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Background/Introduction Age is one of the strongest predictors/risk factors for ischemic stroke in subjects with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) have been shown to be effective in the prevention of this condition; however, clinical evidence on bleeding risk with this therapeutic strategy in very old and frail geriatric patients is poor. Purpose To assess bleeding risk in French geriatric patients aged ≥80 years and diagnosed with AF newly treated with rivaroxaban. Methods Subjects, presenting to one of 33 geriatric centers, with non-valvular AF and recent initiation of a treatment with rivaroxaban were enrolled in the study and followed-up every 3 months for 12 months. Clinical and routine laboratory data and evaluation scores, such as HAS-BLED, HEMORR2HAGES, ATRIA, and CHA2DS2-VASc, as well as comprehensive geriatric evaluation were reported. Major bleeding, as defined in ROCKET AF study, was reported at each visit, and this primary outcome was adjudicated by an independent committee. Results of this cohort were compared with findings from a similar cohort treated with vitamin K antagonists (VKAs) from the same centers (n=924). Results A total of 1045 subjects were enrolled in the study of whom 995 (95%) had a one-year follow-up (analyzed population). The mean (standard deviation (SD)) age was 86.0 (4.3) years, with the majority of patients being female (61%), 23% aged 90 years or older, and 48% having an estimated glomerular filtration rate (eGFR) Conclusions This is the first large-scale prospective study in geriatric population in AF subjects treated with DOAC (rivaroxaban) Major bleeding risk appeared higher in very old than younger population, however major bleeding and ICH rates were significantly lower with rivaroxaban than with VKAs when used in the same geriatric population. This study indicates that Rivaroxaban can be used in very old and frail patients for the treatment of non-valvular AF. Acknowledgement/Funding Unrestricted grant from Bayer

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p

Resume • L’etude S.AGES avait pour objectif principal de decrire les caracteristiques cliniques et les modalites de prise en charge des patients diabetiques de type 2 (DT2) âges, suivis en France en medecine generale. • Il s’agit d’une etude de suivi de cohorte, non interventionnelle, nationale et multicentrique, qui a inclus 959 patients DT2 âges de plus de 65 ans, suivis par 227 medecins generalistes. Les resultats a l’inclusion montrent qu’une proportion importante de ces malades presentait une HbA 1c

International audience; Background: Transcatheter aortic-valve implantation (TAVI) has been shown to improve survival and quality of life in patients with severe aortic stenosis. However, one-third of patients have poor outcome as death, functional decline or quality of life (QoL) decline. The aim of this study was to determine cardiac and geriatric predictors of physical and mental QoL decline 6 months after a TAVI procedure in patients aged 75 and older.Methods: Between January 2013 and June 2014, we did a prospective and multicenter study including patients ≥ 75 years old referred for TAVI. The primary outcome was the measure of QoL, assessed by the Short Form 36 survey (SF-36), before and 6 months after the intervention. Association between QoL decline and baseline characteristics including cardiac and geriatric factors was analysed by logistic regression models.Results: Mean age of the 150 patients studied was 83.7 years old and 56% were men. The primary end point, mean SF-36 physical summary score, significantly improved between baseline and 6-month (33.6 vs. 36.4, p=0.003) whereas mental component score significantly decreased (48.2 vs. 36.4, p-value

International audience; Elderly people are more likely to develop severe infections diseases. Given the significant increase in the number of the elderly population, reducing the risk of infection by vaccination is a major preventive approach. The immunization schedule for 2014 in France yields, for the first time, vaccination recommendations for patients over 65 years. Tetanus-Diphtheria-Poliomyelitis vaccination is recommended to be given at the age of 65 years and then every 10 years, together with the pertussis vaccine to protect infants less than 6 months. Recommendation for vaccinations against seasonal influenza in autumn is maintained by the High Council for Public Health, which estimates that the population benefit persists despite the lower individual effectiveness in the elderly. The pneumococcal vaccine is recommended only in high-risk populations, and only once after the age 65. Zoster vaccine is recommended between 65 and 74, and the first year of its availability, can be proposed to elderly patients between 75 and 79 years. Vaccination in the elderly must be enhanced, and information about its advantages should be disseminated.

