Reference Standard for the Measurement of Loss of Autonomy and Functional Capacities in Long-Term Care Facilities.

The vast majority of people living in long-term care facilities (LTCFs) are octogenarians (i.e., in Québec, 57.4% of the residents are age 85 or older, 26.2% are between age 75 and 84, 10.7% are between age 65 and 74, and 5.7% are below age 65 (1)), who are affected by a great loss of physical or cognitive autonomy due to illnesses and are unable to maintain their independence, safety and mobility at home. For the majority of them, their last living environment will be a LTCF. Moreover, the annual turnover in LTCFs is one-third of all residents (2) while the average length of stay is 823 days (1). Therefore the main challenges for caregivers in LTCFs are the maintenance of functional capacities and preventing patients from becoming bedridden and isolated. Measuring the level of autonomy and functional capacities is therefore a key element in the care of institutionalized people. Several validated tools are available to quantify the degree of dependence and the functional capacities of older people living in long-term care facilities. This narrative review aims to present the characteristics of the specific population living in long-term care facilities and describe the most widely used and validated tools to measure their level of autonomy and functional capacities.

Potential Efficacy of Pragmatic Exercise Program (SPRINT) during Hospitalization in Older Adults on Health Care and Physical Performance: A Pilot Study.

OBJECTIVES: Immobilization contribute to iatrogenic decline in hospitalized older adult. Implementing physical activity (PA) seems to be one of the best and easy solution. However, PA interventions are poorly integrated into usual care and those available are either non-specific, need supervision or requested human/material resources. Thus, we aimed to assess the effect of a pragmatic, unsupervised, and specific PA program (SPRINT) on health care practice and functional capacities in hospitalized older patients. DESIGN: Single arm interventional pragmatic pilot study. SETTING: Geriatric Assessment Unit (GAU). PARTICIPANTS: Of the 39 patients (> 65 years) hospitalized in a GAU and eligible, 19 agreed to participate (AP) and 20 declined (N-AP). INTERVENTION: One of the 4 PA programs, developed by our team, was allocated according to mobility profile. Individual functional capacities (i.e. balance, walking speed, functional mobility profile (PFMP)), active time (METS> 1.5: min), length of hospitalization (LOS), discharge orientation were assessed at admission and discharge of GAU. RESULTS: Baseline characteristics of the 2 groups were comparable. At discharge, the AP group improved more on walking speed (0.57 ± 0.21 vs. 0.64 ± 0.19; p = 0.013), Berg balance scale (41.8 ± 13.7 vs. 45.1 ± 9.7; p = 0.017) and PFMP (54.0 ± 7.1 vs 55.1 ± 5.5; p = 0.042) than the N-AP group. The LOS was significantly shorter in AP group compared to the N-AP group (5 vs. 36 days; p = 0.026) and more subjects in the AP group were oriented at home without health or social services (89.5 vs. 60%; p=0.065). CONCLUSION: SPRINT appears effective to counteract iatrogenic decline and decreased the LOS. Moreover, this simple pragmatic PA tool seems to improve the life trajectory and healthcare practice in aging population. Further researches are needed to confirm these promising pragmatic results.

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

Vitamin B12 Deficiency Induced by the Use of Gastric Acid Inhibitors: Calcium Supplements as a Potential Effect Modifier.

OBJECTIVE: Use of gastric acid inhibitors has emerged as a risk factor of vitamin B12 deficiency, especially in older adults. Calcium supplements could be an effect modifier of this relationship by its role in the absorption process of vitamin B12. The aim of this study is to examine whether the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency. DESIGN: Cross-sectional study based on medical chart reviews. SETTING: Geriatric Assessment Unit (GAU) of a university-affiliated hospital. PARTICIPANTS: The study included 172 patients discharged from the GAU between 2008 and 2012. MEASUREMENTS: Cases of vitamin B12 deficiency were identified as those who had received a diagnosis of vitamin B12 deficiency, and/or were receiving a treatment for vitamin B12 deficiency. Use of gastric acid inhibitors and calcium supplements at admission was determined from the pharmacist report. Associations between medications and vitamin B12 status were investigated using logistic regression models. RESULTS: Seventy-one patients (41%) had vitamin B12 deficiency. At admission, 42% were taking gastric acid inhibitors and 45% calcium supplements. After adjustment for covariates, analyses revealed that vitamin B12 deficiency was more likely among users of gastric acid inhibitors who did not concomitantly received calcium supplements [OR=3.12; P=0.01]. Conversely, no significant association was observed in patients using both, gastric acid inhibitors and calcium supplements [OR=1.30; P=0.59]. CONCLUSIONS: The present study provides the very first evidence that the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency. Failure to consider calcium supplements as an effect modifier could have led to biased risk estimates in previous published studies.

