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1. Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool

Author

Goedegebuur, J., Abbel, D., Accassat, S., Achterberg, W.P., Akbari, A., Arfuch, V.M., Baddeley, E., Bax, J.J., Becker, D., Bergmeijer, B., Bertoletti, L., Blom, J.W., Calvetti, A., Cannegieter, S.C., Castro, L., Chavannes, N.H., Coma-Auli, N., Couffignal, C., Edwards, A., Edwards, M., Enggaard, H., Font, C., Gava, A., Geersing, G.J., Geijteman, E.C.T., Greenley, S., Gregory, C., Gussekloo, J., Hoffmann, I., Højen, A.A., van den Hout, W.B., Huisman, M.V., Jacobsen, S., Jagosh, J., Johnson, M.J., Jørgensen, L., Juffermans, C.C.M., Kempers, E.K., Konstantinides, S., Kroder, A.F., Kruip, M.J.H.A., Lafaie, L., Langendoen, J.W., Larsen, T.B., Lifford, K., van der Linden, Y.M., Mahé, I., Maiorana, L., Maraveyas, A., Martens, E.S.L., Mayeur, D., van Mens, T.E., Mohr, K., Mooijaart, S.P., Murtagh, F.E.M., Nelson, A., Nielsen, P.B., Ording, A.G., Ørskov, M., Pearson, M., Poenou, G., Portielje, J.E.A., Raczkiewicz, D., Rasmussen, K., Trinks-Roerdink, E., Schippers, I., Seddon, K., Sexton, K., Sivell, S., Skjøth, F., Søgaard, M., Szmit, S., Trompet, S., Vassal, P., Visser, C., van Vliet, L.M., Wilson, E., Klok, F.A., and Noble, S.I.R.

Published
2023
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4. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

Author

Segna, D, Bauer, DC, Feller, M, Schneider, C, Fink, HA, Aubert, CE, Collet, T‐H, Costa, BR, Fischer, K, Peeters, RP, Cappola, AR, Blum, MR, Dorland, HA, Robbins, J, Naylor, K, Eastell, R, Uitterlinden, AG, Ramirez, F Rivadeneira, Gogakos, A, Gussekloo, J, Williams, GR, Schwartz, A, Cauley, JA, Aujesky, DA, Bischoff‐Ferrari, HA, Rodondi, N, and Collaboration, the Thyroid Studies

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Clinical Research, Osteoporosis, Musculoskeletal, Aged, Asymptomatic Diseases, Bone Density, Female, Fractures, Bone, Humans, Hyperthyroidism, Hypothyroidism, Male, Risk Factors, bone density, bone loss, hyperthyroidism, hypothyroidism, prospective studies, thyroid disease, Thyroid Studies Collaboration, Cardiovascular System & Hematology, Clinical sciences
Abstract

BackgroundSubclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear.ObjectiveTo investigate the association between subclinical thyroid dysfunction and bone loss.MethodsIndividual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach.ResultsAmongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site.ConclusionAmongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Published
2018

8. A study protocol of external validation of eight COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting.

Author

Zahra, A., Luijken, K., Abbink, E.J., Berg, J.Merlijn van den, Blom, M.T., Elders, P., Festen, J., Gussekloo, J., Joling, K.J., Melis, R.J.F., Mooijaart, S., Peters, J., Polinder-Bos, H.A., Raaij, B.F.M. van, Smorenberg, A., Roi-Teeuw, H.M. la, Moons, K.G., Smeden, M. van, Zahra, A., Luijken, K., Abbink, E.J., Berg, J.Merlijn van den, Blom, M.T., Elders, P., Festen, J., Gussekloo, J., Joling, K.J., Melis, R.J.F., Mooijaart, S., Peters, J., Polinder-Bos, H.A., Raaij, B.F.M. van, Smorenberg, A., Roi-Teeuw, H.M. la, Moons, K.G., and Smeden, M. van

Abstract

Item does not contain fulltext, BACKGROUND: The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. METHODS: Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. DISCUSSION: Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older

Published
2023

9. The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis

Author

Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., Chaker, L., Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., and Chaker, L.

Abstract

Contains fulltext : 297328.pdf (Publisher’s version ) (Closed access), BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT(4) based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT(4), and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT(4), thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 co

Published
2023

10. Towards optimal use of antithrombotic therapy of people with cancer at the end of life:A research protocol for the development and implementation of the SERENITY shared decision support tool

