Medicine (RMH) - Research Publications

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    Digital Technology to Deliver a Lifestyle-Integrated Exercise Intervention in Young Seniors-The PreventIT Feasibility Randomized Controlled Trial
    Taraldsen, K ; Mikolaizak, AS ; Maier, AB ; Mellone, S ; Boulton, E ; Aminian, K ; Becker, C ; Chiari, L ; Follestad, T ; Gannon, B ; Paraschiv-Ionescu, A ; Pijnappels, M ; Saltvedt, I ; Schwenk, M ; Todd, C ; Yang, FB ; Zacchi, A ; van Ancum, J ; Vereijken, B ; Helbostad, JL (FRONTIERS MEDIA SA, 2020-07-31)
    Background: Behavioral change is the key to alter individuals' lifestyle from sedentary to active. The aim was to assess the feasibility of delivering a Lifestyle-integrated Functional Exercise programme and evaluate the delivery of the intervention by use of digital technology (eLiFE) to prevent functional decline in 61-70 year-old adults. Methods: This multicentre, feasibility randomized controlled trial was run in three countries (Norway, Germany, and the Netherlands). Out of 7,500 potential participants, 926 seniors (12%) were screened and 180 participants randomized to eLiFE (n = 61), aLiFE (n = 59), and control group (n = 60). eLiFE participants used an application on smartphones and smartwatches while aLiFE participants used traditional paper-based versions of the same lifestyle-integrated exercise intervention. Participants were followed for 12 months, with assessments at baseline, after a 6 month active trainer-supported intervention, and after a further 6 months of unsupervised continuation of the programme. Results: At 6 months, 87% of participants completed post-test, and 77% completed the final assessment at 12 months. Participants were willing to be part of the programme, with compliance and reported adherence relatively high. Despite small errors during start-up in the technological component, intervention delivery by use of technology appeared acceptable. No serious adverse events were related to the interventions. All groups improved regarding clinical outcomes over time, and complexity metrics show potential as outcome measure in young seniors. Conclusion: This feasibility RCT provides evidence that an ICT-based lifestyle-integrated exercise intervention, focusing on behavioral change, is feasible and safe for young seniors. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03065088. Registered on 14 February 2017.
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    Perceptual rivalry across animal species
    Carter, O ; van Swinderen, B ; Leopold, DA ; Collin, SP ; Maier, A (WILEY, 2020-12-01)
    This review in memoriam of Jack Pettigrew provides an overview of past and current research into the phenomenon of multistable perception across multiple animal species. Multistable perception is characterized by two or more perceptual interpretations spontaneously alternating, or rivaling, when animals are exposed to stimuli with inherent sensory ambiguity. There is a wide array of ambiguous stimuli across sensory modalities, ranging from the configural changes observed in simple line drawings, such as the famous Necker cube, to the alternating perception of entire visual scenes that can be instigated by interocular conflict. The latter phenomenon, called binocular rivalry, in particular caught the attention of the late Jack Pettigrew, who combined his interest in the neuronal basis of perception with a unique comparative biological approach that considered ambiguous sensation as a fundamental problem of sensory systems that has shaped the brain throughout evolution. Here, we examine the research findings on visual perceptual alternation and suppression in a wide variety of species including insects, fish, reptiles, and primates. We highlight several interesting commonalities across species and behavioral indicators of perceptual alternation. In addition, we show how the comparative approach provides new avenues for understanding how the brain suppresses opposing sensory signals and generates alternations in perceptual dominance.
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    Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations
    Beenakker, KGM ; Westendorp, RGJ ; de Craen, AJM ; Chen, S ; Raz, Y ; Ballieux, BEPB ; Nelissen, RGHH ; Later, AFL ; Huizinga, TW ; Slagboom, PE ; Boomsma, D ; Maier, AB (KARGER, 2020-02)
    The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-α, interleukin (IL)-6, IL-12, IL-1β, IL-1RA, and IL-10, but not for interferon-γ. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial.
