Publications by authors named "Simon P Mooijaart"

162 Publications

Association Between Blood Pressure Variability With Dementia and Cognitive Impairment: A Systematic Review and Meta-Analysis.

Hypertension 2021 Sep 20:HYPERTENSIONAHA12117797. Epub 2021 Sep 20.

Adelaide Medical School, Freemasons Centre for Male Health and Wellbeing, The University of Adelaide, Australia. (E.J.L.L., M.O., A.D.V., P.J.T.).

Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derived parameter (ie, variability or mean) holds more significance in understanding vascular contributions to cognitive impairment. We searched PubMed, Embase, PsycINFO, and Scopus and performed a meta-analysis of studies that quantified the association between resting BPV with dementia or cognitive impairment in adults. Two authors independently reviewed all titles, abstracts, and full-texts and extracted data, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Study quality was assessed using the (modified) Newcastle-Ottawa Scale. A multilevel meta-analysis was used, which included effect sizes for both BPV and mean BP, with a combined end point of dementia or cognitive impairment as primary outcome. In the primary analysis, 54 effect sizes were extracted from 20 studies, with a total analytical sample of n=7 899 697. Higher systolic BPV (odds ratio [OR], 1.25 [95% CI, 1.16-1.35]), mean systolic pressure (OR, 1.12 [95% CI, 1.02-1.29]), diastolic BPV (OR, 1.20 [95% CI, 1.12-1.29]), and mean diastolic pressure (OR, 1.16 [95% CI, 1.04-1.29]) were associated with dementia and cognitive impairment. A direct comparison showed that mean BP effect sizes were less strong than BPV effect sizes (OR, 0.92 [95% CI, 0.87-0.97], <0.01), indicating that the relative contribution of BPV exceeded that of mean BP. Methodological and statistical heterogeneity was high. Secondary analyses were less consistent as to whether BPV and mean BP were differentially associated with dementia subtypes and cognitive domains. Future studies are required to investigate BPV as a target for dementia prevention.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17797DOI Listing
September 2021

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

JAMA Intern Med 2021 Sep 7. Epub 2021 Sep 7.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.

Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

Design, Setting, And Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.

Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values.

Main Outcomes And Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated.

Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia.

Conclusions And Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
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http://dx.doi.org/10.1001/jamainternmed.2021.5078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424529PMC
September 2021

Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors.

Cancers (Basel) 2021 Jun 5;13(11). Epub 2021 Jun 5.

Department of Medical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of "real-world" older patients with metastatic melanoma and to identify predictors of outcome.

Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models.

Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65-75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity.

Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.
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http://dx.doi.org/10.3390/cancers13112826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201158PMC
June 2021

Functional Performance After Complex Endovascular Aortic Repair: A Single-Center Retrospective Cohort Study.

J Endovasc Ther 2021 Jun 30:15266028211028222. Epub 2021 Jun 30.

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: Complex endovascular aortic repair (EVAR) procedures provide a treatment option for patients with aortic aneurysms involving visceral branches. Good technical results and short-term outcomes have been reported. Whether complex EVAR provides acceptable outcomes is not clear. The current study aims to describe postoperative functional outcomes in complex EVAR patients-an older and relatively frail patient group.

Materials And Methods: A single-center retrospective cohort study was performed, using data from a computerized database of consecutive patients who underwent complex EVAR in the Leiden University Medical Center (LUMC, The Netherlands) between July 2013 and September 2020. As of May 2017, patients scheduled for complex EVAR were referred to a geriatric care pathway to determine (Instrumental) Activities of Daily Living ((I)ADL) scores at baseline and, if informed consent was given, after 12 months. For the total patient group, adverse functional performance outcomes were: discharge to a nursing home and 12-month mortality. For the patients included in geriatric follow-up, the additional outcome was the incidence of functional decline (defined by a ≥2 point increase in (I)ADL-score) at 12-month follow-up.