Author

Goedegebuur, J., Abbel, D., Accassat, S., Achterberg, W. P., Akbari, A., Arfuch, V. M., Baddeley, E., Bax, J. J., Becker, D., Bergmeijer, B., Bertoletti, L., Blom, J. W., Calvetti, A., Cannegieter, S. C., Castro, L., Chavannes, N. H., Coma-Auli, N., Couffignal, C., Edwards, A., Edwards, M., Enggaard, H., Font, C., Gava, A., Geersing, G. J., Geijteman, E. C.T., Greenley, S., Gregory, C., Gussekloo, J., Hoffmann, I., Højen, A. A., van den Hout, W. B., Huisman, M. V., Jacobsen, S., Jagosh, J., Johnson, M. J., Jørgensen, L., Juffermans, C. C.M., Kempers, E. K., Konstantinides, S., Kroder, A. F., Kruip, M. J.H.A., Lafaie, L., Langendoen, J. W., Larsen, T. B., Lifford, K., van der Linden, Y. M., Mahé, I., Maiorana, L., Maraveyas, A., Martens, E. S.L., Mayeur, D., van Mens, T. E., Mohr, K., Mooijaart, S. P., Murtagh, F. E.M., Nelson, A., Nielsen, P. B., Ording, A. G., Ørskov, M., Pearson, M., Poenou, G., Portielje, J. E.A., Raczkiewicz, D., Rasmussen, K., Trinks-Roerdink, E., Schippers, I., Seddon, K., Sexton, K., Sivell, S., Skjøth, F., Søgaard, M., Szmit, S., Trompet, S., Vassal, P., Visser, C., van Vliet, L. M., Wilson, E., Klok, F. A., Noble, S. I.R., Goedegebuur, J., Abbel, D., Accassat, S., Achterberg, W. P., Akbari, A., Arfuch, V. M., Baddeley, E., Bax, J. J., Becker, D., Bergmeijer, B., Bertoletti, L., Blom, J. W., Calvetti, A., Cannegieter, S. C., Castro, L., Chavannes, N. H., Coma-Auli, N., Couffignal, C., Edwards, A., Edwards, M., Enggaard, H., Font, C., Gava, A., Geersing, G. J., Geijteman, E. C.T., Greenley, S., Gregory, C., Gussekloo, J., Hoffmann, I., Højen, A. A., van den Hout, W. B., Huisman, M. V., Jacobsen, S., Jagosh, J., Johnson, M. J., Jørgensen, L., Juffermans, C. C.M., Kempers, E. K., Konstantinides, S., Kroder, A. F., Kruip, M. J.H.A., Lafaie, L., Langendoen, J. W., Larsen, T. B., Lifford, K., van der Linden, Y. M., Mahé, I., Maiorana, L., Maraveyas, A., Martens, E. S.L., Mayeur, D., van Mens, T. E., Mohr, K., Mooijaart, S. P., Murtagh, F. E.M., Nelson, A., Nielsen, P. B., Ording, A. G., Ørskov, M., Pearson, M., Poenou, G., Portielje, J. E.A., Raczkiewicz, D., Rasmussen, K., Trinks-Roerdink, E., Schippers, I., Seddon, K., Sexton, K., Sivell, S., Skjøth, F., Søgaard, M., Szmit, S., Trompet, S., Vassal, P., Visser, C., van Vliet, L. M., Wilson, E., Klok, F. A., and Noble, S. I.R.

Abstract

Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. Methods: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. Results: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. Conclusions: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Published
2023

12. Vascular disease and apathy symptoms in the very old: A cross-sectional and longitudinal meta-analysis of individual participant data

Author

Klei, V.M.G.T.H. van der, Poortvliet, R.K.E., Bogaerts, J.M.K., Blom, J.W., Mooijaart, S.P., Teh, R., Muru-Lanning, M., Palapar, L., Kingston, A., Robinson, L., Kerse, N., and Gussekloo, J.

Subjects
Aged, 80 and over, Psychiatric Status Rating Scales, vascular apathy, Depression, Apathy, prospective, Stroke, meta-analysis, older people, Psychiatry and Mental health, Cross-Sectional Studies, Ischemic Attack, Transient, Humans, Prospective Studies, Geriatrics and Gerontology, atherosclerosis, Aged
Abstract

Objectives: Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between vascular disease and the presence and development of apathy symptoms in the very old.Methods: Four cohorts of the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium were included in a two-staged, individual participant data meta-analysis using generalized linear mixed models, Vascular disease was defined as a history of any clinical atherosclerotic pathology (angina pectoris, myocardial infarction, intermittent claudication, transient ischemic attack, stroke or related surgeries) and was related to apathy symptoms as repeatedly measured by the Geriatric Depression Scale (GDS-3A >= 2) over a maximum of 5 years.Results: Of all 1868 participants (median age 85 years old), 53.9% had vascular disease and 44.3% experienced apathy symptoms. Participants with vascular disease had a 76% higher risk of apathy symptoms at baseline (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32-2.35), irrespective of depressive symptoms and only partially explained by stroke. Conversely, there was no association of vascular disease with the occurrence of apathy symptoms longitudinally, both in those with apathy at baseline (OR 1.00, 95% CI 0.84-1.20) and without (OR 0.96, 95% CI 0.841.09).Conclusions: Vascular disease in the very old is associated with apathy symptoms cross-sectionally, but not proven longitudinally, independent of depressive symptoms. These findings query a vascular cause underlying apathy symptoms. However, the consistency of our cross-sectional findings in direction and magnitude across the TULIPS-consortium do emphasize international relevance of the interplay of vascular factors and apathy in advanced age, which meaning needs further unravelling.

