Patrick Villani

Bias in the measure of the effectiveness of seasonal influenza vaccination among diabetics.

BACKGROUND The influenza virus is an important cause of morbidity and mortality for diabetics. The seasonal influenza vaccines immunologic effectiveness is proven within the type 1 and type 2 diabetic populations, but the level of evidence is low. This article presents a systematic review for the bias in the measure of the effectiveness of seasonal influenza vaccination among diabetics. METHODS Using systematic review methods, we searched three electronic databases for published literature (MEDLINE, EMBASE and the Cochrane Library) and two grey literature (SIGLE and NHS EED) databases, to identify studies published between 1997 and 2013, examining the effect of seasonal influenza vaccination, among diabetics, on any measure for influenza morbidity or mortality. RESULTS 725 records were identified from the three databases and screening, short-listing was undertaken independently by two reviewers. After de-duplication, all records were screened by title and then abstract, and 34 short-listed records were reviewed in full, with 7 studies included: 4 cohort studies and 3 case-control studies, conducted in 7 countries. The most common outcome of interest in studies (n=4) was all-cause mortality among elderly diabetics (>65 years), with individual studies reporting reductions in risk of between 33% [95%CI: 4%-54%] and 68% [95%CI: 58%-75%]. We found only two studies for working-age adult diabetics: one reporting that vaccination prevented hospitalizations due to pneumonia or influenza (vaccine effectiveness [VE] 43%, [95%CI: 28%-54%]) and all-cause hospitalizations (VE: 28% [95%CI: 24%-32%]); and, another reporting no significant decrease in all-cause mortality for working-age adult diabetics. We have identified three major biases: the use of indirect health outcomes, a risk of selection bias (health-seeking bias), and no adjustment for participant pneumococcal vaccination status. The most recent included article finds that morbimortality is still lower during off-season influenza in both vaccinated and non-vaccinated diabetics, indicating important residual confounding. CONCLUSION To date, the strength of evidence supporting the routine use of seasonal influenza vaccination is low for diabetics older than 65, and very low for working-age diabetics.

Impact of a pharmacist-led medication review on hospital readmission in a pediatric and elderly population: study protocol for a randomized open-label controlled trial

BackgroundEarly hospital readmission of patients after discharge is a public health problem. One major cause of hospital readmission is dysfunctions in integrated pathways between community and hospital care that can cause adverse drug events. Furthermore, the French ENEIS 2 study showed that 1.3% of hospital stays originated from serious adverse drug events in 2009. Pharmacy-led medication reviews at hospital transitions are an effective means of decreasing medication discrepancies when conducted at admission or discharge. However, it is difficult to assess the true impact of pharmacist-led medication reviews in specific high-risk populations, such as pediatric and geriatric populations.In such a context, it is important to demonstrate the effectiveness of medication reconciliation as part of a standardized medication review process—in pediatric and elderly populations—on all-cause readmissions in a large randomized controlled clinical trial.The aim of this study is to assess the impact of the pharmacist-led medication review on the rate of readmissions and/or death after hospital discharge and patient treatment satisfaction.Methods/designThe study is a randomized controlled clinical trial. A total of 1400 hospitalized patients will be randomized in two groups: (1) the experimental group (group receiving a pharmacist-led medication review) and (2) the control group (group receiving usual care). The pharmacist-led medication review process includes medication reconciliation, treatment review and medication liaison service. The primary endpoint will be the rate of readmissions and/or death at 30 days following initial hospitalization discharge. The secondary endpoints will be the rate of hospital readmission, the rate of emergency department visits, the rate of mortality, the number of consultations and patient treatment satisfaction at 30 days following initial hospitalization discharge.DiscussionA randomized controlled trial provides the most extensive evidence on the impact of pharmacist-led medication reviews on early hospital readmission for extreme age populations.Trial registrationCurrent Controlled Trials, NCT02734017. Registered on 4 May 2016.

Les essais cliniques d'équivalence en rhumatologie

A une epoque ou le recours au placebo est de plus en plus conteste pour des raisons ethiques dans les essais cliniques des nouveaux medicaments, et ou le concept et la methodologie des essais d’equivalence commencent a s’imposer, il est legitime de s’interroger sur l’avenir du placebo dans les futurs essais en rhumatologie. L’examen de la question montre, certes, que l’essai de non-inferiorite peut theoriquement permettre d’eteindre la controverse ethique, mais sa signification, sa realisation et l’interpretation de ses resultats sont loin de satisfaire l’ensemble des evaluateurs. Notre communaute medicale devra pourtant s’en accommoder. L’evolution des idees et des comportements comme les donnees actuelles de la science le font deja prevaloir.

