Jacobijn Gussekloo | Leiden University (original) (raw)

Papers by Jacobijn Gussekloo

Research paper thumbnail of Relationship of Patient Volume and Service Concentration With Outcome in Geriatric Rehabilitation

Journal of the American Medical Directors Association, 2013

Geriatric rehabilitation postacute care length of stay discharge destination a b s t r a c t Obje... more Geriatric rehabilitation postacute care length of stay discharge destination a b s t r a c t Objective: Although geriatric rehabilitation (GR) is beneficial for restoration of activities and participation after hospitalization of vulnerable older persons, little is known about the optimal organization of care of these postacute facilities. This study examines the relationship of patient volume and service concentration with successful GR (short length of stay and discharge home) in skilled nursing facilities (SNFs). Design: A national multicenter retrospective cohort study. Setting and participants: All patients indicated for GR in a Dutch SNF. Measurements: Nurses filled out digital registration forms from patient records. Patients were studied in 3 predefined diagnostic groups: total joint replacement, traumatic injuries, and stroke. Facility characteristics were obtained by structured telephone interviews with facility managers. Volume was based on the number of discharges in a 3-month period and categorized in low-, medium-, and high-volume facilities. Concentration was defined at the organizational level in which the population consists of 80% or more of 1 or 2 diagnostic groups, with the prerequisite of having a minimum of 10 rehabilitation beds. Results: From 88 facilities, 2269 GR patients (mean age 78.2 years [SD 9.7]; 68.2% female) were included. The median length of stay in the SNF was 45 days (interquartile range 23e81), 57% of the patients were discharged home, and 9.8% died during GR. Of patients with total joint replacement (n ¼ 501), concentration was related to successful rehabilitation (odds ratio 5.7; 95% confidence interval 1.3e24.3; P ¼ .020, adjusted for age and gender); this relationship was not found for patients with traumatic injuries or stroke. Volume showed no relation with successful rehabilitation in any of the 3 diagnostic groups.

Research paper thumbnail of Assessment of Appropriateness of Screening Community-Dwelling Older People to Prevent Functional Decline

Journal of the American Geriatrics Society, 2012

OBJECTIVES: To identify appropriate screening conditions, stratified according to age and vulnera... more OBJECTIVES: To identify appropriate screening conditions, stratified according to age and vulnerability, to prevent functional decline in older people. DESIGN: A RAND/University of California at Los Angeles appropriateness method. SETTING: The Netherlands. PARTICIPANTS: A multidisciplinary panel of 11 experts. MEASUREMENTS: The panelists assessed the appropriateness of screening for 29 conditions mentioned in guidelines from four countries, stratified according to age (60-74, 75-84, 85) and health status (general, vital, and vulnerable) and received a literature overview for each condition, including the guidelines and up-to-date literature. After an individual rating round, panelists discussed disagreements and performed a second individual rating. The median of the second ratings defined the appropriateness of screening. RESULTS: The panel rated screening to be appropriate in three of the 29 conditions, indicating that screening was expected to prevent functional decline. Screening for insuf-ficient physical activity was considered appropriate for all three age and health groups. Screening for cardiovascular risk factors and smoking was considered appropriate for the general and vital population aged 60 to 74. Of the 261 ratings, 63 (24%) were classified as uncertain, of which 42 (67%) concerned the vulnerable population. The panelists considered conditions inappropriate mainly because of lack of an adequate screening tool or lack of evidence of effective interventions for positive screened persons. CONCLUSION: The expert panel considered screening older people to prevent functional decline appropriate for insufficient physical activity and smoking and cardiovascular risk in specific groups. For other conditions, sufficient evidence does not support screening. Based on their experience, panelists expected benefit from developing tests and interventions, especially for vulnerable older people. J Am Geriatr Soc 2011. * Ranked according to appropriateness and alphabetically.

Research paper thumbnail of Sensory impairment and cognitive functioning in oldest-old subjects: the Leiden 85+ Study

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2005

Because studies on the association of sensory impairment (both hearing and visual impairment) and... more Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study. Within this population-based study of 459 participants aged 85+ years, hearing impairment was measured by audiometry and visual impairment by a visual acuity chart, both under standardized conditions. The Mini-Mental State Exam (MMSE) assessed global cognitive functioning. In participants with MMSE scores >18, the authors further assessed memory (Word-Learning Test, Immediate and Delayed Recall) and cognitive speed (by Stroop Test, Letter-Digit Coding test). Both hearing impairment (prevalence: 85%) and visual impairment (prevalence: 59%) were associated with lower scores on the MMSE. Increasing visual impairment was associated with poorer scores on memory and cognitive speed, as measured with visually presented cognitive tests. In contrast, there w...