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    The association of basic and challenging motor capacity with mobility performance and falls in young seniors
    Gordt, K ; Paraschiv-Ionescu, A ; Mikolaizak, AS ; Taraldsen, K ; Mellone, S ; Bergquist, R ; Van Ancum, JM ; Nerz, C ; Pijnappels, M ; Maier, AB ; Helbostad, JL ; Vereijken, B ; Becker, C ; Aminian, K ; Schwenk, M (ELSEVIER IRELAND LTD, 2020)
    BACKGROUND: Understanding the association between motor capacity (MC) (what people can do in a standardized environment), mobility performance (MP) (what people actually do in real-life) and falls is important for early detection of and counteracting on functional decline, particularly in the rapidly growing population of young seniors. Therefore, this study aims to 1) explore the association between MC and MP, and between MC and falls, and 2) investigate whether challenging MC measures are better associated with MP and falls than basic MC measures. METHODS: Basic (habitual gait speed, Timed Up-and-Go) and challenging (fast gait speed, Community Balance & Mobility Scale) MC measures were performed in 169 young seniors (61-70 years). MP was assessed using one-week sensor-monitoring including time being sedentary, light active, and at least moderately active. Falls in the previous six months were reported. Associations and discriminative ability were calculated using correlation, regression and receiver operating curve analysis. RESULTS: Mean age was 66.4 (SD 2.4) years (50.6 % women). Small to moderate associations (r = 0.06-0.31; p < .001-.461) were found between MC, MP and falls. Challenging MC measures showed closer associations with MP and falls (r = 0.10-0.31; p < .001-.461) compared to basic (r = 0.06-0.22; p = .012-.181), remained significant in three out of four regression models explaining 2.5-8.6 % of the variance, and showed highest discriminative ability (area under the curve = 0.59-0.70) in all analyses. CONCLUSIONS: Challenging MC measures are closer associated with mobility performance and falls as compared to basic MC measures in young seniors. This indicates the importance of applying challenging motor capacity assessments in young seniors. On the same note, small to moderate associations imply a need for an assessment of both MC and MP in order to capture the best possible MC and the actual daily-life MP in young seniors.
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    Frailty, Sarcopenia, and Malnutrition Frequently (Co-)occur in Hospitalized Older Adults: A Systematic Review and Meta-analysis
    Ligthart-Melis, GC ; Luiking, YC ; Kakourou, A ; Cederholm, T ; Maier, AB ; de van der Schueren, MAE (ELSEVIER SCIENCE INC, 2020-09)
    OBJECTIVES: The purpose of this systematic review and meta-analysis was to summarize the prevalence of, and association between, physical frailty or sarcopenia and malnutrition in older hospitalized adults. DESIGN: A systematic literature search was performed in 10 databases. SETTING AND PARTICIPANTS: Articles were selected that evaluated physical frailty or sarcopenia and malnutrition according to predefined criteria and cutoffs in older hospitalized patients. MEASURES: Data were pooled in a meta-analysis to evaluate the prevalence of prefrailty and frailty [together (pre-)frailty], sarcopenia, and risk of malnutrition and malnutrition [together (risk of) malnutrition], and the association between either (pre-)frailty or sarcopenia and (risk of) malnutrition. RESULTS: Forty-seven articles with 18,039 patients (55% female) were included in the systematic review, and 39 articles (8868 patients, 62% female) were eligible for the meta-analysis. Pooling 11 studies (2725 patients) revealed that 84% [95% confidence interval (CI): 77%, 91%, I2 = 98.4%] of patients were physically (pre-)frail. Pooling 15 studies (4014 patients) revealed that 37% (95% CI: 26%, 48%, I2 = 98.6%) of patients had sarcopenia. Pooling 28 studies (7256 patients) revealed a prevalence of 66% (95% CI: 58%, 73%, I2 = 98.6%) (risk of) malnutrition. Pooling 10 studies (2427 patients) revealed a high association [odds ratio (OR): 5.77 (95% CI: 3.88, 8.58), P < .0001, I2 = 42.3%] and considerable overlap (49.7%) between physical (pre-)frailty and (risk of) malnutrition. Pooling 7 studies (2506 patients) revealed a high association [OR: 4.06 (95% CI: 2.43, 6.80), P < .0001, I2 = 71.4%] and considerable overlap (41.6%) between sarcopenia and (risk of) malnutrition. CONCLUSIONS AND IMPLICATIONS: The association between and prevalence of (pre-)frailty or sarcopenia and (risk of) malnutrition in older hospitalized adults is substantial. About half of the hospitalized older adults suffer from 2 and perhaps 3 of these debilitating conditions. Therefore, standardized screening for these conditions at hospital admission is highly warranted to guide targeted nutritional and physical interventions.
