[Translation into French and republication of: "Management of cancer-associated thromboembolism in vulnerable population"]. / Traduction et republication de : « Prise en charge de la maladie thromboembolique veineuse associée au cancer chez les populations vulnérables ¼.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with TAC on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR less than 30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (less than 50,000platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.

The free plasma amyloid Aß1-42/Aß1-40 ratio predicts conversion to dementia for subjects with mild cognitive impairment with performance equivalent to that of the total plasma Aß1-42/Aß1-40 ratio. The BALTAZAR study.

BACKGROUND AND PURPOSE: Blood-based biomarkers are a non-invasive solution to predict the risk of conversion of mild cognitive impairment (MCI) to dementia. The utility of free plasma amyloid peptides (not bound to plasma proteins and/or cells) as an early indicator of conversion to dementia is still debated, as the results of studies have been contradictory. In this context, we investigated whether plasma levels of the free amyloid peptides Aß1-42 and Aß1-40 and the free plasma Aß1-42/Aß1-40 ratio are associated with the conversion of MCI to dementia, in particular AD, over three years of follow-up in a subgroup of the BALTAZAR cohort. We also compared their predictive value to that of total plasma Aß1-42 and Aß1-40 levels and the total plasma Aß1-42/Aß1-40 ratio. METHODS: The plasma Aß1-42 and Aß1-40 peptide assay was performed using the INNO-BIA kit (Fujirebio Europe). Free amyloid levels (defined by the amyloid fraction directly accessible to antibodies of the assay) were obtained with the undiluted plasma, whereas total amyloid levels were obtained after the dilution of plasma (1/3) with a denaturing buffer. Free and total Aß1-42 and Aß1-40 levels were measured at inclusion for a subgroup of participants (N = 106) with mild cognitive impairment (MCI) from the BALTAZAR study (a large-scale longitudinal multicenter cohort with a three-year follow-up). Associations between conversion and the free/total plasma Aß1-42 and Aß1-40 levels and Aß1-42/Aß1-40 ratio were analyzed using logistic and Cox Proportional Hazards models. Demographic, clinical, cognitive (MMSE, ADL and IADL), APOE, and MRI characteristics (relative hippocampal volume) were compared using non-parametric (Mann-Whitney) or parametric (Student) tests for quantitative variables and Chi-square or Fisher exact tests for qualitative variables. RESULTS: The risk of conversion to dementia was lower for patients in the highest quartile of free plasma Aß1-42/Aß1-40 (≥ 25.8%) than those in the three lower quartiles: hazard ratio = 0.36 (95% confidence interval [0.15-0.87]), after adjustment for age, sex, education, and APOE ε4 (p-value = 0.022). This was comparable to the risk of conversion in the highest quartile of total plasma Aß1-42/Aß1-40: hazard ratio = 0.37 (95% confidence interval [0.16-0.89], p-value = 0.027). However, while patients in the highest quartile of total plasma Aß1-42/Aß1-40 showed higher MMSE scores and a higher hippocampal volume than patients in the three lowest quartiles of total plasma Aß1-42/Aß1-40, as well as normal CSF biomarker levels, the patients in the highest quartile of free plasma Aß1-42/Aß1-40 did not show any significant differences in MMSE scores, hippocampal volume, or CSF biomarker levels relative to the three lowest quartiles of free plasma Aß1-42/Aß1-40. CONCLUSION: The free plasma Aß1-42/Aß1-40 ratio is associated with a risk of conversion from MCI to dementia within three years, with performance comparable to that of the total plasma Aß1-42/Aß1-40 ratio. Threshold levels of the free and total plasma Aß1-42/Aß1-40 ratio could be determined, with a 60% lower risk of conversion for patients above the threshold than those below.

Orthostatic hypotension: Review and expert position statement.

Orthostatic hypotension is defined as a drop in systolic blood pressure of at least 20mmHg or a drop in diastolic blood pressure of at least 10mmHg within 3minutes of standing. It is a common disorder, especially in high-risk populations such as elderly subjects and patients with neurological diseases, and is associated with markedly increased morbidity and mortality. Its management can be challenging, particularly in cases where supine hypertension is associated with severe orthostatic hypotension. Education of the patient, non-pharmacological measures, and drug adaptation are the cornerstones of treatment. Pharmacological treatment should be individualized according to the severity, underlying cause, 24-hour blood pressure profile, and associated coexisting conditions. First-line therapies are midodrine and fludrocortisone, which may need to be combined for optimal care of severe cases.