Expression of the kynurenine pathway enzymes in the pancreatic islet cells. Activation by cytokines and glucolipotoxicity.

The tryptophan/kynurenine pathway (TKP) is the main route of tryptophan degradation and generates several neuroactive and immunomodulatory metabolites. Experimental and clinical data have clearly established that besides fat, muscle and liver, pancreatic islet tissue itself is a site of inflammation during obesity and type 2 diabetes. Therefore it is conceivable that pancreatic islet exposure to increased levels of cytokines may induce upregulation of islet kynurenine metabolism in a way resembling that seen in the brain in many neurodegenerative disorders. Using normal rat islets and the INS-1 ß-cell line, we have demonstrated for the first time that: 1/only some TKP genes are constitutively expressed, both in ß-cells as well as non ß-cells; 2/ the regulatory enzyme indoleamine 2,3-dioxygenase (IDO1) is not constitutively expressed; 3/ IDO1 and kynurenine 3-monoxygenase (KMO) expression are potently activated by proinflammatory cytokines (IFN-γ, IL-1ß) and glucolipotoxicity respectively, rather in ß-cells than in non ß-cells; 4/ Islet kynurenine/kynurenic acid production ratio is enhanced following IFN-γ and glucolipotoxicity; 5/ acute exposure to KYN potentiates glucose-induced insulin secretion by normal islets; and 6/ oxidative stress or glucocorticoid modulates TKP genes only marginally. Pancreatic islets may represent a new target tissue for inflammation and glucolipotoxicity to activate the TKP. Since inflammation is now recognized as a crucial mechanism in the development of the metabolic syndrome and more specifically at the islet level, it is needed to evaluate the potential induction of the TKP in the endocrine pancreas during obesity and/or diabetes and its relationship to the islet cell functional alterations.

A comprehensive profile of the sociodemographic, psychosocial and health characteristics of Ontario home care clients with dementia.

INTRODUCTION: This study provides a comprehensive summary of the sociodemographic, psychosocial and health characteristics of a large population-based cohort of Ontario home care clients (aged 50 years and over) with dementia and examines the variation in these characteristics in those with co-existing neurological conditions. METHODS: Clients were assessed with the Resident Assessment Instrument-Home Care (RAI-HC) between January 2003 and December 2010. Descriptive analyses examined the distribution of these characteristics among clients with dementia relative to several comparison groups, as well as clients with other recorded neurological conditions. RESULTS: Approximately 22% of clients (n=104 802) had a diagnosis of dementia (average age 83 years, 64% female) and about one in four within this group had a co-existing neurological condition (most commonly stroke or Parkinson disease). About 43% of those with dementia did not live with their primary caregiver. Relative to several comparison groups, clients with dementia showed considerably higher levels of cognitive and functional impairment, aggression, anxiety, wandering, hallucinations/delusions, caregiver distress and a greater risk for institutionalization. Conversely, they showed a lower prevalence of several chronic conditions and lower levels of recent health service use. Depressive symptoms were relatively common in the dementia and other neurological groups. CONCLUSION: Clients with co-existing neurological conditions exhibited unique clinical profiles illustrating the need for tailored and flexible home care services and enhanced caregiver assistance programs.