Research paper thumbnail of Routine-ECG’s bij oudste ouderen

Huisarts en Wetenschap, 2009

De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. Routine-ECG's bij oudst... more De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. Routine-ECG's bij oudste ouderen. De toegevoegde waarde voor cardiovasculair risicomanagement. Huisarts Wet 2009;52(7):318-23. Doel Wij onderzochten of het routinematig maken van ECG's bij oudste ouderen uit de algemene populatie toegevoegde waarde heeft voor cardiovasculair risicomanagement boven op de informatie die al beschikbaar is uit het medisch dossier. Methode In het kader van de Leiden 85-plus Studie, een prospectief-observationeel onderzoek met 566 deelnemers van 85 jaar (377 vrouwen, 189 mannen) uit de algemene populatie, verkregen we de cardiovasculaire voorgeschiedenis uit medische dossiers van huisartsen. We evalueerden baseline-ECG's op de aanwezigheid van een oud myocardinfarct en/of atriumfibrilleren. Tijdens vijf jaar follow-up verzamelden we totale en cardiovasculaire mortaliteits-en morbiditeitsgegevens. Resultaten Gedurende de follow-up overleden 262 van de 566 (46%) deelnemers, van wie 102 (39%) aan een cardiovasculaire aandoening. Deelnemers met een cardiovasculaire voorgeschiedenis op 85-jarige leeftijd (284/566, 50%) hadden een verhoogde cardiovasculaire mortaliteit (HR 2,7, 95%-BI 1,8-4,1) en morbiditeit (HR myocardinfarct 2,1, 95%-BI 1,3-3,6; HR CVA 2,7, 95%-BI 1, in vergelijking met deelnemers zonder cardiovasculaire voorgeschiedenis. Deelnemers met belangrijke afwijkingen op het baseline-ECG (102/566, 18%) hadden een verhoogde cardiovasculaire mortaliteit , 95%-BI 1,1-2,8), maar geen verhoogde cardiovasculaire morbiditeit in vergelijking met deelnemers zonder deze ECG-afwijkingen. Bij alle deelnemers, zowel met als Leids Universitair Medisch Centrum, afdeling Public Health en Eerstelijnsgeneeskunde (V0-P), Postbus 9600, 2300 RC Leiden: W. de Ruijter, huisarts-klinisch onderzoeker; prof.dr. W.J.J. Assendelft, afdelingshoofd; prof.dr. J. Gussekloo, hoofd sectie Wetenschappelijk Onderzoek. University of Glasgow, Royal Infirmary, Division of Cardiovascular and Medical Sciences, Section of Cardiology, Schotland: prof.dr. P.W. Macfarlane, hoogleraar elektrocardiofysiologie. Leids Universitair Medisch Centrum, afdeling Ouderengeneeskunde: prof.dr. R.G.J. Westendorp, afdelingshoofd. Correspondentie: w.de_ruijter@lumc.nl Belangenverstrengeling: niets aangegeven. Dit artikel is een vertaling van: De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. The additional value of routine electrocardiograms in cardiovascular risk management of older people. Scand J Prim Health Care 2008;26:147-153. Publicatie gebeurt met toestemming van de uitgever.

Research paper thumbnail of Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults

Swiss medical weekly, 2015

As the best management of subclinical hypothyroidism is controversial, we aimed to assess variati... more As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We...

Research paper thumbnail of Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study

Methods: The Leiden 85-plus Study is a population-based prospective follow-up study of 562 people... more Methods: The Leiden 85-plus Study is a population-based prospective follow-up study of 562 people aged 85 years. Anemia was defined according to World Health Organiza- tion criteria. We measured 3 parameters of functional status at baseline and annually thereafter for 5 years: disability in basic and instrumental activities of daily living, cognitive function and the presence of depressive symptoms. We

Research paper thumbnail of Meta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality

Contesto. I dati sull'associazione tra disfunzione sub-clinica tiroidea e malattia coronarica (CH... more Contesto. I dati sull'associazione tra disfunzione sub-clinica tiroidea e malattia coronarica (CHD) e mortalità sono discordanti. Finalità. Riassumere le eventuali evidenze del rapporto fra disfunzione sub-clinica tiroidea e CHD e mortalità. Fonti dei dati. Sono stati esaminati gli articoli da MEDLINE (dal 1950 al gennaio 2008) senza restrizioni di lingua e le voci bibliografiche degli articoli trovati. Selezione degli studi. Due recensori hanno vagliato e selezionato gli studi di coorte che hanno valutato la funzione tiroidea e quindi seguito la popolazione prospetticamente per valutare CHD o la mortalità. Estrazione dei dati. Due recensori indipendentemente hanno riassunto e valutato gli studi utilizzando schede e protocollo standardizzati. Sintesi dei dati. Dieci dei dodici studi identificati coinvolgevano coorti di popolazione che comprendevano 14.449 partecipanti. Tutti i 10 studi di coorte di popolazione hanno esaminato i rischi associati all'ipotiroidismo sub-clinico (2.134 CHD eventi e 2.822 decessi), mentre solo 5 studi hanno esaminato i rischi associati con ipertiroidismo sub-clinico (1.392 CHD eventi e 1.993 decessi). In un modello a componenti di varianza, il rischio relativo (RR) dell'ipotiroidismo sub-clinico per CHD è stato 1,20 (95% intervallo di confidenza (CI), da 0,97 a 1,49; P per eterogeneità = 0,14; I 2 = 33,4%). Le stime di rischio sono risultate inferiori quando sono stati raggruppati studi di qualità superiore (RR, da 1,02 a 1,08) e maggiori nei partecipanti di età inferiore a 65 anni (RR, 1,51 [CI, da 1,09 a 2,09] per gli studi con partecipanti di età media inferiore ai 65 anni e 1,05 [CI, da 0,90 a 1,22] negli gli studi con età media dei partecipanti superiore ai 65 anni). Il RR è stato 1,18 (IC, da 0,98 a 1,42) per la mortalità cardiovascolare e 1,12 (CI, da 0,99 a 1,26) per la mortalità totale. Per l'ipertiroidismo sub-clinico, il RR è stato 1,21 (CI, da 0,88 a 1,68) per CHD, 1,19 (CI, da 0,81 a 1,76) per la mortalità cardiovascolare e 1,12 (CI, da 0,89 a 1,42) per la mortalità totale (P per eterogeneità > 0,50; I 2 = 0% per tutti gli studi). Limiti. I singoli studi erano stati corretti per i diversi potenziali fattori di confondimento, e uno studio forniva solo i dati senza correzione. Non possono essere esclusi bias di pubblicazione o schedatura selettiva dei risultati. Conclusione. L'ipotiroidismo e l'ipertiroidismo sub-clinici possono essere associati ad un modesto incremento del rischio di CHD e mortalità, con stime di rischio minori quando sono raggruppati gli studi di qualità superiore e maggiore CIs per l'ipertiroidismo sub-clinico.

Research paper thumbnail of Association Between Glycosylated Hemoglobin and Cardiovascular Events and Mortality in Older Adults without Diabetes Mellitus in the General Population: The Leiden 85-Plus Study

Journal of the American Geriatrics Society, 2015

To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular di... more To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular disease and mortality in 85-year-old individuals without diabetes mellitus from the general population. Population-based prospective follow-up study. General population. Individuals without known diabetes mellitus (N = 445, n = 291 female). HbA1c levels were categorized into three groups (<5.0% (31 mmol/mol), 5.0-5.7% (31-39 mmol/mol; reference), 5.7-6.5% (39-48 mmol/mol)). At baseline, a history of myocardial infarction (MI) was more prevalent in subjects in the highest HbA1c group (18%) than in the reference group (7%) (P = .001). Prospectively, those with the highest level of HbA1c at baseline had a risk of incident MI during the 5-year follow-up that was 3.6 (95% confidence interval = 1.5-8.3) times as great as that of the reference group. No association was found between HbA1c level and incident stroke, cardiovascular mortality, or all-cause mortality. In individuals aged 85 and ol...

Research paper thumbnail of Subclinical Thyroid Dysfunction and Fracture Risk

JAMA, 2015

Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trial... more Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Research paper thumbnail of Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

JAMA Internal Medicine, 2015

Some experts suggest that serum thyrotropin levels in the upper part of the current reference ran... more Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Research paper thumbnail of Consequences of interaction of functional, somatic, mental and social problems in community-dwelling older people

PloS one, 2015

This study explores the combination of four common health problems in older people and whether pr... more This study explores the combination of four common health problems in older people and whether problems on four domains result in an additional effect on indicators of poor health. For this purpose, a total of 2681 participants (32% male, mean age 82 years) of the Integrated Systematic Care for Older People (ISCOPE) study were screened on the presence of health problems on four domains (functional, somatic, mental, social) with the postal ISCOPE questionnaire. Extensive interview data on health indicators were obtained at baseline and at 12-months follow-up, including disability (Groningen Activities Restriction Scale, GARS), cognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (Geriatric Depression Scale-15, GDS), loneliness (loneliness scale of De Jong Gierveld), and health-related quality of life (EQ-5D). General practitioner (GP) contact time (min/year) was estimated via GP electronic medical records. Of the study population, 9% had no health problems according to the screening, 8% had problems on one domain, 27% on two, 38% on three and 18% on four domains. At baseline, the number of health domains with problems was associated with poorer scores on the GARS, the MMSE, the GDS-15, the loneliness scale, the EQ-5D and with more GP contact time (p <0.001). Problems on all four domains had an additional negative effect on these health indicators (all p interaction <0.001). At follow-up, an increased number of domains with problems was associated with an increased decline in health indicators (all p<0.001) and with an additional negative effect on GP contact time of the presence of problems on all four domains (p interaction <0.001). We conclude that combinations of functional, somatic, mental and social problems are associated with poor health indicators in community-dwelling older people. Since problems on four domains have an additional effect on health, individuals with combined functional, somatic, mental and social problems could benefit from integrated care.

