BackgroundIn 2019, more than 30% of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death... Show moreBackgroundIn 2019, more than 30% of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression.MethodsThis open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (>= 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor<65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is 'successful transplantation', defined as survival with a functioning graft and an eGFR30 ml/min per 1.73 m(2) in stratum A and >= 45 ml/min per 1.73 m(2) in stratum B, after 2 years, respectively.ConclusionsThe OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients.Trial registrationClinicalTrials.gov: NCT03797196, registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019. Show less
Purpose Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric... Show morePurpose Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, to routinely identify major geriatric impairments in older people with advanced CKD. Methods A pragmatic approach was chosen, which included focus groups, literature review, inventory of current practices, an expert consensus meeting, and pilot testing. In preparation of the consensus meeting, we composed a project team and an expert panel (n = 33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the geriatric assessment. Results Selection criteria related to general geriatric domains, clinical relevance, feasibility, and duration of the assessment. The consensus-assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains. Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 min, respectively. Results are discussed in a multidisciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions, and follow-up interventions among which comprehensive geriatric assessment. Conclusion This first multidisciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced CKD.Key Summary pointsAim To propose a consensus-based geriatric assessment for optimizing both routine care and research in older patients with advanced chronic kidney disease. Findings Using a pragmatic approach, we reached consensus on a suitable nephrology-tailored geriatric assessment to routinely identify major geriatric impairments in older patients with advanced chronic kidney disease. This geriatric assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains, and can be administered with patient questionnaires and professional-administered instruments by nurse (practitioners) in approximately 20 and 40 minutes, respectively. Message We propose a consensus test set for standardized nephrology-tailored geriatric assessment, which is currently being implemented in multiple hospitals and studies, to benefit clinical care for older patients with advanced chronic kidney disease and enhance research comparability. Show less
Blomaard, L.C.; Olthof, M.; Meuleman, Y.; Groot, B. de; Gussekloo, J.; Mooijaart, S.P. 2021
BackgroundThe patient perspective on the use of screening for high risks of adverse health outcomes in Emergency Department (ED) care is underexposed, although it is an important perspective... Show moreBackgroundThe patient perspective on the use of screening for high risks of adverse health outcomes in Emergency Department (ED) care is underexposed, although it is an important perspective influencing implementation in routine care. This study explores the experiences with, and attitudes towards geriatric screening in routine ED care among older people who visited the ED.MethodsThis was a qualitative study using individual face-to-face semi-structured interviews. Interviews were conducted in older patients (>= 70years) who completed the 'Acutely Presenting Older Patient' screener while visiting the ED of a Dutch academic hospital. Purposive convenience sampling was used to select a heterogeneous sample of participants regarding age, disease severity and the result from screening. Transcripts were analyzed inductively using thematic analysis.ResultsAfter 13 interviews (7 women, median age 82years), data saturation was reached. The participants had noticed little of the screening administration during triage and screening was considered as a normal part of ED care. Most participants believed that geriatric screening contributes to assessing older patients holistically, recognizing geriatric problems early and comforting patients with communication and attention. None of the participants had a negative attitude towards screening or thought that screening is discrimination on age. Care providers should communicate respectfully with frail older patients and involve them in decision-making.ConclusionsOlder patients experienced geriatric screening as a normal part of ED care and had predominantly positive attitudes towards its use in the ED. This qualitative study advocates for continuing the implementation of geriatric screening in routine ED practice. Show less
Blomaard, L.C.; Mooijaart, S.P.; Meer, L.J. van; Leander, J.; Lucke, J.A.; Gelder, J. de; ... ; Groot, B. de 2021