TITRE: Profil complet des caractéristiques sociodémographiques, psychosociales et sanitaires des clients des soins à domicile atteints de démence en Ontario. INTRODUCTION: Cette étude fournit une synthèse des caractéristiques sociodémographiques, psychosociales et sanitaires d'une vaste cohorte représentative des clients des soins à domicile en Ontario (âgés de 50 ans ou plus) atteints de démence et elle examine les variations de ces caractéristiques chez les clients atteints de maladies neurologiques concomitantes. MÉTHODOLOGIE: Les clients ont été évalués à l'aide de l'Instrument d'évaluation des résidents ­ Soins à domicile (RAI-HC) entre janvier 2003 et décembre 2010. Les analyses descriptives fournissent la répartition de ces caractéristiques en comparant les clients atteints de démence et ceux de plusieurs autres groupes ainsi que ceux atteints d'autres maladies neurologiques documentées. RÉSULTATS: Environ 22 % des clients (n = 104 802) avaient reçu un diagnostic de démence (âge moyen de 83 ans, 64 % de femmes) et un sur quatre parmi eux était atteint d'une maladie neurologique concomitante (AVC ou maladie de Parkinson la plupart du temps). Environ 43 % des clients atteints de démence n'habitaient pas avec leur principal aidant. Par rapport aux clients des groupes de comparaison, les clients atteints de démence présentaient des taux considérablement plus élevés de déficit cognitif et fonctionnel, d'agressivité, d'anxiété, d'errance et d'hallucinations ou de délire, avaient plus souvent un aidant en détresse et couraient un plus grand risque de placement en établissement. Par contre, ils étaient moins souvent atteints de diverses maladies chroniques et étaient moins nombreux à avoir eu recours à des services de santé récemment. Les symptômes de dépression étaient relativement fréquents chez les clients atteints de démence et chez ceux atteints d'une autre maladie neurologique. CONCLUSION: Les clients atteints de maladies neurologiques concomitantes présentaient des profils cliniques bien particuliers illustrant la nécessité de personnaliser et d'assouplir les services de soins à domicile et d'améliorer les programmes de soutien pour les aidants.

Challenges in managing the diet of older adults with early-stage Alzheimer dementia: a caregiver perspective.

UNLABELLED: Caregivers (CG) of older adults suffering from Alzheimer disease (AD) are confronted by many challenges when caring for their family member; these include dietary management. OBJECTIVES: To identify difficulties in dietary management encountered by CG taking part in the Nutrition Intervention Study (NIS), and to gather their opinions on the intervention. DESIGN, SETTING AND PARTICIPANTS: Thirty-three CG of individuals with AD from the NIS intervention group were contacted. Individual interviews were conducted and analyzed using qualitative data analysis, and themes around challenges related to dietary practices experienced by CG were identified. RESULTS: Twenty-four CG were interviewed; 58% were aged 70 and older and 58% were the patient's spouse. Three major thematic categories emerged: 1. Dietary challenges and coping strategies used by CG; 2. CGs' opinion about the NIS; 3. CG interest in participating in a nutrition education support service. Changes in food habits and increasing dependency on the CG were the major themes related to dietary challenges. CONCLUSION: A better understanding of the CG's experience is essential for the development of nutrition interventions adapted to the needs of older adults with AD and their CG.

Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto-Kakizaki (GK) rat.

AIMS/HYPOTHESIS: The adult non-obese Goto-Kakizaki (GK) rat model of type 2 diabetes, particularly females, carries in addition to hyperglycaemia a genetic predisposition towards dyslipidaemia, including hypercholesterolaemia. As cholesterol-induced atherosclerosis may be programmed in utero, we looked for signs of perinatal lipid alterations and islet microangiopathy. We hypothesise that such alterations contribute towards defective pancreas/islet vascularisation that might, in turn, lead to decreased beta cell mass. Accordingly, we also evaluated islet inflammation and endothelial activation in both prediabetic and diabetic animals. METHODS: Blood, liver and pancreas were collected from embryonic day (E)21 fetuses, 7-day-old prediabetic neonates and 2.5-month-old diabetic GK rats and Wistar controls for analysis/quantification of: (1) systemic variables, particularly lipids; (2) cholesterol-linked hepatic enzyme mRNA expression and/or activity; (3) pancreas (fetuses) or collagenase-isolated islet (neonates/adults) gene expression using Oligo GEArray microarrays targeted at rat endothelium, cardiovascular disease biomarkers and angiogenesis, and/or RT-PCR; and (4) pancreas endothelial immunochemistry: nestin (fetuses) or von Willebrand factor (neonates). RESULTS: Systemic and hepatic cholesterol anomalies already exist in GK fetuses and neonates. Hyperglycaemic GK fetuses exhibit a similar percentage decrease in total pancreas and islet vascularisation and beta cell mass. Normoglycaemic GK neonates show systemic inflammation, signs of islet pre-microangiopathy, disturbed angiogenesis, collapsed vascularisation and altered pancreas development. Concomitantly, GK neonates exhibit elevated defence mechanisms. CONCLUSIONS/INTERPRETATION: These data suggest an autoinflammatory disease, triggered by in utero programming of cholesterol-induced islet microangiopathy interacting with chronic hyperglycaemia in GK rats. During the perinatal period, GK rats show also a marked deficient islet vascularisation in conjunction with decreased beta cell mass.