Orthostatic hypotension and orthostatic hypertension are both associated with lower cognitive function: The S.AGES cohort.

BACKGROUND: Blood pressure (BP) postural changes, both orthostatic hypotension (OHYPO) and orthostatic hypertension (OHYPER) are common in older adults. Few studies have investigated their association with cognition, particularly for OHYPER, an emerging cardiovascular risk factor. We aimed to assess the association between OHYPO, OHYPER and cognition in non-institutionalized older subjects. METHODS: The S.AGES (Sujets ÂGES, Aged Subjects) cohort followed every 6 months for 3 years non-institutionalized subjects aged ≥65 years without dementia at inclusion, in France. OHYPO and OHYPER were respectively defined as a fall or an increase of ≥20 mmHg in systolic BP and/or ≥10 mmHg in diastolic BP after standing from a sitting position. Cognition was assessed using the Mini-Mental State Examination (MMSE). Linear mixed models were used for the analyses. RESULTS: Among the 3170 subjects included (mean age 78 years, 56% women), 209 (6.5%) had OHYPO and 226 (7.1%) had OHYPER at baseline. After adjustment for demographics, cardiovascular risk factors and disease, seated SBP/DBP and BP lowering treatment, mean MMSE was 0.52 point lower in participants with OHYPER compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.52 [-0.96; -0.09], p = 0.02) and 0.50 point lower in participants with OHYPO compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.50 [-0.95; -0.06], p = 0.03). Sensitivity analyses showed a dose-response relationship between OHYPO and cognition. CONCLUSION: Although the absolute differences in MMSE were small, both OHYPO and OHYPER were associated with lower cognition. Orthostatic BP measurements could help identify patients with risk of cognitive impairment. Further studies are needed to assess whether controlling orthostatic BP could be a promising interventional target in preserving cognition among older adults.

Sensitivity, Specificity, Positive and Negative Predictive Values of a Postal Mail Self-Screening Tool for Frailty in French Older Adults.

BACKGROUND: Frailty has emerged as one of the major risk factors of loss of autonomy and it can be reverted through early and appropriate interventions. A wide range of available frailty screening tools are administered, mainly in clinical settings. However, few frailty instruments are self-administered. OBJECTIVES: The aim of this study was to determine the diagnostic test accuracy of a modified self-administered questionnaire derived from the Study of Osteoporotic Fractures (SOF) index against the Fried frailty phenotype in identifying frailty. DESIGN: Observational, multicenter, diagnostic test accuracy study. PARTICIPANTS: Participants aged 70 and over, living at home or in community-dwelling (n=5134) in two centers in France were contacted. MEASUREMENTS: Participants were mailed self-administered questionnaires derived from the SOF index. Responders who accepted the home evaluation were assessed by trained nurses, blinded to results of the questionnaire, using the Fried frailty phenotype as the reference method. RESULTS: The questionnaire was sent to 5134 participants, of which 1878 (36.6%) met inclusion criteria and returned the questionnaire. Fried frailty assessments were obtained in 691 (35.4%) participants. A total of 639 subjects had a complete evaluation on both the self-administered questionnaire and the Fried phenotype. Mean age was 78.9 (standard deviation [SD]: 5.95) years and 359 (56.2%) participants were women. According to the questionnaire, 159 (24.9%) subjects were considered frail, 172 (26.9%) pre-frail, and 308 (48.2) robust. With the home evaluation, Fried frailty phenotype results were respectively, 114 (17.8%), 295 (46.2%) and 230 (36%). The self-administered questionnaire presented a sensitivity of 66.6% (95% CI: 57.2-75.2) and a specificity of 84.2% (95% CI: 80.8-87.2). CONCLUSIONS: A self-administered questionnaire can be used in elders and represents an opportunity for empowering them in the management of their health in the context of frailty.

Diagnosis and management of heart failure from hospital admission to discharge: A practical expert guidance.

Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF≤40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management.

Development of the Depist'HTA® score to predict a rise in blood pressure during a self-testing session: PREDIC-HTA bakery survey.