Research paper thumbnail of Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

The Journal of clinical endocrinology and metabolism, Jan 9, 2015

To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Stud... more To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratif...

Research paper thumbnail of Quality of life in community-dwelling older persons with apathy

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2014

To investigate the relationship between apathy and perceived quality of life in groups both with ... more To investigate the relationship between apathy and perceived quality of life in groups both with and without depressive symptoms or cognitive impairment. We conducted a cross-sectional study comparing quality of life in older persons with and without apathy in 19 Dutch general practices. Participants were 1,118 older persons aged at least 75 years without current treatment for depression and a Mini-Mental State Examination score of at least 19. Perceived quality of life was determined using Cantril's Ladder for overall quality of life, EuroQol (EQ)-5D thermometer for subjective health quality, and De Jong-Gierveld Loneliness questionnaire for perceived loneliness. Apathy was assessed with the Apathy Scale. Of the 1,118 older persons, apathy was present in 122 (11%) of them. Overall, apathy was associated with having no work, lower level of education, presence of depressive symptoms, cognitive impairment, and decreased scores on all quality of life measures. Among the 979 (88%) o...

Research paper thumbnail of Monochloroacetic Acid Application Is an Effective Alternative to Cryotherapy for Common and Plantar Warts in Primary Care: A Randomized Controlled Trial

Journal of Investigative Dermatology, 2015

Cryotherapy and salicylic acid (SA) often fail as treatments for skin warts. We examined the effe... more Cryotherapy and salicylic acid (SA) often fail as treatments for skin warts. We examined the effectiveness of monochloroacetic acid (MCA) for patients with common or plantar warts. Consecutive patients aged 4 years and older with one or more newly diagnosed common or plantar warts were recruited in 53 Dutch general practices. We randomly allocated eligible patients to 13-week treatment protocols of office-applied MCA versus liquid nitrogen cryotherapy every 2 weeks for patients with common warts (n=188), and MCA versus cryotherapy combined with daily SA self-application for patients with plantar warts (n=227). The primary outcome was the proportion of patients whose warts were all cured at 13 weeks. In the common wart group, cure rates were 40/92 (43%, 95% confidence interval 34-54) for MCA and 50/93 (54%, 44-64) for cryotherapy (risk difference (RD) -10%, -25-4.0, P=0.16). In the plantar wart group, cure rates were 49/106 (46%, 37-56) for MCA and 45/115 (39%, 31-48) for cryotherapy combined with SA (RD 7.1, 5.9-20, P=0.29). For common warts, MCA is an effective alternative to cryotherapy to avoid pain during the treatment, although pain after the treatment is similar. For plantar warts, office-applied MCA may be preferred over cryotherapy combined with SA, on the basis of comparable effectiveness, less treatment pain, and less treatment burden.Journal of Investigative Dermatology advance online publication, 5 February 2015; doi:10.1038/jid.2015.1.

Research paper thumbnail of Biological correlates of blood pressure variability in elderly at high risk of cardiovascular disease

American journal of hypertension, 2015

Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular diseas... more Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate a...

Research paper thumbnail of Sensory impairment and cognitive functioning in oldest-old subjects: the Leiden 85+ Study

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2005

Because studies on the association of sensory impairment (both hearing and visual impairment) and... more Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study. Within this population-based study of 459 participants aged 85+ years, hearing impairment was measured by audiometry and visual impairment by a visual acuity chart, both under standardized conditions. The Mini-Mental State Exam (MMSE) assessed global cognitive functioning. In participants with MMSE scores >18, the authors further assessed memory (Word-Learning Test, Immediate and Delayed Recall) and cognitive speed (by Stroop Test, Letter-Digit Coding test). Both hearing impairment (prevalence: 85%) and visual impairment (prevalence: 59%) were associated with lower scores on the MMSE. Increasing visual impairment was associated with poorer scores on memory and cognitive speed, as measured with visually presented cognitive tests. In contrast, there w...

Research paper thumbnail of Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study

The American journal of clinical nutrition, 2005

High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are fre... more High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia. We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age. This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models. In the cross-sectional a...

Research paper thumbnail of International variation in GP treatment strategies for subclinical hypothyroidism in older adults

European Geriatric Medicine, 2013

There is limited evidence about the impact of treatment for subclinical hypothyroidism, especiall... more There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people. To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics. Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand. The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L). A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]). GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.

Research paper thumbnail of NT-proBNP, blood pressure, and cognitive decline in the oldest old: The Leiden 85-plus Study

Neurology, 2014

To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used a... more To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old. In 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years. Subjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 0.187). Subjects in the category &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;highest tertile of NT-proBNP and the lowest tertile of systolic BP&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; had a 3.7-point-lower MMSE score at baseline (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and a 0.49-point-steeper decline in MMSE score per year (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) compared with subjects in the other categories. In the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction.