International audience; BackgroundThe aim of this study was to determine the level of adherence to oral anticoagulants in the population of elderly patients treated for a non-valvular atrial fibrillation (AF) in the era of direct oral anticoagulants.Patients and methodThis transversal study used Morisky scale to assess adherence to oral anticoagulants. We also collected patients’ reviews about the treatment and factors explaining a poor adherence.ResultsBetween January and June 2015, 64 patients were included in Loire Atlantique. Average age was 77.8 years, CHA2DS2-VASc score was 4.06 and treatment (vitamin K antagonists [VKAs] in 78% patients) was prescribed since 4.3 years. According to Morisky scale, 84.4% of patients had a good adherence. There was 88% of good adherence with AVK versus 71% with direct oral anticoagulant, there was no statistically significant difference. The prescriber and the knowledge of anticoagulant treatment role seemed to be determinant factors.ConclusionsThe level of adherence for oral anticoagulant appears higher than in most published studies. Diversification of therapeutic options could constitute an aid to personalize the prescription in order to improve it.; ObjectifL’objectif de cette étude était de déterminer un niveau d’observance du traitement anticoagulant oral, dans la population des patients de plus de 65 ans traités dans le cadre d’une fibrillation atriale (FA) non valvulaire, à l’ère des anticoagulants oraux directs (AOD).Patients et méthodeCette étude transversale utilisait le questionnaire de Morisky pour évaluer l’observance du traitement anticoagulant oral. L’avis du patient sur son traitement ainsi que les facteurs qu’il évoquait pour expliquer une mauvaise observance ont été recueillis.RésultatsEntre janvier et juin 2015, 64 patients ont été interrogés en Loire Atlantique. L’âge moyen était de 77,8 ans, le score CHA2DS2-VASc de 4,06 et le traitement (antivitamine K [AVK] dans 78 % des cas) était prescrit depuis 4,3 ans. Selon le questionnaire de Morisky, 84,4 % des patients étaient « bons observants ». Il y avait 88 % de « bons observants » sous AVK versus 71 % sous AOD, sans différence statistique significative. Le prescripteur initial ainsi que la connaissance du rôle du traitement anticoagulant semblaient être des facteurs déterminants.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

Summary Background & aims Hydration disorders are frequent in clinical practice and can be a life threatening issue in frail patients. Mild dehydration (1–2% loss of body weight) appears to impair cognitive and muscular performance. There is, however, no infallible indicator of correct hydration, and of hydration disorders. This study aim at describing total body water (TBW), extra-cellular water (ECW) and intracellular water (ICW) in a cohort of healthy subjects varying in age, gender and body composition. Two indicators of cellular hydration (TBW over fat free mass, and ICW over fat free mass) were studied. Methods The study cohort was made of 944 men and 874 women (mean age 42.7±13.1 yrs, BMI 24.3±3.5kg/m 2 ). All were volunteers for a preventive health examination. TBW, ECW, ICW were measured with bioelectrical impedance analysis. Body composition was assessed with the 3-compartment model. Results Values for TBW, ECW, and ICW differed with gender and with BMI categories (lean, overweight, and obese). The ratio of TBW over weight decreased with increasing BMI and was lower in women than in men. ECW (as a proportion of TBW) increased with BMI. The ratio of TBW over fat free mass decreased in obese subjects. The ratio of ICW over fat free mass was normally distributed, and decreased with BMI, more so in women than in men. Conclusions This study provides reference values for body water spaces in healthy adults that are negatively correlated with BMI. Women and obese people display indicators of cellular dehydration, and are more at risk of dehydration.

