Metrological performances of the global chronic morbidity indicator of the Minimum European Health Module and implications for chronic disease prevalence and socioeconomic gradient estimations.

BACKGROUND: Although the global chronic morbidity indicator (GCMI) of the Minimum European Health Module (MEHM) was not specifically designed to monitor chronic disease in the population, it is increasingly used for this purpose in Europe and elsewhere. However, its metrological characteristics have seldom been examined, with various sensitivity issues being raised. The present study investigated the metrological performances of the GCMI and analyzed its implications in terms of prevalence and demographic and socioeconomic gradients of chronic conditions in the population. METHODS: We used data from two large French nationwide representative surveys with cross-sectional and longitudinal data conducted between 2010 and 2021. The surveys used MEHM and collected data on numerous chronic conditions and socioeconomic indicators. Criterion and predictive validity of the GCMI regarding chronic conditions and the resultant socioeconomic gradients were compared with indicators based on reports of individual chronic conditions. RESULTS: GCMI sensitivity to capture chronic conditions varied from <20 to 80% depending on the chronic condition. Number of chronic conditions, gender, age and education were also associated with GCMI endorsement. However, the GCMI was predictive of mortality and activity limitations independently of individual conditions. CONCLUSION: The varying lack of sensitivity depending on the chronic condition and the respondent's sociodemographic status may bias estimates of demographic and socioeconomic gradients compared with indicators based on reports of individual chronic conditions. Differences between GCMI and list-based approaches should be more cautiously considered when monitoring chronic conditions in the population. These approaches should be viewed as complementary rather than contradictory or interchangeable.

Equating and linking Patient-Reported Outcomes Measurement Information System 29-item questionnaire and 36-item Short-Form Health Survey domains using Rasch modeling.

OBJECTIVES: To develop a simple, practical methodology to equate or link equivalent domains of the 36-item Short-Form Health Survey (SF-36) and the Patient-Reported Outcomes Measurement Information System 29-item questionnaire (PROMIS-29) using the Rasch framework. STUDY DESIGN AND SETTING: In April 2016, the PROMIS-29 and SF-36 were completed by 1501 individuals selected to be representative of the French population. For each domain common to the two questionnaires, a Partial Credit Model was fitted to the items related to that dimension in the two questionnaires. These items were then calibrated on the same metric, which enabled the scores from one questionnaire to be associated with the scores from the other. RESULTS: Six of the seven PROMIS-29 scales and five of the six SF-36 subscales (physical, pain, social, vitality, depression and anxiety domains) were equated or linked. Correspondence tables between scores, with a 95% confidence interval, were established for each domain. A freely available Stata macro program was developed to automatize the equating or linking process. CONCLUSION: These results should facilitate comparisons across studies using the SF-36 and the PROMIS-29 in France. The equating or linking process developed is simple to implement and can be used in other countries and for other instruments.

Prevalence of long COVID in the general adult population according to different definitions and sociodemographic and infection characteristics. A nationwide random sampling survey in France in autumn 2022.

OBJECTIVES: Long COVID has been recognized since early 2020, but its definition is not unanimous, which complicates epidemiological assessments. This study estimated the prevalence of long COVID based on several definitions and severity thresholds in the adult population of mainland France and examined variations according to sociodemographic and infection characteristics. METHODS: A cross-sectional survey using random sampling was conducted in August-November 2022. Participants declaring SARS-CoV-2 infection were assessed for infection dates and context, post-COVID symptoms (from a list of 31, with onset time, daily functioning impact, and alternative diagnosis), and perceived long COVID. Long COVID prevalence was estimated according to the WHO, National Institute for Health and Care Excellence, United States National Centre for Health Statistics, and United Kingdom Office for National Statistics definitions. RESULTS: Of 10 615 participants, 5781 (54.5%) reported SARS-CoV-2 infection, with 123-759 (1.2-13.4%) having long COVID, depending on the definition. The prevalence of WHO post-COVID condition (PCC) was 4.0% (95% CI: 3.6-4.5) in the overall population and 8.0% (95% CI: 7.0-8.9) among infected individuals. Among the latter, the prevalence varied from 5.3% (men) to 14.9% (unemployed) and 18.6% (history of hospitalization for COVID-19). WHO-PCC overlapped poorly with other definitions (kappa ranging from 0.18 to 0.59) and perceived long COVID (reported in only 43% of WHO-PCC). DISCUSSION: Regardless of its definition, long COVID remains a significant burden in the French adult population that deserves surveillance, notably for forms that strongly impact daily activities. More standardized definitions will improve integrated surveillance of, and better research on, long COVID.