Background Falls in older Emergency Department (ED) patients may indicate underlying frailty. Geriatric follow-up might help improve outcomes in addition to managing the direct cause and... Show moreBackground Falls in older Emergency Department (ED) patients may indicate underlying frailty. Geriatric follow-up might help improve outcomes in addition to managing the direct cause and consequence of the fall. We aimed to study whether fall characteristics and the result of geriatric screening in the ED are independently related to adverse outcomes in older patients with fall-related ED visits. Methods This was a secondary analysis of the observational multicenter Acutely Presenting Older Patient (APOP) study, of which a subset of patients aged >= 70 years with fall-related ED visits were prospectively included in EDs of two Dutch hospitals. Fall characteristics (cause and location) were retrospectively collected. The APOP-screener was used as a geriatric screening tool. The outcome was 3- and 12-months functional decline and mortality. We assessed to what extent fall characteristics and the geriatric screening result were independent predictors of the outcome, using multivariable logistic regression analysis. Results We included 393 patients (median age 80 (IQR 76-86) years) of whom 23.0% were high risk according to screening. The cause of the fall was extrinsic (49.6%), intrinsic (29.3%), unexplained (6.4%) or missing (14.8%). A high risk geriatric screening result was related to increased risk of adverse outcomes (3-months adjusted odds ratio (AOR) 2.27 (1.29-3.98), 12-months AOR 2.20 (1.25-3.89)). Independent of geriatric screening result, an intrinsic cause of the fall increased the risk of 3-months adverse outcomes (AOR 1.92 (1.13-3.26)) and a fall indoors increased the risk of 3-months (AOR 2.14 (1.22-3.74)) and 12-months adverse outcomes (AOR 1.78 (1.03-3.10)). Conclusions A high risk geriatric screening result and fall characteristics were both independently associated with adverse outcomes in older ED patients, suggesting that information on both should be evaluated to guide follow-up geriatric assessment and interventions in clinical care. Show less
Oevelen, M. van; Abrahams, A.C.; Bos, W.J.W.; Emmelot-Vonk, M.H.; Mooijaart, S.P.; Diepen, M. van; ... ; DIALOGICA Study Grp 2021
Background The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on... Show moreBackground The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on mortality in subgroups of these patients when compared to conservative care. As the focus is shifting towards health-related quality of life (HRQoL), current evidence of effects of conservative care or dialysis on HRQoL in older patients is both limited and biased. Dialysis comes with both high treatment burden for patients and high costs for society; better identification of patients who might not benefit from dialysis could result in significant cost savings. The aim of this prospective study is to compare HRQoL, clinical outcomes, and costs between conservative care and dialysis in older patients.MethodsThe DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study is a prospective, observational cohort study that started in February 2020. It aims to include 1500 patients from 25 Dutch and Belgian centres. Patients aged >= 70years with an eGFR of 10-15mL/min/1.73m(2) are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10mL/min/1.73m(2) or lower, the second stage of the study commences. In both stages nephrogeriatric assessments will be performed annually, consisting of questionnaires and tests to assess most common geriatric domains, i.e. functional, psychological, somatic, and social status. The primary outcome is HRQoL, measured with the Twelve-item Short-Form Health Survey. Secondary outcomes are clinical outcomes (mortality, hospitalisation, functional status, cognitive functioning, frailty), cost-effectiveness, and decisional regret. All outcomes are (repeated) measures during the first year of the second stage. The total follow-up will be a maximum of 4 years with a minimum of 1 year in the second stage.DiscussionBy generating more insight in the effects of conservative care and dialysis on HRQoL, clinical outcomes, and costs, findings of this study will help patients and physicians make a shared decision on the best individual treatment option for kidney failure.Trial registrationThe study was registered in the Netherlands Trial Register (NL-8352) on 5 February 2020. Show less
Background: Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented... Show moreBackground: Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study.Methods: A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged >= 70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year.Discussion: Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients.Trial registration: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL81 07. Date of registration: 22-10-2019. Show less
Vlies, E. van der; Smits, A.B.; M. los; Hengel, M. van; Bos, W.J.W.; Dijksman, L.M.; ... ; Noordzij, P.G. 2020
