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.

The Effect of Exercise and Social Activity Interventions on Nutritional Status in Older Adults with Dementia Living in Nursing Homes: A Randomised Controlled Trial.

OBJECTIVES: Examine the effects of a 24-week exercise intervention against a social intervention on body weight, body mass index (BMI) and nutritional status in PWD living in nursing homes. DESIGN: Randomized controlled trial. PARTICIPANTS: Ninety-one older people with dementia living in nursing homes. INTERVENTIONS: Exercise (n=44) or social-based activities (n=47), taking place twice per week, for 60 minutes/session, during 24 weeks. MEASUREMENTS: Nutritional status was measured with the mini-nutritional assessment (MNA), weight and BMI. RESULTS: After the 24-week intervention, none of MNA (B-coeff. 1.28; 95% CI -2.55 to 0.02), weight (-0.06; -1.58 to 1.45) and BMI (-0.05; -0.85 to 0.74) differed significantly between groups after adjustment for multiplicity. In the social group, MNA significantly improved while it remained stable in the exercise group. The percentage of at-risk and malnourished patients reduced in both groups by more than 6%. CONCLUSION: The results suggest that social activities have as good effects as exercise activities on nutritional status in PWD nursing home residents.

Hospitalization Drug Regimen Changes in Geriatric Patients and Adherence to Modifications by General Practitioners in Primary Care.

OBJECTIVES: To evaluate the overall rate of adherence by general practitioners (GPs) to treatment modifications suggested at discharge from hospital and to assess the way communication between secondary and primary care could be improved. DESIGN: Observational prospective cohort study. SETTING: Patients hospitalized from the emergency department to the acute geriatric care unit of a university hospital. PARTICIPANTS: 206 subjects with a mean age of 85 years. MEASUREMENTS: Changes in drug regimen undertaken during hospitalization were collected with the associated justifications. Adherence at one month by GPs to treatment modifications was assessed as well as modifications implemented in primary care with their rationale in case of non-adherence. Community pharmacists' and GPs' opinions about quality of communication and information transfer at hospital-general practice interface were investigated. RESULTS: 5.5 ± 2.8 drug regimen changes were done per patient during hospitalization. The rate of adherence by GPs to treatment modifications suggested at discharge from hospital was 83%. In most cases, non-adherence by GPs to treatment modifications done during hospitalization was due to dosage adjustments, symptoms resolution but also worsening of symptoms. The last of which was particularly true for psychotropic drugs. All GPs received their patients' discharge letters but the timely dissemination still needs to be improved. Only 6.6% of community pharmacists were informed of treatment modifications done during their patients' hospitalization. CONCLUSION: Our findings showed a successful rate of adherence by GPs to treatment modifications suggested at discharge from hospital, due to the fact that optimization was done in a collaborative way between geriatricians and hospital pharmacists and that justifications for drug regimen changes were systematically provided in discharge letters. Communication processes at the interface between secondary and primary care, particularly with community pharmacists, must be strengthened to improve seamless care.

Drug Prescription Including Interactions with Anticancer Treatments in the Elderly: A Global Approach.

BACKGROUND: Consequences of inappropriate prescriptions and polymedication in patients suffering from cancer are beginning to be well documented. However, the methods used to evaluate these consequences are often discussed. Few studies evaluate the risk of interaction with anticancer drugs in elderly patients suffering from cancer. OBJECTIVES: To describe the prevalence (i) of polypharmacy, (ii) of potentially inappropriate drug prescriptions and (iii) of drug interactions involving anticancer treatments, using a multiple reference tools. DESIGN: A retrospective, cross-sectional, multicenter study performed from January to December 2012. PARTICIPANTS: Patients aged 65 years or older suffering from cancer presented at the oncogeriatric multidisciplinary meeting. MEASUREMENTS: Polymedication (>6 drugs), potentially inappropriate prescriptions and drug interactions involving anticancer treatment were analyzed in combination with explicit and implicit criteria within a global approach. RESULTS: Among the 106 patients included in this study, polypharmacy was present in 60.4% of cases, potentially inappropriate drug prescription in 63.1% and drug interactions in 16% of case, of which 47% involved anti-cancer treatments. Twenty-seven major drug interactions were identified and eight interactions involved chemotherapy. CONCLUSION: Polymedication, inappropriate prescribing and drug interactions involving anti-cancer drugs are common and largely underestimated in elderly cancer patients.

Ischaemic stroke after exposure to aflibercept: interaction with vitamin K antagonist and/or direct pharmacodynamic effect?

WHAT IS KNOWN AND OBJECTIVE: Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD). CASE SUMMARY: We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive. WHAT IS NEW AND CONCLUSION: A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.

Description of 1,108 older patients referred by their physician to the "Geriatric Frailty Clinic (G.F.C) for Assessment of Frailty and Prevention of Disability" at the gerontopole.