Multimorbidity and frailty are associated with poorer SARS-CoV-2-related outcomes: systematic review of population-based studies.

BACKGROUND: Estimating the risks and impacts of COVID-19 for different health groups at the population level is essential for orienting public health measures. Adopting a population-based approach, we conducted a systematic review to explore: (1) the etiological role of multimorbidity and frailty in developing SARS-CoV-2 infection and COVID-19-related short-term outcomes; and (2) the prognostic role of multimorbidity and frailty in developing short- and long-term outcomes. This review presents the state of the evidence in the early years of the pandemic. It was conducted within the European Union Horizon 2020 program (No: 101018317); Prospero registration: CRD42021249444. METHODS: PubMed, Embase, World Health Organisation COVID-19 Global literature on coronavirus disease, and PsycINFO were searched between January 2020 and 7 April 2021 for multimorbidity and 1 February 2022 for frailty. Quantitative peer-reviewed studies published in English with population-representative samples and validated multimorbidity and frailty tools were considered. RESULTS: Overall, 9,701 records were screened by title/abstract and 267 with full text. Finally, 14 studies were retained for multimorbidity (etiological role, n = 2; prognostic, n = 13) and 5 for frailty (etiological role, n = 2; prognostic, n = 4). Only short-term outcomes, mainly mortality, were identified. An elevated likelihood of poorer outcomes was associated with an increasing number of diseases, a higher Charlson Comorbidity Index, different disease combinations, and an increasing frailty level. DISCUSSION: Future studies, which include the effects of recent virus variants, repeated exposure and vaccination, will be useful for comparing the possible evolution of the associations observed in the earlier waves.

Prevalence, demographic and spatial distribution of treated epilepsy in France in 2020: a study based on the French national health data system.

BACKGROUND: Although still incomplete, the epidemiology of epilepsy shows substantial variations in the burden of the condition according to demographic, social and territorial characteristics. This study aimed to estimate the prevalence of treated epilepsy and to investigate its demographic and spatial distribution in 2020 in France, a country where the nationwide epidemiological situation of the condition remains largely unknown. METHODS: We used the French national health data system, which covers nearly the entire population residing in France (over 67 million of inhabitants in metropolitan and overseas departments). Prevalent cases were identified using long-term disease status, hospitalisation for epilepsy (ICD-10 codes G40 or G41), and reimbursements for antiseizure medications and electroencephalograms. RESULTS: In 2020, we identified 685,122 epilepsy cases, corresponding to an overall prevalence of 10.2 per 1000 inhabitants [95% confidence interval 10.1-10.2], with similar rates in men and women. Estimates were found to increase with age, with an accelerated rise in the second half of the life, which occurred earlier in men than in women. We observed a monotonic gradient of variation with socio-economic deprivation (in non-military metropolitan subjects aged 18-54 years) as well as territorial heterogeneity, with the mountainous centre of France as well as some French overseas departments having the highest prevalence. CONCLUSIONS: Our results revise upwards the estimation of epilepsy prevalence in France, showing that it now ranks among the highest in developed countries. Our study also confirms the important socio-territorial heterogeneity of the condition that reflects health inequalities in this country.

Complex association between post-COVID-19 condition and anxiety and depression symptoms.