Published
2022

13. Disentangling the varying associations between systolic blood pressure and health outcomes in the very old

Author

Bogaerts, J.M.K., Poortvliet, R.K.E., Klei, V.M.G.T.H. van der, Achterberg, W.P., Blom, J.W., Teh, R., Muru-Lanning, M., Kerse, N., Rolleston, A., Jagger, C., Kingston, A., Robinson, L., Arai, Y., Shikimoto, R., Gussekloo, J., and TULIPS Consortium

Subjects
Aged, 80 and over, Male, cognition, Physiology, cardiovascular, blood pressure, body mass index, frailty, aged, Cardiovascular Diseases, Risk Factors, grip strength, Hypertension, Outcome Assessment, Health Care, Internal Medicine, Humans, Female, antihypertensive, Hypotension, Cardiology and Cardiovascular Medicine, activities of daily living, Antihypertensive Agents, older adults
Abstract

Objectives: While randomized controlled trials have proven the benefits of blood pressure (BP) lowering in participating octogenarians, population-based observational studies suggest an association between low systolic blood pressure (SBP) and faster overall decline. This study investigates the effects of BP-lowering treatment, a history of cardiovascular diseases (CVD), and cognitive and physical fitness on the associations between SBP and health outcomes in the very old. Methods: Five cohorts from the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included in a two-step individual participant data meta-analysis (IPDMA). We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality and estimates of linear mixed models for change in cognitive and functional decline. Models were stratified by BP-lowering treatment, history of CVD, Mini-Mental State Examination scores, grip strength (GS) and body mass index (BMI). Results: Of all 2480 participants (59.9% females, median 85 years), median baseline SBP was 149 mmHg, 64.3% used BP-lowering drugs and 47.3% had a history of CVD. Overall, higher SBP was associated with lower all-cause mortality (pooled HR 0.91 [95% confidence interval 0.88-0.95] per 10 mmHg). Associations remained irrespective of BP-lowering treatment, history of CVD and BMI, but were absent in octogenarians with above-median MMSE and GS. In pooled cohorts, SBP was not associated with cognitive and functional decline. Conclusion: While in the very old with low cognitive or physical fitness a higher SBP was associated with a lower all-cause mortality, this association was not evident in fit octogenarians. SBP was not consistently associated with cognitive and functional decline.

Published
2022

15. Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Author

Du Puy, R. S., Postmus, I., Stott, D. J., Blum, M. R., Poortvliet, R. K. E., Den Elzen, W. P. J., Peeters, R. P., van Munster, B. C., Wolffenbuttel, B. H. R., Westendorp, R. G. J., Kearney, P. M., Ford, I., Kean, S., Messow, C. M., Watt, T., Jukema, J. W., Dekkers, O. M., Smit, J. W. A., Rodondi, N., Gussekloo, J., and Mooijaart, S. P.

Published
2018
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16. Assessment of the appropriateness of cardiovascular preventive medication in older people: using the RAND/UCLA Appropriateness Method

Author

Ploeg, M.A. van der, Poortvliet, R.K.E., Achterberg, W.P., Mooijaart, S.P., Gussekloo, J., and Drewes, Y.M.

Subjects
Preventive medicine, Cardiovascular diseases, Life Expectancy, Geriatrics, Clinical Decision-Making, Quality of Life, Humans, Drug therapy, Health Services, Geriatrics and Gerontology, Aged
Abstract

Background In clinical practice and science, there is debate for which older adults the benefits of cardiovascular preventive medications (CPM) still outweigh the risks in older age. Therefore, we aimed to assess how various clinical characteristics influence the judgement of appropriateness of CPM in older adults. Method We assessed the appropriateness of CPM for adults ≥75 years with regard to clinical characteristics (cardiovascular variables, complexity of health problems, age, side effects and life expectancy) using the RAND/ University of California at Los Angeles Appropriateness Method. A multidisciplinary panel, including 11 medical professionals and 3 older representatives of the target population, received an up-to-date overview of the literature. Using 9-point Likert scales (1 = extremely inappropriate; 9 = extremely appropriate), they assessed the appropriateness of starting and stopping cholesterol lowering medication, antihypertensives and platelet aggregation inhibitors, for various theoretical clinical scenarios. There were two rating rounds, with one face-to-face discussion in between. The overall appropriateness judgments were based on the median panel ratings of the second round and level of disagreement. Results The panelists emphasized the importance of the individual context of the patient for appropriateness of CPM. They judged that in general, a history of atherosclerotic cardiovascular disease strongly adds to the appropriateness of CPM, while increasing complexity of health problems, presence of hindering or severe side effects, and life expectancy Conclusion Next to the patients’ individual context, which was considered decisive in the final decision to start or stop CPM, there were general trends of how clinical characteristics influenced the appropriateness, according to the multidisciplinary panel. The decision to stop, and not start CPM, appeared to be two distinct concepts. Results of this study may be used in efforts to support clinical decision making about CPM in older adults.

Published
2022

17. Incorporating Baseline Outcome Data in Individual Participant Data Meta-Analysis of Non-randomized Studies

Author

Syrogiannouli, L., Wildisen, L., Meuwese, C., Bauer, D.C., Cappola, A.R., Gussekloo, J., Elzen, W.P.J. den, Trompet, S., Westendorp, R.G.J., Jukema, J.W., Ferrucci, L., Ceresini, G., Asvold, B.O., Chaker, L., Peeters, R.P., Imaizumi, M., Ohishi, W., Vaes, B., Volzke, H., Sgarbi, J.A., Walsh, J.P., Dullaart, R.P.F., Bakker, S.J.L., Iacoviello, M., Rodondi, N., Giovane, C. del, Thyroid Studies Collaboration, Epidemiology, Internal Medicine, Laboratory for Endocrinology, APH - Personalized Medicine, APH - Aging & Later Life, Groningen Institute for Organ Transplantation (GIOT), and Groningen Kidney Center (GKC)

Subjects
baseline imbalance, cohorts, continuous outcome, individual participant data, non-randomized studies, Prevention, Clinical Sciences, 360 Soziale Probleme, Sozialdienste, 610 Medicine & health, Psychiatry and Mental health, SDG 3 - Good Health and Well-being, 360 Social problems & social services, Public Health and Health Services, Psychology, 610 Medizin und Gesundheit
Abstract

BackgroundIn non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC).MethodsFor the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA.ResultsTen of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score.ConclusionANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly.