The use of an automatic blood pressure monitor with the help of a protocol given by an e-health application allows self-testing of blood pressure without the help of a health professional. OBJECTIVE: Conduct a screening campaign for high blood pressure in artisanal bakeries in France and develop a score to predict the observation of an increase in blood pressure during self-testing. METHOD: Cross-sectional survey conducted in mainland France in 2018 using 1000 screening kits including a tablet, Predic'HTA® application and a connected electronic blood pressure monitor (BP Track, IHealth). Available for one week in 14,000 artisanal bakeries, in turn. Used in the workplace, on a voluntary basis, by bakery employees. Completion of a health questionnaire with an estimate of excessive salt consumption. Self-screening of 3 blood pressure measurements with centralization of data on a secure database for epidemiological analysis. The average of the last 2 measurements characterizes each subject. RESULTS: Full use of Predic'HTA® was obtained in 62.4% of users or 7502 subjects (44% under 35 years of age, 44% 35 to 54 years of age, 12% 55 years of age and over). Antihypertensive treatment was followed by 27% of those aged 55 and over and 1% of those under 35. Among untreated subjects, the prevalence of BP>140/90 was 21.1%, increasing with age (13%, 27%, 33%) and higher among men (27.2%) than among women (15.4%). With the parameters age, sex, weight, IMC, family history of high blood pressure, excessive salt consumption, previous intake of an antihypertensive drug, a score is calculated to associate a probability of having an BP >120/80 with self-screening. The ROC curve shows an AUC at 0.723 with a PPV at 91% and a NPV at 41%. The depist'HTA® score is available at www.depisthta.net CONCLUSION: Self-testing of blood pressure is possible with an electronic blood pressure monitor if a dedicated appliance is used at the same time. The development of the prediction score depist'HTA® for a blood pressure level>120/80 would be useful to target subjects who need to self-test their blood pressure in the short term.

Anticoagulants in frail patients. Seven situations at risk.

In the case of venous thromboembolic disease (VTE), physicians are facing more and more difficulties in managing VTE and their treatment in frail patients. These patients could present several risk situations such as: chronic kidney disease (CKD), underweight or malnourished, falls, cognitive impairment, multi-medicated patients, cancer and pregnancy. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. The objective of this review is to explore these at-risk situations and to suggest adequate anticoagulation therapy, when possible, in each of these complex situations.

The repercussion of stopping reimbursement of olmésartan on antihypertensive drugs prescription and blood pressure control of treated hypertensive patients in France.

OBJECTIVE: Since January 2017, olmesartan-based treatments are no longer reimbursed by French health insurance. Health authorities have recommended switch to one of the "many effective, better tolerated and reimbursed alternatives". The objective of this study was to evaluate the consequences on the prescription of antihypertensive drugs in France and to evaluate the blood pressure control of treated hypertensive patients after the switch from olmesartan to another Angiotensin receptor blocker (ARB). METHODS: To evaluate antihypertensive prescriptions, the French League Against Hypertension Survey (FLAHS) was conducted in 2007, 2012 and 2017 by self-questionnaire sent by mail to a representative panel of the population living in metropolitan France aged 35 years and over. Antihypertensive treatments were grouped by pharmacological class. To evaluate blood pressure control in hypertensive patients treated with olmesartan alone or in combination, 3 home blood pressure monitoring (HBPM) were performed. The first and the second were performed without modification of the dose of olmesartan. The third was performed 1 month after the switch to another ARB. RESULTS: Antihypertensive prescriptions changed between 2007 and 2017. Beta-blockers decreased between 2007 and 2012 and then increased slightly. Between 2012 and 2017, ARB and diuretics decreased and ACE inhibitors (ACE-I) and calcium antagonist (CA) drugs increased. Blood pressure control was assessed in 82 hypertensive patients aged 63±11 years treated with olmesartan. The difference in SBP/DBP between the first 2 self-measurements was -0.96/-0.83mmHg. After therapy switch, the 3rd self-measurement showed an increase in SBP/DBP of 3.4/1.2mmHg. In the subgroup of olmesartan-treated controlled hypertensive patients, the switch to another ARB lead to uncontrolled hypertension for 20% of patients with a 12.1mmHg increase in SBP. CONCLUSION: With the halt of reimbursement of olmesartan, there was a decrease in the prescription of ARB in France. When olmersartan was replaced by another ARB, a worse blood pressure control was observed in treated hypertensive patients. The cessation of the reimbursement of olmesartan has had consequences on the treatment of hypertension in France.

[Use of the EvalObs® adherence scale in an unselected French population of treated subjects with antihypertensive, hypolipemiants or oral antidiabetics medications: The FLAHS 2017 adherence survey]. / Utilisation de l'échelle d'observance EvalObs® dans une population de sujets traités pour une hypertension, une dyslipidémie ou un diabète : enquête FLAHS observance 2017.