Objective: To determine the influence of a preoperative multidisciplinary evaluation for frail older patients with colorectal cancer (CRC) on preoperative decision making and postoperative outcomes... Show moreObjective: To determine the influence of a preoperative multidisciplinary evaluation for frail older patients with colorectal cancer (CRC) on preoperative decision making and postoperative outcomes.Background: Surgery is the main treatment for CRC. Older patients are at increased risk for adverse outcomes. For complex surgical cases, a multidisciplinary team (MDT) approach has been suggested to improve postoperative outcome. Evidence is lacking.Methods: Historical cohort study from 2015 to 2018 in surgical patients >= 70 years with CRC. Frailty screening was used to appraise the somatic, functional and psychosocial health status. An MDT weighed the risk of surgery versus the expected gain in survival to guide preoperative decision making and initiate a prehabilitation program. Primary endpoint was the occurrence of a Clavien-Dindo (CD) Grade III-V complication. Secondary endpoints included the occurrence of any complication (CD II-V), length of hospital stay, discharge destination, readmission rate and overall survival.Results: 466 patients were included and 146 (31.3%) patients were referred for MDT evaluation. MDT patients were more often too frail for surgery compared to non-MDT patients (10.3% vs 2.2%, P = .01). Frailty was associated with overall mortality (aOR 2.6 95% CI 1.1-6.1). Prehabilitation was more often performed in MDT patients (74.8% vs 23.4% in non-MDT patients). Despite an increased risk, MDT patients did not suffer more postoperative complications (CD III-V) than non-MDT patients (14.9% vs 12.4%; P = .48). Overall survival was worse in MDT patients (35 (32-37) vs 48 (47-50) months in non-MDT patients; P < .01).Conclusions: Implementation of preoperative MDT evaluation for frail patients with CRC improves risk stratification and prehabilitation, resulting in comparable postoperative outcomes compared to non-frail patients. However, frail patients are at increased risk for worse overall survival. (C) 2020 Published by Elsevier Ltd. Show less
Purpose To investigate the longitudinal association between the macronutrient composition of the diet and frailty. Methods Data were obtained from 5205 Dutch middle-aged and older adults... Show morePurpose To investigate the longitudinal association between the macronutrient composition of the diet and frailty. Methods Data were obtained from 5205 Dutch middle-aged and older adults participating in the Rotterdam Study. Frailty was measured using a frailty index based on the accumulation of 38 health-related deficits, score between 0 and 100, and a higher score indicating more frailty. Frailty was assessed at baseline and 11 years later (range of 23 years). Macronutrient intake was assessed using food-frequency questionnaires. The association between macronutrients and frailty over time was evaluated using multivariable linear regression, adjusted for the frailty index at baseline, energy intake, and other relevant confounders. All analyses were performed in strata of BMI. Results Median frailty index score was 13.8 points (IQR 9.6; 19.1) at baseline and increased by a median of 2.3 points (IQR - 2.0; 7.6) after 11 years. Overall, we found no significant associations between intake of carbohydrates or fat and frailty over time. We did observe a significant positive association between an iso-energetic intake of 10 g protein and frailty over time (beta 0.31 (95% CI 0.06; 0.55)) which was mainly driven by animal protein (beta 0.31 (95% CI 0.07; 0.56)). It did not depend on whether it was substituted fat or carbohydrates. Conclusions Our findings suggest that a reduction in the intake of animal protein may improve the overall health status over time in a relatively healthy population. More research is needed on the optimal macronutrient composition of the diet and frailty in more vulnerable populations. Show less
Key summary pointsAim The consensus statement about core principles and future priorities of geriatric rehabilitation has the aim to help healthcare providers which need strategies to support older... Show moreKey summary pointsAim The consensus statement about core principles and future priorities of geriatric rehabilitation has the aim to help healthcare providers which need strategies to support older people who have experienced functional decline. Findings Geriatric rehabilitation is now defined in a way that is compatible with existing service models across Europe. Message This consensus statement can provide a starting point for further development of geriatric rehabilitation.Purpose In response to the growing recognition of geriatric rehabilitation and to support healthcare providers which need strategies to support older people with frailty who have experienced functional decline, we developed a consensus statement about core principles and future priorities for geriatric rehabilitation. Methods We used a three-stage approach to establish consensus-preparation, consensus and review. Results The consensus statement is grouped under 11 headings from (1) "Definition of GR" to (11) "Effective strategies to develop GR in Europe", which define geriatric rehabilitation in a way that is compatible with existing service models across Europe. Additionally future goals around research and education are highlighted. Conclusion The definitions of the consensus statement can provide a starting point for those wishing to further develop geriatric rehabilitation in their jurisdiction and help to develop strategic alliances with other specialties, serving as a basis for a pan-European approach to geriatric rehabilitation. Show less
Background: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely... Show moreBackground: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group.Methods: Patients aged >= 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk >= 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation.Results: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients (5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients.Conclusion: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients. Show less