Results: Eighty-two patients underwent complex EVAR, of which 68 (82.9%) were male. Mean age was 73.3 years (SD=6.3). Within 30 days postsurgery, 6 patients (7.3%) died. Mortality within 12 months for the total patient group was 14.6% (n=12). After surgery, no patients had to be discharged to a nursing home. Fifteen patients (18.3%) were discharged to a rehabilitation center. Twenty-three patients gave informed consent and were included in geriatric follow-up. Five patients (21.7%) presented functional decline 12 months postsurgery and 4 patients had died (17.4%) by that time. This means that 39.1% of the patients in the care pathway suffered an adverse outcome.

Conclusion: To our knowledge, this is the only study that examined functional performance after complex EVAR, using a prospectively maintained database. No patients were newly discharged to a nursing home and functional performance results at 12 months are promising. Future multidisciplinary research should focus on determining which patients are most prone to deterioration of function, so that efforts can be directed toward preventing postoperative functional decline.
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http://dx.doi.org/10.1177/15266028211028222DOI Listing
June 2021

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

Clin Gastroenterol Hepatol 2021 Jun 19. Epub 2021 Jun 19.

Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, the Netherlands.

Background & Aims: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life).

Methods: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2-3 moderate deficits and 4-5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score >2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed.

Results: Somatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284-3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936-5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life.

Conclusion: Deficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.
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http://dx.doi.org/10.1016/j.cgh.2021.06.015DOI Listing
June 2021

Differential insulin sensitivity of NMR-based metabolomic measures in a two-step hyperinsulinemic euglycemic clamp study.

Metabolomics 2021 06 9;17(6):57. Epub 2021 Jun 9.

Section of Gerontology and Geriatrics; Department of Internal Medicine, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands.

Background: Insulin is the key regulator of glucose metabolism, but it is difficult to dissect direct insulin from glucose-induced effects. We aimed to investigate the effects of hyperinsulemia on metabolomic measures under euglycemic conditions in nondiabetic participants.

Methods: We assessed concentrations of 151 metabolomic measures throughout a two-step hyperinsulinemic euglycemic clamp procedure. We included 24 participants (50% women, mean age = 62 [s.d. = 4.2] years) and metabolomic measures were assessed under baseline, low-dose (10 mU/m/min) and high-dose (40 mU/m/min) insulin conditions. The effects of low- and high-dose insulin infusion on metabolomic measures were analyzed using linear mixed-effect models for repeated measures.

Results: After low-dose insulin infusion, 90 metabolomic measures changed in concentration (p < 1.34e), among which glycerol (beta [Confidence Interval] =  - 1.41 [- 1.54, - 1.27] s.d., p = 1.28e) and three-hydroxybutyrate (- 1.22 [- 1.36, - 1.07] s.d., p = 1.44e) showed largest effect sizes. After high-dose insulin infusion, 121 metabolomic measures changed in concentration, among which branched-chain amino acids showed the largest additional decrease compared with low-dose insulin infusion (e.g., Leucine, - 1.78 [- 1.88, - 1.69] s.d., P = 2.7e). More specifically, after low- and high-dose insulin infusion, the distribution of the lipoproteins shifted towards more LDL-sized particles with decreased mean diameters.

Conclusion: Metabolomic measures are differentially insulin sensitive and may thus be differentially affected by the development of insulin resistance. Moreover, our data suggests insulin directly affects metabolomic measures previously associated with increased cardiovascular disease risk.
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http://dx.doi.org/10.1007/s11306-021-01806-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190027PMC
June 2021

Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials.

Front Endocrinol (Lausanne) 2021 20;12:674841. Epub 2021 May 20.

Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.

Background: The cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).

Objective: To determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.

Methods: Combined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.

Results: The median [IQR] age was 75.0 [69.7-81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (p<0.001), at a median dose of 50 μg. Levothyroxine did not significantly change the risk of any of the prespecified cardiovascular outcomes, including cardiovascular events (HR 0.74 [0.41-1.25]), atrial fibrillation (HR 0.69 [0.32-1.52]), or heart failure (0.41 [0.13-1.35]), or all-cause mortality (HR 1.28 [0.54-3.03]), irrespective of history of CVD and age.