OBJECTIVE: A Visual Analog Scale (VAS) is useful for diagnosing medication nonadherence and its validity has been evaluated using electronic pillbox as the gold standard. We have developed the EvaLobs® scale for use on paper or on smartphone and the aim of the study was to administrate the scale among FLAHS 2017 participants treated for an hypertension, a dyslipidemia or diabetes. In subjects treated with antihypertensive medications, participants completed the 6-item Girerd Scale and EvaLobs®. METHODS: The French League Against Hypertension Survey (FLAHS) are carried out by self-questionnaire sent by mail to individuals from the French Kantar Health sampling frame (representative panel of the population living in metropolitan France). In 2017, FLAHS was conducted in 4783 subjects aged 35 and over. The EvaLobs® has a scale from 0 to 15 and the use instruction is "how many days have you taken the drug in the past 15 days". A score>12 indicates a "good compliance". The 6-item Girerd scale was also completed. "Good adherence" was determined for a score of 0 to 2 and "nonadherence" for a score of 3 or more. The agreement between EvaLobs® and the 6-item Girerd scale was evaluated in treated hypertensives. RESULTS: The survey included 4783 subjects with 1308 treated hypertensives, 942 subjects treated with lipid-lowering drugs and 405 subjects treated with anti-diabetics. EVALOBS® indicates "Good adherence" in 96% of subjects and the 6 questions questionnaire indicates "good adherence" in 95% of subjects. An excellent agreement is noted in 93.8%. An EvaLobs® score indicating nonadherence or an absence of response to EvaLobs® is observed in 3.6% [CI 95, 2.5-4.7] of hypertensives, in 6.0% [CI 95, 3.9-8.1] of diabetics and in 8.2% [CI 95, 6.5-9.9] of dyslipidemic patients. CONCLUSION: In the population living in France and in unselected patients treated for metabolic disease or hypertension, non-adherence is lowest for antihypertensive medications and highest for statins. EvaLobs®, which shows good agreement with an adherence questionnaire, is a quick and simple tool for assessing adherence. The smartphone app EvaLobs® is available for free on Google play and the Apple store.

T1- or T2-weighted magnetic resonance imaging: what is the best choice to evaluate atrophy of the hippocampus?

BACKGROUND AND PURPOSE: Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1-weighted (T1WI) and T2-weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy. METHODS: Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests. RESULTS: The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, P = 0.0001; T2WI, P = 7.072 × 10-5 ) and right (T1WI, P = 0.008; T2WI, P = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests. CONCLUSIONS: The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy.

Real-Life Peak and Trough Dabigatran Plasma Measurements over Time in Hospitalized Geriatric Patients with Atrial Fibrillation.

BACKGROUND: Few geriatric patients were included in studies on direct oral anticoagulants and data on dabigatran concentration and safety are needed in this population. Our objectives were to evaluate peak and trough dabigatran plasma concentrations over time in a geriatric population and to identify factors associated with dabigatran plasma concentrations and to assess the relationship with bleeding events. METHODS: Peak and trough dabigatran plasma concentration were performed 4,8,15,30,45 days after inception of dabigatran treatment in 68 consecutive patients ≥75 years old hospitalized in a geriatric hospital with atrial fibrillation. Bleeding events were monitored for 1 year. RESULTS: Mean age was 85.8(5.1) years old and 76.5% were women. Overall, 541 dabigatran plasma measurements (270 peak, 271 trough) were performed. Mean dabigatran concentrations of the 5 sequential measurements ranged 106-146ng/mL for peak and 66-84ng/mL for trough. Renal failure was associated with high peak and trough dabigatran concentration. Inter- and intra-individual coefficients of variation were 59.5% and 44.7% for peak and 74.5% and 44.6% for trough. Participants in the lower two tertiles of dabigatran concentration at day 8 (D8) remained below the 90th percentile (243.9ng/ml) on the next measurements. Bleeding events were associated with high trough dabigatran concentrations. Trough dabigatran concentration at D8>243.9ng/mL significantly predicted bleeding. CONCLUSION: In this geriatric population, renal function and low albumin were associated with dabigatran concentrations. Despite large variability, participants in the lower two tertiles of dabigatran concentration at D8 remained below the 90th percentile on the following measurements. D8 dabigatran trough concentration≥243.9ng/mL identified patients at risk of bleeding.