Resume Le dosage de l'excretion urinaire d'albumine (EUA) peut se faire sur un echantillon urinaire sur les premieres urines du matin, sur les urines de 24 heures ou sur prelevement urinaire minute. Les valeurs definissant la microalbuminurie sont : urines de 24 heures : 30–300 mg/24 h ; echantillon urinaire : 20–200 mg/ml ou 30–300 mg/g creatinine urinaire ou 2,5–25 mg/mol (chez l'homme), ou 3,5–35 mg/mol (chez la femme) creatinine urinaire ; echantillon urinaire minute : 20–200 μg/min. La place du dosage semi-quantitatif (bandelettes) n'est pas clairement definie. La microalbuminurie est consideree comme un reflet d'une atteinte generalisee de l'endothelium, mais ce n'est pas demontre. Chez le sujet diabetique La microalbuminurie est un marqueur independant de risque cardiovasculaire (CV), renal et de mortalite totale chez les diabetiques de type 1 et 2. L'augmentation de l'EUA au cours du temps est un marqueur de risque CV et renal chez le diabetique de type 1 ; sa regression est associee a une regression de ces risques. Chez le sujet non diabetique La microalbuminurie est un marqueur independant de risque CV, de risque de diabete, d'alteration de la fonction renale et de mortalite totale. Elle est un marqueur de risque de developper une hypertension arterielle chez le sujet normotendu et un marqueur de risque d'evolution defavorable, ou de deces au cours de cancers et de lymphomes. L'elevation ou la persistance d'une EUA elevee au cours du temps est associee a un pronostic pejoratif chez certains hypertendus. La mesure d'EUA peut etre recommandee chez certains hypertendus ayant un ou deux facteurs de risque CV associes dont le risque CV semble mal evalue ou ayant une hypertension arterielle (HTA) refractaire : la microalbuminurie indique ici un risque CV eleve et incite a assurer un controle tensionnel strict. Il y a peu d'etudes chez les sujets non hypertendus et non diabetiques ; elles suggerent globalement que la microalbuminurie est un facteur de comorbidite et de mauvais pronostic comme chez les sujets hypertendus ou diabetiques. En prevention secondaire, la microalbuminurie est un marqueur de risque independant, mais n'a pas de retombees therapeutiques specifiques. Il n'est pas recommande de rechercher systematiquement une microalbuminurie chez le sujet non hypertendu, non diabetique, sans antecedent de maladie renale. Il est recommande d'effectuer une surveillance de la fonction renale annuelle (excretion urinaire d'albumine creatininemie et estimation du debit de filtration glomerulaire) chez les sujets microalbuminuriques. Therapeutique Chez tout patient ayant une microalbuminurie : reduction ponderale et de l'apport sode excessif ( chez le diabetique , prescription d'un inhibiteur de l'enzyme de conversion (diabete de type 1) ou d'un antagoniste des recepteurs de l'angiotensine 2 (diabete de type 2) a dose suffisante en premiere intention. Les diuretiques thiazidiques ont un effet synergique avec les bloqueurs du systeme renine angiotensine sur la reduction de l'EUA ; chez le non diabetique , les cinq grandes classes d'antihypertenseurs (IEC, ARA2, diuretiques, antagonistes calciques, betabloquants) sont utilisables en premiere intention.

Summary Background & Aims Knee-heel length has been validated in elderly patients as a means to estimate body height. It is accurate and conveys a sufficient precision when it is used to calculate body mass index, and body surface area. This study was undertaken to validate body height estimated from knee-heel length in middle age Caucasian adults. Methods A population of 2789 subjects was recruited in health care centres. They had a measurement of body height, knee-heel length and body weight. Results Knee-heel length was positively correlated with body weight ( r =0.52, p r =0.83, p r =−0.12, p p p 2 of body mass index (BMI) for 41% of population. Conclusions Knee-heel length is not recommended to estimate body height in middle age adults. Alternative methods should be studied.

Resume Sous l’egide de la Societe Francaise de Geriatrie et Gerontologie, un groupe pluridisciplinaire de specialistes en geriatrie, neurologie, epidemiologie, psychiatrie, neuroradiologie, pharmacologie, sante publique a entrepris une demarche de consensus sur les modalites d’evaluation, de suivi et de prise en charge globale de la demence de type Alzheimer au stade severe. Cette reflexion, fondee sur l’etat des connaissances en 2005, a permis de formuler 21 recommandations a destination des praticiens hospitaliers, medecins traitants, medecins coordonnateurs et specialistes. Quel que soit le stade evolutif de la maladie, l’objectif de la prise en charge est d’ameliorer la qualite de vie de la personne malade et de sa famille, en associant projet de soins et projet de vie et ce jusqu’en fin de vie. La prise en charge, pour etre globale, doit etre necessairement pluridisciplinaire et coordonnee, en mobilisant les ressources sanitaires et medico-sociales de proximite pour optimiser leur utilisation. Le groupe a souligne egalement l’importance d’une recherche dynamique : recherche clinique visant a mieux connaitre l’evolution des troubles, evaluation des strategies de prise en soins.