Conclusion: Treatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.

Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT01660126] (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+).
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http://dx.doi.org/10.3389/fendo.2021.674841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173189PMC
May 2021

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

Age Ageing 2021 05;50(3):631-640

Department of Internal Medicine, Haga Teaching Hospital, The Hague, the Netherlands.

Background: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting.

Objective: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands.

Methods: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality.

Results: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)).

Conclusions: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.
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http://dx.doi.org/10.1093/ageing/afab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929372PMC
May 2021

Genetically Determined Higher TSH Is Associated With a Lower Risk of Diabetes Mellitus in Individuals With Low BMI.

J Clin Endocrinol Metab 2021 Jun;106(7):e2502-e2511

Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2300RC Leiden, the Netherlands.

Context: Thyroid status is hypothesized to be causally related with the risk of diabetes mellitus (DM), but previous results were conflicting possibly because of a complex interaction between thyrotropin (TSH), body mass index (BMI) and DM.

Objective: This work aims to investigate the causal association between thyroid status with DM and glucose homeostasis and to what extent this association is dependent on BMI.

Methods: A mendelian randomization study was conducted of European-ancestry participants from the UK Biobank population. The present study involved 408 895 individuals (mean age 57.4 years [SD 8.0], 45.9% men), of whom 19 773 had DM. Genetic variants for circulatory TSH, free thyroxine (fT4) concentrations and BMI to calculate weighted genetic risk scores. The main outcome measures included self-reported DM-stratified analyses by BMI. Analyses were repeated for nonfasting glucose and glycated hemoglobin A1c (HbA1c) among individuals without DM.

Results: Genetically determined TSH and fT4 levels were not associated with risk of DM in the total UK Biobank population. However, in analyses stratified on genetically determined BMI, genetically determined higher TSH, and not fT4, was associated with a lower risk for DM only in the low BMI group (odds ratio 0.91; 95% CI, 0.85-0.98 in low BMI; P value for interaction = .06). Similar results were observed for glucose and HbA1c among individuals without DM.

Conclusion: TSH, but not fT4, is a potential causal risk factor for DM in individuals with genetically determined low BMI highlighting potential protective effects of TSH only in low-risk populations.
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http://dx.doi.org/10.1210/clinem/dgab277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208661PMC
June 2021

A narrative review of frailty assessment in older patients at the emergency department.

Eur J Emerg Med 2021 Aug;28(4):266-276

Department of Internal Medicine and Geriatrics, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.

Optimizing emergency care for the aging population is an important future challenge, as the proportion of older patients at the emergency department (ED) rapidly increases. Older patients, particularly those who are frail, have a high risk of adverse outcomes after an ED visit, such as functional decline, institutionalization, and death. The ED can have a key position in identifying frail older patients who benefit most from comprehensive geriatric care [including delirium preventive measures, early evaluation of after-discharge care, and a comprehensive geriatric assessment (CGA)]. However, performing extensive frailty assessment is not suitable at the ED. Therefore, quick and easy-to-use instruments are needed to identify older patients at risk for adverse outcomes. This narrative review outlines the importance and complexity of frailty assessment at the ED. It aligns the available screening instruments, including clinical judgment as frailty assessment, and summarizes arguments for and against frailty assessment at the ED.
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http://dx.doi.org/10.1097/MEJ.0000000000000811DOI Listing
August 2021

Emergency department management of older people living with frailty: a guide for emergency practitioners.

Emerg Med J 2021 Sep 21;38(9):724-729. Epub 2021 Apr 21.

Department of Health Sciences, University of Leicester, Leicester, UK.