Clinical effectiveness of osteoporosis treatment in older patients: A fracture liaison service-based prospective study

ABSTRACT The clinical efficacy of anti-osteoporotic treatments in old patients is discussed. The aim of this study was to assess if the use of anti-osteoporotic treatments for the secondary prevention of osteoporotic fractures could reduce the risk of refractures in patients over 75 years old in a Fracture Liaison Service. In this population of frail, elderly patients presenting with a recent osteoporotic fracture, we observed that the refracture incidence was similar in the treated group and the untreated group during the first year. However, 30 months after the index fracture, the osteoporosis medication for a year or more reduced the incidence of refractures by 70%.

MALDI-TOF MS monitoring of PBMC activation status in sepsis

BackgroundMALDI-TOF mass spectrometry (MS) on whole cells enables the detection of different cell types and cell activation. Here, we wondered whether this approach would be useful to investigate the host response in sepsis.MethodsPeripheral blood mononuclear cells (PBMCs) from patients with severe sepsis and healthy donors were analyzed with MALDI-TOF MS. PBMCs from healthy donors were also stimulated with lipopolysaccharide, peptidoglycan, CpG oligonucleotides, polyinosinic polycytidylic acid, and with heat-inactivated bacteria. Averaged spectra of PBMCs stimulated in vitro by different agonists were generated from the database using the Biotyper software and matching scores between each spectrum from patients and averaged spectra from the database were calculated.ResultsWe show that the MALDI-TOF MS signature of PBMCs from septic patients was specific, compared with healthy controls. As the fingerprints observed in patients may be related to PBMC activation, PBMCs from healthy controls were stimulated with cytokines, soluble Pathogen-Associated Molecular Patterns (PAMPs) and heat-killed bacteria, and we created a database of reference spectra. The MALDI-TOF MS profiles of PBMCs from septic patients were then compared with the database. No differences were found between patients with documented infection (n = 6) and those without bacteriological documentation (n = 6). The spectra of PBMCs from septic patients matched with those of interferon-γ- and interleukin-10-stimulated PBMCs, confirming that sepsis is characterized by both inflammatory and immunoregulatory features. Interestingly, the spectra of PBMCs from septic patients without documented infection matched with the reference spectrum of PBMCs stimulated by CpG oligonucleotides, suggesting a bacterial etiology in these patients.ConclusionsDespite the limits of this preliminary study, these results indicate that the monitoring of functional status of PBMCs in peripheral blood by whole cell MALDI-TOF MS could provide unique opportunities to assess disease progression or resolution in clinical settings.

Effectiveness of seasonal influenza vaccination in patients with diabetes: protocol for a nested case–control study

Introduction Seasonal influenza vaccination (SIV) is recommended for people with diabetes, but its effectiveness has not been demonstrated. All of the available studies are observational and marred with the healthy vaccine bias, that is, bias resulting from the generally better health behaviours practised by people who choose to be vaccinated against influenza, compared with those who do not. This protocol is intended to study the effectiveness of SIV in people with treated diabetes and simultaneously to control for bias. Methods and analyses This case-control study is nested in a historical cohort and is designed to study vaccine effectiveness (VE) assessed by morbidity, mortality and anti-infective drug use. The cohort will comprise a representative sample of health insurance beneficiaries in France and will cover 10 consecutive epidemic seasons. It will include all patients reimbursed three separate times for drugs to treat diabetes. The first study of VE will use reasons for hospitalisation as the primary end point, and the second with the use of neuraminidase inhibitors and of antibiotics as the end points. A case will be defined as any person in the cohort reaching any end point at a given date. The case patient will be matched with the largest possible number of controls (individuals not reaching the end point by this date) according to the propensity score method with an optimal calliper width. A conditional logistic model will be used to estimate ORs to take into account both the matching and the repetition of measurements. The model will be applied separately during and outside of epidemic periods to estimate the residual confounding. Ethics and dissemination The study has been approved by the French Commission on Individual Data Protection and Public Liberties (ref: AT/CPZ/SVT/JB/DP/CR05222O). The studys findings will be published in peer-reviewed journals and disseminated at international conferences and through social media.