Published
2022

18. No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials

Author

Puy, R.S. Du, Poortvliet, R.K.E., Mooijaart, S.P., Stott, D.J., Quinn, T., Sattar, N., Westendorp, R.G., Kearney, P.M., McCarthy, V.J., Byrne, S., Rodondi, N., Baretella, O., Collet, T.H., Heemst, D. van, Dekkers, O.M., Jukema, J.W., Smit, J.W.A., Gussekloo, J., Elzen, W.P.J. Den, Puy, R.S. Du, Poortvliet, R.K.E., Mooijaart, S.P., Stott, D.J., Quinn, T., Sattar, N., Westendorp, R.G., Kearney, P.M., McCarthy, V.J., Byrne, S., Rodondi, N., Baretella, O., Collet, T.H., Heemst, D. van, Dekkers, O.M., Jukema, J.W., Smit, J.W.A., Gussekloo, J., and Elzen, W.P.J. Den

Abstract

Item does not contain fulltext, CONTEXT: Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. OBJECTIVE: The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism. METHODS: This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months. RESULTS: Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ± 1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]). CONCLUSION: In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.

Published
2022

21. Declining daily functioning as a prelude to a hip fracture in older persons-an individual patient data meta-analysis

Author

Ravensbergen, W.M., Blom, J.W., Kingston, A., Robinson, L., Kerse, N., Teh, R.O., Groenwold, R.H.H., Gussekloo, J., and TULIPS Consortium

Subjects
Aged, 80 and over, Aging, function, Hip Fractures, General Medicine, ageing/5, older people, AcademicSubjects/MED00280, disability, hip fracture, Activities of Daily Living, ageing/10, Humans, ageing/11, Longitudinal Studies, Geriatrics and Gerontology, ageing/15, Research Paper, Aged, Netherlands, New Zealand
Abstract

Background Daily functioning is known to decline after a hip fracture, but studies of self-reported functioning before the fracture suggest this decline begins before the fracture. Objective Determine whether change in functioning in the year before a hip fracture in very old (80+) differs from change in those without a hip fracture. Design Two-stage individual patient data meta-analysis including data from the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium. Setting Four population-based longitudinal cohorts from the Netherlands, New Zealand and the UK. Subjects Participants aged 80+ years. Methods Participants were followed for 5 years, during which (instrumental) activities of daily living [(I)ADL] scores and incident hip fractures were registered at regular intervals. Z-scores of the last (I)ADL score and the change in (I)ADL in the year before a hip fracture were compared to the scores of controls, adjusted for age and sex. Results Of the 2,357 participants at baseline, the 161 who sustained a hip fracture during follow-up had a worse (I)ADL score before the fracture (0.40 standard deviations, 95% CI 0.19 to 0.61, P = 0.0002) and a larger decline in (I)ADL in the year before fracture (−0.11 standard deviations, 95% CI −0.22 to 0.004, P = 0.06) compared to those who did not sustain a hip fracture. Conclusions In the very old a decline in daily functioning already starts before a hip fracture. Therefore, a hip fracture is a sign of ongoing decline and what full recovery is should be seen in light of the pre-fracture decline.

Published
2022

22. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies

Author

Alwan, H., Villoz, F., Feller, M., Dullaart, R.P.F., Bakker, S.J.L., Peeters, R.P., Kavousi, M., Bauer, D.C., Cappola, A.R., Yeap, B.B., Walsh, J.P., Brown, S.J., Ceresini, G., Ferrucci, L., Gussekloo, J., Trompet, S., Iacoviello, M., Moon, J.H., Razvi, S., Bensenor, I.M., Azizi, F., Amouzegar, A., Valdes, S., Colomo, N., Wareham, N.J., Jukema, J.W., Westendorp, R.G.J., Kim, K.W., Rodondi, N., Giovane, C. del, Thyroid Studies Collaboration, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Internal Medicine, Epidemiology, Alwan, Heba [0000-0001-5516-6022], Bakker, Stephan JL [0000-0003-3356-6791], Peeters, Robin P [0000-0001-7732-9371], Yeap, Bu B [0000-0002-7612-5892], Razvi, Salman [0000-0002-9047-1556], Amouzegar, Atieh [0000-0001-9433-9408], and Apollo - University of Cambridge Repository

Subjects
Adult, Data Analysis, Male, Endocrinology, Diabetes and Metabolism, Clinical Sciences, Thyrotropin, 610 Medicine & health, Hyperthyroidism, Paediatrics and Reproductive Medicine, Cohort Studies, Endocrinology & Metabolism, Endocrinology, SDG 3 - Good Health and Well-being, Hypothyroidism, 360 Social problems & social services, Clinical Research, Diabetes Mellitus, Humans, Prospective Studies, Metabolic and endocrine, screening and diagnosis, Prevention, Diabetes, General Medicine, Middle Aged, Thyroid Diseases, Detection, Female, 4.2 Evaluation of markers and technologies
Abstract

ObjectiveFew prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes.MethodsWe performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up.ResultsAmong 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88–1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82–1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87–1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88–1.29). The results were robust in all sub-group and sensitivity analyses.ConclusionsThis is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes.Significance statementEvidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future. Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes. Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses. Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Published
2022
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23. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies

