Association between anticholinergic burden and anticholinergic adverse outcomes in the elderly: Pharmacological basis of their predictive value for adverse outcomes.

The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes.

Effects of long-term multicomponent exercise on health-related quality of life in older adults with type 2 diabetes: evidence from a cohort study.

PURPOSE: To establish the effect of a long-term multicomponent exercise (LTMEX) intervention (24 months) on health-related quality of life (HRQoL), in older adults with type 2 diabetes (T2D). METHODS: This longitudinal retrospective cohort study analyzes the effects of a supervised LTMEX program on HRQoL in older adults with T2D (n = 279). Participants underwent one of two conditions: LTMEX (n = 241) trained three times per week; and unchanged lifestyle-the control group (CO; n = 38). Participants completed baseline, and 2-year follow-up evaluations including the Short Form Health Survey 36 (SF-36), anthropometric, hemodynamic components, and cardiorespiratory fitness (VO2 peak). RESULTS: LTMEX improves HRQoL, specifically physical functioning (P < 0.001), general health (P < 0.05), vitality (P < 0.001), mental health (MH; P < 0.05), physical component score (P < 0.001), mental component score (P < 0.001), and total SF-36 (P < 0.001). LTMEX group also decreased body weight (BW; P < 0.005), waist circumference (WC; P < 0.001), waist-to-hip ratio (WHR; P < 0.001), and systolic blood pressure (SBP; P < 0.001), and increased VO2 peak (P < 0.001). CO group increased WC (P = 0.012), BMI (P = 0.024), waist-to-hip ratio (WHR; P = 0.003) and SBP (P < 0.001), and decreased vitality (P < 0.001) and MH (P < 0.05). CONCLUSIONS: A LTMEX intervention improves physical and mental HRQoL in older adults with T2D, and also anthropometric, hemodynamic profile, and cardiorespiratory fitness.

A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity.

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings.

Glycated hemoglobin and associated risk factors in older adults.

BACKGROUND: The aim of this study is to investigate the relationships between HbA1c and other risk factors like obesity, functional fitness, lipid profile, and inflammatory status in older adults. Epidemiological evidence suggests that HbA1c is associated with cardiovascular and ischemic heart disease risk. Excess of body weight and obesity are considered to play a central role in the development of these conditions. Age is associated with several risk factors as increased body fat and abdominal fat, deterioration of the lipid profile, diabetes, raising in inflammatory activity, or decreased functional fitness. METHODS: Data were available from 118 participants aged 65-95 years, including 72 women and 46 men. Anthropometric variables were taken, as was functional fitness, blood pressure and heart rate. Blood samples were collected after 12 h fasting, and HbA1c, hs-CRP, TG, TC, HDL-C, LDL-C, and glycaemia were calculated. Bivariate and partial correlations were performed to explore associations amongst the variables of interest. Differences between groups were explored by performing factorial analysis of variance. RESULTS: HbA1c levels ranged from 4.6%-9.4% with 93% of the cases below 6.5%. Women had higher HbA1c, glycaemia, TC, BMI, and lower and upper flexibility than men. Men had higher BW, WC, 6-min walking distance, and VO2peak than women. Age, SBP, DBP, HRrest, HRpeak, HDL-C, LDL-C, TG, TG/HDL-C ratio, Log10 hs-CRP, upper and lower strength, and agility and dynamic balance were similar in men and women. HbA1c had positive associations with glycaemia, HDL-C, TG/HDL-C, BW, WC, BMI, but not with functional fitness, TC, LDL-C, Log10 hs-CRP, PAD, or PAS. Obese participants had higher HbA1c than non-obese only when IDF and not USDHHS criteria were applied. CONCLUSIONS: Older women had higher HbA1c than men, even after controlling for BMI. HbA1c associates equally with BW, BMI or WC. Population-based criteria are recommended to classify obesity and to identify higher levels of HbA1c in obese older adults. HbA1c associates with atherogenic dyslipidemia particularly with TG and TG/HDL-C ratio, but not with TC, HDL-C, or LDL-C. HbA1c is not associated with hs-CRP, and with functional fitness and aerobic endurance.

