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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 (β 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 (β 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. [ABSTRACT FROM AUTHOR]

Objective: Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. Patients and methods: From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. Results: One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8 %), 55 (53.4 %) and 3 (2.9 %) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9 %) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. Conclusion: DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients. [ABSTRACT FROM AUTHOR]

Aims: The main aim of the present work was to assess if sex influences the occurrence of major clinical events in elderly people with type 2 diabetes followed up in the primary care., Methods: 983 subjects aged ≥65years with type 2 diabetes were included by 213 general practitioners and followed up prospectively for three years. Major clinical events were recorded every six month. The first endpoint was a composite of all-cause death and major vascular events (acute coronary syndrome, non-fatal stroke or transient ischemic attack, or revascularization for peripheral artery disease). The second endpoint was all-cause hospitalization. The occurrence of each endpoint was analyzed in order to estimate the role of sex and determine other predictors of major clinical events., Results: At baseline, women were older than men but they had a lower prevalence of coexisting diseases (cardiovascular disease and cancer) and equivalent diabetes control (Glycated hemoglobin A1C: 6.9%±0.9 vs. 7.0%±1.1). Over the follow-up period, women were at lower risk to develop the composite endpoint (HR 0.60, 95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases, functional ability and concomitant medications emerged as significant predictors of both endpoints., Conclusions: Elderly women with well-controlled type 2 diabetes were less likely to experience major clinical events than their male counterparts. More studies are needed to determine the reasons for the higher hospitalization rate in men., Competing Interests: Al-Salameh A.: investigator for Alnylam Pharmaceuticals, Ionis (Isis) Pharmaceuticals, Novartis, MedDay Pharmaceuticals, Auris Medical, Gilead Sciences, Euroscreen (Ogeda), Alexion, Faron Pharmaceuticals, Actelion (Idorsia) Pharmaceuticals, and IPSEN. None of these studies is related to the subject discussed in the manuscript. Bucher S., Benattar-Zibi L., Ourabah R., Ringa V.: declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of this report. Bauduceau B.: received consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, Novo Nordisk. Berrut G.: received fees from Sanofi-Aventis, Lundbeck, Eisai, Novartis, Merck Sharp and Dohme, Amgen, Boehringer Ingelheim, Bayer. Bertin P.: received consulting fees from Sanofi-Aventis, Pfizer, Ethypharm, Reckitt Benckiser; speaking fees from Laboratoires Genevrier, Roche, Bristol-Myers Squibb, Merck Sharpand Dohme. Corruble E.: received consulting fees from Lundbeck, Eisai. Danchin N.: received consulting or speaking fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, MSD–Schering Plough, Novartis, Novo Nordisk, Laboratoires Pierre Fabre, Pfizer, Roche, Sanofi-Aventis, Servier, Takeda, The Medicines Company. Derumeaux G.: received consulting or speaking fees from Actelion, Boehringer Ingelheim, Pfizer, Sanofi-Aventis, Servier; research grant from Actelion and AstraZeneca. Doucet J.: received speaking fees from Novo Nordisk; consulting fees from Sanofi-Aventis, Novo Nordisk, Merck Serono; research partnership with Eli Lilly. Falissard B.: received consulting fees from Sanofi-Aventis, Servier, Roche, AstraZeneca, Grünenthal, Eli Lilly, HRAPharma, Boehringer Ingelheim, Bayer, Novartis, Genzyme, Stallergenes, Daiichi Sankyo, Otsuka Pharmaceutical, Bristol-Myers Squibb. Forette F.: received speaking and consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exonhit Therapeutics, Laboratoires Pierre Fabre, Ipsen, Janssen-Cilag, Eli Lilly, Lundbeck, Novartis, Merck Sharp and Dohme, Merz, Pfizer, Roche, Sanofi-Aventis, Servier, Schwarz Pharma, Specia, Warner-Lambert, Wyeth. Hanon O.: received speaking and consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Exonhit Therapeutics, Janssen-Cilag, Lundbeck, Novartis, Pfizer, Sanofi-Aventis, Servier. Pasquier F.: investigator for Pfizer, Piramal, Roche, Eli Lilly, AstraZeneca, Noscira, Pharnext, Forum Pharmaceuticals, GE Healthcare; received consulting fees from Eli Lilly, Novartis, Nutricia Advanced Medical Nutrition, Sanofi-Aventis. Pinget M.: received speaking and consulting fees from Asdia, AstraZeneca, Bristol-Myers Squibb, Medtronic, Merck Sharp and Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Ypsomed. Becquemont L.: investigator for Antisense Therapeutics, Alnylam Pharmaceuticals, PregLem SA, Ionis Pharmaceuticals, Novartis, Auris Medical, MedDay Pharma, Gilead Sciences; received consulting fees from Sanofi-Aventis, Pfizer, Servier; lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb, Merck Sharp and Dohme; a close family member works at Sanofi France., (© Georg Thieme Verlag KG Stuttgart · New York.)

The primary objective of the S.AGES cohort is to describe the real-life therapeutic care of elderly patients. Patients and methods. This is a prospective observational cohort study of 3 700 non-institutionalized patients over the age of 65 years with either type 2 diabetes mellitus (T2DM), chronic pain or atrial fibrillation (AF) recruited by French general practitioners (GPs). Follow-up is planned for 3 years. Baseline characteristics. In the chronic pain sub-cohort, 33% of patients are treated with only grade 1 analgesics, 29% with grade 2 analgesics and 3% with grade 3 analgesics, and 22% have no pain treatment. In the T2DM sub-cohort, 61% of patients have well-controlled diabetes (Hb1c<7%) and 18% are treated with insulin. In the AF sub-cohort, 65% of patients have a CHADS2 score greater than 2, 77% are treated with oral anticoagulants, 17% with platelet inhibitors, 40% with antiarrhythmic drugs and 56% with rate slowing medications. Conclusion. The S.AGES cohort presents a unique opportunity to clarify the real-life therapeutic management of ambulatory elderly subjects and will help to identify the factors associated with the occurrence of major clinical events., (© 2013 Société Française de Pharmacologie et de Thérapeutique.)

Background: The cytotoxic T lymphocyte-associated antigen 4 gene (CTLA-4) encode the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. The receptor protein is a specific T lymphocyte surface antigen that is detected on cells only after antigen presentation. Thus, CTLA-4 is directly involved in both immune and autoimmune responses and may be involved in the pathogenesis of multiple T cell-mediated autoimmune disorders. There is polymorphism at position 49 in exon 1 of the CTLA-4 gene, providing an A-G exchange. Moreover, we assessed the CTLA-4 49 (Thr/Ala) polymorphism in diabetic patients and first-degree relatives as compared to control subjects., Research Design and Methods: Three loci (HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 first-degree relatives and 84 nondiabetic control subjects by means of PCR-RFLP., Results: A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) and DQA1 alleles encoding for Arg in position 52 was observed in diabetic subjects and first-degree relatives as compared to controls. The genotype and allele frequencies of these polymorphisms in type 1 diabetic patients and first-degree relatives differed significantly from those of controls (p < 0.001 and 0.05 respectively). CTLA-49 Ala alleles frequencies were 75.8% in type 1 diabetic patients and 68.1% in first-degree relatives in comparison to 35.7% in control subjects. The Ala/Ala genotype conferred a relative risk of 18.8 (p < 0.001)., Conclusion: The CTLA-4 49 Ala allele confers an increased risk of type 1 diabetes, independent of age and HLA-DQ genetic markers.