Research paper thumbnail of The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good

European Thyroid Journal, 2014

Research paper thumbnail of Relationship of Patient Volume and Service Concentration With Outcome in Geriatric Rehabilitation

Journal of the American Medical Directors Association, 2013

Geriatric rehabilitation postacute care length of stay discharge destination a b s t r a c t Obje... more Geriatric rehabilitation postacute care length of stay discharge destination a b s t r a c t Objective: Although geriatric rehabilitation (GR) is beneficial for restoration of activities and participation after hospitalization of vulnerable older persons, little is known about the optimal organization of care of these postacute facilities. This study examines the relationship of patient volume and service concentration with successful GR (short length of stay and discharge home) in skilled nursing facilities (SNFs). Design: A national multicenter retrospective cohort study. Setting and participants: All patients indicated for GR in a Dutch SNF. Measurements: Nurses filled out digital registration forms from patient records. Patients were studied in 3 predefined diagnostic groups: total joint replacement, traumatic injuries, and stroke. Facility characteristics were obtained by structured telephone interviews with facility managers. Volume was based on the number of discharges in a 3-month period and categorized in low-, medium-, and high-volume facilities. Concentration was defined at the organizational level in which the population consists of 80% or more of 1 or 2 diagnostic groups, with the prerequisite of having a minimum of 10 rehabilitation beds. Results: From 88 facilities, 2269 GR patients (mean age 78.2 years [SD 9.7]; 68.2% female) were included. The median length of stay in the SNF was 45 days (interquartile range 23e81), 57% of the patients were discharged home, and 9.8% died during GR. Of patients with total joint replacement (n ¼ 501), concentration was related to successful rehabilitation (odds ratio 5.7; 95% confidence interval 1.3e24.3; P ¼ .020, adjusted for age and gender); this relationship was not found for patients with traumatic injuries or stroke. Volume showed no relation with successful rehabilitation in any of the 3 diagnostic groups.

Research paper thumbnail of Assessment of Appropriateness of Screening Community-Dwelling Older People to Prevent Functional Decline

Journal of the American Geriatrics Society, 2012

OBJECTIVES: To identify appropriate screening conditions, stratified according to age and vulnera... more OBJECTIVES: To identify appropriate screening conditions, stratified according to age and vulnerability, to prevent functional decline in older people. DESIGN: A RAND/University of California at Los Angeles appropriateness method. SETTING: The Netherlands. PARTICIPANTS: A multidisciplinary panel of 11 experts. MEASUREMENTS: The panelists assessed the appropriateness of screening for 29 conditions mentioned in guidelines from four countries, stratified according to age (60-74, 75-84, 85) and health status (general, vital, and vulnerable) and received a literature overview for each condition, including the guidelines and up-to-date literature. After an individual rating round, panelists discussed disagreements and performed a second individual rating. The median of the second ratings defined the appropriateness of screening. RESULTS: The panel rated screening to be appropriate in three of the 29 conditions, indicating that screening was expected to prevent functional decline. Screening for insuf-ficient physical activity was considered appropriate for all three age and health groups. Screening for cardiovascular risk factors and smoking was considered appropriate for the general and vital population aged 60 to 74. Of the 261 ratings, 63 (24%) were classified as uncertain, of which 42 (67%) concerned the vulnerable population. The panelists considered conditions inappropriate mainly because of lack of an adequate screening tool or lack of evidence of effective interventions for positive screened persons. CONCLUSION: The expert panel considered screening older people to prevent functional decline appropriate for insufficient physical activity and smoking and cardiovascular risk in specific groups. For other conditions, sufficient evidence does not support screening. Based on their experience, panelists expected benefit from developing tests and interventions, especially for vulnerable older people. J Am Geriatr Soc 2011. * Ranked according to appropriateness and alphabetically.

Research paper thumbnail of Sensory impairment and cognitive functioning in oldest-old subjects: the Leiden 85+ Study

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2005

Because studies on the association of sensory impairment (both hearing and visual impairment) and... more Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study. Within this population-based study of 459 participants aged 85+ years, hearing impairment was measured by audiometry and visual impairment by a visual acuity chart, both under standardized conditions. The Mini-Mental State Exam (MMSE) assessed global cognitive functioning. In participants with MMSE scores >18, the authors further assessed memory (Word-Learning Test, Immediate and Delayed Recall) and cognitive speed (by Stroop Test, Letter-Digit Coding test). Both hearing impairment (prevalence: 85%) and visual impairment (prevalence: 59%) were associated with lower scores on the MMSE. Increasing visual impairment was associated with poorer scores on memory and cognitive speed, as measured with visually presented cognitive tests. In contrast, there w...