Emergency Departments (EDs) are increasingly seeing more seriously unwell older people living with frailty. In the context of limited resources and increasing demand it's the ED practitioner's challenge to unpick this constellation of physical, psychological, functional and social issues.To properly assess older people living with frailty at the ED it is crucial to use an holistic approach. This consists of triage with algorithms sensitive to the higher risk of older people living with frailty, a frailty assessment, and an assessment with the help of the principles of Comprehensive Geriatric Assessment. Multi-disciplinary care, a tailor-made treatment plan, based on what the person values most, will help the ED practitioner to deliver appropriate and valuable care during the ED stay, but also in transition from hospital to home.
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http://dx.doi.org/10.1136/emermed-2020-210014DOI Listing
September 2021

Design of a consensus-based geriatric assessment tailored for older chronic kidney disease patients: results of a pragmatic approach.

Eur Geriatr Med 2021 Oct 19;12(5):931-942. Epub 2021 Apr 19.

Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: 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.
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http://dx.doi.org/10.1007/s41999-021-00498-0DOI Listing
October 2021

Experiences with and attitudes towards geriatric screening among older emergency department patients: a qualitative study.

BMC Geriatr 2021 03 20;21(1):198. Epub 2021 Mar 20.

Department of Internal Medicine, section Geriatrics, Leiden University Medical Center, PO Box 9600, 2300, RC, Leiden, The Netherlands.

Background: The 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.

Methods: This was a qualitative study using individual face-to-face semi-structured interviews. Interviews were conducted in older patients (≥70 years) 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.

Results: After 13 interviews (7 women, median age 82 years), 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.

Conclusions: Older 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.
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http://dx.doi.org/10.1186/s12877-021-02144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981953PMC
March 2021

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses.

BMC Med 2021 03 18;19(1):69. Epub 2021 Mar 18.

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.

Methods: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.

Results: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.

Conclusions: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
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http://dx.doi.org/10.1186/s12916-021-01939-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971964PMC
March 2021

Improving the care for older emergency department patients: the Acutely Presenting Older Patient study.

Z Gerontol Geriatr 2021 03 10;54(2):97-98. Epub 2021 Mar 10.

Leids Universitair Medisch Centrum, Gebouw 1, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

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http://dx.doi.org/10.1007/s00391-021-01856-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945600PMC
March 2021

Geriatric screening, fall characteristics and 3- and 12 months adverse outcomes in older patients visiting the emergency department with a fall.

Scand J Trauma Resusc Emerg Med 2021 Mar 4;29(1):43. Epub 2021 Mar 4.

Department of Emergency Medicine, Leiden University Medical Center, Leiden, The Netherlands.

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 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.
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http://dx.doi.org/10.1186/s13049-021-00859-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934471PMC
March 2021

Association between Clinical Frailty Scale score and hospital mortality in adult patients with COVID-19 (COMET): an international, multicentre, retrospective, observational cohort study.

Lancet Healthy Longev 2021 Mar 9;2(3):e163-e170. Epub 2021 Feb 9.

Department of Geriatrics, Amphia Hospital, Breda, Netherlands.

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe.

Methods: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS), mildly frail (CFS), or frail (CFS). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities).

Findings: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55-77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS CFS odds ratio [OR] 2·71 [95% CI 2·04-3·60], p<0·0001 and CFS CFS OR 1·54 [1·16-2·06], p=0·0030; age ≥65 years: CFS CFS OR 2·90 [2·12-3·97], p<0·0001 and CFS CFS OR 1·64 [1·20-2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS CFS OR 2·22 [1·08-4·57], p=0·030; CFS CFS OR 1·08 [0·48-2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS CFS OR 1·54 [1·21-1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS CFS OR 0·71 [0·55-0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS CFS OR 2·96 [1·98-4·43], p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS CFS OR 0·93 [0·63-1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS CFS OR 1·27 [0·92-1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS CFS OR 0·66 [0·47-0·93], p=0·018).

Interpretation: The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution.

Funding: LOEY Foundation.
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http://dx.doi.org/10.1016/S2666-7568(21)00006-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906710PMC
March 2021

Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism: An Ancillary Study of a Randomized Clinical Trial.

JAMA Netw Open 2021 02 1;4(2):e2036645. Epub 2021 Feb 1.

Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.

Importance: Previous trials on the effect of levothyroxine on depressive symptom scores in patients with subclinical hypothyroidism were limited by small sample sizes (N = 57 to 94) and potential biases.

