Statin treatment and mortality in community-dwelling frail older patients with diabetes mellitus

Background: Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that statin treatment in older patients with DM was differentially effective across strata of mortality risk assessed by the Multidimensional Prognostic Index (MPI), based on information collected with the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA). Methods: In this retrospective observational study, we estimated the mortality risk in 1712 community-dwelling subjects with DM ≥ 65 years who underwent a SVaMA evaluation to establish accessibility to homecare services/nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) risk of mortality at baseline and propensity score-adjusted hazard ratios (HR) of three-year mortality were calculated according to statin treatment. Results: Higher MPI-SVaMA scores were associated with lower rates of statin treatment (MPI-SVaMA-1 = 39% vs MPI-SVaMA-2 = 36% vs MPI-SVaMA-3 = 24.9%. p<0.001) and higher three-year mortality (MPI-SVaMA-1 = 12.9% vs MPI-SVaMA-2 = 24% vs MPI-SVaMA-3 = 34.4%, p<0.001). After adjustment for propensity score quintiles, statin treatment was significantly associated with lower three-year mortality irrespective of MPI-SVaMA group (interaction test p = 0.303). HRs [95% confidence interval (CI)] were 0.19 (0.14-0.27), 0.28 (0.21-0.36), and 0.26 (0.20-0.34) in the MPI-SVaMA-1, MPI-SVaMA-2, and MPI-SVaMA-3 groups, respectively. Subgroup analyses showed that statin treatment was also beneficial irrespective of age. HRs (95% CI) were 0.21 (0.15-0.31), 0.26 (0.20-0.33), and 0.26 (0.20-0.35) among patients aged 65-74, 75-84, and ≥ 85 years, respectively (interaction test p=0.812). Conclusions: Statin treatment was significantly associat

Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia

PURPOSE: Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. METHODS: A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication. RESULTS: A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. CONCLUSIONS: The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk

Recent sarcopenia definitions—prevalence, agreement and mortality associations among men: findings from population‐based cohorts

Background The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. Methods White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m2), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. Results Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2: 0.0%]; SDOC [2.75 (2.28, 3.31), I2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2: 58.3%]. Conclusions There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance

Rivastigmine as treatment for patients with mild to moderately severe Alzheimer disease under normal clinical practice conditions. The ENTERPRISE study

Introduction: Alzheimer disease (AD) causes progressive cognitive decline leading to loss of independence for activities of daily living; rivastigmine is one of the drugs used for symptomatic management. Objective: To assess the therapeutic use of different pharmaceutical forms of rivastigmine in patients with AD in normal clinical practice. Patients and methods: Cross-sectional, observational, multi-centre study conducted on patients with mild to moderate AD treated with rivastigmine in Spanish outpatient clinics specialising in Geriatrics, Psychiatry, and Neurology. Data regarding use of oral (OR) and transdermal (TDR) rivastigmine, compliance (degree of adherence), and caregiver satisfaction with treatment were evaluated. Results: In total, 2252 patients with a mean age of 77.2 years were included; 60.2% were women. AD was moderate to moderately severe in 58.4%. Rivastigmine treatment was started orally in 54.4% of the patients and transdermally in 45.6%; 35.6% of those who started treatment by the OR route switched to TDR. A single dose adjustment was sufficient for 77.5% of patients on TDR treatment vs. 11.8% of patients receiving OR treatment. More patients on TDR treatment (80.8% vs. 57.1% on OR treatment) reached the maximum therapeutic dose of rivastigmine and did so in a shorter period of time (51.6 vs. 205.8 days). Compliance rates (60.5% vs. 47.2%) and caregivers’ satisfaction with treatment (89.4% vs. 81.9%) were also higher for TDR. Conclusions: In normal clinical practice, using the TDR route of administration improves dose titration and drug compliance, allowing more patients to reach the maximum recommended dose of rivastigmine in a shorter time period. Resumen: Introducción: La enfermedad de Alzheimer (EA) produce un deterioro cognitivo progresivo que conlleva la pérdida de independencia para las actividades de la vida diaria, siendo la rivastigmina uno de los fármacos utilizados para su tratamiento sintomático. Objetivo: Evaluar el manejo terapéutico con distintas formas galénicas de rivastigmina, en sujetos con EA en la práctica clínica habitual. Pacientes y métodos: Estudio transversal, multicéntrico realizado en consultas españolas de Geriatría, Psiquiatría y Neurología, en sujetos con EA de leve a moderadamente grave que recibían rivastigmina. Se recogieron datos sobre el modo de uso de rivastigmina oral (RO) y transdérmica (RTD), el cumplimiento terapéutico (grado de adherencia) y la satisfacción del cuidador. Resultados: Se evaluaron 2.252 sujetos con edad media de 77,2 años; 60,2% mujeres. El 58,4% presentaban EA moderada-moderadamente grave. El 54,4% habían iniciado el tratamiento con RO y el 45,6% con RTD; el 35,6% de aquellos con RO cambiaron a la vía transdérmica. El 77,5% con RTD requirió un solo ajuste de dosis vs. 11,8% con RO. El 80,8% de los sujetos con RTD alcanzaron la dosis máxima de rivastigmina (vs. 57,1% RO) en menos tiempo (51,6 vs. 205,8 días). El cumplimiento fue mayor con RTD (60,5 vs. 47,2%) así como el porcentaje de cuidadores satisfechos con el tratamiento (89,4 vs.81,9%). Conclusiones: En la práctica clínica habitual, la RTD facilita la dosificación y mejora el cumplimiento, permitiendo a un mayor porcentaje de sujetos alcanzar la dosis máxima recomendada de rivastigmina en un plazo de tiempo menor. Keywords: Alzheimer, Compliance, Treatment management, Rivastigmine, Satisfaction, Administration route, Palabras clave: Alzheimer, Cumplimiento, Manejo terapéutico, Rivastigmina, Satisfacción, Vía de administració