Author

Alwan H, Villoz F, Feller M, Dullaart RPF, Bakker SJL, Peeters RP, Kavousi M, Bauer DC, Cappola AR, Yeap BB, Walsh JP, Brown SJ, Ceresini G, Ferrucci L, Gussekloo J, Trompet S, Iacoviello M, Moon JH, Razvi S, Bensenor IM, Azizi F, Amouzegar A, Valdés S, Colomo N, Wareham NJ, Jukema JW, Westendorp RGJ, Kim KW, Rodondi N, Giovane CD

Published
2022
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24. Additional file 2 of Positive health during the COVID-19 pandemic: a survey among community-dwelling older individuals in the Netherlands

Author

Moens, I. S., van Gerven, L. J., Debeij, S. M., Bakker, C. H., Moester, M. J. C., Mooijaart, S. P., van der Pas, S., Vangeel, M., Gussekloo, J., Drewes, Y. M., and Elzen, W. P. J.den

Subjects
sense organs
Abstract

Additional file 2. Self-rated change in the six dimensions of Positive Health compared to the year before the COVID-19 pandemic in older individuals living in the Netherlands (n=834).

Published
2022
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25. Additional file 3 of Positive health during the COVID-19 pandemic: a survey among community-dwelling older individuals in the Netherlands

Author

Moens, I. S., van Gerven, L. J., Debeij, S. M., Bakker, C. H., Moester, M. J. C., Mooijaart, S. P., van der Pas, S., Vangeel, M., Gussekloo, J., Drewes, Y. M., and Elzen, W. P. J.den

Abstract

Additional file 3. Self-rated change (%), compared to before the COVID-19 pandemic, in the six dimensions of Positive Health of older individuals living in the Netherlands depending on sex, age, living situation and self-rated general health (n=834). * = statistically significant.

Published
2022
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27. Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism:A pooled analysis of two randomized controlled trials

Author

Lyko, C., Blum, M.R., Abolhassani, N., Stuber, M.J., Giovane, C. del, Feller, M., Moutzouri, E., Oberle, J., Jungo, K.T., Collet, T.H., Elzen, W.P.J. den, Poortvliet, R.K.E., Puy, R.S. du, Dekkers, O.M., Trompet, S., Jukema, J.W., Aujesky, D., Quinn, T., Westendorp, R., Kearney, P.M., Gussekloo, J., Heemst, D. van, Mooijaart, S.P., Bauer, D.C., Rodondi, N., Laboratory for Endocrinology, Laboratory for General Clinical Chemistry, APH - Personalized Medicine, and APH - Aging & Later Life

Subjects
Male, SYMPTOMS, Hormone Replacement Therapy, Clinical Trials and Supportive Activities, Clinical Sciences, 610 Medicine & health, DISEASE, Hypothyroidism, Clinical Research, 360 Social problems & social services, QUALITY-OF-LIFE, Internal Medicine, Humans, autoimmune thyroid disease, levothyroxine treatment, subclinical hypothyroidism, Aged, Randomized Controlled Trials as Topic, THYROTROPIN, CARDIOVASCULAR RISK, L-THYROXINE, Evaluation of treatments and therapeutic interventions, ASSOCIATION, COMMUNITY, Thyroxine, Good Health and Well Being, Cardiovascular System & Hematology, PEROXIDASE ANTIBODIES, 6.1 Pharmaceuticals, Female, HEALTH
Abstract

BACKGROUND Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

Published
2022

35. Cognitive Impairment and Survival in Very Elderly People

Author

Forester, Pete, Heckford, Emma, Huckler, Claire, Keong, Nicole, Al-Khabaz, Ahmed, Rozzini, Renzo, Franzoni, Simone, Frisoni, Giovanni B., Trabucchi, Marco, Gussekloo, J., Remarque, E. J., Lagaay, A. M., Knook, D. L., Westendorp, R. G. J., and Heeren, T. J.

Published
1998

36. Anaemia and physical and mental health in the very old: An individual participant data meta-analysis of four longitudinal studies of ageing

Author

Palapar, L., Kerse, N., Rolleston, A., Elzen, W.P.J. den, Gussekloo, J., Blom, J.W., Robinson, L., Martin-Ruiz, C., Duncan, R., Arai, Y., Takayama, M., Teh, R., and TULIP Consortium

Subjects
Aging, Activities of daily living, Anemia, Anaemia, 03 medical and health sciences, 0302 clinical medicine, 030502 gerontology, 80 and over, Humans, Medicine, Longitudinal Studies, 030212 general & internal medicine, Functional ability, Depression (differential diagnoses), Aged, Aged, 80 and over, business.industry, Depression, Cognition, General Medicine, medicine.disease, Mental health, Mental Health, Meta-analysis, Cohort, Cognitive function, Geriatrics and Gerontology, 0305 other medical science, business, Demography
Abstract