Research paper thumbnail of Routine-ECG’s bij oudste ouderen

Huisarts en Wetenschap, 2009

De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. Routine-ECG's bij oudst... more De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. Routine-ECG's bij oudste ouderen. De toegevoegde waarde voor cardiovasculair risicomanagement. Huisarts Wet 2009;52(7):318-23. Doel Wij onderzochten of het routinematig maken van ECG's bij oudste ouderen uit de algemene populatie toegevoegde waarde heeft voor cardiovasculair risicomanagement boven op de informatie die al beschikbaar is uit het medisch dossier. Methode In het kader van de Leiden 85-plus Studie, een prospectief-observationeel onderzoek met 566 deelnemers van 85 jaar (377 vrouwen, 189 mannen) uit de algemene populatie, verkregen we de cardiovasculaire voorgeschiedenis uit medische dossiers van huisartsen. We evalueerden baseline-ECG's op de aanwezigheid van een oud myocardinfarct en/of atriumfibrilleren. Tijdens vijf jaar follow-up verzamelden we totale en cardiovasculaire mortaliteits-en morbiditeitsgegevens. Resultaten Gedurende de follow-up overleden 262 van de 566 (46%) deelnemers, van wie 102 (39%) aan een cardiovasculaire aandoening. Deelnemers met een cardiovasculaire voorgeschiedenis op 85-jarige leeftijd (284/566, 50%) hadden een verhoogde cardiovasculaire mortaliteit (HR 2,7, 95%-BI 1,8-4,1) en morbiditeit (HR myocardinfarct 2,1, 95%-BI 1,3-3,6; HR CVA 2,7, 95%-BI 1, in vergelijking met deelnemers zonder cardiovasculaire voorgeschiedenis. Deelnemers met belangrijke afwijkingen op het baseline-ECG (102/566, 18%) hadden een verhoogde cardiovasculaire mortaliteit , 95%-BI 1,1-2,8), maar geen verhoogde cardiovasculaire morbiditeit in vergelijking met deelnemers zonder deze ECG-afwijkingen. Bij alle deelnemers, zowel met als Leids Universitair Medisch Centrum, afdeling Public Health en Eerstelijnsgeneeskunde (V0-P), Postbus 9600, 2300 RC Leiden: W. de Ruijter, huisarts-klinisch onderzoeker; prof.dr. W.J.J. Assendelft, afdelingshoofd; prof.dr. J. Gussekloo, hoofd sectie Wetenschappelijk Onderzoek. University of Glasgow, Royal Infirmary, Division of Cardiovascular and Medical Sciences, Section of Cardiology, Schotland: prof.dr. P.W. Macfarlane, hoogleraar elektrocardiofysiologie. Leids Universitair Medisch Centrum, afdeling Ouderengeneeskunde: prof.dr. R.G.J. Westendorp, afdelingshoofd. Correspondentie: w.de_ruijter@lumc.nl Belangenverstrengeling: niets aangegeven. Dit artikel is een vertaling van: De Ruijter W, Assendelft WJJ, Macfarlane PW, Westendorp RGJ, Gussekloo J. The additional value of routine electrocardiograms in cardiovascular risk management of older people. Scand J Prim Health Care 2008;26:147-153. Publicatie gebeurt met toestemming van de uitgever.

Research paper thumbnail of Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults

Swiss medical weekly, 2015

As the best management of subclinical hypothyroidism is controversial, we aimed to assess variati... more As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We...

Research paper thumbnail of Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study

Methods: The Leiden 85-plus Study is a population-based prospective follow-up study of 562 people... more Methods: The Leiden 85-plus Study is a population-based prospective follow-up study of 562 people aged 85 years. Anemia was defined according to World Health Organiza- tion criteria. We measured 3 parameters of functional status at baseline and annually thereafter for 5 years: disability in basic and instrumental activities of daily living, cognitive function and the presence of depressive symptoms. We

Research paper thumbnail of Meta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality

Contesto. I dati sull'associazione tra disfunzione sub-clinica tiroidea e malattia coronarica (CH... more Contesto. I dati sull'associazione tra disfunzione sub-clinica tiroidea e malattia coronarica (CHD) e mortalità sono discordanti. Finalità. Riassumere le eventuali evidenze del rapporto fra disfunzione sub-clinica tiroidea e CHD e mortalità. Fonti dei dati. Sono stati esaminati gli articoli da MEDLINE (dal 1950 al gennaio 2008) senza restrizioni di lingua e le voci bibliografiche degli articoli trovati. Selezione degli studi. Due recensori hanno vagliato e selezionato gli studi di coorte che hanno valutato la funzione tiroidea e quindi seguito la popolazione prospetticamente per valutare CHD o la mortalità. Estrazione dei dati. Due recensori indipendentemente hanno riassunto e valutato gli studi utilizzando schede e protocollo standardizzati. Sintesi dei dati. Dieci dei dodici studi identificati coinvolgevano coorti di popolazione che comprendevano 14.449 partecipanti. Tutti i 10 studi di coorte di popolazione hanno esaminato i rischi associati all'ipotiroidismo sub-clinico (2.134 CHD eventi e 2.822 decessi), mentre solo 5 studi hanno esaminato i rischi associati con ipertiroidismo sub-clinico (1.392 CHD eventi e 1.993 decessi). In un modello a componenti di varianza, il rischio relativo (RR) dell'ipotiroidismo sub-clinico per CHD è stato 1,20 (95% intervallo di confidenza (CI), da 0,97 a 1,49; P per eterogeneità = 0,14; I 2 = 33,4%). Le stime di rischio sono risultate inferiori quando sono stati raggruppati studi di qualità superiore (RR, da 1,02 a 1,08) e maggiori nei partecipanti di età inferiore a 65 anni (RR, 1,51 [CI, da 1,09 a 2,09] per gli studi con partecipanti di età media inferiore ai 65 anni e 1,05 [CI, da 0,90 a 1,22] negli gli studi con età media dei partecipanti superiore ai 65 anni). Il RR è stato 1,18 (IC, da 0,98 a 1,42) per la mortalità cardiovascolare e 1,12 (CI, da 0,99 a 1,26) per la mortalità totale. Per l'ipertiroidismo sub-clinico, il RR è stato 1,21 (CI, da 0,88 a 1,68) per CHD, 1,19 (CI, da 0,81 a 1,76) per la mortalità cardiovascolare e 1,12 (CI, da 0,89 a 1,42) per la mortalità totale (P per eterogeneità > 0,50; I 2 = 0% per tutti gli studi). Limiti. I singoli studi erano stati corretti per i diversi potenziali fattori di confondimento, e uno studio forniva solo i dati senza correzione. Non possono essere esclusi bias di pubblicazione o schedatura selettiva dei risultati. Conclusione. L'ipotiroidismo e l'ipertiroidismo sub-clinici possono essere associati ad un modesto incremento del rischio di CHD e mortalità, con stime di rischio minori quando sono raggruppati gli studi di qualità superiore e maggiore CIs per l'ipertiroidismo sub-clinico.

Research paper thumbnail of Association Between Glycosylated Hemoglobin and Cardiovascular Events and Mortality in Older Adults without Diabetes Mellitus in the General Population: The Leiden 85-Plus Study

Journal of the American Geriatrics Society, 2015

To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular di... more To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular disease and mortality in 85-year-old individuals without diabetes mellitus from the general population. Population-based prospective follow-up study. General population. Individuals without known diabetes mellitus (N = 445, n = 291 female). HbA1c levels were categorized into three groups (<5.0% (31 mmol/mol), 5.0-5.7% (31-39 mmol/mol; reference), 5.7-6.5% (39-48 mmol/mol)). At baseline, a history of myocardial infarction (MI) was more prevalent in subjects in the highest HbA1c group (18%) than in the reference group (7%) (P = .001). Prospectively, those with the highest level of HbA1c at baseline had a risk of incident MI during the 5-year follow-up that was 3.6 (95% confidence interval = 1.5-8.3) times as great as that of the reference group. No association was found between HbA1c level and incident stroke, cardiovascular mortality, or all-cause mortality. In individuals aged 85 and ol...

Research paper thumbnail of Subclinical Thyroid Dysfunction and Fracture Risk

JAMA, 2015

Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trial... more Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Research paper thumbnail of Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

JAMA Internal Medicine, 2015

Some experts suggest that serum thyrotropin levels in the upper part of the current reference ran... more Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Research paper thumbnail of Consequences of interaction of functional, somatic, mental and social problems in community-dwelling older people

PloS one, 2015

This study explores the combination of four common health problems in older people and whether pr... more This study explores the combination of four common health problems in older people and whether problems on four domains result in an additional effect on indicators of poor health. For this purpose, a total of 2681 participants (32% male, mean age 82 years) of the Integrated Systematic Care for Older People (ISCOPE) study were screened on the presence of health problems on four domains (functional, somatic, mental, social) with the postal ISCOPE questionnaire. Extensive interview data on health indicators were obtained at baseline and at 12-months follow-up, including disability (Groningen Activities Restriction Scale, GARS), cognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (Geriatric Depression Scale-15, GDS), loneliness (loneliness scale of De Jong Gierveld), and health-related quality of life (EQ-5D). General practitioner (GP) contact time (min/year) was estimated via GP electronic medical records. Of the study population, 9% had no health problems according to the screening, 8% had problems on one domain, 27% on two, 38% on three and 18% on four domains. At baseline, the number of health domains with problems was associated with poorer scores on the GARS, the MMSE, the GDS-15, the loneliness scale, the EQ-5D and with more GP contact time (p <0.001). Problems on all four domains had an additional negative effect on these health indicators (all p interaction <0.001). At follow-up, an increased number of domains with problems was associated with an increased decline in health indicators (all p<0.001) and with an additional negative effect on GP contact time of the presence of problems on all four domains (p interaction <0.001). We conclude that combinations of functional, somatic, mental and social problems are associated with poor health indicators in community-dwelling older people. Since problems on four domains have an additional effect on health, individuals with combined functional, somatic, mental and social problems could benefit from integrated care.