Relationship between home hazards and falling among community-dwelling seniors using home-care services.

BACKGROUND: Evidence linking home hazards to falls has not been well established. The evidence-based approach to fall-risk assessment in longitudinal studies becomes difficult because of exposures that change during follow-up. We conducted a cohort study to determine the prevalence of hazards and to resolve whether they are linked to the risk of falls among 959 seniors receiving home-care services. METHODS: A home hazards assessment was completed at entry and every six months thereafter using a standardized form. The adjusted (for a number of confounding factors) relationship between home hazards and falls was estimated using a survival model taking into account updated time-varying exposures and multiple events. Falls leading to a medical consultation were examined as a secondary outcome, hypothesized as a measure of severity. FINDINGS: Home environmental hazards were found in 91% of homes, with a mean of 3.3 risks per individual. The bathroom was the most common place for hazards. The presence of hazards was significantly associated with all falls and fall-related medical consultations, and showed relatively constant effects from one fall to another. IMPLICATIONS: The current study is innovative in its approach and useful in its contribution to the understanding of the interaction between home environmental hazards and falls. Our results indicate that inattention to changes in exposure masks the statistical association between home hazards and falls. Each environmental hazard identified in the home increases the risk of falling by about 19%. These findings support the positive findings of trials that demonstrate the effectiveness of this home hazard reduction program, particularly for at-risk people.

IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat.

Recent studies suggest an inflammatory process, characterized by local cytokine/chemokine production and immune cell infiltration, regulates islet dysfunction and insulin resistance in type 2 diabetes. However, the factor initiating this inflammatory response is not known. Here, we characterized tissue inflammation in the type 2 diabetic GK rat with a focus on the pancreatic islet and investigated a role for IL-1. GK rat islets, previously characterized by increased macrophage infiltration, displayed increased expression of several inflammatory markers including IL-1beta. In the periphery, increased expression of IL-1beta was observed primarily in the liver. Specific blockade of IL-1 activity by the IL-1 receptor antagonist (IL-1Ra) reduced the release of inflammatory cytokines/chemokines from GK islets in vitro and from mouse islets exposed to metabolic stress. Islets from mice deficient in IL-1beta or MyD88 challenged with glucose and palmitate in vitro also produced significantly less IL-6 and chemokines. In vivo, treatment of GK rats with IL-1Ra decreased hyperglycemia, reduced the proinsulin/insulin ratio, and improved insulin sensitivity. In addition, islet-derived proinflammatory cytokines/chemokines (IL-1beta, IL-6, TNFalpha, KC, MCP-1, and MIP-1alpha) and islet CD68(+), MHC II(+), and CD53(+) immune cell infiltration were reduced by IL-1Ra treatment. Treated GK rats also exhibited fewer markers of inflammation in the liver. We conclude that elevated islet IL-1beta activity in the GK rat promotes cytokine and chemokine expression, leading to the recruitment of innate immune cells. Rather than being directly cytotoxic, IL-1beta may drive tissue inflammation that impacts on both beta cell functional mass and insulin sensitivity in type 2 diabetes.

The evolution of nutritional status of geriatric patients without cachexia is associated with food intake in sub-acute care.

OBJECTIVES: To determine if changes in patients' nutritional status during hospitalization are related to daily energy and protein intakes when cachectic/inflammatory conditions are controlled for. DESIGN: Prospective study. SUBJECTS: A total of 32 non-cachectic patients (21 women; 65-92 y). METHODS: Nutritional status was evaluated at admission and discharge using the Protein-Energy Malnutrition Index which includes BMI, %IBW, TS, MAC, albumin, hemoglobin and lymphocyte count. Food intake was assessed 3 meals/day every other day for an average of 46.2 +/- 14.6 meals/participant. RESULTS: In all, 47% of the study sample was malnourished at admission. Nutritional status improved in 73% of patients who had been identified as malnourished and in 30 % of non-malnourished patients at admission. Total energy intake correlated with improvements in BMI, %IBW and total lymphocyte count (all p < 0.04). Improvement in PEMI score for the whole group was associated with functional status (p < 0.05). Controlling for this variable, energy (kj/kg body weight) and protein (g/kg body weight) intakes correlated positively with improvements in BMI, %IBW and MAC (Energy: partial r = 0.644, 0.624, 0.466 respectively; Protein: partial r = 0.582, 0.554, 0.433 respectively; all p < 0.05). CONCLUSIONS: Results from this study offer strong evidence that when cachectic/inflammatory conditions are controlled for, standard nutrition care is compatible with the maintenance or improvement of nutritional status during the hospital stay.

