Medicine (RMH) - Research Publications

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    Pilot 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)
    Canty, DJ ; Heiberg, J ; Yang, Y ; Royse, AG ; Margale, S ; Nanjappa, N ; Scott, D ; Maier, A ; Sessler, DI ; Chuan, A ; Palmer, A ; Bucknill, A ; French, C ; Royse, CF (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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    Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer
    Versteeg, KS ; Blauwhoff-Buskermolen, S ; Buffart, LM ; de van der Schueren, MAE ; Langius, JAE ; Verheul, HMW ; Maier, AB ; Konings, IR (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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    Methodology for senior-proof guidelines: A practice example from the Netherlands
    van Munster, BC ; Portielje, JEA ; Maier, AB ; Arends, AJ ; de Beer, JJA (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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    Malnutrition and Risk of Structural Brain Changes Seen on Magnetic Resonance Imaging in Older Adults
    de van der Schueren, MAE ; Lonterman-Monasch, S ; van der Flier, WM ; Kramer, MH ; Maier, AB ; Muller, M (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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    Undiagnosed delirium is frequent and difficult to predict: Results from a prevalence survey of a tertiary hospital
    Lange, PW ; Lamanna, M ; Watson, R ; Maier, AB (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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    Orofacial pain and its potential oral causes in older people with mild cognitive impairment or dementia
    Delwel, S ; Scherder, EJA ; de Baat, C ; Binnekade, TT ; van der Wouden, JC ; Hertogh, CMPM ; Maier, AB ; Perez, RSGM ; Lobbezoo, F (WILEY, 2019-01)
    BACKGROUND: The number of people with dementia and natural dentition is growing. As dementia progresses, the degree of self-care decreases and the risk of oral health problems and orofacial pain increases. OBJECTIVES: To examine and compare the presence of orofacial pain and its potential causes in older people with Mild Cognitive Impairment (MCI) or dementia. METHODS: In this cross-sectional observational study, the presence of orofacial pain and its potential causes was studied in 348 participants with MCI or dementia with all levels of cognitive impairment in two outpatient memory clinics and ten nursing homes. RESULTS: Orofacial pain was reported by 25.7% of the 179 participants who were considered to present a reliable pain self-report (Mini-Mental State Examination score ≥14 points), while it could not be determined in people with more severe cognitive impairment. The oral health examination of the 348 participants indicated that potential painful conditions, such as coronal caries, root caries, tooth root remnants or ulcers were present in 50.3%. There was a significant correlation between the level of cognitive impairment and the number of teeth, r = 0.185, P = 0.003, teeth with coronal caries, r = -0.238, P < 0.001, and the number of tooth root remnants, r = -0.229, P = 0.004, after adjusting for age. CONCLUSIONS: This study indicated that orofacial pain and its potential causes were frequently present in participants with MCI or dementia. Therefore, a regular oral examination by (oral) healthcare providers in people with MCI or dementia remains imperative, even if no pain is reported.
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    Age dependency of risk factors for cognitive decline
    Legdeur, N ; Heymans, MW ; Comijs, HC ; Huisman, M ; Maier, AB ; Visser, PJ (BMC, 2018-08-20)
    BACKGROUND: Risk factors for cognitive decline might depend on chronological age. The aim of the study was to explore the age dependency of risk factors for cognitive decline in cognitively healthy subjects aged 55-85 years at baseline. METHODS: We included 2527 cognitively healthy subjects from the Longitudinal Aging Study Amsterdam (LASA). Median follow-up was 9.1 (IQR: 3.2-19.0) years. The association of genetic and cardiovascular risk factors, depressive symptoms, inflammation markers and lifestyle risk factors with decline in MMSE and memory function was tested using spline regression analyses. RESULTS: Subjects were on average 70.1 (SD 8.8) years old at baseline. Based on a spline regression model, we divided our sample in three age groups: ≤70 years (young-old), > 70-80 years (old) and > 80 years (oldest-old). The association of LDL cholesterol, homocysteine, hypertension, history of stroke, depressive symptoms, interleukin-6, a1-antichymotrypsin, alcohol use and smoking with cognitive decline significantly differed between the age groups. In general, the presence of these risk factors was associated with less cognitive decline in the oldest-old group compared to the young-old and old group. CONCLUSIONS: The negative effect of various risk factors on cognitive decline decreases with higher age. A combination of epidemiological factors, such as the selection towards healthier subjects during follow-up, but also risk factor specific features, for example ensuring the cerebral blood flow in case of hypertension, explain this diminished association at higher age. It is important to take these age differences into account when applying preventive strategies to avert cognitive decline.