Objective: To assess the effect of levothyroxine on the development of depressive symptoms in older adults with subclinical hypothyroidism in the largest trial on this subject and to update a previous meta-analysis including the results from this study.

Design, Setting, And Participants: This predefined ancillary study analyzed data from participants in the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism (TRUST) trial, a double-blind, randomized, placebo-controlled, parallel-group clinical trial conducted from April 2013 to October 31, 2016. The TRUST trial included adults aged 65 years or older diagnosed with subclinical hypothyroidism, defined as the presence of persistently elevated thyroid-stimulating hormone (TSH) levels (4.6-19.9 mIU/L) with free thyroxine (T4) within the reference range. Participants were identified from clinical and general practitioner laboratory databases and recruited from the community in Switzerland, the Netherlands, Ireland, and the UK. This ancillary study included a subgroup of 472 participants from the Netherlands and Switzerland; after exclusions, a total of 427 participants (211 randomized to levothyroxine and 216 to placebo) were analyzed. This analysis was conducted from December 1, 2019, to September 1, 2020.

Interventions: Randomization to either levothyroxine or placebo.

Main Outcomes And Measures: Depressive symptom scores after 12 months measured with the Geriatric Depression Scale (GDS-15), with higher scores indicating more depressive symptoms (minimal clinically important difference = 2).

Results: A total of 427 participants with subclinical hypothyroidism (mean [SD] age, 74.52 [6.29] years; 239 women [56%]) were included in this analysis. The mean (SD) TSH level was 6.57 (2.22) mIU/L at baseline and decreased after 12 months to 3.83 (2.29) mIU/L in the levothyroxine group; in the placebo group, it decreased from 6.55 (2.04) mIU/L to 5.91 (2.66) mIU/L. At baseline, the mean (SD) GDS-15 score was 1.26 (1.85) in the levothyroxine group and 0.96 (1.58) in the placebo group. The mean (SD) GDS-15 score at 12 months was 1.39 (2.13) in the levothyroxine and 1.07 (1.67) in the placebo group with an adjusted between-group difference of 0.15 for levothyroxine vs placebo (95% CI, -0.15 to 0.46; P = .33). In a subgroup analysis including participants with a GDS-15 of at least 2, the adjusted between-group difference was 0.61 (95% CI, -0.32 to 1.53; P = .20). Results did not differ according to age, sex, or TSH levels. A previous meta-analysis (N = 278) on the association of levothyroxine with depressive symptoms was updated to include these findings, resulting in an overall standardized mean difference of 0.09 (95% CI, -0.05 to 0.22).

Conclusions And Relevance: This ancillary study of a randomized clinical trial found that depressive symptoms did not differ after levothyroxine therapy compared with placebo after 12 months; thus, these results do not provide evidence in favor of levothyroxine therapy in older persons with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Trial Registration: ClinicalTrials.gov Identifier: NCT01853579.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.36645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876592PMC
February 2021

Predicting disease-related and patient-reported outcomes in older patients with breast cancer - a systematic review.

J Geriatr Oncol 2021 06 30;12(5):696-704. Epub 2021 Jan 30.

Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.

The number of older patients with breast cancer has increased due to the aging of the general population. The use of a geriatric assessment in this population has been advocated in many studies and guidelines as it can be used to identify high risk populations for early mortality and toxicity. Additionally, geriatric parameters could predict relevant outcome measures. This systematic review summarizes all available evidence on predictive factors for various outcomes (disease-related and survival, toxicity, and patient-reported outcomes), with a special focus on geriatric parameters and patient-reported outcomes, in older patients with breast cancer. Studies were identified through systematic review of the literature published up to September 1st 2019 in the PubMed database and EMBASe. A total of 173 studies were included. Most studies investigated disease-related and survival outcomes (n = 123, 71%). Toxicity was investigated in 40 studies (23%) and a mere 15% (n = 26) investigated patient-reported outcomes. Various measures that can be derived from a geriatric assessment were predictive for survival endpoints. Furthermore, geriatric parameters were among the most frequently found predictors for toxicity and patient-reported outcomes. In conclusion, this study shows that geriatric parameters can predict survival, toxicity, and patient-reported outcomes in older patients with breast cancer. These findings can be used in daily clinical practice to identify patients at risk of early mortality, high risk of treatment toxicity or poor functional outcome after treatment. A minority of studies used relevant outcome measures for older patients, showing the need for studies that are tailored to the older population.
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http://dx.doi.org/10.1016/j.jgo.2021.01.008DOI Listing
June 2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Hum Mol Genet 2021 04;30(5):393-409

