groups and followed a quadratic trend (p < 0.001). Between 20 and 49 years, the average M/F ratio was 2.26 (95% confidence interval [CI] = 1.96–2.62); it was 1.41 (95% CI = 1.35–1.47) between 50 and 84 years, and 1.88 (95% CI = 1.64–2.17) after 85 years. Incidence was lower in women than men at younger ages, but increased more steeply in women than men. Similar patterns were observed in the meta-analysis of incidence studies, especially in 19 higher-quality studies.ConclusionThe relation between age and M/F incidence ratios of MND follows a quadratic U-shaped pattern with an abrupt drop after the fifth decade. The change in M/F ratios before and after menopause suggests that reproductive/hormonal protective factors have a role in women and should prompt further studies to explore this hypothesis.

RESUME Il existe en France des bases de donnees medico-administratives (BDMA) nationales qui permettent de fournir pour la quasi-totalite de la population francaise des donnees de recours aux soins et d’hospitalisation depuis 2006 ; il s’agit du Systeme national d’information inter-regimes d’assurance maladie ou SNIIRAM gere par la Caisse nationale d’assurance maladie des travailleurs salaries. Ces donnees representent une opportunite considerable pour la surveillance et pour la recherche, notamment en epidemiologie et dans le domaine des services de sante. Neanmoins, l’identification des patients atteints de maladies specifiques grâce a des algorithmes construits a partir de ces sources de donnees pose des difficultes methodologiques non negligeables. L’objectif de cet article est de discuter l’utilisation du SNIIRAM pour identifier les patients atteints par trois maladies neurodegeneratives (maladie d’Alzheimer ou autres demences, maladie de Parkinson, maladie du motoneurone) et de presenter quelques exemples recents de leur utilisation dans le cadre du programme de surveillance des maladies neurodegeneratives mis en place par Sante publique France avec le conseil scientifique de l’Inserm. Nous montrons que la validite des estimations de frequence obtenues a partir du SNIIRAM sont variables et dependent notamment des caracteristiques de la maladie d’interet et de l’existence d’un algorithme valide. Compte tenu de la facilitation de l’acces aux donnees du SNIIRAM et les travaux autour de la qualite des algorithmes, les travaux utilisant ces donnees sont amenes a se developper dans les annees a venir et devraient contribuer a ameliorer les connaissances sur ces maladies graves et au cout sanitaire, economique et social eleve.

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.

To estimate the prevalence of pre-frailty, frailty and multimorbidity in individuals without disability in France. To describe independent determinants of each indicators. Two nationally representative cross-sectional French surveys. Wave 2012 of the Health, Health Care and Insurance Survey (Enquete Sante et Protection Sociale, ESPS) and data from the Disability Healthcare Household section Survey (Enquete Handicap Sante–Menages, HSM) from 2008. Two representative samples of the French population aged 55 and older (n=4,328 and n=12,295). Frailty was assessed using Fried’s frailty phenotype and multimorbidity was defined as having had at least two groups of the following groups of comorbidities in the last 12 months (cardio or cerebrovascular disease, diabetes, chronic respiratory disease, arthralgia, depression). Independent determinants were studied using weighted logistic regressions. In the French population over 55 and free of disability, 55 to 62% of individuals were either frail, pre-frail or multimorbid, 22 to 25% being frail or multimorbid. ESPS and HSM prevalences for frailty (11.1% [9.3%-12.1%] and 12.3% [11.5%-13.0%]) and multimorbidity (14.9% [13.6%-16.2%] and 16.8% [15.9%-17.7%]) were consistent across studies. Both frailty and multimorbidity prevalences were associated with age. On the other hand, pre-frailty prevalence varied consistently between studies (from 38 to 48%) and was not significantly associated with age. We found that more than 60% of frail subjects did not present with multimorbidity and around 70% of subjects with multimorbidity were not frail. Determinants of pre-frailty and multimorbidity but not frailty depended on sex. Similar factors were associated with frailty and multimorbidity in women (older age, functional decline, poor mental health, financial difficulties) while only poor mental health was independently associated with both indicators in men. Our study highlights that in France, among individuals older than 55 years-old and free of disability, around 25% are either frail or multimorbid; another 30% to 40% being pre-frail. Pre-frailty, frailty and multimorbidity are known to be associated with adverse health outcomes and important economic costs. The health system must adapt to respond to the needs of its aging population. In addition, given the efficient impact of prevention actions, our findings emphasize the need to implement prevention strategies against Frailty and multimorbidity in France.