BACKGROUND: To assess the associations between anxiety and depressive symptoms and post-COVID-19 condition (PCC) by exploring the direction of these associations and their relevance in the definition of PCC. METHODS: Nationwide survey among French adults, recruited between March and April, 2022, using a quota method to capture a representative sample of the general population with regard to sex, age, socioeconomic status, size of the place of residence, and region. We included all participants who met the World Health Organization (WHO) definition of PCC in addition to a random sample of participants infected with SARS-COV-2 for at least 3 months but without PCC. Self-reported anxiety and depressive symptoms, chronic anxiety and depression (for more than 3 years), and anxiety and depression were measured using the GAD-2 and PHQ-2 questionnaires, respectively. RESULTS: In a sample of 1,095 participants with PCC and 1,021 participants infected with SARS-COV-2 without PCC, 21% had self-reported anxiety and 18% self-reported depression, whereas 33% and 20% had current measured symptoms of anxiety and depression, respectively. The high prevalence of these symptoms cannot only be explained by the characterization of PCC, as only 13.4% of anxiety symptoms and 7.6% of depressive symptoms met the WHO criteria for PCC. Only one participant met the WHO criteria based on self-reported anxiety or depressive symptoms alone, as these were always combined with other symptoms in patients with PCC. Chronic symptoms were associated with PCC (aOR 1.27; 95% CI: 1.00-1.61). In addition, measured anxiety was associated with PCC (aOR = 1.29; 95% CI: 1.02-1.62). CONCLUSIONS: Pre-COVID-19 chronic anxiety and depression may play a role in the development of PCC or share vulnerability factors with it. Our results challenge the inclusion of anxiety and depression in the definition of PCC.

Collider and reporting biases involved in the analyses of cause of death associations in death certificates: an illustration with cancer and suicide.

BACKGROUND: Mortality data obtained from death certificates have been studied to explore causal associations between diseases. However, these analyses are subject to collider and reporting biases (selection and information biases, respectively). We aimed to assess to what extent associations of causes of death estimated from individual mortality data can be extrapolated as associations of disease states in the general population. METHODS: We used a multistate model to generate populations of individuals and simulate their health states up to death from national health statistics and artificially replicate collider bias. Associations between health states can then be estimated from such simulated deaths by logistic regression and the magnitude of collider bias assessed. Reporting bias can be approximated by comparing the estimates obtained from the observed death certificates (subject to collider and reporting biases) with those obtained from the simulated deaths (subject to collider bias only). As an illustrative example, we estimated the association between cancer and suicide in French death certificates and found that cancer was negatively associated with suicide. Collider bias, due to conditioning inclusion in the study population on death, increasingly downwarded the associations with cancer site lethality. Reporting bias was much stronger than collider bias and depended on the cancer site, but not prognosis. RESULTS: The magnitude of the biases ranged from 1.7 to 9.3 for collider bias, and from 4.7 to 64 for reporting bias. CONCLUSIONS: These results argue for an assessment of the magnitude of both collider and reporting biases before performing analyses of cause of death associations exclusively from mortality data. If these biases cannot be corrected, results from these analyses should not be extrapolated to the general population.

Dimensionality and invariance of ADL, IADL, BI-M2/WG-SS, and GALI in large surveys in France (2008-2014) and implications for measuring disability in epidemiology.

BACKGROUND: The epidemiological investigation and surveillance of disability requires well-constructed, invariant, and, if possible, exchangeable measures. However, the current or recommended measures have not been thoroughly investigated with respect to these issues. Here we examined the dimensional structure and invariance of four measures across sociodemographic groups: Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Budapest Initiative Mark 2 (BI-M2) and Washington Group on Disability Statistics Short Set (WG-SS), and Global Activity Limitation Indicator (GALI). METHODS: We used data from three large nationwide representative surveys conducted in France between 2008 and 2014. The surveys included these four measures and classical and modern approaches (correlations, principal component analysis, Rasch modeling) were used to assess their dimensional structure as well as their invariance through differential item functioning (DIF) for sociodemographic characteristics. Polytomous logistic regression models were used to assess gradients in health inequalities associated with these measures. RESULTS: For many items of ADL, IADL, and BI-M2/WG-SS, we consistently observed disordered response thresholds, rejection of unidimensionality, and DIF evidence for sociodemographic characteristics across the survey samples. Health inequality gradients were erratic. In addition, it was impossible to identify a common continuum for GALI, ADL, IADL, and BI-M2/WG-SS or their constituent items. CONCLUSION: This study warns against the current practice of investigating disability in epidemiology using measures that are unsuitable for epidemiological use, incommensurable, and inadequate regarding the basic requisites of dimensionality and invariance. Developing invariant measures and equating them along a common continuum to enlarge the common bases of measurement should therefore be a priority.