The GK rat beta-cell: a prototype for the diseased human beta-cell in type 2 diabetes?

Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of type 2 diabetes (T2D) mellitus. Nowadays, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased beta-cell number, impaired beta-cell function, and their multifactorial aetiologies. This review is aimed to illustrate to what extend the Goto-Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved be a valuable tool offering sufficient commonalities to study these aspects. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of multiple pathogenic players: (i) several independent loci containing genes responsible for some diabetic traits (but not decreased beta-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased beta-cell neogenesis and/or proliferation) which is transmitted to the next generation; and (iii) loss of beta-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammatory mediators, oxidative stress and to perturbed islet microarchitecture.

Risk factors for falling among community-dwelling seniors using home-care services: an extended hazards model with time-dependent covariates and multiple events.

The identification of risk factors for falls in longitudinal studies becomes difficult because of exposures that change during the follow-up and also because individual subjects may experience an event more than once. These issues have been neglected and improper statistical techniques have been used. The typical approaches have been to report the proportion of fallers or the time to first fall. Both avoid the underlying assumption of independence between events and discard pertinent data. We review the existing methods and propose a Cox hazards extension. We exemplify it in the study of potential risk factors associated with all falls in 959 seniors. Finally, we compare the results of the proposed Wei, Lin, & Weissfeld (WLW) method with those of several other techniques. Stable exposure variables measured at baseline and updated time-varying exposures include socio-demographic characteristics, BMI, nutritional risk, alcohol consumption, home hazards, gait and balance, and medications. Results demonstrate that the usual methods of analyzing risk factors for falling are inappropriate, as they produce considerable biases relative to the WLW model using time-dependent covariates. Results also show that modeling for first events may be inefficient, given that the risk of occurrence varies between falls.

Dietary intervention in older adults with early-stage Alzheimer dementia: early lessons learned.

In older adults, an adequate diet depends on their ability to procure and prepare food and eat independently or the availability of dietary assistance when needed. Inadequate food intake or increased nutritional requirements lead to poor nutritional status, which is considered a key determinant of morbidity, increased risk of infection, and mortality in elderly individuals. Weight loss among seniors also heralds increased morbidity and mortality. Dietary behaviour disorders affecting food consumption, nutrition status and maintenance of body weight are common in older adults, and have a substantial impact on nutritional status and quality of life among older adults with Alzheimer Dementia (AD). The Nutrition Intervention Study (NIS) is ongoing. It employs a quasi-experimental pre-post intervention design in physically-well, community-dwelling early stage AD patients aged 70 y or older. To date, 34 intervention group patients and 25 control group participants have been recruited with their primary caregivers (CG) from 6 hospital-based memory and geriatric clinics in Montreal. The NIS uses clinical dietetics principles to develop and offer tailored dietary strategies to patients and their CG. This paper reports on the application of dietary intervention strategies in two intervention group participants; one was deemed successful while the other was considered unsuccessful. The report documents challenges encountered in assessing and counselling this clientele, and seeks to explain the outcome of intervention in these patients.

The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase.

We previously demonstrated that type 2C protein phosphatases (PP2C) Ptc2 and Ptc3 are required for DNA checkpoint inactivation after DNA double-strand break repair or adaptation in Saccharomyces cerevisiae. Here, we show the conservation of this pathway in mammalian cells. In response to DNA damage, ataxia telangiectasia mutated (ATM) phosphorylates the Chk2 tumour suppressor kinase at threonine 68 (Thr68), allowing Chk2 kinase dimerization and activation by autophosphorylations in the T-loop. The oncogenic protein Wip1, a PP2C phosphatase, binds Chk2 and dephosphorylates phospho-Thr68. Consequently, Wip1 opposes Chk2 activation by ATM after ionizing irradiation of cells. In HCT15 colorectal cancer cells corrected for functional Chk2 activity, Wip1 overexpression suppressed the contribution of Chk2 to the G2/M DNA damage checkpoint. These results indicate that Wip1 is one of the phosphatases regulating the activity of Chk2 in response to DNA damage.

Nutritional implications of patient-provider interactions in hospital settings: evidence from a within-subject assessment of mealtime exchanges and food intake in elderly patients.