INTRODUCTION: Frailty is considered as an early stage of disability which, differently from disability, is still amenable for preventive interventions and is reversible. In 2011, the "Geriatric Frailty Clinic (G.F.C) for Assessment of Frailty and Prevention of Disability" was created in Toulouse, France, in association with the University Department of General Medicine and the Midi-Pyrénées Regional Health Authority. This structure aims to support the comprehensive and multidisciplinary assessment of frail older persons, to identify the specific causes of frailty and to design a personalized preventive plan of intervention against disability. In the present paper, we describe the G.F.C structure, organization, details of the global evaluation and preventive interventions against disability, and provide the main characteristics of the first 1,108 patients evaluated during the first two years of operation. METHODS: Persons aged 65 years and older, considered as frail by their physician (general practitioner, geriatrician or specialist) in the Toulouse area, are invited to undergo a multidisciplinary evaluation at the G.F.C. Here, the individual is assessed in order to detect the potential causes for frailty and/or disability. At the end of the comprehensive evaluation, the team members propose to the patient (in agreement with the general practitioner) a Personalized Prevention Plan (PPP) specifically tailored to his/her needs and resources. The G.F.C also provides the patient's follow-up in close connection with family physicians. RESULTS: Mean age of our population was 82.9 ± 6.1 years. Most patients were women (n=686, 61.9%). According to the Fried criteria, 423 patients (39.1%) were pre-frail, and 590 (54.5%) frail. Mean ADL (Activities of Daily Living) score was 5.5 ± 1.0. Consistently, IADL (Instrumental ADL) showed a mean score of 5.6 ± 2.4. The mean gait speed was 0.78 ± 0.27 and 25.6% (272) of patients had a SPPB (Short Physical Performance Battery) score equal to or higher than 10. Dementia was observed in 14.9% (111) of the G.F.C population according to the CDR scale (CDR ≥2). Eight percent (84) presented an objective state of protein-energy malnutrition with MNA (Mini Nutritional Assessment) score < 17 and 39.5% (414) were at risk of malnutrition (MNA=17-23.5). Concerning PPP, for 54.6% (603) of patients, we found at least one medical condition which needed a new intervention and for 32.8% (362) substantial therapeutic changes were recommended. A nutritional intervention was proposed for 61.8% (683) of patients, a physical activity intervention for 56.7% (624) and a social intervention for 25.7% (284). At the time of analysis, a one-year reassessment had been carried out for 139 (26.7%) of patients. CONCLUSIONS: The G.F.C was developed to move geriatric medicine to frailty, an earlier stage of disability still reversible. Its particularity is that it is intended for a single target population that really needs preventive measures: the frail elderly screened by physicians. The screening undergone by physicians was really effective because 93.6% of the subjects who referred to this structure were frail or pre-frail according to Fried's classification and needed different medical interventions. The creation of units like the G.F.C, specialized in evaluation, management and prevention of disability in frail population, could be an interesting option to support general practitioners, promote the quality of life of older people and increase life expectancy without disability.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Multidisciplinary team meetings (MDTM) in detection of Alzheimer's disease: data from the IDEM study.

INTRODUCTION: The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom, the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWIG) in Germany and the Haute Autorité de Santé (HAS) in France have recently set out guidelines on prescription of anti-dementia medication. The HAS proposes in particular that continuation of these drugs for longer than one year should be decided in multidisciplinary team meetings (MDTM). OBJECTIVE: To assess the feasibility of MDTM and the satisfaction of coordinating physicians from institutions for the dependent elderly (nursing home, NH) and expert physicians from memory clinics who have participated in the meetings. METHODS: Survey carried out among physicians who had participated in the MDTM held as part of the IDEM study (Interest of systematic tracking of dementia cases in NH: analysing the contribution of MDTM in Alzheimer's disease and related diseases; PHRC National 2009, Code 0910701). The survey evaluated the organization of MDTM and the physicians' opinion of these meetings. RESULTS: The cases of 574 patients were discussed in MDTM involving 133 healthcare professionals (32 coordinating physicians, 48 expert physicians, 4 general practitioners and 49 other health professionals). The mean number of participants was 4.2±1.6. About 16 minutes were spent discussing the case of each resident. About 90% of physicians considered that the meetings were useful. Overall assessment of their efficacy was 11.5/20 for the coordinating physicians and 14.1/20 for the expert physicians. The benefits of MDTM in relation to the work entailed were considered important by 60% of expert physicians and 33% of coordinating physicians. CONCLUSIONS: Our survey confirmed the feasibility of MDTM in the field of Alzheimer's disease. The overall benefit/workload ratio of the meetings was considered to be favorable for the expert physicians. The benefits of MDTM were turned out to be less appreciated by the coordinating physicians according to high workload involved.

[Treatment of a septic patient with acquired haemophilia]. / Traitement d'une hémophilie acquise chez un patient septique.

INTRODUCTION: Acquired haemophilia is a rare bleeding diathesis caused by auto-immune depletion of factor VIII. It is characterised by spontaneous haemorrhagic syndrome, which can be fatal sometimes. EXEGESIS: A 71 year-old man presents in a dysimmunitary context (rheumatoid arthritis complicates by an acquired haemophilia) a septicemia with a methicillin resistant staphylococcus aureus. At the time of the hospitalization, the patient is febrile (39 degrees C). The activated partial thromboplastin time is very much increased, the level of factor VIII is lowered by 7% and the title of the inhibitor to factor VIII amounts to 140 Bethesda unities. An haematoma of the right root thigh is also noted. In that case, the concomitant presence of septicemia makes difficult the use of immunosuppressive therapy usually recommended to decrease auto-antibody's level. For the management of the septicemia, an adapted antibiotherapy (vancomycin then teicoplanin) is organized to J1. To control haemorrhagic risk, immunoglobulins are prescribed from d12 to d16, without immediate results. Then prednisone is introduced. We observe a very fast decrease of the anticoagulant circulating title with a neat improvement of the clinical state, allowing so to realize a draining puncture of the psoas. This invasive investigation required the use of prothrombinic complex concentrates ((Feiba) in the dose of 80 UI/kg two to three times a day). Biopsy does not show infection source. CONCLUSION: The infection delayed the prescription of immunosuppressive therapy and the surgery. Use of corticoids, following 5 days of intravenous polyvalent immunoglobulin, was the good choice. After 7 weeks of hospitalization the patient has recovered a normal haemostasis results, and a good general state.