Membership in a diabetes-care network and adherence to clinical practice guidelines for treating type 2 diabetes among general practitioners: A four-year follow-up

OBJECTIVES To assess whether private general practitioners (GPs) belonging to a diabetes-care network adhered more closely to clinical practice guidelines for diabetes care than GPs not in such a network, for all their patients with type 2 diabetes treated with medication (patients with diabetes), regardless of whether they received care through a network (that is, whether a halo effect occurred). RESEARCH DESIGN AND MEASURES The study, based on health insurance reimbursement databases in southeastern France, included 468 GPs in two networks and 468 non-network GPs in the same geographical area, matched one-to-one by propensity scores. We followed up their patients with diabetes (n=22,808) from 2008 through 2011, conducting multivariate time-to-event analyses (Cox models) that took the matching design into account to evaluate time from inclusion until performance of the given number of each of six recommended examinations/tests. RESULTS GPs belonging to a diabetes-care network adhered more closely to clinical practice guidelines but our result were slightly pronounced. Hazard ratios (HR) were significantly higher for patients of network GPs for the implementation of 3 HbA1C assays (HRa=1.13; [95%CI=1.10-1.16]), or 1 microalbuminuria assay (1.4 [1.35-1.45]); they were lower for LDL-cholesterol assays (1.04 [1.01-1.07]) and ophthalmological checkups (1.07 [1.04-1.10]), and not significant for creatinemia or cardiac monitoring. CONCLUSIONS Network GPs had better diabetes monitoring practices for all their patients with diabetes than the other GPs, especially for the most diabetes-specific tests. Further research is needed in other settings to confirm the existence of this halo effect.

Erratum à l’article « Controverse des estroprogestatifs de 3e et 4e génération : quelle influence sur le comportement des femmes ? » [Presse Med. 45/4 (2016) e68–78]

La Presse Medicale - In Press.Proof corrected by the author Available online since mercredi 29 juin 2016

Un syndrome cave supérieur pourtant bénin

Une patiente de 94 ans est hospitalisee pour chutes repetees dans un contexte de dyspnee d’aggravation progressive. Elle est traitee pour une insuffisance cardiaque sur coronaropathie compliquee d’une fibrillation auriculaire non anticoagulee du fait d’un hematome sous-dural post-traumatique un an auparavant. Elle presente une hyperthyroidie depuis quatre ans, developpee sous Cordarone® stoppee depuis, traitee par Neo-Mercazole®. Cliniquement, elle est dyspneique au moindre [...]

Pratiques transfusionnelles en court séjour gériatrique avant et après les recommandations de 2014 de la Haute autorité de santé

Anemia is the most common hematological pathology in geriatrics. Its prevalence increases with age. It is considered as a fragility factor because leading to loss of autonomy and other complications. Transfusion is a common practice in geriatrics. In 2014, the French national health authority guidelines recommended hemoglobin concentration rates for transfusion on the elderly over 80 years-old. The objective of this study is to compare transfusion practices in geriatric short-stay units, before and after these guidelines were edited. METHODS Retrospective descriptive study in two geriatric short stay units, including patients aged 80 years-old or over, transfused in 2012 and 2015. RESULTS 103 patients were included. More than 30% patients had a chronic heart failure, and there was no significant difference on general characteristics between the groups in the two years. Compared to 2012, the transfused population in 2015 was more fragile with a higher Charlson comorbidity index (p=0.005). The main symptoms of anemia bad tolerance were cardiovascular symptoms. The average pre-transfusion hemoglobin concentration was 7.9 g/dL in 2015, 8 g/dL in 2012 (p=0.63). By 2015, 72.3% transfusions respected the hemoglobin thresholds recommended in guidelines, compared to 50% in 2012 (p=0.023). Transfusion thresholds in our study were lower than those recommended; 13 adverse reactions were identified, 12 of them were heart failure. There was no significant difference in transfusion benefit between the two years. CONCLUSION This study helped describe profile of elderly transfused patients, their geriatric characteristics and the transfusion data, without showing any changes in transfusion practices following the guidelines, despite a more fragile population in 2015. It seems difficult, because of the diversity in the geriatric population, to have a single threshold of hemoglobin recommended, only non-specific symptoms of intolerance and to consider only the cardiovascular comorbidities to decide whether or not to provide a transfusion.