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    Morbidity Measures Predicting Mortality in Inpatients: A Systematic Review
    Soh, CH ; Ul Hassan, SW ; Sacre, J ; Maier, AB (ELSEVIER SCIENCE INC, 2020-04)
    OBJECTIVES: Morbidity is an important risk factor for mortality and a variety of morbidity measures have been developed to predict patients' health outcomes. The objective of this systematic review was to compare the capacity of morbidity measures in predicting mortality among inpatients admitted to internal medicine, geriatric, or all hospital wards. DESIGN: A systematic literature search was conducted from inception to March 6, 2019 using 4 databases: Medline, Embase, Cochrane, and CINAHL. Articles were included if morbidity measures were used to predict mortality (registration CRD42019126674). SETTING AND PARTICIPANTS: Inpatients with a mean or median age ≥65 years. MEASUREMENTS: Morbidity measures predicting mortality. RESULTS: Of the 12,800 articles retrieved from the databases, a total of 34 articles were included reporting on inpatients admitted to internal medicine, geriatric, or all hospital wards. The Charlson Comorbidity Index (CCI) was reported most frequently and a higher CCI score was associated with greater mortality risk, primarily at longer follow-up periods. Articles comparing morbidity measures revealed that the Geriatric Index of Comorbidity was better predicting mortality risk than the CCI, Cumulative Illness Rating Scale, Index of Coexistent Disease, and disease count. CONCLUSIONS AND IMPLICATIONS: Higher morbidity measure scores are better in predicting mortality at longer follow-up period. The Geriatric Index of Comorbidity was best in predicting mortality and should be used more often in clinical practice to assist clinical decision making.
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    Prevalence of malnutrition comparing the GLIM criteria, ESPEN definition and MST malnutrition risk in geriatric rehabilitation patients: RESORT
    Clark, AB ; Reijnierse, EM ; Lim, WK ; Maier, AB (CHURCHILL LIVINGSTONE, 2020-11)
    BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) has developed new criteria for the diagnosis of malnutrition. This study aimed 1) to determine and compare malnutrition prevalence and risk using the GLIM criteria, European Society for Clinical Nutrition and Metabolism (ESPEN) definition of malnutrition and the Malnutrition Screening Tool (MST) in patients admitted to subacute geriatric rehabilitation wards, 2) to explore the agreement of malnutrition prevalence determined by each definition, and 3) to determine the accuracy of the MST against the GLIM criteria and ESPEN definition as references. METHODS: Geriatric rehabilitation patients (n = 444) from the observational, longitudinal REStORing health of acutely unwell adulTs (RESORT) cohort in Melbourne, Australia were included. The GLIM criteria, ESPEN definition and MST were applied. Accuracy was determined by the sensitivity, specificity and Area Under the Curve (AUC). RESULTS: According to the GLIM criteria, the overall prevalence of malnutrition was 52.0%. The ESPEN definition diagnosed 12.6% of patients as malnourished and the MST identified 44.4% of patients at risk for malnutrition. Agreement was low; 7% of patients were malnourished and at risk for malnutrition according to all three definitions. The accuracy of the MST compared to the GLIM criteria was fair (sensitivity 56.7%, specificity 69.0%) and sufficient (AUC 0.63); MST compared to the ESPEN definition was fair (sensitivity 60.7%, specificity 58.0%) and poor (AUC 0.59). CONCLUSIONS: According to the GLIM criteria, half of geriatric rehabilitation patients were malnourished, whereas the prevalence was much lower applying the ESPEN definition. This highlights the need for further studies to determine diagnostic accuracy of the GLIM criteria compared to pre-existing validated tools.
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    Development and validation of the delirium risk assessment score (DRAS)
    Vreeswijk, R ; Kalisvaart, I ; Maier, AB ; Kalisvaart, KJ (SPRINGER, 2020-04)
    PURPOSE: Development and validation of a delirium risk assessment score. Predisposing risk factors for delirium were used, which are easily assessed at hospital admission without additional clinical or laboratory testing. METHODS: A systematic literature search identified ten risk factors: acute admission, alcohol use > 4 units/day, cognitive impairment, ADL impairment, age > 75 years, earlier delirium, hearing/vision problems, number of medication ≥ 5, number of morbidities > 2 and male. The DRAS was developed in a mixed patient population (N = 842) by the use of univariate and multivariate analyses and -2 log-likelihood calculation to weigh the risk factors. Based on the sensitivity and specificity, a cutoff score was calculated. The validation was performed in 3 cohorts (N = 408, N = 186, N = 365). In cohort 3, the DRAS was compared (AUC, sensitivity and specificity) to 3 instruments (Inouye, Kalisvaart, VMS rules). RESULTS: The delirium incidence was 31.8%, 20.3%, 15.6% and 15.1%. All risk factors were independently predictive for delirium, except male. The multivariate analyses excluded morbidities. The final DRAS consists of 8 items; acute admission, cognitive impairment, alcohol use (3 points), ADLimpairment/mobilityproblems (2 points), higher age, earlier delirium, hearing/vision problems, and medication (1 point). The total score is 15 points and at a cut-of score of 5 or higher the patient is at risk of developing a delirium. The cutoff was at 5 or more points, AUC: 0.76 (95% CI 0.72-0.79), sensitivity 0.77, specificity 0.60. Validation cohorts AUC was 0.75 (95% CI 0.96-0.81), 0.76 (95% CI 0.70-0.83) and 0.78 (95% CI 0.70-0.87), sensitivity 0.71, 0.67 and 0.89 and specificity 0.70, 0.72 and 0.60. The comparison revealed the highest AUC for the DRAS. CONCLUSION: Based on an admission interview, the delirium risk can be easily evaluated using the DRAS shortlist score of predisposing risk factors for delirium in older inpatients.
