Medicine (RMH) - Research Publications
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ItemDigital Technology to Deliver a Lifestyle-Integrated Exercise Intervention in Young Seniors-The PreventIT Feasibility Randomized Controlled Trial(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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ItemPilot multi-centre randomised trial of the impact of pre-operative focused cardiac ultrasound on mortality and morbidity in patients having surgery for femoral neck fractures (ECHONOF-2 pilot)(WILEY, 2018-04)Hip fracture surgery is common, usually occurs in elderly patients who have multiple comorbidities, and is associated with high morbidity and mortality. Pre-operative focused cardiac ultrasound can alter diagnosis and management, but its impact on outcome remains uncertain. This pilot study assessed feasibility and group separation for a proposed large randomised clinical trial of the impact of pre-operative focused cardiac ultrasound on patient outcome after hip fracture surgery. Adult patients requiring hip fracture surgery in four teaching hospitals in Australia were randomly allocated to receive focused cardiac ultrasound before surgery or not. The primary composite outcome was any death, acute kidney injury, non-fatal myocardial infarction, cerebrovascular accident, pulmonary embolism or cardiopulmonary arrest within 30 days of surgery. Of the 175 patients screened, 100 were included as trial participants (screening:recruitment ratio 1.7:1), 49 in the ultrasound group and 51 as controls. There was one protocol failure among those recruited. The primary composite outcome occurred in seven of the ultrasound group patients and 12 of the control group patients (relative group separation 39%). Death, acute kidney injury and cerebrovascular accident were recorded, but no cases of myocardial infarction, pulmonary embolism or cardiopulmonary arrest ocurred. Focused cardiac ultrasound altered the management of 17 participants, suggesting an effect mechanism. This pilot study demonstrated that enrolment and the protocol are feasible, that the primary composite outcome is appropriate, and that there is a treatment effect favouring focused cardiac ultrasound - and therefore supports a large randomised clinical trial.
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ItemHigher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer(WILEY, 2018-05)BACKGROUND: Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older. MATERIALS AND METHODS: Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively. RESULTS: The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS. CONCLUSION: Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer. IMPLICATIONS FOR PRACTICE: This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and therefore in identifying older patients who will benefit from anticancer treatment.
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ItemMethodology for senior-proof guidelines: A practice example from the Netherlands(WILEY, 2018-02)RATIONALE, AIMS AND OBJECTIVES: Evidence-based guidelines constitute a foundation for medical decision making. It is often unclear whether recommendations in general guidelines also apply to older people. This study aimed to develop a methodology to increase the focus on older people in the development of guidelines. METHODS: The methodology distinguishes 4 groups of older people: (1) relatively healthy older people; (2) older people with 1 additional specific (interfering) comorbid condition; (3) older people with multimorbidity; and (4) vulnerable older people. RESULTS: The level of focus on older people required may be determined by the prevalence of the disease or condition, level of suffering, social relevance, and the expectation that a guideline may improve the quality of care. A specialist in geriatric medicine may be involved in the guideline process via participation, provision of feedback on drafts, or involvement in the analysis of problem areas. Regarding the patient perspective, it is advised to involve organisations for older people or informal carers in the inventory of problem areas, and additionally to perform literature research of patient values on the subject. If the guideline focuses on older people, then the relative importance of the various outcome measures for this target group needs to be explicitly stated. Search strategies for all the 4 groups are suggested. For clinical studies that focus on the treatment of diseases that frequently occur in older people, a check should be made regarding whether these studies produce the required evidence. This can be achieved by verifying if there is sufficient representation of older people in the studies and determining if there is a separate reporting of results applying to this age group.