Objective To determine the physical and mental health of very old people (aged 80+) with anaemia. Methods Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ Māori, LiLACS NZ non-Māori, Leiden 85-plus Study, Newcastle 85+ Study, and TOOTH. Mixed models of change in functional ability, cognitive function, depressive symptoms, and self-rated health over time were separately fitted for each cohort. We combined individual cohort estimates of differences according to the presence of anaemia at baseline, adjusting for age at entry, sex, and time elapsed. Combined estimates are presented as differences in standard deviation units (i.e. standardised mean differences–SMDs). Results The combined prevalence of anaemia was 30.2%. Throughout follow-up, participants with anaemia, on average, had: worse functional ability (SMD −0.42 of a standard deviation across cohorts; CI -0.59,-0.25); worse cognitive scores (SMD -0.27; CI -0.39,-0.15); worse depression scores (SMD -0.20; CI -0.31,-0.08); and lower ratings of their own health (SMD -0.36; CI -0.47,-0.25). Differential rates of change observed were: larger declines in functional ability for those with anaemia (SMD −0.12 over five years; CI -0.21,-0.03) and smaller mean difference in depression scores over time between those with and without anaemia (SMD 0.18 over five years; CI 0.05,0.30). Conclusion Anaemia in the very old is a common condition associated with worse functional ability, cognitive function, depressive symptoms, and self-rated health, and a more rapid decline in functional ability over time. The question remains as to whether anaemia itself contributes to worse outcomes or is simply a marker of chronic diseases and nutrient deficiencies.

Published
2021

38. Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults

Author

Chen, S, Pawelec, G, Trompet, S, Goldeck, D, Mortensen, LH, Slagboom, PE, Christensen, K, Gussekloo, J, Kearney, P, Buckley, BM, Ford, I, Jukema, JW, Westendorp, RGJ, Maier, AB, Chen, S, Pawelec, G, Trompet, S, Goldeck, D, Mortensen, LH, Slagboom, PE, Christensen, K, Gussekloo, J, Kearney, P, Buckley, BM, Ford, I, Jukema, JW, Westendorp, RGJ, and Maier, AB

Abstract

BACKGROUND: Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts. METHODS: Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders. RESULTS: CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses. CONCLUSIONS: CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.

Published
2021

40. The Bidirectional Relationship between Vision and Cognition: A Systematic Review and Meta-Analysis

Author

Vu, T.A., Fenwick, E.K., Gan, A.T.L., Man, R.E.K., Tan, B.K.J., Gupta, P., Ho, K.C., Reyes-Ortiz, C.A., Trompet, S., Gussekloo, J., O'Brien, J.M., Mueller-Schotte, S., Wong, T.Y., Tham, Y.C., Cheng, C.Y., Lee, A.T.C., Rait, G., Swenor, B.K., Varadaraj, V., Brenowitz, W.D., Medeiros, F.A., Nael, V., Narasimhalu, K., Chen, C.L.H., Lamoureux, E.L., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Visual acuity, Bidirectional, Vision Disorders, Neuropsychological Tests, Visual impairment, Global Health, Cognition, Cognitive impairment, Risk Factors, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cognitive Dysfunction, Dementia, Public Health, Morbidity
Abstract

TOPIC: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. While the bidirectional association of VI and CIM has been hypothesized, findings have been equivocal. Hence, we conduct a systematic review and meta-analysis to examine the bidirectional relationship between VI and CIM. CLINICAL RELEVANCE: 60% risk of CIM has not been well-elucidated in the literature. A bidirectional relationship between CIM and VI may provide opportunities for developing public health strategies for early detection and management of risk factors for both VI and CIM in older people. METHODS: Pubmed, Embase and Cochrane Central registers were systematically searched for observational studies, published from inception until 6 April 2020, in adults aged ? 40 years reporting objectively measured VI, and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests, and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (OR), and 95% confidence interval (CI). Publication bias and heterogeneity were examined using Egger's test, meta-regression, and trim-and-fill methods. RESULTS: Forty studies were included (N=47,913,570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds [OR (95%CI)] of: (i) any CIM [cross-sectional: 2.38 (1.84-3.07); longitudinal: 1.66 (1.46-1.89)], and (ii) clinically diagnosed dementia [(cross-sectional: 2.43 (1.48-4.01); longitudinal: 2.09 (1.37-3.21)], compared to persons without VI. Significant heterogeneity was partially explained by differences in age, sex and follow-up duration. There was also some evidence that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most papers (8/9, 89%) reporting significantly positive associations, however meta-analyses on this association could not be conducted due to insufficient data. CONCLUSIONS: Overall, our work suggests that VI is a risk factor of CIM while further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both visual and cognitive impairment in older people may minimize individual clinical and public health consequences.

Published
2020

41. An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms

Author

Wildisen, L., Giovane, C. del, Moutzouri, E., Beglinger, S., Syrogiannouli, L., Collet, T.H., Cappola, A.R., Asvold, B.O., Bakker, S.J.L., Yeap, B.B., Almeida, O.P., Ceresini, G., Dullaart, R.P.F., Ferrucci, L., Grabe, H., Jukema, J.W., Nauck, M., Trompet, S., Volzke, H., Westendorp, R., Gussekloo, J., Kloppel, S., Aujesky, D., Bauer, D., Peeters, R., Feller, M., Rodondi, N., Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), and Internal Medicine

Subjects
Male, Quality of life, endocrine system, endocrine system diseases, Thyroid Gland, lcsh:Medicine, 610 Medicine & health, Thyroid Function Tests, Severity of Illness Index, Article, DISEASE, Endocrinology, Medical research, DESIGN, STAGE, Clinical Research, OSTEOPOROTIC FRACTURES, 360 Social problems & social services, Behavioral and Social Science, BASE-LINE CHARACTERISTICS, Humans, Psychology, lcsh:Science, METAANALYSIS, Public health, Depression, lcsh:R, MEN, Thyroid Diseases, Brain Disorders, Mental Health, HYPOTHYROIDISM, RISK-FACTORS, lcsh:Q, Female, HEALTH, Hormonal therapies
Abstract

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I 2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I 2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Published
2020

44. Temporal Dynamics of Depressive Symptoms and Cognitive Decline in the Oldest Old: Dynamic Time Warp analysis of the Leiden 85-plus Study.