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    The association between age and accelerometry-derived types of habitual daily activity: an observational study over the adult life span in the Netherlands
    van Schooten, KS ; van Dieen, JH ; Pijnappels, M ; Maier, AB ; van't Hul, AJ ; Niessen, M ; van Lummel, RC (BMC, 2018-07-04)
    BACKGROUND: Advances in sensor technology allow for objective and high-resolution monitoring of physical activity and sedentary behaviour. Novel epidemiological data is required to provide feedback on an individual's habitual daily activity in comparison to peers and might eventually lead to refined physical activity guidelines. METHODS: We merged data of 762 people between 18 and 99 years of age, who all wore a DynaPort MoveMonitor accelerometer on their lower back during 1 week in daily-life, to provide insight into habitual types and durations of daily activities, and examine the association between age and physical activity and sedentary behaviour. RESULTS: We found associations between age and almost all activity outcomes. These associations suggested that physical activity declines and sedentary behaviour increases from the age of 50. We further describe an association with gender, with men walking more often in fewer but longer bouts and having fewer, longer bouts of sitting and standing. CONCLUSIONS: These data provide a valuable reference and may call for more age- and gender-specific activity interventions.
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    Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting
    Beets-Tan, RGH ; Lambregts, DMJ ; Maas, M ; Bipat, S ; Barbaro, B ; Curvo-Semedo, L ; Fenlon, HM ; Gollub, MJ ; Gourtsoyianni, S ; Halligan, S ; Hoeffel, C ; Kim, SH ; Laghi, A ; Maier, A ; Rafaelsen, SR ; Stoker, J ; Taylor, SA ; Torkzad, MR ; Blomqvist, L (SPRINGER, 2018-04)
    OBJECTIVES: To update the 2012 ESGAR consensus guidelines on the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. METHODS: Fourteen abdominal imaging experts from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) participated in a consensus meeting, organised according to an adaptation of the RAND-UCLA Appropriateness Method. Two independent (non-voting) Chairs facilitated the meeting. 246 items were scored (comprising 229 items from the previous 2012 consensus and 17 additional items) and classified as 'appropriate' or 'inappropriate' (defined by ≥ 80 % consensus) or uncertain (defined by < 80 % consensus). RESULTS: Consensus was reached for 226 (92 %) of items. From these recommendations regarding hardware, patient preparation, imaging sequences and acquisition, criteria for MR imaging evaluation and reporting structure were constructed. The main additions to the 2012 consensus include recommendations regarding use of diffusion-weighted imaging, criteria for nodal staging and a recommended structured report template. CONCLUSIONS: These updated expert consensus recommendations should be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI. KEY POINTS: • These guidelines present recommendations for staging and reporting of rectal cancer. • The guidelines were constructed through consensus amongst 14 pelvic imaging experts. • Consensus was reached by the experts for 92 % of the 246 items discussed. • Practical guidelines for nodal staging are proposed. • A structured reporting template is presented.
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    Patterns of muscle strength loss with age in the general population and patients with a chronic inflammatory state
    Beenakker, KGM ; Ling, CH ; Meskers, CGM ; de Craen, AJM ; Stijnen, T ; Westendorp, RGJ ; Maier, AB (ELSEVIER IRELAND LTD, 2010-10)
    BACKGROUND: There is growing recognition of the serious consequences of sarcopenia on the functionality and autonomy in old age. Recently, the age-related changes in several inflammatory mediators have been implicated in the pathogenesis of sarcopenia. The purposes of this systematic review were two-fold: (1) to describe the patterns of muscle strength loss with age in the general population, and (2) to quantify the loss of muscle strength in rheumatoid arthritis as representative for an underlying inflammatory state. Handgrip strength was used as a proxy for overall muscle strength. RESULTS: Results from 114 studies (involving 90,520 subjects) and 71 studies (involving 10,529 subjects) were combined in a meta-analysis for the general and rheumatoid arthritis population respectively and standardized at an equal sex distribution. For the general population we showed that between the ages of 25 years and 95 years mean handgrip strength declined from 45.5 kg to 23.2 kg for males and from 27.1 kg to 12.8 kg for females. We noted a steeper handgrip strength decline after 50 years of age (rate of 0.37 kg/year). In the rheumatoid arthritis population handgrip strength was not associated with chronological age between the ages of 35 years and 65 years and was as low as 20.2 kg in male and 15.1 in female. Rheumatoid arthritis disease duration was inversely associated with handgrip strength. CONCLUSIONS: This meta-analysis shows distinct patterns of age-related decrease of handgrip strength in the general population. Handgrip strength is strongly associated with the presence and duration of an inflammatory state as rheumatoid arthritis. The putative link between age-related inflammation and sarcopenia mandates further study as it represents a potential target for intervention to maintain functional independence in old age.