Size of the associations between anticholinergic burden tool scores and adverse outcomes in older patients.

Background Several anticholinergic scales and equations to evaluate the anticholinergic burden have been previously created. Association of these instruments with the anticholinergic outcomes are usually estimated by means of hypothesis contrast tests, which ignore the size of the association effect. Objective To evaluate the effect size of the associations between the scores on cumulative anticholinergic burden instruments with peripheral or central anticholinergic adverse outcomes in older patients. Setting Internal medicine ward of a Tertiary University Hospital. Methods A case-control study was conducted in patients over 65 years who were admitted to two internal medicine wards of a Portuguese university hospital. The Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden scale and Drug Burden Index were used to calculate the patients' anticholinergic burden. Peripheral (dry mouth-swab technique; dry eye-Schirmer test) and central (falls and cognitive impairment-Mini-Mental State Examination) anticholinergic adverse outcomes were investigated. The Barthel Index was used to assess overall physical functionality. The Mann-Whitney test was used to evaluate probabilistic differences in the anticholinergic scores between case and control individuals. To establish the effect size of the associations, the area under the curve of the receiver operating characteristics curve was calculated. Main outcome measure Anticholinergic adverse effects. Results A total of 250 patients (mean age 81.67 years, standard deviation 7.768; 50% females) were included. In total, 148 patients (59.2%) presented with dry mouth, 85 (34%) with dry eye, 141 (56.4%) with impaired functionality, 44 (17.6%) with a history of falls and 219 (87.6%) with cognitive impairment. Significant differences (p < 0.05) were obtained for the majority of the associations between Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden and Drug Burden Index and adverse effects. Conversely, the effect sizes of these associations ranged from "fail" (area under the curve 0.5 to 0.6) to "fair" (area under the curve 0.7 to 0.8). Conclusion Although significant differences in the scores of anticholinergic burden instruments and adverse outcomes may exist, the effect sizes of these associations ranged from 'fail' to 'fair', which limits their utility in preventing anticholinergic adverse outcomes with medication review interventions.

Effects of aerobic and strength-based training on metabolic health indicators in older adults.

BACKGROUND: The weakening of the cardiovascular system associated with aging could be countered by increasing levels of physical activity and functional fitness. However, inconsistent findings have been found, and the variety of characteristics of exercise used in previous studies may partly explain that inconsistent results. OBJECTIVE: To investigate the training effect of sixteen weeks of moderate intensity, progressive aerobic and strength-based training on metabolic health of older women and men. METHODS: Sixty three sedentary individuals (mean (SD) age 76 (8) years) were randomly assigned to control (n = 31) or exercising (n = 32) groups. The training group was separated to aerobic (n = 18) or strength-based (n = 14). Training took place three times a week. Subjects agreed not to change their diet or lifestyle over the experimental period. RESULTS: Exercising group attained after treatment significant differences on body weight, waist circumference, body mass index, diastolic blood pressure, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol relationship, high sensitivity C-reactive protein, and 6-minute walk distance. The control group only had significant differences on waist circumference. CONCLUSION: The training programs produced significant benefits on metabolic health indicators of sedentary older women and men.

The effect of aerobic versus strength-based training on high-sensitivity C-reactive protein in older adults.