Author

van der Slot, A. J., Bertens, A. S., Trompet, S., Mooijaart, S. P., Gussekloo, J., van den Bos, F., and Giltay, E. J.

Subjects
GERIATRIC Depression Scale, COGNITION disorders, COGNITIVE aging, MEDICAL personnel, MENTAL depression
Abstract

Introduction: The prevalence of depressive symptoms and cognitive decline increases with age, reducing quality of life. However, the temporal relationship between the two remains elusive. Objectives: We aimed to explore the temporal relationship between depressive symptoms and cognitive decline in individuals aged 85 years, during up to 5 years follow-up. Methods: Participants eligible for this study were selected from the Leiden 85-plus Study, who participated for at least 3 follow-up measurements. Depressive symptoms were assessed at baseline and at follow-up in a period of 6 yearly assessments, utilizing the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests including the Mini Mental State Exam (MMSE), Stroop Test, Letter Digit Coding Test, and immediate and delayed recall using the 12-word learning test. Dynamic Time Warping (DTW) analysis was employed to model their temporal dynamics, in undirected and directed analysis, to ascertain whether depressive symptoms precede cognitive decline, or vice versa. Results: The study included a total of 325 (54.2%) of 599 patients, of whom 68.0% were female, 45.0% with intermediate to higher education, and all aged 85 years. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the parameters of cognitive decline in the oldest old. Of the 15 GDS symptoms, those with the strongest outstrength were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all p<.01). Conclusions: We found a strong temporal link between depressive symptoms and subsequent cognitive decline in a population of the oldest old. This highlights the importance of a holistic approach that considers both mental and cognitive well-being in the aging population. As depressive symptoms were an early indicator of cognitive decline, it is of importance that healthcare professionals recognize and address depressive symptoms early to allow for appropriate interventions and support, to potentially mitigate the impact on cognitive decline. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Published
2024
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47. What do older adults with multimorbidity and polypharmacy think about deprescribing? The LESS study - a primary care-based survey

Author

Rozsnyai, Z., Jungo, K.T., Reeve, E., Poortvliet, R.K.E., Rodondi, N., Gussekloo, J., and Streit, S.

Subjects
Male, Primary Health Care, Multimorbidity, 610 Medicine & health, lcsh:Geriatrics, lcsh:RC952-954.6, Deprescriptions, Deprescribing, 360 Social problems & social services, Older adults, Surveys and Questionnaires, Polypharmacy, Patient attitudes, Humans, Female, General practice, Research Article, Aged
Abstract

Background Multimorbidity and polypharmacy are very common in older adults in primary care. Ideally, general practitioners (GPs), should regularly review medication lists to identify inappropriate medication(s) and, where appropriate, deprescribe. However, it remains challenging to deprescribe given time constraints and few recommendations from guidelines. Further, patient related barriers and enablers to deprescribing have to be accounted for. The aim of this study was to identify barriers and enablers to deprescribing as reported by older adults with polypharmacy and multimorbidity. Methods We conducted a survey among participants aged ≥70 years, with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 chronic medications). We invited Swiss GPs, to recruit eligible patients who then completed a paper-based survey on demographics, medications and chronic conditions. We used the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire and added twelve additional Likert scale questions and two open-ended questions to assess barriers and enablers towards deprescribing, which we coded and categorized into meaningful themes. Result Sixty four Swiss GPs consented to recruit 5–6 patients each and returned 300 participant responses. Participants were 79.1 years (SD 5.7), 47% female, 34% lived alone, and 86% managed their medications themselves. Sixty-seven percent of participants took 5–9 regular medicines and 24% took ≥10 medicines. The majority of participants (77%) were willing to deprescribe one or more of their medicines if their doctor said it was possible. There was no association with sex, age or the number of medicines and willingness to deprescribe. After adjustment for baseline characteristics, there was a strong positive association between willingness to deprescribe and saying that because they have a good relationship with their GP, they would feel that deprescribing was safe OR 11.3 (95% CI: 4.64–27.3) and agreeing that they would be willing to deprescribe if new studies showed an avoidable risk OR 8.0 (95% CI 3.79–16.9). From the open questions, the most mentioned barriers towards deprescribing were patients feeling well on their current medicines and being convinced that they need all their medicines. Conclusions Most older adults with polypharmacy are willing to deprescribe. GPs may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-020-01843-x.

