Effectiveness of a Community Program for Older Adults with Type 2 Diabetes and Multimorbidity: A Pragmatic Randomized Controlled Trial

Background Type II diabetes mellitus (T2DM) affects upwards of 25% of Canadian older adults and is associated with high comorbidity and burden. Studies show that lifestyle factors and self-management are associated with improved health outcomes, but many studies lack rigour or exclude older adults, particularly those with multimorbidity. More evidence is needed on the effectiveness of community-based self-management programs in older adults with T2DM and multimorbidity. The study purpose is to evaluate the effect of a community-based intervention versus usual care on physical functioning, mental health, depressive symptoms, anxiety, self-efficacy, self-management, and healthcare costs in older adults with T2DM and 2 or more comorbidities. Methods Community-living older adults with T2DM and two or more chronic conditions were recruited from three Primary Care Networks (PCNs) in Alberta, Canada. Participants were randomly allocated to the intervention or control group in this pragmatic randomized controlled trial comparing the intervention to usual care. The intervention involved up to three in-home visits, a monthly group wellness program, monthly case conferencing, and care coordination. The primary outcome was physical functioning. Secondary outcomes included mental functioning, anxiety, depressive symptoms, self-efficacy, self-management, and the cost of healthcare service use. Intention-to-treat analysis was performed using ANCOVA modeling. Results Of 132 enrolled participants (70-Intervention, 62-Control), 42% were 75 years or older, 55% were female, and over 75% had at least six chronic conditions (in addition to T2DM). No significant group differences were seen for the baseline to six-month change in physical functioning (mean difference: -0.74; 95% CI: − 3.22, 1.74; p-value: 0.56), mental functioning (mean difference: 1.24; 95% CI: − 1.12, 3.60; p-value: 0.30), or other secondary outcomes.. Conclusion No significant group differences were seen for the primary outcome, physical functioning (PCS). Program implementation, baseline differences between study arms and chronic disease management services that are part of usual care may have contributed to the modest study results. Fruitful areas for future research include capturing clinical outcome measures and exploring the impact of varying the type and intensity of key intervention components such as exercise and diet

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Deprescribing—A Few Steps Further

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Deprescribing—A Few Steps Further

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Use of Oral Bisphosphonates by Older Adults with Fractures and Impaired Renal Function

ABSTRACTBackground: The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who have osteoporosis or who are at risk of fracture are elderly and may have renal impairment. This situation poses a quandary for clinicians in deciding how best to manage osteoporosis in this high-risk population.Objective: To synthesize published evidence regarding the use and safety of oral bisphosphonates for patients with impaired renal function.Methods: The following databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane Library, and International Pharmaceutical Abstracts. The following key words and terms were used for the searches: bisphosphonates, alendronate, risedronate, Fosamax, Actonel, "renal failure", "renal insufficiency", "chronic kidney disease", and "end-stage renal disease". The manufacturers of Fosamax and Actonel were asked to provide information about use of their products in patients with renal impairment, including unpublished pharmaco - kinetic studies or reports of adverse drug events.Results: The search yielded 2 post hoc analyses of safety data, 1 case-control study, 1 case series, 4 retrospective chart analyses, and 2 prospective studies. According to these publications, numerous patients with decreased renal function have received bisphosphonates and have experienced improvement in bone mineral density and/or reduction in risk of fractures, with no increase in adverse effects. Increased renal damage occurred in some individuals with underlying renal disorders, as described in case reports.Conclusions: Although the literature is limited, there is evidence that alendronate and risedronate are well tolerated and effective when used by individuals with renal impairment. Further research is required to confirm the benefits and risks of using these medications in patients with renal impairment.RÉSUMÉContexte : Les fabricants de bisphosphonates oraux (alendronate, risédronate) recommandent d'éviter l'emploi de ces médicaments chez les patients souffrant d'insuffisance rénale. Cependant, de nombreux patients souffrant d'ostéoporose ou qui sont à risque de fracture sont des personnes âgées qui pourraient souffrir d'insuffisance rénale. Cette situation est un véritable dilemme pour les cliniciens qui doivent décider de la meilleure conduite à tenir pour traiter l'ostéoporose chez cette population à risque élevé.Objectif : Mettre en lumière les données probantes publiées sur l'emploi et l'innocuité des bisphosphonates oraux chez les patients souffrant d'insuffisance rénale.Méthodes : Les bases de données suivantes ont été examinées : PubMed, MEDLINE, Embase, Bibliothèque Cochrane et International Pharmaceutical Abstracts. Les mots clés et termes suivants ont été utilisés pour les recherches : bisphosphonates, alendronate, risédronate, Actonel, Fosamax, « insuffisance rénale », « maladie rénale chronique » et « insuffisance rénale terminale ». Les recherches dans les bases de données ont été faites jusqu'en octobre 2010. On a demandé aux fabricants d'Actonel et de Fosamax de fournir de l'information sur l'utilisation de leurs produits chez les patients atteints d'insuffisance rénale, y compris les résultats d'études pharmacocinétiques inédites ou les rapports d'événements indésirables liés aux médicaments.Résultats : La recherche a révélé deux analyses a posteriori de données sur l'innocuité, une étude cas-témoin, une série de cas, quatre analyses rétrospectives de dossiers médicaux et deux études prospectives. D'après ces documents, de nombreux patients atteints d'insuffisance rénale ont reçu des bisphosphonates et présenté un accroissement de leur densité minérale osseuse ou une réduction du risque de fractures, sans augmentation des effets indésirables. On a observé une augmentation des lésions rénales chez certains patients présentant des troubles rénaux sous-jacents, comme décrit dans plusieurs observations cliniques.Conclusions : Bien que la documentation soit limitée, des données probantes montrent que l'alendronate et le risédronate sont bien tolérés et efficaces dans les cas d'insuffisance rénale. Des recherches plus approfondies sont nécessaires pour confirmer les bienfaits et les risques de ces médicaments chez les personnes souffrant d'insuffisance rénale