Research paper thumbnail of Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

The Journal of clinical endocrinology and metabolism, Jan 9, 2015

To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Stud... more To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratif...

Research paper thumbnail of Quality of life in community-dwelling older persons with apathy

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2014

To investigate the relationship between apathy and perceived quality of life in groups both with ... more To investigate the relationship between apathy and perceived quality of life in groups both with and without depressive symptoms or cognitive impairment. We conducted a cross-sectional study comparing quality of life in older persons with and without apathy in 19 Dutch general practices. Participants were 1,118 older persons aged at least 75 years without current treatment for depression and a Mini-Mental State Examination score of at least 19. Perceived quality of life was determined using Cantril's Ladder for overall quality of life, EuroQol (EQ)-5D thermometer for subjective health quality, and De Jong-Gierveld Loneliness questionnaire for perceived loneliness. Apathy was assessed with the Apathy Scale. Of the 1,118 older persons, apathy was present in 122 (11%) of them. Overall, apathy was associated with having no work, lower level of education, presence of depressive symptoms, cognitive impairment, and decreased scores on all quality of life measures. Among the 979 (88%) o...

Research paper thumbnail of Monochloroacetic Acid Application Is an Effective Alternative to Cryotherapy for Common and Plantar Warts in Primary Care: A Randomized Controlled Trial

Journal of Investigative Dermatology, 2015

Cryotherapy and salicylic acid (SA) often fail as treatments for skin warts. We examined the effe... more Cryotherapy and salicylic acid (SA) often fail as treatments for skin warts. We examined the effectiveness of monochloroacetic acid (MCA) for patients with common or plantar warts. Consecutive patients aged 4 years and older with one or more newly diagnosed common or plantar warts were recruited in 53 Dutch general practices. We randomly allocated eligible patients to 13-week treatment protocols of office-applied MCA versus liquid nitrogen cryotherapy every 2 weeks for patients with common warts (n=188), and MCA versus cryotherapy combined with daily SA self-application for patients with plantar warts (n=227). The primary outcome was the proportion of patients whose warts were all cured at 13 weeks. In the common wart group, cure rates were 40/92 (43%, 95% confidence interval 34-54) for MCA and 50/93 (54%, 44-64) for cryotherapy (risk difference (RD) -10%, -25-4.0, P=0.16). In the plantar wart group, cure rates were 49/106 (46%, 37-56) for MCA and 45/115 (39%, 31-48) for cryotherapy combined with SA (RD 7.1, 5.9-20, P=0.29). For common warts, MCA is an effective alternative to cryotherapy to avoid pain during the treatment, although pain after the treatment is similar. For plantar warts, office-applied MCA may be preferred over cryotherapy combined with SA, on the basis of comparable effectiveness, less treatment pain, and less treatment burden.Journal of Investigative Dermatology advance online publication, 5 February 2015; doi:10.1038/jid.2015.1.

Research paper thumbnail of Biological correlates of blood pressure variability in elderly at high risk of cardiovascular disease

American journal of hypertension, 2015

Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular diseas... more Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate a...

Research paper thumbnail of Sensory impairment and cognitive functioning in oldest-old subjects: the Leiden 85+ Study

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2005

Because studies on the association of sensory impairment (both hearing and visual impairment) and... more Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study. Within this population-based study of 459 participants aged 85+ years, hearing impairment was measured by audiometry and visual impairment by a visual acuity chart, both under standardized conditions. The Mini-Mental State Exam (MMSE) assessed global cognitive functioning. In participants with MMSE scores >18, the authors further assessed memory (Word-Learning Test, Immediate and Delayed Recall) and cognitive speed (by Stroop Test, Letter-Digit Coding test). Both hearing impairment (prevalence: 85%) and visual impairment (prevalence: 59%) were associated with lower scores on the MMSE. Increasing visual impairment was associated with poorer scores on memory and cognitive speed, as measured with visually presented cognitive tests. In contrast, there w...

Research paper thumbnail of Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study

The American journal of clinical nutrition, 2005

High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are fre... more High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia. We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age. This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models. In the cross-sectional a...

Research paper thumbnail of International variation in GP treatment strategies for subclinical hypothyroidism in older adults

European Geriatric Medicine, 2013

There is limited evidence about the impact of treatment for subclinical hypothyroidism, especiall... more There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people. To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics. Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand. The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L). A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]). GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.

Research paper thumbnail of NT-proBNP, blood pressure, and cognitive decline in the oldest old: The Leiden 85-plus Study

Neurology, 2014

To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used a... more To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old. In 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years. Subjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 0.187). Subjects in the category &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;highest tertile of NT-proBNP and the lowest tertile of systolic BP&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; had a 3.7-point-lower MMSE score at baseline (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and a 0.49-point-steeper decline in MMSE score per year (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) compared with subjects in the other categories. In the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction.

Research paper thumbnail of The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good

European Thyroid Journal, 2014