[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.

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.

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.

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.

Therapeutic management in ambulatory elderly patients with atrial fibrillation: the S.AGES cohort.

UNLABELLED: Few epidemiologic studies have specifically focused on very old community dwelling population with atrial fibrillation (AF). The objectives of the AF-S.AGES cohort were to describe real-life therapeutic management of non-institutionalized elderly patients with AF according to age groups, i.e., 65-79 and ≥ 80 and to determine the main factors associated with anticoagulant treatment in both groups. METHODS: Observational study (N=1072) aged ≥ 65 years old, recruited by general practitioners. Characteristics of the sample were first evaluated in the overall sample and according to age (< 80 or ≥ 80 years) and to use of anticoagulant treatment at inclusion. Logistic models were used to analyze the determinants of anticoagulant prescription among age groups. RESULTS: Mean age was 78.0 (SD=6.5) years and 42% were ≥ 80 years. Nineteen percent had paroxysmal AF, 15% persistent, 56% permanent and 10% unknown type, 77% were treated with vitamin K antagonists (VKA), 17% with antiplatelet therapy with no differences between age groups. Rate-control drugs were more frequently used than rhythm-control drugs (55% vs. 37%, p < 0.001). VKA use was associated with permanent AF, younger age and cancer in patients ≥ 80 years old and with permanent AF and preserved functional autonomy in patients < 80 years old. Hemorrhagic scores were independently associated with non-use of VKA whereas thromboembolic scores were not associated with VKA use. CONCLUSIONS: In this elderly AF outpatient population, use of anticoagulant therapy was higher even after 80 years than in previous studies suggesting that recent international guidelines are better implemented in the elderly population.

[Risk factors of serious bleeding among ambulatory patients taking antivitamin K aged 75 and over]. / Les déterminants d'hémorragies graves des sujets ambulatoires âgés de 75ans et plus sous antivitamine K.

The benefits of anti-vitamin K (AVK) drugs have been acknowledged in several indications. Such indications increasing with increasing age, AVK prescriptions also increases with age. At the same time, conditions involving significant bleeding are common in this elderly population. It is thus essential to recognize the determining factors. This study included all patients taking AVK drugs aged 75 years and older who sought emergency care at the Cochin Hospital from January to December 2011 for significant bleeding. These patients were compared with a cohort of patients aged 75 years or older who were taking AVK drugs and who were admitted to the same unit during the same time period for other reasons. The case-control comparison included demographic data, comorbidity factors, multiple medications, emergency measured INR, and CHA2DS2VASC level. The hemorrhagic risk was evaluated by HEMORR2HAGES and HAS-BLED. A total of 34 patients were studied and compared with 70 case-controls. The Charlson comorbidity index was higher in patients than case-controls (P<0.05), with a much higher hemorrhagic risk for scores ≥ 9 (OR=2.5; P<0.05). Multiple medication was also more predominant in patients (P<0.05). The risk of serious hemorrhage was also higher when the hemorrhagic scores were high, especially for HEMORR2HAGES (P<0.0001) and HAS-BLED (P<0.001). The risk of serious hemorrhage in elderly outpatients taking AVK drugs is related to their higher comorbidity and hemorrhagic levels which need to be evaluated before starting or stopping AVK treatment.

The therapeutic management of chronic pain in ambulatory care patients aged 65 and over in France: the S.AGES Cohort. Baseline data.

OBJECTIVE: The main objective of the S.AGES (Elderly Subjects) cohort study is to describe the current therapeutic strategy for chronic pain in non-institutionalised elderly patients in France. METHODS: In this prospective cohort study, non-institutionalised patients aged 65 years and over with chronic pain were recruited by general practitioners (GP) across France. All medicinal and non- medicinal prescriptions were recorded at inclusion and will be followed up over 3 years via an eCRF. Data recorded at baseline are presented in this paper. RESULTS: Two hundred and sixty GPs enrolled 1379 evaluable patients between June 3rd, 2009 and June 3rd, 2011. Pain was mainly of a mechanical nature, due to osteoarthritis or common back pain. 80% of the patients had moderate or severe pain. More than a third of patients were treated with a step 1 analgesic (mainly paracetamol), and approximately 30% received a step 2 analgesic (23% dextropropoxyphene and 40.3% tramadol/paracetamol combination). Only 3% received step 3 analgesics; this rate remained low even in patients with severe pain. The proportion of patients treated with an antiepileptic was higher in case of neuropathic pain. More than 25% of patients did not receive any analgesic medication. CONCLUSION: The baseline S.AGES study results exhibit a well-balanced therapeutic management of chronic pain by GPs for ambulatory elderly patients. Clinicaltrials.org NCT01065909.

[Multicenter study on lumbar puncture indication, clinical practice and feasibility]. / Indications, réalisation et faisabilité de la ponction lombaire dans 18 centres mémoires de ressources et de recherche.

INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have been extensively studied as diagnostic markers for Alzheimer's disease (AD). However, results are variable probably due to lumbar puncture (LP) procedure, CSF collection and transport. This intercenter variability highlights the need for an efficient standardization of clinical and technical procedures. The aims of this study were firstly to compare the LP procedure and CSF transport process in all French Memory Centers and secondly to evaluate the incidence of LP side effects in 100 patients with cognitive disturbances. METHODS: LP practice and side effect prospective questionnaires were sent to all French Memory Centers in May 2010. Memory Centers were asked about their LP procedure. The prospective study over a three-week-period has evaluated the LP feasibility and side effects. All data were collected until the end of July 2010. RESULTS: The answers of 18 out of 26 Memory Centers were collected. Although, these centers did not have the same LP procedure and CSF transport, the majority of them proceeded according to Innogenetics's advices concerning the use of polypropylene tubes and transport duration but not sample conditioning. Polypropylene tubes were different from one center to the other. CSF volume, pharmacological premedication and prevention of post-LP syndrome were variable in all responding centers. The prospective study carried out in 100 patients revealed a very good LP acceptability (93/100 patients). LP feasibility was 97 % (90/93) and failed LP were consequently performed with success using radiological scopes. Three minor complications were observed. DISCUSSION AND CONCLUSION: All French Centers complied with Innogenetics' recommendations for pretechnical CSF procedures; however each Center put in place its own procedure that was different one center to the other. It will be very interesting to compare cut-off and result values for Aß, tau and phosphorylated tau protein on threonine 181 between several centers that used their own procedures. Acceptability and safety were very good in our short but significant prospective study. These results confirm the data of Zetterberg et al., 2010.

APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

Relevance of 10-min delayed recall in dementia screening.

Within the context of early diagnosis of Alzheimer's disease (AD), there is a growing interest in neuropsychological screening tests. Amongst these tests, we focused on the largely used Memory Impairment Screen (MIS). The objective of the present work was to show that adding a 10-min delayed recall to the MIS, improves the test psychometric characteristics in order to detect dementia in the earliest stages. A prospective study was carried out on a cohort of 270 consecutive elderly ambulatory subjects attending the Broca Hospital Memory Clinic: normal controls (n = 67), mild cognitive impairment subjects (n = 98) and mildly demented patients [n = 105, Mini Mental State Examination (MMSE) = 23 +/- 4]. This study consisted in testing the advantage of the 10-min delayed recall entitled MIS-D compared with the MIS. At a cut-off score of 6, the MIS-D revealed satisfying psychometric characteristics with a sensitivity of 81% and a specificity of 91%, whilst the MIS alone indicated a sensitivity of 60% and a specificity of 88% in detecting dementia. In demented patients with MMSE score > or =26, MIS-D properties still remained satisfying (sensitivity: 75%, specificity: 92%). MIS-D is a more relevant screening test than MIS alone at very early stages of dementia.

[Blood pressure self-monitoring contributes to improved patient education among hypertensive subjects]. / La possession d'un appareil d'automesure tensionnelle contribue à améliorer l'éducation des patients hypertendus.

UNLABELLED: Education of hypertensive subject must sensitize the patient to its pathway and to the prescribed treatment. Self-measurement of blood pressure, which directly implicates the patient, should ameliorate the education of hypertensive subject. OBJECTIVES: To evaluate if the possession of a self-measurement blood pressure device improves patients' knowledge of hypertension. METHODS: In 484 treated hypertensive subjects referred to hypertension specialists, a questionnaire evaluating patients knowledge of hypertension and its treatment was given before the consultation. During this consultation, the practitioner evaluated the concordance between antihypertensive treatments declared by the patient and those effectively prescribed. RESULTS: In this population, aged 61 +/- 12 years, with 55% of men, a self-measurement blood pressure device was possessed by 165 subjects (34%). These devices have been bought without medical advice by 83 patients. For a minority of subjects (n = 41), self-measurements of blood pressure were made at the wrist. Blood pressure level was similar in subjects with (141 +/- 19/80 +/- 10 mmHg) or without (140 +/- 19/80 +/- 10 mmHg) self-measurement devices. Subjects possessing a self measurement device had a better knowledge of their usual blood pressure level and of the normal blood pressure values (< 140/90 mmHg), than subjects without self measurement device (93% vs 77%, p < 0.01, and 56% vs 33%, p < 0.01, respectively). Moreover, subjects in possession of self-measurement devices had a better knowledge of their antihypertensive treatment than those without device (83% vs 70%, p < 0.05). Logistic regression analysis including age, sex, smoking, education level, blood pressure level and the number of antihypertensive tablets confirm the statistical differences observed. CONCLUSION: Hypertensive subjects who possess a self-measurement blood pressure device have a better knowledge of their hypertension. These results indicate that the possession of a self-measurement device contributes to the education of hypertensive patients.

[The estimation of cardiovascular risk in hypertensive patients is not modified by management of the hypertension]. / L'estimation du risque cardiovasculaire chez des patients hypertendus ne modifie pas la prise en charge de l'HTA.