Manejo terapéutico con rivastigmina en pacientes con enfermedad de Alzheimer de leve a moderadamente grave en condiciones de práctica clínica habitual. Estudio ENTERPRISE

Resumen: Introducción: La enfermedad de Alzheimer (EA) produce un deterioro cognitivo progresivo que conlleva la pérdida de independencia para las actividades de la vida diaria, siendo la rivastigmina uno de los fármacos utilizados para su tratamiento sintomático. Objetivo: Evaluar el manejo terapéutico con distintas formas galénicas de rivastigmina, en sujetos con EA en la práctica clínica habitual. Pacientes y métodos: Estudio transversal, multicéntrico realizado en consultas españolas de Geriatría, Psiquiatría y Neurología, en sujetos con EA de leve a moderadamente grave que recibían rivastigmina. Se recogieron datos sobre el modo de uso de rivastigmina oral (RO) y transdérmica (RTD), el cumplimiento terapéutico (grado de adherencia) y la satisfacción del cuidador. Resultados: Se evaluaron 2.252 sujetos con edad media de 77,2 años; 60,2% mujeres. El 58,4% presentaban EA moderada-moderadamente grave. El 54,4% habían iniciado el tratamiento con RO y el 45,6% con RTD; el 35,6% de aquellos con RO cambiaron a la vía transdérmica. El 77,5% con RTD requirió un solo ajuste de dosis vs. 11,8% con RO. El 80,8% de los sujetos con RTD alcanzaron la dosis máxima de rivastigmina (vs. 57,1% RO) en menos tiempo (51,6 vs. 205,8 días). El cumplimiento fue mayor con RTD (60,5 vs. 47,2%) así como el porcentaje de cuidadores satisfechos con el tratamiento (89,4 vs.81,9%). Conclusiones: En la práctica clínica habitual, la RTD facilita la dosificación y mejora el cumplimiento, permitiendo a un mayor porcentaje de sujetos alcanzar la dosis máxima recomendada de rivastigmina en un plazo de tiempo menor. Abstract: Introduction: Alzheimer disease (AD) causes progressive cognitive decline leading to loss of independence for activities of daily living; rivastigmine is one of the drugs used for symptomatic management. Objective: To assess the therapeutic use of different pharmaceutical forms of rivastigmine in patients with AD in normal clinical practice. Patients and methods: Cross-sectional, observational, multi-centre study conducted on patients with mild to moderate AD treated with rivastigmine in Spanish outpatient clinics specialising in Geriatrics, Psychiatry, and Neurology. Data regarding use of oral (OR) and transdermal (TDR) rivastigmine, compliance (degree of adherence), and caregiver satisfaction with treatment were evaluated. Results: In total, 2252 patients with a mean age of 77.2 years were included; 60.2% were women. AD was moderate to moderately severe in 58.4%. Rivastigmine treatment was started orally in 54.4% of the patients and transdermally in 45.6%; 35.6% of those who started treatment by the OR route switched to TDR. A single dose adjustment was sufficient for 77.5% of patients on TDR treatment vs 11.8% of patients receiving OR treatment. More patients on TDR treatment (80.8% vs. 57.1% on OR treatment) reached the maximum therapeutic dose of rivastigmine and did so in a shorter period of time (51.6 vs 205.8 days). Compliance rates (60.5% vs 47.2%) and caregivers’ satisfaction with treatment (89.4% vs 81.9%) were also higher for TDR. Conclusions: In normal clinical practice, using the TDR route of administration improves dose titration and drug compliance, allowing more patients to reach the maximum recommended dose of rivastigmine in a shorter time period. Palabras clave: Alzheimer, Cumplimiento, Manejo terapéutico, Rivastigmina, Satisfacción, Vía de administración, Keywords: Alzheimer, Compliance, Treatment management, Rivastigmine, Satisfaction, Administration rout

A Core Outcome Set for nutritional intervention studies in older adults with malnutrition and those at risk: a study protocol

Background: Malnutrition (i.e., protein-energy malnutrition) in older adults has severe negative clinical consequences, emphasizing the need for effective treatments. Many, often small, randomized controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and a need for meta-analyses and data pooling has been expressed. However, evidence synthesis is hampered by the wide variety of outcomes and their method of assessment in previous RCTs. This paper describes the protocol for developing a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk. Methods: The project consists of five phases. The first phase consists of a scoping review to identify frequently used outcomes in published RCTs and select additional patient-reported outcomes. The second phase includes a modified Delphi Survey involving experienced researchers and health care professionals working in the field of malnutrition in older adults, followed by the third phase consisting of a consensus meeting to discuss and agree what critical outcomes need to be included in the COS. The fourth phase will determine how each COS outcome should be measured based on a systematic literature review and a second consensus meeting. This will be followed by a dissemination and implementation phase. Patient and Public Involvement (PPI) representatives will contribute to study design, oversight, consensus, and dissemination. Conclusions: The result of this project is a COS that should be included in any RCT evaluating the effect of nutritional interventions in older adults with malnutrition and those at risk. This COS will facilitate comparison of RCT results, will increase efficient use of research resources and will reduce bias due to measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults. © 2023, The Author(s).No funding was received for this project. NM was funded by the Fundação para a Ciência e a Tecnologia (2021.00745.CEECIND). This funder will play no role in this project.Fundação para a Ciência e a Tecnologia, FCT: 2021.0074