Dyspnea-induced Limitation (DYSLIM), a new self-administered concise questionnaire to evaluate dyspnea-related activity limitation in chronic respiratory diseases.

BACKGROUND AND AIM: Few questionnaires are available for routine assessment of dyspnea. The study aimed to design a self-administered questionnaire assessing the impact of chronic dyspnea on daily activities, named DYSLIM (Dyspnea-induced Limitation). METHODS: The development followed 4 steps: 1: selection of relevant activities and related questions (focus groups); 2: clinical study: internal and concurrent validity vs. modified Medical Research Council (mMRC), Baseline Dyspnea Index (BDI) and Saint George Respiratory Questionnaire (SGRQ); 3: item reduction; 4: responsiveness. Eighteen activities (from eating to climbing stairs) were considered with 5 modalities for each: doing the task slowly, taking breaks, seeking assistance, changing habits, and activity avoidance. Each modality was graded from 5 (never) to 1 (very often). Validation study included 194 patients: COPD (FEV1 ≥ 50% pred: n = 40; FEV1 < 50% pred: n = 65); cystic fibrosis (n = 30), interstitial lung disease (n = 30), pulmonary hypertension (n = 29). Responsiveness was evaluated by post-pulmonary rehabilitation data in 52 COPD patients. RESULTS: Acceptability was high and short term (7 days) reproducibility was satisfactory (Kappa mostly above 0.7). Concurrent validity was high vs. mMRC (Spearman correlation coefficient, r = 0.71), BDI (r = - 0.75) and SGRQ (r = - 0.79). The reduced questionnaire with 8 activities (from cleaning to climbing stairs) and 3 modalities (slowly, seeking help, changing habits) showed a comparable validity and was chosen as the final short version. Effect size of rehabilitation was good for both the full (0.57) and short (0.51) versions. A significant correlation was also found between changes of SGRQ and DYSLIM post rehabilitation: r = - 0.68 and r = - 0.60 for full and reduced questionnaires, respectively. CONCLUSION: The DYSLIM questionnaire appears promising for the evaluation of dyspnea-induced limitations in chronic respiratory diseases and seems suitable for use in various contexts.

Positive Correlation Between 18 F-FDG Uptake and Tumor-Proliferating Antigen Ki-67 Expression in Adrenocortical Carcinomas.

PURPOSE OF THE REPORT: Adrenocortical carcinoma (ACC) is an extremely rare endocrine malignancy, which cannot always be diagnosed during conventional radiology and hormonal investigations. 18 F-FDG PET could help predict malignancy, but more data are necessary to support future guidelines. METHODS: A cohort of 63 patients with histologically proven ACC (n = 55) or metastatic ACC with steroid oversecretion (n = 8) was assembled. All patients underwent an 18 F-FDG PET, and the SUV max and the adrenal-to-liver SUV max ratio were calculated. The 18 F-FDG PET parameters were compared with clinical, pathological, and outcome data. RESULTS: Fifty-six of 63 patients (89%) had an ACC with an adrenal-to-liver SUV max ratio >1.45, which was a previously defined cutoff value to predict malignancy with 100% sensitivity. Seven ACCs (11%) had a lower uptake (adrenal-to-liver SUV max <1.45), most of them with a proliferation marker Ki-67 expression level <10%. A positive correlation between 18 F-FDG PET parameters (SUV max and adrenal-to-liver SUV max ratio) and tumor size, ENSAT (European Network for the Study of Adrenal Tumors) staging, total Weiss score, and the Ki-67 was found. The strong correlation between SUV max and Ki-67 ( r = 0.47, P = 0.0009) suggests a relationship between 18 F-FDG uptake levels and tumor proliferation. No statistically significant associations between outcome parameters (progression-free or overall survival) and 18 F-FDG PET parameters were found. CONCLUSIONS: This large cohort study shows that most cases of ACC demonstrate high 18 F-FDG uptake. However, the positive correlation observed between SUV max and Ki-67 expression levels seems to explain the possibility of identifying some ACC with a low or inexistent 18 F-FDG uptake. These findings have practical implications for the management of patients with an adrenal mass.