OBJECTIVES: To compare antihypertensive therapeutic strategies and efficacy whether the physicians were aware or not of the calculated cardiovascular risk at 10 years obtained from the Framingham equation. It was also possible to evaluate the concordance of the general physicians estimation of the cardiovascular risk with the calculated percentage. METHODS: The participation of 953 general physicians to the study allowed to achieve an estimation of the absolute cardiovascular risk for 1,243 hypertensives. Patients were randomised in 2 groups according to the knowledge or not by the physicians of the calculated risk. The therapeutic strategy included a monotherapy (Fosinopril 20 mg/days) for a follow up of 8 weeks, with the possibility to increase the treatment after 4 weeks (Fosinopril + hydrochlorotiazide). To be included, patients had to be more than 18 and less than 75 years, and a blood pressure above 140/90 mmHg. Estimated and calculated cardiovascular risk at 10 years, were classified according to the 1999 WHO-ISH guidelines: low risk < 15%, medium risk 15-20%, high risk 20-30%, very high risk > 30%. RESULTS: In this population, aged 60 +/- 10 years, with 54% of men, the concordance between estimated risk and calculated risk was of 35%. This concordance was better for the "low risk" and "very high risk", but remains inferior to 50%. The determinants of concordance were: gender (male), smoking and a low HDL cholesterol. After 8 weeks of treatment, no difference was observed between the 2 groups concerning final blood pressure level, percentage of normalised patients and number of patients with bi-therapy. CONCLUSIONS: General physicians estimation of cardiovascular risk at 10 years of hypertensive subjects has a bad concordance with the calculated risk according to Framingham equation. The results of this study indicate that the estimation of cardiovascular risk of hypertensive subjects does not modify the management of hypertension.

[Validity of the clinical prediction rule for the diagnosis of renal arterial stenosis in hypertensive patients resistant to treatment]. / Validation d'une règle clinique de prédiction pour le diagnostic d'une sténose artérielle rénale chez des patients hypertendus résistants aux traitements.

PURPOSE: To perform an external validation of the clinical prediction rule established by Krijnen et al. (Ann Intern Med 1998; 129: 705-11) designed to identify renal artery stenoses (RAS) in hypertensive patients. METHODS: We included 102 patients with a refractory hypertension treated with at least two antihypertensive drugs. All subjects had the research of RAS by renal angiography, or angio-computed tomography, or doppler ultrasound. Probability to detect RAS was calculated with Krijnen's algorithm (Pre-test probability) from the following parameters: age, smoking status, diffuse atherosclerosis, recent hypertension (< 2 y), obesity (BMI > 25), abdominal bruit, hypercholesterolemia (> 6.5 mmol/L), creatinine. ROC curves were plotted for each pre-test probability value. A "post-test probability" was obtained from the likelihood ratio calculated at each pre-test probability level. RESULTS: RAS prevalence in this population was 49%. Area under the ROC curve was 0.79 and Youden index was maximal for a pre-test probability of 15%. Maximal likelihood ratio was obtained for a pre-test probability of 46%. Table shows post-test probability as a function of pre-test probability obtained with Krijnen's algorithm. [table: see text] CONCLUSION: Krijnen's algorithm is valid in a population of resistant hypertensives treated with a bi-therapy. This external validation obtained on a population with a high prevalence of RAS should also be tested on a population with a lower prevalence of SAR.

Association between the apolipoprotein E polymorphism and arterial wall thickness in asymptomatic adults.

OBJECTIVES: The polymorphism of the apolipoprotein E gene (epsilon2, epsilon3, epsilon4) affects plasma cholesterol but the relationship with artery wall thickness has indicated contradictory results. This study investigated the relationship between apolipoprotein E polymorphism and vascular phenotypes of the carotid and radial arteries, two arterial sites differently affected by atherosclerosis. METHODS: We studied a cohort of 320 Caucasian subjects (age 49 +/- 12 years) without evidence of cardiovascular disease. Structural (internal diameter and wall thickness) and functional phenotypes (compliance, distensibility) were evaluated for the common carotid and the radial arteries using high resolution echo-tracking devices. Genotypes of apolipoprotein E were determined by allele-specific oligonucleotides hybridization. Because of the relative low frequency of some apolipoprotein E genotypes, they were designated as E2 (epsilon2/epsilon2, epsilon2/epsilon3), E3 (epsilon3/epsilon3), and E4 (epsilon4/epsilon4, epsilon3/epsilon4). RESULTS: Apolipoprotein E allele frequencies were epsilon2 = 0.08, epsilon3 = 0.79, epsilon4 = 0.13. Subjects with epsilon4 allele had the highest levels of total serum cholesterol and low density lipoprotein cholesterol; subjects with epsilon2 allele had the lowest levels (P < 0.001). Considering carotid hypertrophy as intima-media thickness > 660 microm, and radial hypertrophy as intima-media thickness > 260 microm, a logistic regression model testing determinants of arterial hypertrophy (age, gender, weight, systolic blood pressure, smoking habits, and total serum cholesterol) observed a significant and positive association between carotid hypertrophy and epsilon2 allele carriers (P= 0.03). In contrast, no association was found between hypertrophy and apolipoprotein E genotypes for the radial artery. No association was observed between the apolipoprotein E genotypes and functional artery parameters. CONCLUSIONS: In subjects without any evidence of cardiovascular disease, the presence of the epsilon2 allele is related to wall hypertrophy in carotid artery despite favourable effect on the lipid profile.