Self-controlled designs in pharmacoepidemiology involving electronic healthcare databases: a systematic review

International audienceBackgroundObservational studies are widely used in pharmacoepidemiology. Several designs can be used, in particular self-controlled designs (case-crossover and self-controlled case series). These designs offer the advantage of controlling for time-invariant confounders, which may not be collected in electronic healthcare databases. They are particularly useful in pharmacoepidemiology involving healthcare database. To be valid, they require the presence of some characteristics (key validity assumptions), and in such situations, these designs should be preferred. We aimed at describing the appropriate use and reporting of the key validity assumptions in self-controlled design studies.MethodsArticles published between January 2011 and December 2014, and describing a self-controlled study design involving electronic healthcare databases were retrieved. The appropriate use (fulfilment of key assumptions) was studied in terms of major (abrupt onset event, rare or recurrent event, and intermittent exposure) and minor assumptions (those for which the design can be adapted).ResultsAmong the 107 articles describing a self-controlled design, 35/53 (66%) case-crossover studies, and 48/55 (87%) self-controlled case series fulfilled the major validity assumptions for use of the design; 4/35 and 14/48 respectively did not fulfill the minor assumptions. Overall, 31/53 (58%) case-crossover studies and 34/55 (62%) self-controlled case series fulfilled both major and minor assumptions. The reporting of the methodology or the results was appropriate, except for power calculation.ConclusionsSelf-controlled designs were not appropriately used in34% and 13% of the articles we reviewed that described a case-crossover or a self-controlled case series design, respectively. We encourage better use of these designs in situations in which major validity assumptions are fulfilled (i.e., for which they are recommended), accounting for situations for which the design can be adapted

A prescription support-tool for chronic management of oral antithrombotic combinations in adults based on a systematic review of international guidelines

International audienceBACKGROUND: Oral antithrombotic (AT) drugs, which include antiplatelet and anticoagulant therapies, are widely implicated in serious preventable bleeding events. Avoiding inappropriate oral AT combinations is a major concern. Numerous practical guidelines have been released; a document to enhance prescriptions of oral AT combinations for adults would be of great help.OBJECTIVE: To synthesize guidelines on the prescription of oral AT combinations in adults and to create a prescription support-tool for clinicians about chronic management (≥ one month) of oral AT combinations.METHODS: A systematic review of guidelines published between January 2012 and April 2017, in English or in French, from Trip database, Guideline International Network and PubMed, dealing with the prescription of oral ATs in adults was conducted. In-hospital management of ATs, bridging therapy and switches of ATs were not considered. Some specific topics requiring specialized follow-up (cancer, auto-immune disease, haemophilia, HIV, paediatrics and pregnancy) were excluded. Last update was made in November 2018.RESULTS: A total of 885 guidelines were identified and 70 met the eligibility criteria. A prescription support-tool summarizing medical conditions requiring chronic management of oral AT combinations in adults with drug types, dosage and duration, on a double-sided page, was provided and tested by an external committee of physicians. The lack of specific guidelines for old people (age 75 years and older) is questioned considering the specific vulnerability of this age group to serious bleedings.CONCLUSIONS:Recommendations on prescriptions about chronic management of oral AT combinations in adults were mainly consensual but dispersed in numerous guidelines according to the medical indication. We provide a prescription support-tool for clinicians. Further studies are needed to assess the impact of this tool on appropriate prescribing and the prevention of serious adverse drug events

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review

International audienceBackground: Intensivists’ clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients.Methods: Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other).Results: Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge.Conclusion: Patient-important outcomes are rarely primary outcomes in RCTs in critically ill patients published in 2013. Among them, mortality accounted for the majority. We promote the use of patient-important outcomes in critical care trials

Evolution of public funding since primary care research was considered as a priority research domain in france

International audiencePURPOSE: Annually, the French Ministry of Health funds clinical research projects based on a national call for projects. Since 2013, the Ministry has prioritized funding of primary care. Projects selected for funding are made public without distinguishing the specific area of research. The objective of this study was to identify and describe the evolution of the primary care research projects funded by the Ministry of Health between 2013 and 2019. METHOD: We reviewed all of the 1796 medical research projects funded between 2013 and 2019 and categorized projects as primary care projects by using a list of specific keywords. This list was established through two approaches: (1) selected by an expert committee, the RECaP primary care working group, and (2) using an automated textual analysis of published articles in the field. The keywords were used to screen the titles of the medical research projects funded. The abstracts (at www. CLINICALTRIALS: gov ) or details (from project leaders) were then analyzed by two independent reviewers to determine true primary care projects. RESULTS: Finally, 49 primary care projects were identified, representing 2.7% of all medical research projects funded, without any significant change over the period. These projects were predominantly interventional (69%), with a median number of patients expected per project of 902. CONCLUSION: Despite the prioritization of primary care research in 2013 by the French ministry of health, the number and proportion of projects funded remains low, with no significant change over the years. TRIAL REGISTRATION: Not applicable