The rate of adverse health outcomes 90 days after an emergency department (ED) visit is high for older patients.A comprehensive geriatric assessment (CGA) can effectively identify patients at... Show moreThe rate of adverse health outcomes 90 days after an emergency department (ED) visit is high for older patients.A comprehensive geriatric assessment (CGA) can effectively identify patients at highest risk and improve outcomes. Unfortunately, the fast-paced environment and the medical condition of the acutely ill older patient make it virtually impossible to perform a CGA in all patients in the ED. Therefore, it was the aim of the present thesis to develop a screening instrument for the ED setting to identify older patients at high risk for adverse health outcomes, in order to target them for future interventions to preserve their independency and quality of life. In a multicenter prospective cohort study a total of 2629 older ED patients were included with a mean age of 79 years old. After 90 days 805 patients (30.6%) experienced functional decline or mortality. A new screeninginstrument to identify older ED patients at risk for adverse health outcomes was developed and validated: the APOP screener. The APOP screener adequately identifies older ED patients at highest risk for functional decline or mortality and is promising for clinical use. Show less
The main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction... Show moreThe main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction in HF. Data from two studies (OPERA-HF study in the UK and SAPHIRE study in US) has been used to explore a wide range of variables as potential risk factors. We found that depression is a significant and independent predictor of all-cause mortality among HF patients. Depression was also significantly associated with recurrent events: unplanned readmission or mortality. Other psychosocial or non-clinical variables independently associated with increasing risk of recurrent events in the year following discharge after a HF hospital admission were: presence of frailty, moderate-to-severe anxiety, living alone and the presence of cognitive impairment. We then used data from the OPERA-HF study to develop a 30-day composite outcome model and to explore the added predictive value of non-clinical predictors to early outcomes: 30-day unplanned readmission or mortality. The performance of the model improved by including physical frailty and social support next to clinical variables. The transportability of the model to a different geography was proved in the external validation of the model on the SAPHIRE study data. Show less
This dissertation presents methodological advances in the field of frailty models. Time to event data is very common in biomedical applications. Multivariate data, such as recurrent event... Show moreThis dissertation presents methodological advances in the field of frailty models. Time to event data is very common in biomedical applications. Multivariate data, such as recurrent event histories or clustered failures, typically require special modeling techniques. Frailty models extend the proportional hazards models by employing random effects. In this book, the first chapter represents an introduction to the field of frailty models. The second chapter studies the small sample properties of such models in more depth. In particular, it addresses the questions of identifiability of frailty models. The third chapter describes a score test that may be used to test whether a recurrent events process is associated with a terminal event. The fourth chapter studies the problem of event-dependent selection in the context of recurrent events data. This problem is relevant when the data are collected from registries. The fifth chapter introduces a novel R package and presents an overview of available software for estimating frailty models. Show less
With increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year... Show moreWith increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year-olds when they have multimorbidity, polypharmacy or frailty. Large trials showed that lowering BP in >60-year-olds is beneficial and lowers the risk for myocardial infarction, stroke and all-cause mortality. However, these trials lack generalizability and typically excluded multimorbid patients that are frail. At the same time, observational studies rose concerns about lowering BP too much since there are several cohort studies showing a reverse association of low BP and increased mortality especially in >75-year-olds. The general aim of this thesis is to increase the scientific knowledge about the effects of treating hypertension in >75-year-olds with frailty. This thesis has three aims: 1) to measure the prevalence of polypharmacy in older patients; 2) to test for an association between low SBP and mortality, cognitive function, daily functioning, and QoL in older patients under antihypertensive treatment; and 3) to understand the role that frailty plays in GP decisions about treating hypertension in old age across countries and see if those differences can be explained by country-specific cardiovascular disease burden and life expectancy. Show less