Increased levels of inflammatory markers, namely, high-sensitive C-reactive protein (hs-CRP), have been associated with several chronic diseases including atherosclerosis, type 2 diabetes and hypertension. Forty-five women and men aged >64 years participated in the study and were randomly assigned to two exercise intervention groups and a non-exercising control group. The participants assigned to the exercising groups followed a 16-week exercise protocol based either on aerobic training (AT) or strength training (ST) followed by a further 16 weeks off-training period. The control group (C) remained sedentary throughout the study. Evaluation of body mass, BMI, waist circumference, aerobic endurance, lower-body strength, upper-body strength, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol and hs-CRP were performed at baseline, after 16 weeks (post-training for the exercise groups) and at 32 weeks (follow-up). Both, AT and ST groups significantly increased functional fitness at the end of the exercise programs when compared to baseline values. hs-CRP concentrations were maintained throughout the study for the C group, while decreasing 10% at 16 weeks and 51% at 32 weeks for the AT group. In the ST group the hs-CRP concentrations decreased by 11 and 39% at 16 and 32 weeks, respectively. Decreases in hs-CRP concentrations were statistically significant for the AT and ST groups at the 32-week evaluation when compared to baseline. Reduction in hs-CRP concentrations seemed to be associated with strength gains and adiposity loss.

The Effects of Concurrent Training Combining Both Resistance Exercise and High-Intensity Interval Training or Moderate-Intensity Continuous Training on Metabolic Syndrome.

To date, there are several knowledge gaps on how to properly prescribe concurrent training to achieve the best dose-response, especially regarding the optimal intensity or volume of the aerobic component. Thus, the objective of this study is to analyze the effects of different aerobic exercise modes and intensities [i.e. aerobic high-intensity interval training (HIIT) versus moderate-intensity continuous aerobic training (MICT) combined with a resistance training (RT) program] on metabolic outcomes in participants with metabolic syndrome (MetS). Thirty-nine men and women (67.0 ± 6.7 years) volunteered to a 12-weeks exercise intervention (3 week-1, 50 min/session) and were randomly assigned to one of three groups: (a) RT plus MICT (RT+MICT) (2 males; 11 females); (b) RT plus HIIT (RT+HIIT) (4 males; 9 females); and (c) control group (CON) - without formal exercise (4 males; 9 females). Intensity was established between 60 and 70% of maximum heart rate (HRmax) in RT+MICT and ranged from 55-65% to 80-90% HRmax in the RT+HIIT group. Dependent outcomes included morphological, metabolic and hemodynamic variables. Both training groups improved waist circumference (RT+MICT: P = 0.019; RT+HIIT: P = 0.003), but not body weight, fat mass or fat-free mass (P ≥ 0.114). RT+HIIT group improved fasting glucose (P = 0.014), low density lipoprotein [LDL (P = 0.022)], insulin (P = 0.034) and homeostatic model assessment (P = 0.028). RT+MICT group reduced triglycerides (P = 0.053). Both exercise interventions did not change high sensitivity C-reactive protein, glycated hemoglobin, high density lipoprotein and total cholesterol, systolic, diastolic or mean arterial blood pressure (P ≥ 0.05). The CON group reduced the LDL (P = 0.031). This trial suggests that short-term exercise mode and intensity may differently impact the metabolic profile of individuals with MetS. Further, our data suggests that both concurrent trainings promote important cardiometabolic gains, particularly in the RT+HIIT. Nonetheless, due to the small-to-moderate effect size and the short-term intervention length, our data suggests that the intervention length also has an important modulating role in these benefits in older adults with MetS. Therefore, more research is needed to confirm our results using longer exercise interventions and larger groups.

Patients' clinical information requirements to apply the STOPP/START criteria.