Resume Propos. – L’hyperhomocysteinemie moderee est un facteur de risque de thrombose veineuse profonde. La mutation C677T du gene de la 5,10–methyltetrahydrofolate reductase (MTHFR) a l’etat homozygote est associee a une augmentation moderee de l’homocysteine plasmatique totale. L’association entre la mutation C677T a l’etat homozygote et la thrombose veineuse profonde demeure controversee. Methodes. – Afin d’evaluer cette association, la prevalence de la mutation C677T de la 5,10–methyltetrahydrofolate reductase a ete recherchee chez 168 patients ayant presentes une thrombose veineuse profonde confirmee ; 31 avec une thrombose veineuse profonde idiopathique (groupe A) et 137 patients, chez qui, l’episode thrombotique etait explique par un ou plusieurs facteurs de risques cliniques et/ou biologiques (groupe B). Resultat. – La distribution des genotypes etait differente entre le groupe A et B (++/+ –/– –[n(%)] : 9(29)/10(32)/12(39) vs 16(12)/57(42)/64(46), χ 2 : 6,03; p : 0,049). La comparaison entre les homozygotes d’un part et les deux autres genotypes d’autre part, a montre une relation statistiquement significative entre le genotype +/+ et le caractere idiopathique de la thrombose veineuse profonde (χ 2 : 6,01 ; p : 0,014 ; OR : 3,09 [IC 95 % : 1,06–8,53]). Conclusion. – Ces resultats montrent que la mutation C677T de la 5,10–methyltetrahydrofolate reductase peut etre consideree comme un facteur de risque genetique de thrombose veineuse profonde.

Resume Propos. – Les complications vasculaires arterielles ou veineuses sont classiques chez les patients homocystinuriques. Leur incidence reelle, notamment en France, est mal connue du fait de la rarete de lˈanomalie. Methodes. – Nous rapportons les manifestations vasculaires constatees chez 37 patients homocystinuriques dont 34 par deficit en cystathionine-β synthase et trois par deficit en 5,10-methylenetetrahydrofolate reductase. Resultats. – Les atteintes vasculaires sont notes chez 12 des 34 patients totalisant 18 episodes de thrombose veineuse ou arterielle symptomatique. Les complications thromboemboliques veineuses sont plus frequentes et precoces que les manifestations arterielles. Elles sont le fait des expositions prolongees au trouble metabolique alors que lorsque l’homocystinurie est traitee, elles sont rares et compliquent une chirurgie a haut risque thromboembolique. Le facteur V Leiden augmente le risque de thrombose.

Abstract —Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I–converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia (≈5 mmol/L) and hyperglycemia (≈15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145±22 mL/min per 1.73 m 2 ) and ERPF (636±69 mL/min per 1.73 m 2 ) of II subjects declined by 8±10% and 10±9%, respectively, during hyperglycemia; whereas baseline GFR (138±16 mL/min per 1.73 m 2 ) and ERPF (607±93 mL/min per 1.73 m 2 ) increased by 4±7% and 6±11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P =0.0007 and P =0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration ( P =0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 31 octobre 2013

International audience; PURPOSE:Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors.METHODS:In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system.RESULTS:No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P

The definition of normal pressure hydrocephalus (NPH), in adults, associates clinical signs (Adams and Hakim triad) involving gait disorders, urinary incontinence and dementia, associated with aspects on brain imaging that are consistent with this hypothesis and also normal or slightly increased intracranial pressure. The aim of this study was to clarify the techniques and methods facilitating the diagnosis of NPH. The literature review has been conducted from the Medline database without date limitation including the keywords "normal pressure hydrocephalus" and "diagnosis." They should appear in the article title. From the 43 initially sorted, only 13 have been selected using exclusion criteria. The proposed methods are very sparse and focused on the improvement after surgical shunt. This focus is independent from the diagnosis criteria proposed in 2005. This introduces an ambiguity in the interpretation of the results. In practice, the diagnosis of NPH is more difficult in the elderly population where differential diagnoses are frequent, particularly vascular lesions (notably microangiopathy) and Alzheimer's disease. The more invasive techniques as continuous spinal drainage (usually during 3 days) or some features of CSF dynamics (Rout, compliance) seem to be the best predictors of after shunt improvement. However, these techniques are difficult to use in routine in the elderly. The combination of Evans index and corpus callosum angle on MRI is very useful to improve the differential diagnosis with cerebral atrophy. Spinal tap test (lumbar puncture with the removal of 40 mL of CSF) can be repeated two or three times for consecutive days to improve the predictive value before shunting. Gait and balance often improve after shunt, more than cognition and bladder disorders. In the elderly population, the prognosis after 3 years is non conclusive despite initial improvement. Poor prognosis seems to be due to associated pathologies in particular neurodegenerative diseases. This should be considered in decision-making of CSF shunt.