International audience; Importance: Parkinson disease (PD) is an increasingly common neurodegenerative disorder in many aging societies. Although comorbidities with mental disorders are common in PD, whether PD is associated with an increased risk of suicide is unclear. Objective: To use a large national representative PD cohort to compare the risk of suicide in patients with PD and control participants and identify potential risk factors. Design, Setting, and Participants: This nationwide population-based cohort study used linked data from Taiwan's National Health Insurance data set and Taiwan Death Registry between January 2002 and December 2016. Patients with incident PD diagnosed between January 2005 and December 2014 were followed up until December 2016. Four control participants from the general population were randomly selected by risk set sampling and were matched on age, sex, and residence to each affected individual. Data analysis occurred from June 2019 to October 2020. Exposures: Diagnosis of PD retrieved from the National Health Insurance data set. Main Outcomes and Measures: Suicide was recorded in the Taiwan Death Registry. Cox proportional models and hazard ratios (HRs) were used to estimate the association between PD and the risk of suicide over the follow-up period. Results: Over 11 years, 35891 patients with PD were followed up (17482 women [48.7%]; mean [SD] age, 72.5 [10.1] years) and matched to 143557 control participants (69928 women [48.7%]; mean [SD] age, 72.5 [10.1] years). A total of 151 patients with PD (cumulative incidence, 66.6 per 100000 [95% confidence limits [CL], 78.1-91.7]) and 300 control participants (cumulative incidence, 32.3 per 100000 [95% CL, 36.2-40.5]) died by suicide. The risk of suicide was higher (HR, 2.1 [95% CL, 1.7-2.5]) in patients with PD than control participants, after adjustment for markers of socioeconomic position, medical comorbidities, and dementia. After controlling for mental disorders, the association between PD and suicide risk remained (HR, 1.9 [95% CL, 1.6-2.3]). Compared with control participants who died by suicide, those who died by suicide in the PD group were slightly younger (mean [SD] age: patients with PD, 74.0 [10.4] years vs control participants, 76.0 [10.2] years; P =.05) and more likely to be urban dwelling (medium urbanization, 39 patients with PD [25.8%] vs 115 control participants [38.3%]; high urbanization, 84 patients with PD [55.6%] vs 136 control participants [45.3%]; P =.03), have mental disorders (depression, 15 of 151 patients with PD [9.9%] vs 15 of 300 control participants [5.0%]; other mental disorders, 12 patients with PD [8.0%] vs 11 control participants [3.7%]; P =.02), and adopt jumping as a method of suicide (21 patients with PD [13.9%] vs 16 control participants [5.3%]; P