Bisphosphonates for Osteoporosis in Patients with Renal Insufficiency: Pharmacists’ Practices and Beliefs

ABSTRACTBackground: Clinicians often face challenges in deciding how to treat osteoporosis in patients with chronic kidney disease. As background to offering guidance to health care providers, it is important to understand their practices and beliefs.Objectives: To describe the practices and beliefs of pharmacists regarding use of bisphosphonates for patients with osteoporosis and chronic kidney disease.Methods: A cross-sectional survey of pharmacists working in hospitals and related health care settings was conducted. A 34-item online questionnaire was developed consisting of 4 sections: demographic characteristics, practices, beliefs, and comfort level with making decisions about osteoporosis treatment. An e-mail invitation was sent to members of the Canadian Society of Hospital Pharmacists (n = 2499) in November 2012.Results: A total of 367 pharmacists completed the survey. Most of the respondents were women (258 [70%]), had more than 10 years in practice (213 [58%]), and were providing care to 1 or more osteoporosis patients per week (212 [58%]). Over one-third (150 [41%]) stated that they would use a bisphosphonate for patients with creatinine clearance (CrCl) of 15–30 mL/min, but more than half (207 [56%]) stated that they would avoid a bisphosphonate (and recommend another medication) for patients with CrCl below 15 mL/min. Forty-eight percent (176/363) agreed that oral bisphosphonates could be used for patients with renal failure (defined as CrCl < 30 mL/min), so long as dosage adjustments are made. More than half (206/363 [57%]) believed that the adverse effects of oral bisphosphonates increase for patients with renal failure. Respondents expressed a low level of comfort in assessing and initiating osteoporosis treatment for patients with renal failure.Conclusions: Pharmacists had varying beliefs about managing osteoporosis in patients with chronic kidney disease. This study highlights the need for practice tools and targeted education addressing the use of bisphosphonates for these patients.RÉSUMÉContexte : Les cliniciens sont souvent confrontés à des défis lorsqu’ils doivent choisir un traitement contre l’ostéoporose chez les patients atteints d’insuffisance rénale chronique. Afin d’être en mesure de guider les fournisseurs de soins de santé, il importe de comprendre leurs pratiques et leurs croyances.Objectif : Offrir un portrait des pratiques et croyances des pharmaciens en ce qui a trait à l’emploi des bisphosphonates chez les insuffisants rénaux chroniques atteints d’ostéoporose.Méthodes : Une enquête transversale a été réalisée auprès de pharmaciens exerçant en établissements de santé. Un questionnaire en ligne a été élaboré. Il contenait 34 éléments répartis en 4 sections, soit : les caractéristiques démographiques; les pratiques; les croyances; et le degré d’aisance en ce qui a trait au choix d’un traitement contre l’ostéoporose. Un courriel d’invitation a été envoyé aux membres de la Société canadienne des pharmaciens d’hôpitaux (n = 2499) en novembre 2012.Résultats : Au total, 367 pharmaciens ont participé au sondage. La plupart des répondants étaient des femmes (258 [70 %]), possédaient plus de 10 années de pratique (213 [58 %]) et fournissaient hebdomadairement des soins à au moins un patient ostéoporotique (212 [58 %]). Plus d’un tiers (150 [41 %]) ont indiqué qu’ils emploieraient un bisphosphonate chez les patients affichant une clairance de la créatinine (ClCr) entre 15 et 30 mL/min, mais plus de la moitié (207 [56 %]) ont affirmé qu’ils n’en utiliseraient pas (et qu’ils recommandaient un autre médicament) chez les patients présentant une ClCr en deçà de 15 mL/min. Quarante-huit pour cent (176/363) ont affirmé que les bisphosphonates oraux pouvaient être employés pour les patients présentant une insuffisance rénale (définie comme une ClCr < 30 mL/min), pourvu que l’on procède à des ajustements posologiques. Plus de la moitié (206/363 [57 %]) croyaient que les effets indésirables des bisphosphonates oraux sont plus importants chez les patients souffrant d’insuffisance rénale. Les répondants ont indiqué être peu à l’aise lorsque vient le temps d’évaluer et d’amorcer un traitement contre l’ostéoporose chez les insuffisants rénaux.Conclusions : Les pharmaciens adhéraient à diverses croyances en ce qui touche la prise en charge de l’ostéoporose chez les insuffisants rénaux. La présente étude met en évidence le besoin d’outils pour la pratique ainsi que d’enseignement ciblé portant sur l’emploi des bisphosphonates chez les patients atteints d’insuffisance rénale