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies

International audienceAimsTwo post-authorisation studies assessed the safety and persistence of patients’ use of nalmefene.MethodsThe START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted ‘all comers’ without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities.ResultsSTART study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were ‘goal reached’ and ‘drug cost’. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year.ConclusionsDespite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits

Additional file 1: S1. of Self-controlled designs in pharmacoepidemiology involving electronic healthcare databases: a systematic review

MEDLINE search algorithm. S2. Standardized extraction form and specific validity assumptions. S3. Articles included in the review. S4. Validity assumptions for each article describing a case-crossover (4a) or a self-controlled case-series design (4b). S5. Validity assumptions for the use of a self-controlled design. Sensitivity analysis when unclear assumptions are considered invalid. S6. Validity assumptions for the use of a self-controlled design. Sensitivity analysis after excluding articles for the same series. (DOC 797 kb

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France

International audienceUntil 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management

Les soins primaires : une définition du champ pour développer la recherche

International audienceBackground - Research in the field of primary care has dramatically increased in France in recent years, especially since 2013 with the introduction of primary care as a thematic priority for research proposals launched by the Ministry of Health (Direction générale de l'offre de soins). Material and methods - The RECaP (Research in Clinical Epidemiology and Public Health) network is a French research network supported by Inserm, which recently implemented a specific working group focusing on research in primary care, based on a multidisciplinary approach. Researchers from different specialties participate in this group. The first aim of the group was to reach a common definition of the perimeter and of the panel of healthcare professionals and structures potentially involved in the field of primary care. For this purpose, a selection of different data sets of sources defining primary care was analyzed by the group, each participant collecting a set of sources, from which a synthesis was made and discussed. Results - A definition of primary care at different levels (international, European and French) was summarized. A special attention was given to the French context in order to adapt the perimeter to the characteristics of the French healthcare system, notably by illustrating the different key elements of the definition with the inclusion of primary care actors and the type of practice premises. Conclusion - In conclusion, this work illustrates the diversity of primary care in France and the potential offered for research purposes

Ce que le genre fait aux personnes

Comment échapper à l’alternative entre étudier l’individu (universel mais asexué) ou les rapports hommes-femmes (sexués mais séparés) ? En apercevant que la distinction masculin/féminin n’est pas une simple différence : elle ne désigne aucune propriété substantielle, aucun attribut identitaire de l’individu. C’est pourquoi de plus en plus d’études en sciences sociales tiennent à définir le « genre » non pas comme un attribut des personnes, mais comme une modalité des relations. Les auteurs de ce livre ne se revendiquent pas d’une théorie commune. Mais tous questionnent les conceptions du genre trop dépendantes des représentations occidentales modernes. Il ne va pas de soi de considérer l’individu comme un être composé de deux entités, «un moi» et «un corps». En nous incitant à renouer avec les ambitions d’une véritable anthropologie comparative, ils montrent qu’étudier le genre c’est revenir aux fondamentaux de nos disciplines. Toujours et partout, ce qui est en jeu à travers le genre n’est jamais simplement ni «l’esprit», ni «le corps», mais cet être vivant capable d’agir et de pâtir à la manière des humains, dont chaque société construit sa propre représentation: la personne. Comment échapper à l’alternative entre étudier l’individu (universel mais asexué) ou les rapports hommes-femmes (sexués mais séparés) ? En apercevant que la distinction masculin/féminin n’est pas une simple différence : elle ne désigne aucune propriété substantielle, aucun attribut identitaire de l’individu. C’est pourquoi de plus en plus d’études en sciences sociales tiennent à définir le « genre » non pas comme un attribut des personnes, mais comme une modalité des relations. Les auteurs de ce livre ne se revendiquent pas d’une théorie commune. Mais tous questionnent les conceptions du genre trop dépendantes des représentations occidentales modernes. Il ne va pas de soi de considérer l’individu comme un être composé de deux entités, « un moi » et « un corps ». En nous incitant à renouer avec les ambitions d’une véritable anthropologie comparative, ils montrent qu’étudier le genre c’est revenir aux fondamentaux de nos disciplines. Toujours et partout, ce qui est en jeu à travers le genre n’est jamais simplement ni « l’esprit », ni « le corps », mais cet être vivant capable d’agir et de pâtir à la manière des humains, dont chaque société construit sa propre représentation : la personne

Severe asthma care trajectories: the French RAMSES cohort

International audienceBackground The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs).Methods Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients’ characteristics were analysed at inclusion and compared between TRCs and SCCs.Results 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm −3 ; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390).Conclusions Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care