OBJECTIVE: To examine the nutritional implications of the interactions taking place between patients and care providers during mealtimes in hospital settings. Specifically, we tested research propositions that the amount and nature of interpersonal behaviours exchanged between patients and providers impact patients' food intake. These propositions were derived from prior evidence of social influences on eating behaviour and a well-established framework that identifies two fundamental modalities of human interaction: striving for mastery and power (agency) and efforts to promote union with others (communion). DESIGN: In a within-subject naturalistic study, participants were observed on multiple meals (n=1477, 46.2 meals/participant on average), during which participants' and providers' agency- and communion-related behaviours and patients' protein and energy intake were recorded. Meal-level frequency and complementarity of patients' and providers' behaviours were computed to test research propositions. SETTING: Dining room of a geriatric rehabilitation unit. SUBJECTS: Thirty-two elderly patients (21 females, mean age:78.8, 95% CI: 76.4, 81.1). RESULTS: Meal-level frequency of patient-provider exchanges (P=0.016) and patients' agency-related behaviours (P=0.029), as well as mutual reciprocation of patients' and providers' communion-related behaviours (P=0.015) on a given meal were positively linked to protein intake. Higher energy intake was found during meals where patients expressed more agency-related behaviours (P=0.029). CONCLUSION: Results present evidence that the amount and nature of patient-provider interpersonal exchanges on a given meal influence the nutritional quality of food intake in hospitalized elderly. They provide insights into how to improve the design and delivery of routine care to this malnutrition-prone population. SPONSORSHIP: This study was supported by the Canadian Institutes of Health Research (Operating grant to Laurette Dubé, Doctoral Fellowship to Catherine Paquet) the Fonds de la Recherche en santé du Québec and by the Danone Institute (Doctoral fellowship to Danielle St-Arnaud McKenzie).

[Cholinesterase inhibitor therapy in long term care settings]. / Les anticholinestérasiques en soins de longue durée: analyse des pratiques actuelles à partir d'une étude observationnelle francoquébécoise.

PURPOSE: Cholinesterase Inhibitors (ChEIs) have proven efficacy in outpatients with mild to moderate Alzheimer's Disease (AD). The benefits of maintaining this treatment once patients are institutionalised remain controversial. The aim of this study was to present current therapeutic strategies regarding ChEIs use in long-term care settings (LTC). METHODS: A multicentric, retrospective, observational study was conducted on currently available ChEIs (donezepil, rivastigmine, galantamine) prescribed in LTC. Data were obtained from medical records. Judgement was based on three criteria: ChEIs indication, follow-up, and justification for maintenance of treatment. RESULTS: Among the 1,373 patients evaluated, 6% (N=81) were receiving ChEIs. They represented various stages of the disease, with cognitive and functional decline ranging from severe (18%) to very mild (10%). Among patients receiving ChEIs, 29% met neither the indication for which these drugs were approved, nor professional guidelines. Patient evaluation at entry was of high quality, with 90% of records including cognitive, functional and behavioural evaluation. Follow-up evaluations were weaker, with at least one assessment domain missing in 40% of the medical records. ChEIs treatment was maintained, although almost half of patients experienced a worsening of their clinical state. CONCLUSION: This study shows that follow-up of institutionalised patients receiving ChEIs could be improved. While treatment maintenance seems to be the rule, it should be questioned on ethical, efficacy, and economic grounds. The rationale for use and discontinuation of these therapeutic strategies in institutional settings requires urgent review.

Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies.

One of the major requirements for a successful and life-lasting organ transplant is the access to safe, least toxic and permanent tolerance-inducing drugs. In this study we wished to evaluate the effects of tolerogenic doses of the immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal beta-cell lines, both in vivo and in vitro. Here we demonstrate that combined administration of low-dose MPA and Tac for 23 days induced permanent tolerance in an allogeneic beta-cell line transplant in Wistar rat liver through the portal vein. This short-term treatment of tolerogenic doses of the two drugs was deleterious to the survival of the transplanted cells but a small percentage of the cells could resist the effect and become fully active when the drugs were removed. The surviving cells, retrieved from growth in vivo, did not exhibit increased resistance in comparison to the original cells when tested in vitro at two glucose concentrations, 10 and 20 mM. The presence of a small percentage of resistant cells at the two glucose concentrations was also detected in the in vitro study after a continuous 8-day treatment demonstrating that the in vivo resistance was not related to micro-environmental protection but possibly to a phenotypic cell state that is yet to be determined.