The antihypertensive efficacy and acceptability of perindopril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 2,927 elderly (≥70 years) hypertensive patients in general practice, as part of an open 6-month trial conducted on a total of 23,460 patients with mild-to-moderate hypertension. Patients were ambulatory and selected if diastolic blood pressure (DBF) was between 94 and 115 mm Hg and no serious illness or ACE inhibitor intolerance was known. Perindopril was started at 2 or 4 mg once daily and, if supine DBP remained >90 mm Hg, the daily dose could be doubled after 1 or 3 months (or a diuretic added if perindopril titration reached 8 mg). At entry, the 2,927 patients (65% females) were on average 74 years old, body weight was 68.2 kg, duration of hypertension was 9.4 years, and prior antihypertensive treatment was present in 78%. Percentage of normal DBP (≤90 mm Hg) was 69% at 1 month, 86% at 3 months (in patients on perindopril alone), and 94% at 6 months. At 6 months the reduction of systolic blood pressure and DBP was 28 and 16.6 mm Hg, respectively. Of the 2,927 patients at entry, 8.6% dropped out during the trial, including 6.1% due to side effects. Cough was the most common symptom (8.9%) leading to withdrawal in 3.4% of cases. In one patient, serum creatinine increased (3-fold at 1 month), but overall no significant variation of renal function occurred, as shown by stable plasma creatinine and potassium levels.

« Le Pot de fer proposaAu Pot de terre un voyage… »La solidite du fer associee a la fragilite de l’âge, voila sans doute qui merite quelques detours afin que la repartie du pot de fer y trouve sa verite : «Si quelque matiere dure vous menace… je vous sauverai ».La carence martiale au-dela de sa relation etiologique avec l’anemie est associee a d’autres pathologies telles que l’insuffisance cardiaque, la depression, le syndrome des jambes sans repos, les insuffisances [...]

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans.Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria.In patients with microalbuminuria, weight reduction, sodium restriction (6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

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Diabetic nephropathy is the main cause for premature death among type 1, insulin-dependent diabetic subjects [1]. To date, aggressive antihypertensive treatment is the main intervention along with better metabolic control able to improve prognosis of these patients [2]. The term diabetic nephropathy designates glomerular injury attributable to diabetes [3]. As in all glomerular diseases, its diagnosis is based upon three functional abnormalities: proteinuria (mainly, albuminuria), elevated blood pressure, and reduced glomerular filtration rate. Technical improvements lead to early detection of glomerular dysfunction in type 1, insulin-dependent diabetic subjects: the first ones were sensitive assays for urinary albumin measurement [4, 5]; also sensitive techniques to detect glomerular hyperfiltration early in the course of diabetic renal disease, and only recently automatic blood pressure monitoring to detect minimal blood pressure changes [6, 7]. The concept of incipient diabetic nephropathy was validated by 4 follow-up studies of patients whose urinary albumin was measured serially with sensitive techniques [8–11]. These studies indicated that minimal increases in Urinary Albumin Excretion (UAE) (called microalbuminuria) can have a prognostic value. Therefore, the concept of incipient diabetic nephropathy is based upon the premise that persistent microalbuminuria can already indicate initial glomerular injury, and not only glomerular dysfunction as discussed elsewhere

Ambulatory blood pressure monitoring (ABPM) is currently proposed for measuring blood pressure in type I, insulin-dependent diabetic subjects with incipient diabetic nephropathy. However, the value of this method, in comparison with conventional ones in detecting blood pressure differences between normotensive type I, insulin-dependent diabetic subjects with or without microalbuminuria, is questionable. We obtained systolic, diastolic, and mean blood pressures (SBP/DBP/MBP) in 10 hospitalized normotensive type I, insulin-dependent diabetic subjects with microalbuminuria, and in 29 others without, using a mercury sphygmomanometer (method 1) and an automatic device (Dinamap; method 2) to obtain morning (9 to 11 AM) measurements, and ABPM (SpaceLabs 90207; method 3) to obtain daytime (7 AM to 10 PM) and nighttime (10 PM to 7 AM) measurements. During the daytime, SBP/DBP/MBP values were higher in microalbuminuric than in normoalbuminuric patients, whatever the blood pressure measurement method used (P = .034/.061/.033, two-factor ANOVA). Analysis of 24-h ABPM also showed higher SBP/DBP/MBP in microalbuminuric than in normoalbuminuric patients (P = .022/.040/.016), and demonstrated a defect in nocturnal SBP decrease in microalbuminuric compared with normoalbuminuric patients (P = .028). Stepwise multiple regression analysis indicated nocturnal SBP as the only independent factor determining for microalbuminuria (F = 6.72). Thus ABPM, in relation to other methods, indicates above all that the most relevant blood pressure change in type I insulin-dependent diabetic subjects with microalbuminuria is a defect in nocturnal SBP decrease.