[Development of a risk calculator for drug compliance in treated hypertensives: The FLAHS Compliance Calculator]. / Mise au point d'un calculateur du risque d'inobservance aux traitements antihypertenseurs chez des hypertendus traités : le calculateur FLAHS Observance.

OBJECTIVE: To investigate the determinants of non-compliance with antihypertensive treatments among participants in the FLAHS 2015 survey and to develop a risk calculator for drug compliance in a hypertensive population. METHODS: The FLAHS surveys are carried out by self-questionnaire sent by mail to individuals from the TNS SOFRES (representative panel of the population living in metropolitan France) sampling frame. In 2015, FLAHS was performed in subjects aged 55years and older. Using the Girerd questionnaire, the "perfect observance" was determined for a score of 0 and "nonobservance" for a score of 1 or higher. A Poisson regression was conducted in univariate and multivariate to estimate risk ratios for each determinant. A non-compliance risk calculator is constructed from multivariate analysis. A Poisson regression was performed in univariate and multivariate to estimate risk ratios. For each sex, a probability table is produced from the equation of the multivariate analysis and then the calculation of a nonobservance probability ratio (PR) using the profile with the best probability as a reference. Each subject is then classified into one of the three classes of risk of non-compliance: low (PR <1.5), high (PR>=2) and intermediate (PR>=1.5 and <2). RESULTS: The survey included 6379 subjects and analysis based on 2370 treated hypertensives. The onset of treatment was less than 2years in 7% of subjects and the median follow-up duration of treatment was 10years. Perfect compliance was observed in 64% of subjects. Independent determinants of non-compliance are: male sex, young age, number of antihypertensive tablet, treatment for a metabolic disease (diabetes, dyslipidemia), presence of other chronic illness, secondary prevention of cardiovascular disease. To get the risk class of nonobservance a web page is available at http://www.comitehta.org/flahs-observance-hta/. CONCLUSION: The development of the FLAHS Compliance Test is a tool whose use is possible during an office visit. Its free availability for French doctor will be one of the actions undertaken as part of the "call for action for adherence in hypertension" proposed by the French League Against Hypertension in 2017.

Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients.

AIM: Recent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA1c target and the occurrence of major clinical events under real-life conditions. METHODS: The T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged>65 years. The recommended personalized HbA1c targets were<7%, <8% and <9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses. RESULTS: Of the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69-1.31; P=0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40-1.94; P=0.75), 1.14 (95% CI: 0.7-1.83; P=0.59) and 0.84 (95% CI: 0.60-1.18; P=0.32), respectively. CONCLUSION: Over a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.

Exploring anterograde memory: a volumetric MRI study in patients with mild cognitive impairment.

BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. RESULTS: Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. CONCLUSIONS: The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

Association between depression and anemia in otherwise healthy adults.

OBJECTIVE: It remains debated whether anemia is associated with depression, independently of physical health factors. We report a large-scale cross-sectional study examining this association in adults free of chronic disease and medication from the general population. METHOD: Hemoglobin levels were measured among 44 173 healthy participants [63% men; mean [standard deviation] age = 38.4 (11.1) years] from the 'Investigations Préventives et Cliniques' (IPC) cohort study. Depression was measured with the Questionnaire of Depression 2nd version, Abridged. Logistic regression analyses were performed to examine the association between anemia and depression, while adjusting for a wide range of sociodemographic characteristics and health-related factors (i.e., sex, age, living status, education level, occupational status, alcohol intake, smoking status, physical activity, and body mass index). RESULTS: Depressed participants were significantly more likely to have anemia compared to non-depressed participants, even after adjustment for sociodemographic and health-related variables [odds ratio = 1.36; 95% confidence interval = (1.18; 1.57)]. Anemia prevalence increased with depression severity, suggesting a dose-response relationship (P for trend <0.001). CONCLUSION: In healthy adults from the general population, we found a significant and robust association between depression and anemia. Further studies are needed to assess the longitudinal relationship between both conditions and determine the mechanisms underlying this association.

[Determinants of controlled hypertension in patients treated with antihypertensive drugs in France: The French League Against Hypertension Survey (FLAHS 2015)]. / Déterminants de l'hypertension artérielle contrôlée chez les sujets traités par antihypertenseurs en France : enquête FLAHS 2015.