Impact of the First COVID-19 Pandemic Wave on Hospitalizations and Deaths Caused by Geriatric Syndromes in France: A Nationwide Study.

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.

Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation.

ABSTRACT: Persistent pain despite satisfactory disease treatment is frequent in rheumatoid arthritis (RA) and spondyloarthritis (Spa) and may result from specific changes in central pain processing. We assessed these mechanisms further by systematically comparing thermal pain thresholds and conditioned pain modulation (CPM) between patients with active RA or Spa and healthy controls. We included 50 patients with RA and 50 patients with Spa and 100 age-matched and sex-matched controls. Heat and cold pain thresholds (HPT-CPT) were measured on the dominant forearm, and CPM was assessed by applying conditioning stimuli (immersion in a cold-water bath) to one foot and the nondominant hand in 2 successive randomized sequences. Descending pain modulation was assessed as the difference in HPTs (in °C) before and after conditioning. Larger HPT differences (ie, a larger CPM effect) reflected more efficient descending inhibition. Potential associations between changes in CPM and clinical data, including disease activity, pain intensity, and psychological and functional variables, were systematically assessed. Heat pain threshold and cold pain threshold were similar in patients and controls. The mean CPM effect was significantly weaker in patients than that in controls for conditioning applied to either the foot (0.25°C ±2.57 vs 2.79°C ±2.31; P < 0.001) or the nondominant hand (0.57°C ±2.74 vs 2.68°C ±2.12; P < 0.001). The smaller CPM effect in patients was correlated with average pain intensity, but not with disease activity or other clinical characteristics, suggesting a significant pathophysiological role for changes in endogenous pain modulation in the mechanisms of chronic pain associated with inflammatory rheumatism.

Aetiological and prognostic roles of frailty, multimorbidity and socioeconomic characteristics in the development of SARS-CoV-2 health outcomes: protocol for systematic reviews of population-based studies.

INTRODUCTION: There is growing evidence that the impact of COVID-19 crisis may be stronger for individuals with multimorbidity, frailty and lower socioeconomic status. Existing reviews focus on few, mainly short-term effects of COVID-19 illness and patients with single chronic disease. Information is also largely missing for population representative samples.Applying population-based approach, the systematic reviews will have two objectives: (1) to evaluate the aetiological roles of frailty, multimorbidity and socioeconomic status on SARS-CoV-2 infection probability, hospitalisation, intensive care unit (ICU) admission, mechanical ventilation and COVID-19 related mortality among general population and (2) to investigate the prognostic roles of frailty, multimorbidity and socioeconomic characteristics on the risk of hospitalisation, ICU admission, mechanical ventilation, COVID-19 mortality, functioning, quality of life, disability, mental health and work absence. METHODS AND ANALYSIS: For this ongoing work, four databases were searched: PubMed, Embase, WHO COVID-19 Global literature on coronavirus disease and PsycINFO, for the period between January 2020 and April 7 2021. Peer-reviewed published literature in English and all types of population-based studies will be considered. Studies using standard tools to assess multimorbidity such as disease count, comorbidity indices or disease combinations will be retained, as well as studies with standard scales and scores for frailty or measurement of a socioeconomic gradient. Initial search included 10 139 articles, 411 for full-text reading. Results will be summarised by risk factor, objective and outcome. The feasibility of meta-analysis will be determined by the findings and will aim to better understand uncertainties of the results. Quality of studies will be assessed using standardised scales. ETHICS AND DISSEMINATION: The study will be based on published evidence, and it is exempt from the ethical approval. This work is part of the Population Health Information Research Infrastructure (PHIRI) project. Dissemination of the results will imply conference presentation, submission for scientific publication and PHIRI project report. PROSPERO REGISTRATION NUMBER: CRD42021249444.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

"FastSchool": A single session of an interprofessional pain management program for chronic pain patients inspired by cognitive behavioral therapy.