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    Creating and Validating a Shortened Version of the Community Balance and Mobility Scale for Application in People Who Are 61 to 70 Years of Age
    Gordt, K ; Mikolaizak, AS ; Taraldsen, K ; Bergquist, R ; Van Ancum, JM ; Nerz, C ; Pijnappels, M ; Maier, AB ; Helbostad, JL ; Vereijken, B ; Becker, C ; Schwenk, M (OXFORD UNIV PRESS INC, 2020-01)
    BACKGROUND: The Community Balance and Mobility Scale (CBM) has been shown to be reliable and valid for detecting subtle balance and mobility deficits in people who are 61 to 70 years of age. However, item redundancy and assessment time call for a shortened version. OBJECTIVE: The objective was to create and validate a shortened version of the CBM (s-CBM) without detectable loss of psychometric properties. DESIGN: This was a cross-sectional study. METHODS: Exploratory factor analysis with data from 189 young seniors (aged 61-70 years; mean [SD] age = 66.3 [2.5] years) was used to create the s-CBM. Sixty-one young seniors (aged 61-70 years; mean [SD] age = 66.5 [2.6] years) were recruited to assess construct validity (Pearson correlation coefficient) by comparing the CBM versions with Fullerton Advance Balance Scale, Timed Up-and-Go, habitual and fast gait speed, 8 Level Balance Scale, 3-m tandem walk, and 30-second chair stand test. Internal consistency (Cronbach α), ceiling effects, and discriminant validity (area under the curve [AUC]) between fallers and nonfallers, and self-reported high and low function (Late-Life Function and Disability Index) and balance confidence (Activities-Specific Balance Confidence Scale), respectively, were calculated. RESULTS: The s-CBM, consisting of 4 items, correlated excellently with the CBM (r = 0.97). Correlations between s-CBM and other assessments (r = 0.07-0.72), and CBM and other assessments (r = 0.06-0.80) were statistically comparable in 90% of the correlations. Cronbach α was .84 for the s-CBM, and .87 for the CBM. No CBM-version showed ceiling effects. Discriminative ability of the s-CBM was statistically comparable with the CBM (AUC = 0.66-0.75 vs AUC = 0.65-0.79). LIMITATIONS: Longitudinal studies with larger samples should confirm the results and assess the responsiveness for detecting changes over time. CONCLUSIONS: The psychometric properties of the s-CBM were similar to those of the CBM. The s-CBM can be recommended as a valid and quick balance and mobility assessment in young seniors.
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    A study protocol for the development of a multivariable model predicting 6- and 12-month mortality for people with dementia living in residential aged care facilities (RACFs) in Australia.
    Bicknell, R ; Lim, WK ; Maier, AB ; LoGiuidice, D (Springer Science and Business Media LLC, 2020)
    BACKGROUND: For residential aged care facility (RACF) residents with dementia, lack of prognostic guidance presents a significant challenge for end of life care planning. In an attempt to address this issue, models have been developed to assess mortality risk for people with advanced dementia, predominantly using long-term care minimum data set (MDS) information from the USA. A limitation of these models is that the information contained within the MDS used for model development was not collected for the purpose of identifying prognostic factors. The models developed using MDS data have had relatively modest ability to discriminate mortality risk and are difficult to apply outside the MDS setting. This study will aim to develop a model to estimate 6- and 12-month mortality risk for people with dementia from prognostic indicators recorded during usual clinical care provided in RACFs in Australia. METHODS: A secondary analysis will be conducted for a cohort of people with dementia from RACFs participating in a cluster-randomized trial of a palliative care education intervention (IMPETUS-D). Ten prognostic indicator variables were identified based on a literature review of clinical features associated with increased mortality for people with dementia living in RACFs. Variables will be extracted from RACF files at baseline and mortality measured at 6 and 12 months after baseline data collection. A multivariable logistic regression model will be developed for 6- and 12-month mortality outcome measures using backwards elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of the model for 6- and 12-month mortality will be presented as receiver operating curves with c statistics. Calibration curves will be presented comparing observed and predicted event rates for each decile of risk as well as flexible calibration curves derived using loess-based functions. DISCUSSION: The model developed in this study aims to improve clinical assessment of mortality risk for people with dementia living in RACFs in Australia. Further external validation in different populations will be required before the model could be developed into a tool to assist with clinical decision-making in the future.