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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http://dx.doi.org/10.1093/hmg/ddab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112PMC
April 2021

DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA): rationale and design.

BMC Nephrol 2021 01 23;22(1):39. Epub 2021 Jan 23.

Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

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 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.

Methods: The 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 ≥70 years with an eGFR of 10-15 mL/min/1.73m are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10 mL/min/1.73m 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.

Discussion: By 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 Registration: The study was registered in the Netherlands Trial Register ( NL-8352 ) on 5 February 2020.
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http://dx.doi.org/10.1186/s12882-021-02235-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825220PMC
January 2021

Implementation of the acutely presenting older patient (APOP) screening program in routine emergency department care : A before-after study.

Z Gerontol Geriatr 2021 Mar 20;54(2):113-121. Epub 2021 Jan 20.

Department of Internal Medicine, section Geriatrics, Leiden University Medical Center, 9600, 2300 RC, Leiden, The Netherlands.

Objective: The aim of this study was to evaluate the effects of implementation of the acutely presenting older patient (APOP) screening program for older patients in routine emergency department (ED) care shortly after implementation.

Methods: We conducted an implementation study with before-after design, using the plan-do-study-act (PDSA) model for quality improvement, in the ED of a Dutch academic hospital. All consecutive patients ≥ 70 years during 2 months before and after implementation were included. The APOP program comprises screening for risk of functional decline, mortality and cognitive impairment, targeted interventions for high-risk patients and education of professionals. Outcome measures were compliance with interventions and impact on ED process, length of stay (LOS) and hospital admission rate.

Results: Two comparable groups of patients (median age 77 years) were included before (n = 920) and after (n = 953) implementation. After implementation 560 (59%) patients were screened of which 190 (34%) were high-risk patients. Some of the program interventions for high-risk patients in the ED were adhered to, some were not. More hospitalized patients received comprehensive geriatric assessment (CGA) after implementation (21% before vs. 31% after; p = 0.002). In 89% of high-risk patients who were discharged to home, telephone follow-up was initiated. Implementation did not influence median ED LOS (202 min before vs. 196 min after; p = 0.152) or hospital admission rate (40% before vs. 39% after; p = 0.410).

Conclusion: Implementation of the APOP screening program in routine ED care did not negatively impact the ED process and resulted in an increase of CGA and telephone follow-up in older patients. Future studies should investigate whether sustainable changes in management and patient outcomes occur after more PDSA cycles.
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http://dx.doi.org/10.1007/s00391-020-01837-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946672PMC
March 2021

Design and rationale of a routine clinical care pathway and prospective cohort study in older patients needing intensive treatment.

BMC Geriatr 2021 01 7;21(1):29. Epub 2021 Jan 7.

Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands.

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 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 NL8107 . Date of registration: 22-10-2019.
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http://dx.doi.org/10.1186/s12877-020-01975-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791733PMC
January 2021

Perspectives and experiences of patients and healthcare professionals with geriatric assessment in chronic kidney disease: a qualitative study.

BMC Nephrol 2021 01 6;22(1). Epub 2021 Jan 6.

Department of Internal Medicine (Nephrology), Leiden University Medical Centre, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.

Background: Older patients with end-stage kidney disease (ESKD) often live with unidentified frailty and multimorbidity. Despite guideline recommendations, geriatric assessment is not part of standard clinical care, resulting in a missed opportunity to enhance (clinical) outcomes including quality of life in these patients. To develop routine geriatric assessment programs for patients approaching ESKD, it is crucial to understand patients' and professionals' experiences with and perspectives about the benefits, facilitators and barriers for geriatric assessment.