OBJECTIVES: Multidisciplinary approaches to treating chronic pain have been proven effective. Currently, chronic pain patients face lengthy waitlists in pain medicine departments. To overcome this problem, we developed the "FastSchool" program to educate patients about pain management and treatment. In this study, we evaluated the benefit of a "FastSchool" session on pain and catastrophizing in chronic pain patients. METHODS: Included patients had chronic non-cancer pain, no more than 2 visits to a pain medicine department. Patients attended a single 3-hour session, conducted by an interprofessional team. Four topics were addressed: chronic pain mechanisms, pharmacological therapies, physical activity, and the management of analgesics. Patients completed questionnaires at baseline and at 3 months post-session to assess pain interference, pain intensity, and catastrophizing. RESULTS: The study population included 88 patients; 71 completed the follow-up questionnaires. Pain interference (p = 0.002), average pain intensity (p = 0.013), and catastrophizing (p < 0.001) decreased 3 months after FastSchool. At M3, 35 % of patients felt their pain had improved based on the Patient Global Impression of Change. CONCLUSION: FastSchool, an innovative short-term educational program inspired by cognitive behavioral therapy, showed positive results in reducing pain impact. PRACTICE IMPLICATIONS: Implementation of FastSchool in pain medicine departments would reduce waitlist times for non-pharmacological treatment.

Risk of intracranial meningioma with three potent progestogens: A population-based case-control study.

BACKGROUND AND PURPOSE: A dose-dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75-5 mg/day) and chlormadinone acetate (CMA) (2-10 mg/day). METHODS: In this nationwide population-based case-control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls. RESULTS: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3-7.1). The OR was 1.2 (1.0-1.4) for short-term use (<1 year) and 9.5 (8.8-10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5-26.4), NOMAC (OR = 6.5, 95% CI 5.8-7.2) and CMA (OR = 4.7, 95% CI 4.5-5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5-48.2) and 23.9 (95% CI 17.8-32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028-2220) (212/year). CONCLUSION: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk.

Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study.

AIMS/HYPOTHESIS: Insulin allergy is a rare but significant clinical challenge. We aimed to develop a management workflow by (1) validating clinical criteria to guide diagnosis, based on a retrospective cohort, and (2) assessing the diagnostic performance of confirmatory tests, based on a case-control study. METHODS: In the retrospective cohort, patients with suspected insulin allergy were classified into three likelihood categories according to the presence of all (likely insulin allergy; 26/52, 50%), some (possible insulin allergy; 9/52, 17%) or none (unlikely insulin allergy; 17/52, 33%) of four clinical criteria: (1) recurrent local or systemic immediate or delayed hypersensitivity reactions; (2) reactions elicited by each injection; (3) reactions centred on the injection sites; and (4) reactions observed by the investigator (i.e. in response to an insulin challenge test). All underwent intradermal reaction (IDR) tests. A subsequent case-control study assessed the diagnostic performance of IDR, skin prick and serum anti-insulin IgE tests in ten clinically diagnosed insulin allergy patients, 24 insulin-treated non-allergic patients and 21 insulin-naive patients. RESULTS: In the retrospective cohort, an IDR test validated the clinical diagnosis in 24/26 (92%), 3/9 (33%) and 0/14 (0%) likely, possible and unlikely insulin allergy patients, respectively. In the case-control study, an IDR test was 80% sensitive and 100% specific and identified the index insulin(s). The skin prick and IgE tests had a marginal diagnostic value. Patients with IDR-confirmed insulin allergy were treated using a stepwise strategy. CONCLUSIONS/INTERPRETATION: Subject to validation, clinical likelihood criteria can effectively guide diabetologists towards an insulin allergy diagnosis before undertaking allergology tests. An IDR test shows the best diagnostic performance. A progressive management strategy can subsequently be implemented. Continuous subcutaneous insulin infusion is ultimately required in most patients. CLINICALTRIALS: gov: NCT01407640.

The epidemiology of multimorbidity in France: Variations by gender, age and socioeconomic factors, and implications for surveillance and prevention.

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.