Introduction Des symptomes non moteurs (troubles du sommeil, depression, anxiete, constipation) sont decrits pendant la phase prodromale de la maladie de Parkinson (MP). Ils pourraient impacter la vie professionnelle (capacites de travail, desinsertion, stigmatisation) des patients avant leur diagnostic. Objectifs Cette etude cas-temoin nationale vise a : – quantifier la proportion de patients parkinsoniens en arret maladie avant leur diagnostic et de la comparer a celles de temoins ; – evaluer le role mediateur de certains symptomes non moteurs. Methodes Les cas incidents de MP (2014–2015) âges de moins de 60 ans ont ete identifies parmi les affilies au regime general a partir d’un algorithme valide utilisant les remboursements de medicaments du Systeme national des donnees de sante. Trois temoins par cas ont ete tires au sort et apparies sur l’annee d’incidence du cas, l’âge, le sexe et le departement. Les indemnites journalieres pour arret maladie ont ete identifiees chaque annee au cours des 8 ans avant le diagnostic (meme periode pour les temoins). L’evolution de la proportion annuelle d’arrets a ete comparee a l’aide de modeles log-Poisson pour donnees repetees et des ratios de prevalence (RP) ajustes et leur intervalle de confiance [IC95 %] ont ete calcules. Des comparaisons suivant les durees d’arret dans l’annee ont ete conduites en estimant des odds ratios (OR) a l’aide d’un modele logistique multinomial. Le role respectif des symptomes anxio-depressifs et de la constipation a ete evalue dans une analyse de mediation. Resultats L’etude inclut 4060 cas et 11 534 temoins (53 % d’hommes). L’âge median est de 53 ans. Au cours des 8 ans avant le diagnostic, les proportions annuelles d’arrets sont stables chez les temoins (p = 0,286) mais elles augmentent chez les cas avec la proximite avec l’annee de diagnostic (p = 0,003 ; difference entre cas et temoins, p Conclusions Les patients atteints de MP en âge de travailler ont plus d’arrets maladie que des temoins apparies avant leur diagnostic, meme 7 ans avant. Les differences sont plus prononcees pour les durees d’arrets plus longues. Ces resultats demontrent l’impact des symptomes non moteurs, notamment anxio-depressifs, sur la vie professionnelle au cours de la phase prodromale de la MP.

Little is known about programmes or interventions for the screening, monitoring and surveillance of frailty at population level.Three systematic searches and an opportunistic grey literature review from the countries participating in the ADVANTAGE Joint Action were performed.Three studies reported local interventions to screen for frailty, two of them using a two-step screening and assessment method and one including monitoring activities. Another paper reviewed both providers' and participants' experiences of screening activities. Three on-going European projects and population-screening programmes in primary care await evaluation. An electronic Frailty Index for use with patients' primary care records has been recently validated. No study described systematic processes for the surveillance of frailty.There is insufficient evidence for the effectiveness of population-level screening, monitoring and surveillance of frailty. Development and evaluation of community-based two-step programmes including those that incorporate electronic health records, particularly in primary care, are now needed.

Although frailty is common among community-dwelling older adults, its prevalence in Europe and how this varies between countries is unclear.A systematic review and meta-analysis of literature on frailty prevalence in 22 European countries involved in the Joint Action ADVANTAGE was conducted.Sixty-two papers, representing 68 unique datasets were included. Meta-analysis showed an overall estimated frailty prevalence of 18% (95% confidence interval, CI, 15-21%). The prevalence in community (n = 53) vs non-community based studies (n = 15) was 12% (95% CI 10-15%) and 45% (95% CI 27-63%), respectively. Pooled prevalence in community studies adopting a physical phenotype was 12% (95% CI 10-14%, n = 45) vs 16% (95% CI 7-29%, n = 8) for all other definitions. Sub-analysis of a subgroup of studies assessed as high-quality (n = 47) gave a pooled estimate of 17% (95% CI 13-21%).The considerable and significant heterogeneity found warrants the development of common methodological approaches to provide accurate and comparable frailty prevalence estimates at population-level.

Frailty is a dynamic syndrome and may be reversible. Despite this, little is known about trajectories or transitions between different stages of frailty.A systematic review was conducted, selecting studies reporting frailty trajectories or transition states for adults in any settings in European ADVANTAGE Joint Action Member States.Only three papers were included. Data were from longitudinal community-based cohorts in the United Kingdom, Netherlands and Italy. The English study investigated the effect of physical activity on the progression of frailty over a 10-year period. Two presented data on the proportion of participants experiencing at least one frailty transition over time (32.6% in the Italian sample aged ≥ 65 years followed for 4.4 years; 34.3% in the Dutch sample aged 65-75 years, followed for 2 years).Data on frailty trajectories and transition states were limited and heterogeneous. Well-designed prospective studies and harmonized approaches to data collection are now needed.