Methods: In this qualitative study, semi-structured focus group discussions were conducted with ESKD patients, caregivers and professionals. Participants were purposively sampled from three Dutch hospital-based study- and routine care initiatives involving geriatric assessment for (pre-)ESKD care. Transcripts were analysed inductively using thematic analysis.

Results: In six focus-groups, participants (n = 47) demonstrated four major themes: (1) Perceived characteristics of the older (pre)ESKD patient group. Patients and professionals recognized increased vulnerability and (cognitive) comorbidity, which is often unrelated to calendar age. Both believed that often patients are in need of additional support in various geriatric domains. (2) Experiences with geriatric assessment. Patients regarded the content and the time spent on the geriatric assessment predominantly positive. Professionals emphasized that assessment creates awareness among the whole treatment team for cognitive and social problems, shifting the focus from mainly somatic to multidimensional problems. Outcomes of geriatric assessment were observed to enhance a dialogue on suitability of treatment options, (re)adjust treatment and provide/seek additional (social) support. (3) Barriers and facilitators for implementation of geriatric assessment in routine care. Discussed barriers included lack of communication about goals and interpretation of geriatric assessment, burden for patients, illiteracy, and organizational aspects. Major facilitators are good multidisciplinary cooperation, involvement of geriatrics and multidisciplinary team meetings. (4) Desired characteristics of a suitable geriatric assessment concerned the scope and use of tests and timing of assessment.

Conclusions: Patients and professionals were positive about using geriatric assessment in routine nephrology care. Implementation seems achievable, once barriers are overcome and facilitators are endorsed. Geriatric assessment in routine care appears promising to improve (clinical) outcomes in patients approaching ESKD.
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http://dx.doi.org/10.1186/s12882-020-02206-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789317PMC
January 2021

A European Research Agenda for Geriatric Emergency Medicine: a modified Delphi study.

Eur Geriatr Med 2021 Apr 21;12(2):413-422. Epub 2020 Nov 21.

Emergency Department, Warrington and Halton Hospitals NHS Teaching Trust, Warrington, England, UK.

Purpose: Geriatric Emergency Medicine (GEM) focuses on delivering optimal care to (sub)acutely ill older people. This involves a multidisciplinary approach throughout the whole healthcare chain. However, the underpinning evidence base is weak and it is unclear which research questions have the highest priority. The aim of this study was to provide an inventory and prioritisation of research questions among GEM professionals throughout Europe.

Methods: A two-stage modified Delphi approach was used. In stage 1, an online survey was administered to various professionals working in GEM both in the Emergency Department (ED) and other healthcare settings throughout Europe to make an inventory of potential research questions. In the processing phase, research questions were screened, categorised, and validated by an expert panel. Subsequently, in stage 2, remaining research questions were ranked based on relevance using a second online survey administered to the same target population, to identify the top 10 prioritised research questions.

Results: In response to the first survey, 145 respondents submitted 233 potential research questions. A total of 61 research questions were included in the second stage, which was completed by 176 respondents. The question with the highest priority was: Is implementation of elements of CGA (comprehensive geriatric assessment), such as screening for frailty and geriatric interventions, effective in improving outcomes for older patients in the ED?

Conclusion: This study presents a top 10 of high-priority research questions for a European Research Agenda for Geriatric Emergency Medicine. The list of research questions may serve as guidance for researchers, policymakers and funding bodies in prioritising future research projects.
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http://dx.doi.org/10.1007/s41999-020-00426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990812PMC
April 2021

Metabolic Age Based on the BBMRI-NL H-NMR Metabolomics Repository as Biomarker of Age-related Disease.

Circ Genom Precis Med 2020 10 14;13(5):541-547. Epub 2020 Aug 14.

Department of Internal Medicine, Maastricht University Medical Center, the Netherlands (C.D.A.S., C.J.H.v.d.K., M.M.J.v.G.).