Published
2020

48. Managing hypertension in frail oldest-old—The role of guideline use by general practitioners from 29 countries

Author

Roulet, C., Rozsnyai, Z., Jungo, K.T., Ploeg, M.A. van der, Floriani, C., Kurpas, D., Vinker, S., Pestic, S.K., Petrazzuoli, F., Hoffmann, K., Viegas, R.P.A., Mallen, C., Tatsioni, A., Maisonneuve, H., Collins, C., Lingner, H., Tsopra, R., Mueller, Y., Poortvliet, R.K.E., Gussekloo, J., Streit, S., University of Bern, Leiden University Medical Center (LUMC), Wrocław Medical University, Tel Aviv University [Tel Aviv], University of Tuzla, Lund University [Lund], Medizinische Universität Wien = Medical University of Vienna, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Keele University [Keele], University of Ioannina, Université de Genève = University of Geneva (UNIGE), Irish College of General Practitioners [Dublin, Irlande] (ICGP), Hannover Medical School [Hannover] (MHH), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Leiden University, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Bodescot, Myriam, University of Wrocław [Poland] (UWr), Tel Aviv University (TAU), Univerzitet u Tuzli [Tuzla, Bosnie-Herzégovine], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Prof. Streit’s research was supported by grants (P2BEP3_165353) from the Swiss National Science Foundation (SNF) and the Gottfried and Julia Bangerter-Rhyner Foundation, Switzerland. Christian Mallen is funded by the NIHR Collaborations for Leadership in Applied Health Research and Care West Midlands, the NIHR SPCR and a NIHR Research Professorship in General Practice, (NIHR-RP-2014-04-026)., University of Geneva [Switzerland], Sciences de l’information au service de la médecine personnalisée = Information Sciences to support Personalized Medicine [CRC], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Lausanne (UNIL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)

Subjects
Medical Doctors, Health Care Providers, [SDV]Life Sciences [q-bio], Blood Pressure, Cardiovascular Medicine, Vascular Medicine, MESH: Hypertension, Geographical Locations, MESH: Aged, 80 and over, MESH: Practice Guidelines as Topic, RA0421, Medicine and Health Sciences, Medical Personnel, Aged, 80 and over, MESH: Aged, Frailty, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Agricultural and Biological Sciences(all), [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MESH: Clinical Decision-Making, Drugs, MESH: Blood Pressure, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: General Practitioners, Europe, Professions, Cardiovascular Diseases, Hypertension, Practice Guidelines as Topic, Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Research Article, Frail Elderly, Science, Clinical Decision-Making, education, 610 Medicine & health, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, General Practitioners, 360 Social problems & social services, Physicians, Humans, General, Aged, Pharmacology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Treatment Guidelines, Health Care Policy, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Frail Elderly, R1, Health Care, Geriatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RA, Antihypertensives
Abstract

BackgroundThe best management of hypertension in frail oldest-old (≥80 years of age) remains unclear and we still lack guidelines that provide specific recommendations. Our study aims to investigate guideline use in general practitioners (GPs) and to examine if guideline use relates to different decisions when managing hypertension in frail oldest-old.Design/settingCross-sectional study among currently active GPs from 29 countries using a case-vignettes survey.MethodsGPs participated in a survey with case-vignettes of frail oldest-olds varying in systolic blood pressure (SBP) levels and cardiovascular disease (CVD). GPs from 26 European countries and from Brazil, Israel and New Zealand were invited. We compared the percentage of GPs reporting using guidelines per country and further stratified on the most frequently mentioned guidelines. To adjust for patient characteristics (SBP, CVD and GPs' sex, years of experience, prevalence of oldest-old and location of their practice), we used a mixed-effects regression model accounting for clustering within countries.ResultsOverall, 2,543 GPs from 29 countries were included. 59.4% of them reported to use guidelines. Higher guideline use was found in female (p = 0.031) and less-experienced GPs (pConclusionMany GPs reported using guidelines to manage hypertension in frail oldest-old patients, however guideline users did not decide differently from non-users concerning hypertension treatment decisions. Instead of focusing on the fact if GPs use guidelines or not, we as a scientific community should put an emphasis on what guidelines suggest in frail and oldest-old patients.

Published
2020

49. The APOP screener and clinical outcomes in older hospitalised internal medicine patients

Author

Blomaard, L.C., Lucke, J.A., Gelder, J. de, Anten, S., Alsma, J., Schuit, S.C.E., Gussekloo, J., Groot, B. de, Mooijaart, S.P., and Internal Medicine

Subjects
Aged, 80 and over, Male, Frailty, risk stratification, Length of Stay, Risk Assessment, Severity of Illness Index, geriatric emergency medicine, Hospitalization, older people, internal medicine, Treatment Outcome, Humans, Female, Emergency Service, Hospital, Geriatric Assessment, Aged, Netherlands
Abstract

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 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.

Published
2020

50. Potentially inappropriate medication and attitudes of older adults towards deprescribing

Author

Achterhof, A.B., Rozsnyai, Z., Reeve, E., Jungo, K.T., Floriani, C., Poortvliet, R.K.E., Rodondi, N., Gussekloo, J., and Streit, S.

Subjects
Male, Questionnaires, Patients, Epidemiology, Health Care Providers, Science, Social Sciences, 610 Medicine & health, Comorbidity, Research and Analysis Methods, Deprescriptions, Elderly, Adverse Reactions, Psychological Attitudes, 360 Social problems & social services, Physicians, hemic and lymphatic diseases, Medicine and Health Sciences, Humans, Psychology, Adults, Medical Personnel, Potentially Inappropriate Medication List, Aged, Aged, 80 and over, Pharmacology, Survey Research, Biology and Life Sciences, Patient Acceptance of Health Care, Health Care, Professions, Cross-Sectional Studies, Geriatrics, Age Groups, Research Design, Medical Risk Factors, People and Places, Polypharmacy, Medicine, Female, Population Groupings, Self Report, Attitude to Health, Research Article
Abstract

IntroductionMultimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to assess patients' attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe.MethodWe analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness.ResultsData from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81).ConclusionThe willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients' awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice.

Published
2020
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