Background The STOPP/START criteria are an explicit tool to detect potentially inappropriate medications (PIMs). Patient clinical information may not be available in all settings. Objective To identify patient clinical information needed to apply the STOPP/START criteria. Setting: Four nursing homes in Portugal. Methods First, a theoretical analysis was performed to identify the patient information required to apply the STOPP/START criteria (v2), according to the following categories: patients' current medication, medication history (previous medication and duration), medical records (current and past medical conditions), and laboratory test results. A verification of the information requirements was conducted through a cross-sectional study on a nursing home population with patients over 65 years old. Patients' medical records were appraised to extract only demographic data and current medication profiles. Main outcome measure Information requirements of STOPP/START. Results For only 29 of the 81 STOPP criteria and 1 of the 34 START criteria, a judgement could be made with only the information in the patient's medication profile. 52 STOPP and 33 START criteria require additional information, (i.e. duration of therapy, previous medication, current and past medical conditions, and laboratory data). The 208 evaluated persons (87 years; 68.75% female) used 1770 medications, with 989 (55.9%) potentially involved in 1629 STOPP criteria. Sufficient information to judge STOPP criteria was available for only 529 (32.5%) potential STOPP criteria situations, with a positive identification of a STOPP PIM in 397 instances (75.0%). Conclusions Although STOPP/START criteria can be considered a high-level tool to identify PIMs, their use may be compromised in scenarios where access to patients' clinical information is limited.

Development of a Healthy Lifestyle Assessment Toolkit for the General Public.

The prevalence of age-related non-communicable chronic diseases has increased worldwide, being the leading causes of morbidity and death in many world regions, including in Europe. Innovative models and strategies focused on preventive care, including early identification of risk factors underlying disease onset and progression, and proper modification of lifestyle habits and behaviors, might contribute to promote quality of life, healthy living and active aging. Healthy Lifestyle Innovative Quarters for Cities and Citizens (HeaLIQs4cities) is an EIT Health-funded project aiming to engage, empower and educate citizens toward healthy lifestyles. One of the major objectives of this project was to develop a toolkit for a rapid and informal assessment of healthy lifestyles, to be used at different levels of care pathways, including in informal public environments. In this paper, we describe the methodology underlying the development of the toolkit, which resulted from the collaboration of an interdisciplinary focus group of academic experts, from medicine, sport sciences, psychology, health economics, and innovative technologies applied to health. The following eight components were included in the toolkit: (1) anthropometric assessment and cardiometabolic parameters; (2) physical activity and exercise; (3) well-being, social cohesion, and functional independence; (4) nutrition; (5) mental health; (6) smoking, drinking, and use of illicit substances; (7) sleep habits and quality; and (8) health and disease. A traffic light rating system indicating the risk score was used (low: green; moderate: yellow; and relevant: orange) for each of the 8 components, together with recommendations for the toolkit users. After completing the reduced version of the toolkit, individuals showing moderate or relevant risk in one or more of the 8 dimensions, were invited to participate in a more detailed assessment (toolkit long version), based on deeper and scientifically validated tools. The toolkit was incorporated in eVida, a web-based platform that focuses on delivering services to personalized health and well-being. The validation of the current toolkit has been applied in wide-ranging public events in three different European Regions. Large scale deployment of the toolkit is expected to profit from the Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Aging (EIP on AHA).

The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens.

Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.

AIM: The impact of sarcopenia on hospitalisation has been under intense investigation; however, little is known about the association between sarcopenia and their costs among hospitalised patients. The aim of the present study was to quantify the association between sarcopenia and hospitalisation costs among older adults. METHODS: A cross-sectional study was conducted in 201 hospitalised older adults in a general hospital. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Muscle mass was assessed by anthropometric measurements, muscle strength through handgrip strength evaluation and physical performance by Timed Up and Go Test. Nutritional status was evaluated using the Mini Nutritional Assessment-Short Form (MNA-SF), and hospital costs were assessed with the Diagnosis Related Groups (DRGs) system. Multivariable logistic regression models were fitted to quantify the association between sarcopenia and hospital costs. Increased hospital costs were considered when a patients' cost was higher than the mean cost of an average patient (€2396.24). RESULTS: Within this sample, 10.4% sarcopenic, 43.8% at nutritional risk and 14.9% undernourished older adults were identified. After adjustment, sarcopenia (OR = 5.70, 95% CI 1.57-20.71) and low muscle strength (OR = 2.40, 95% CI 1.12-5.15) were associated with increased hospital costs. CONCLUSIONS: Sarcopenia and low muscle strength at hospital admission were independently associated with increased hospital costs.