The association of arterial hypertension and diabetes mellitus is frequent: one third of patients attending a diabetic clinic. Excess hypertension frequency is marked in type II, non insulin-dependent diabetes, a condition often associated with other vascular risk factors such as obesity and lipid disorders. Insulin resistance is a common feature between type II diabetes, hypertension and other risk factors. In type I, insulin-dependent diabetes, hypertension is often linked to diabetic nephropathy. There is a genetic basis for diabetic nephropathy, which may share a common background with familial hypertension. Apart from possible genetic predispositions to hypertension diabetes association, chronic hyperglycaemia can lead to alteration in functional and structural properties of blood and vessels, which both contribute to elevated vascular resistance and blood pressure. From a therapeutic viewpoint, blood pressure values above 140/90 mmHg are not tolerable in diabetic subjects under 40 years of age. Due to their renal haemodynamic effects, angiotensin I converting enzyme inhibitors may be of special interest to protect kidney function in diabetic subjects.

Mitochondria are the cells' powerhouse that produce the ubiquitous energy currency (ATP) by consuming oxygen, producing water and building up the proton motive force. Oxygen consumption is a classical means of assessing energy expenditure, one component of energy balance. When energy balance is positive, weight increases. This is observed during the dynamic phase of obesity, and during body composition changes associated with aging. Whether intrinsic defaults in mitochondria occur is the matter of this review. Indeed, the ratio of ATP over oxygen consumed, which is not fixed, is one way of regulating heat release and ATP flux, but can also be the consequence of environmental conditions of mitochondrial work. For example, various hormones (T3, glucocorticoids), changes in lipid membrane composition, changes in food intake and exercise, and various drugs, can modify the ratio of ATP over oxygen consumed. Aging and insulin resistance are other regulators of this ratio. Finally there is a rising body of evidence linking diabetes to mitochondrial functions.

Successful aging and frailty are emerging constructs becoming necessary to define prevention and treatment goals in elderly subjects. Frailty corresponds to the stages between full autonomy or successful aging and irreversible functional dependency or pathological aging. However its definition is imprecise and potential clinical criteria are numerous and interrelated. Diabetes decreases the likelihood for successful aging and particularly increases the risk for functional dependency. One major end-point in the care of elderly diabetic subjects is to investigate the impact of blood glucose control on progression of disability. Geriatric intervention based on comprehensive geriatric assessment (CGA) in the frail elderly population has been shown effective to prevent the loss of autonomy and to improve quality of life, but seems ineffective on mortality. It is now recommended to screen elderly diabetic patients for frailty criteria. The effect of combined individualized diabetes care and CGA on the aging profile should be investigated.

Seven non haemophilic patients with acquired Factor VIII inhibitor were treated as first line therapy with a cyclophosphamide — prednisone combination. In 6 patients complete suppression of the inhibitor was observed within 9 to 60 days. Relapses occurred in two patients and this treatment was again successfull. In the 7th patient a significant decrease of the inhibitor was observed allowing porcine Factor VIII replacement therapy if desired.

Fibrinogen is supposed to be a risk factor of atherosclerosis. In a group of 890 patients, serum fibrinogen was related to the atherosclerotic complications, mainly coronary heart disease and peripheral vascular disease. In a subgroup of 450 non infected patients, fibrinogen presented significant relations of metabolic variables, body mass index and albuminemia. It is suggested that nutritional factors are determinants of fibrinogenemia.

Unlike classical methods, ambulatory blood pressure monitoring detects significant blood pressure increase in a group of insulin dependent diabetics with incipient nephropathy. Except for microalbuminuria, nocturnal systolic blood pressure appears to be the best parameter related to the existence of incipient diabetic nephropathy.