Background: The blood metabolome incorporates cues from the environment and the host's genetic background, potentially offering a holistic view of an individual's health status.

Methods: We have compiled a vast resource of proton nuclear magnetic resonance metabolomics and phenotypic data encompassing over 25 000 samples derived from 26 community and hospital-based cohorts.

Results: Using this resource, we constructed a metabolomics-based age predictor (metaboAge) to calculate an individual's biological age. Exploration in independent cohorts demonstrates that being judged older by one's metabolome, as compared with one's chronological age, confers an increased risk on future cardiovascular disease, mortality, and functionality in older individuals. A web-based tool for calculating metaboAge (metaboage.researchlumc.nl) allows easy incorporation in other epidemiological studies. Access to data can be requested at bbmri.nl/samples-images-data.

Conclusions: In summary, we present a vast resource of metabolomics data and illustrate its merit by constructing a metabolomics-based score for biological age that captures aspects of current and future cardiometabolic health.
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http://dx.doi.org/10.1161/CIRCGEN.119.002610DOI Listing
October 2020

Outcomes of Thyroid Dysfunction in People Aged Eighty Years and Older: An Individual Patient Data Meta-Analysis of Four Prospective Studies (Towards Understanding Longitudinal International Older People Studies Consortium).

Thyroid 2021 04 2;31(4):552-562. Epub 2020 Nov 2.

Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.

Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older. Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality. Of the total 2116 participants at baseline (mean age 87 years, range 80-109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6-1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7-1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8-1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4-5.9]). Results did not differ after excluding participants using thyroid-influencing medication. In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance.
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http://dx.doi.org/10.1089/thy.2020.0567DOI Listing
April 2021

Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial.

J Gerontol A Biol Sci Med Sci 2020 09;75(9):e89-e94

Institute of Primary Health Care (BIHAM), University of Bern, Switzerland.

Background: Fatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.

Method: This study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60-19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose.

Results: Among 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI -1.8 to 2.1; p = .88), or mental fatigability (-1.0; 95% CI -2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI -3.6 to 2.8, p = .79) and -2.2 (95% CI -8.8 to 4.5, p = .51).

Conclusions: Levothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability.
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http://dx.doi.org/10.1093/gerona/glaa123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494024PMC
September 2020

Health-related quality of life and symptoms of conservative care versus dialysis in patients with end-stage kidney disease: a systematic review.

Nephrol Dial Transplant 2021 07;36(8):1418-1433

Department of Internal Medicine, St Antonius Hospital, Nieuwegein, the Netherlands.

Background: Non-dialytic conservative care (CC) has been proposed as a viable alternative to maintenance dialysis for selected older patients to treat end-stage kidney disease (ESKD). This systematic review compares both treatment pathways on health-related quality of life (HRQoL) and symptoms, which are major outcomes for patients and clinicians when deciding on preferred treatment.

Methods: We searched PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus and PsycINFO from inception to 1 October 2019 for studies comparing patient-reported HRQoL outcomes or symptoms between patients who chose either CC or dialysis for ESKD.

Results: Eleven observational cohort studies were identified comprising 1718 patients overall. There were no randomized controlled trials. Studies were susceptible to selection bias and confounding. In most studies, patients who chose CC were older and had more comorbidities and worse functional status than patients who chose dialysis. Results were broadly consistent across studies, despite considerable clinical and methodological heterogeneity. Patient-reported physical health outcomes and symptoms appeared to be worse in patients who chose CC compared with patients who chose dialysis but had not yet started, but similar compared with patients on dialysis. Mental health outcomes were similar between patients who chose CC or dialysis, including before and after dialysis start. In patients who chose dialysis, the burden of kidney disease and impact on daily life increased after dialysis start.

Conclusions: The available data, while heterogeneous, suggest that in selected older patients, CC has the potential to achieve similar HRQoL and symptoms compared with a dialysis pathway. High-quality prospective studies are needed to confirm these provisional findings.
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http://dx.doi.org/10.1093/ndt/gfaa078DOI Listing
July 2021
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