OBJECTIVE: The FLASH 2015 survey sought the determinants of hypertension control in subjects treated with antihypertensive drugs in France. METHOD: Sending self-administered questionnaire by mail to a representative sample of the population living in metropolitan France (MetaScope basis, TNS Sofres, France). Patients who declare taking antihypertensive drugs are considered treated hypertensives. A home blood pressure monitoring during 3 days was asked in subjects owing a blood pressure monitor and the average of 18 measurements was calculated. RESULTS: A total of 6379 subjects aged 55 and older were included with 2814 (44.1%) treated with antihypertensive drugs. Home blood pressure was obtained from 1455 subjects including 882 (60.6%) treated. SBP/DBP are 129.3±13.5/75.5±9.0mmHg and are higher in treated subjects in each age category. BP<135/85 was observed in 55.4% and BP<140/90 in 71.7%. Determinants of BP control (<135/85) are the number of measurement for averaging (18 measures over 3 days vs 3 measurements on a morning; 55.4%/44.3%), age (55-64 years vs 80 years old; 57.6%/49.1%), gender (women vs men; 60.3%/50.1%), BMI (<25 vs >30; 63.1%/46.1%). In the 80 and older, a SBP<145 was observed in 74.7% of subjects. The control was 61% when considering an SBP/DBP<135/85 in 55-79 years and SBP<145 among 80 and older. CONCLUSION: The control of hypertension evaluated by home blood pressure on a representative population living in metropolitan France is estimated at between 44.3% and 74.7% and several determinants influence the control of blood pressure like age, gender and BMI.

Association between current perceived stress and incident diabetes is dependent on occupational status: Evidence from the IPC cohort study.

AIM: The role of stress in the onset of type 2 diabetes is a widespread lay belief, yet observational studies have produced inconsistent results. This study aimed to test the hypothesis that the association between perceived stress and incident diabetes might depend on occupational status (OS). METHODS: The four-item Perceived Stress Scale (PSS-4) was completed at baseline by 22,567 participants in the labour force (16,193 men, 6374 women; mean age: 44.5±9.8 years) who had undergone two health checkups subsidized by the French national healthcare system. All subjects were free from diabetes at baseline, defined as a fasting blood glycaemia≥7mmol/L or the use of antidiabetic drugs. RESULTS: After a mean follow-up of 5.3±2.1 years, 527 participants (2.3%) had incident diabetes. After adjusting for sociodemographic, behavioural and biomedical risk factors as well as self-rated health, the association between baseline perceived stress and diabetes at follow-up was non-significant for the total study population. However, perceived stress was significantly associated with incident diabetes in participants of low OS [odds ratio (OR) for a five-point increment: 1.39; 95% confidence interval (CI): 1.02-1.90]. In contrast, there was a negative association between perceived stress and diabetes among those of high OS (OR: 0.60; 95% CI: 0.41-0.88) and no association within other occupational categories. The interaction between perceived stress and OS was significant (P<0.01). CONCLUSION: This study suggests that the association between perceived stress and diabetes onset is dependent on OS. Furthermore, this association does not appear to be explained by the classical risk factors for diabetes.

A novel Alzheimer disease locus located near the gene encoding tau protein.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

Individual 6-year systolic blood pressure change and impact on cardiovascular mortality in a French general population.

Impact of blood pressure (BP) visit-to-visit variability remains controversial for untreated hypertensives and for normotensive subjects. Association between 6-year systolic BP change and all-cause and cardiovascular (CVD) mortality was studied in general primary care population including untreated hypertensive and normotensive subjects. Normotensive individuals and untreated high BP patients (40,926 and 14,283, respectively) had two check-ups (interval: 5.8±2.2 years) at the IPC center (Paris). Follow-up was 6.1±3.2 years: 1131 people died, 114 from CVD causes. Systolic BP (SBP) change was assessed by tertiles of absolute differences between V1 and V2, and the relationship with mortality was analysed with multivariate Cox models (hazard ratio (HR), 95% confidence interval (CI)) including V1 or V2 parameters notably SBP. Adjusting for V1 variables, mortality was associated with SBP change, for the entire population (all-cause: HR=1.15 (95%: 1.01-1.30) and CVD: HR=1.95 (95%: 1.25-3.05)) and in hypertensive individuals: (HR=1.31 (95%: 1.08-1.59) and HR=2.51 (95%: 1.34-4.72), respectively). Adjustments for V2 variables gave similar results. For those who were normotensive at V1, the associations were not significant. In this primary care population, individual long-term visit-to-visit change of BP is an independent predictor of all-cause mortality in hypertensive individuals but not in those with normal BP.