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ItemMalnutrition and Risk of Structural Brain Changes Seen on Magnetic Resonance Imaging in Older Adults(WILEY, 2016-12)OBJECTIVES: To study the associations between protein energy malnutrition, micronutrient malnutrition, brain atrophy, and cerebrovascular lesions. DESIGN: Cross-sectional. SETTING: Geriatric outpatient clinic. PARTICIPANTS: Older adults (N = 475; mean age 80 ± 7). MEASUREMENTS: Nutritional status was assessed using the Mini Nutritional Assessment (MNA) and according to serum micronutrient levels (vitamins B1, B6, B12, D; folic acid). White matter hyperintensities (WMHs), global cortical brain atrophy, and medial temporal lobe atrophy on magnetic resonance imaging (MRI) were rated using visual rating scales. Logistic regression analyses were performed to assess associations between the three MNA categories (<17, 17-23.5, ≥23.5) and micronutrients (per SD decrease) and WMHs and measures of brain atrophy. RESULTS: Included were 359 participants. Forty-eight participants (13%) were malnourished (MNA <17), and 197 (55%) were at risk of malnutrition (MNA = 17-23.5). Participants at risk of malnutrition (odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.01-3.71) or who were malnourished (OR = 2.80, 95% CI = 1.19-6.60) had a greater probability of having severe WMHs independent of age and sex than those with adequate nutritional status. Results remained significant after further adjustments for cognitive function, depressive symptoms, cardiovascular risk factors, history of cardiovascular disease, smoking and alcohol use, and micronutrient levels. Lower vitamin B1 (OR = 1.51, 95% CI = 1.11-2.08) and B12 (OR = 1.45, 95% CI = 1.02-2.04) levels were also related to greater risk of severe WMHs, independent of age and sex. Results remained significant after additional adjustments. MNA and vitamin levels were not associated with measures of brain atrophy. CONCLUSION: Malnutrition and lower vitamin B1 and B12 levels were independently associated with greater risk of WMHs. Underlying mechanisms need to be further clarified, and whether nutritional interventions can modify these findings also needs to be studied.
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ItemUndiagnosed delirium is frequent and difficult to predict: Results from a prevalence survey of a tertiary hospital(WILEY, 2019-07)AIMS AND OBJECTIVES: To study the prevalence and determinants of undiagnosed delirium in a tertiary hospital. BACKGROUND: Delirium is a common inpatient condition. It is frequently undiagnosed in a variety of settings, but determinants of undiagnosed delirium are largely unknown, and the frequency of undiagnosed delirium across all inpatient units is uncertain. The utility of hospital-wide screening then is also uncertain. METHODS: Hospital-wide prevalence study conducted over 4 months, using a chart-based method. Gender, age, admitting unit, history of dementia and comorbidity were used in univariate and multivariate analyses to search for differences in patients with no delirium, with undiagnosed delirium and with diagnosed delirium. Sensitivity, specificity and number needed to screen were calculated from proportions in each group. Study was conducted in concordance with STROBE guidelines. RESULTS: Delirium was prevalent in 12.5% of all patients and undiagnosed in 24.1% of patients. Only age ≥65 years and a history of dementia predicted delirium, and undiagnosed delirium in both univariate and multivariate analyses. Age ≥65 years accounts for 92.3% sensitivity and 50.8% specificity for undiagnosed delirium in this group. History of dementia had a 23.0% sensitivity and 97.0% specificity. Twenty-eight patients would need to be screened to detect a case of undiagnosed delirium. DISCUSSION: There was a high rate of delirium and undiagnosed delirium in this cohort. Known risk factors for delirium also independently predict undiagnosed delirium; other factors were not found. CONCLUSION: Undiagnosed delirium is common and difficult to predict from patient baseline characteristics other than age. RELEVANCE TO CLINICAL PRACTICE: Assessment of all inpatients for delirium is recommended.
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ItemPerceptual rivalry across animal species(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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ItemMen 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(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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ItemNo Preview AvailableThe association of basic and challenging motor capacity with mobility performance and falls in young seniors(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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ItemNo Preview AvailableFrailty, Sarcopenia, and Malnutrition Frequently (Co-)occur in Hospitalized Older Adults: A Systematic Review and Meta-analysis(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.