Aims The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost... Show moreAims The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost-effectiveness analysis from a societal perspective of a patient-centred CMR. Methods A trial-based cost-utility and cost-effectiveness analysis was performed as part of the DREAMeR study, a pragmatic controlled trial that randomised patients aged >= 70 years using at least seven drugs to either CMR or usual care. Over six months, healthcare consumption and drug use were collected to estimate costs, and effects were collected in terms of quality-adjusted life years (QALYs) measured with EQ-5D-5 L and EQ-VAS and as reduced health-related complaints with impact on patients' daily lives. Results The total mean costs per patient (n= 588) over six months were euro4,189 +/- 6,596 for the control group (n= 294) and euro4,008 +/- 6,678 for the intervention group (n= 294), including estimated intervention costs of euro199 +/- 67, which resulted in a mean incremental total cost savings of euro181 for the intervention group compared to the control group. Compared to the control group, for the intervention group, the mean incremental QALYs over six months were: -0.00217 measured with EQ-5D and 0.003 measured with EQ-VAS. The incremental effect of reduced health-related complaints with impact was -0.34. There was a likelihood of >90% that the intervention was cost-saving. Conclusions The benefits of a patient-centred CMR were inconsistent with no benefits on HR-QoL measured with EQ-5D-5 L and small benefits on HR-QoL measured with EQ-VAS and health-related complaints with impact on patients' daily lives. Additionally, a CMR could potentially be cost saving from a societal perspective. Show less
Background Age-related decline in muscle strength, dynapenia, is linked to serious adverse health outcomes. Evidence on the determinants of muscle strength decline in the oldest old is lacking.... Show moreBackground Age-related decline in muscle strength, dynapenia, is linked to serious adverse health outcomes. Evidence on the determinants of muscle strength decline in the oldest old is lacking. Aims To identify clinical variables associated with handgrip strength and its change over a 4-year period in an oldest old cohort. Methods We included 555 participants from the Leiden 85-plus Study, a prospective population-based study of 85-year-old inhabitants of Leiden, the Netherlands. Handgrip strength was assessed at age 85 and 89 years. Anthropometry, mental status, functional performance, and biochemical variables were obtained at baselines. Significant univariates were included into multivariable regression models to extract the final predictive variables. Results Handgrip strength for men and women at age 85 years was 30.6 kg (SD 8.2) and 18.7 kg (SD, 5.5), respectively. In the cross-sectional analysis, body height and weight were positively associated with handgrip strength in both genders. Higher functional performance was associated with stronger handgrip strength in women. Mean absolute handgrip strength decline over 4 years was greater for men than women (- 6.1 kg (SD, 5.2) vs. - 3.4 kg (SD, 4.1),p < 0.001). Men with better baseline cognitive functioning had smaller decline in handgrip strength. Conclusions This study further strengthens evidence linking functional and cognitive performances to muscle strength in the oldest old. Future research is needed to ascertain causality and determine if these markers represent potential targets for intervention. Show less
Montmollin, M. de; Feller, M.; Beglinger, S.; McConnachie, A.; Aujesky, D.; Collet, T.H.; ... ; Bauer, D.C. 2020
Background: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit... Show moreBackground: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit.Objective: To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden.Design: Secondary analysis of the randomized, placebocontrolled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126)Setting: Switzerland, Ireland, the Netherlands, and Scotland.Participants: 638 persons aged 65 years or older with persistent SCH (thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for >3 months and normal free thyroxine level) and complete outcome data.Intervention: L-thyroxine or matching placebo with mock dose titration.Measurements: 1-year change in Hypothyroid Symptoms and Tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire among participants with high symptom burden (baseline Hypothyroid Symptoms score >30 or Tiredness score >40) versus lower symptom burden.Results: 132 participants had Hypothyroid Symptoms scores greater than 30, and 133 had Tiredness scores greater than 40. Among the group with high symptom burden, the Hypothyroid Symptoms score improved similarly between those receiving L-thyroxine (mean within-group change, -12.3 [95% CI, -16.6 to -8.0]) and those receiving placebo (mean within-group change, -10.4 [CI, -15.3 to -5.4]) at 1 year; the adjusted between-group difference was -2.0 (CI, -5.5 to 1.5; P = 0.27). Improvements in Tiredness scores were also similar between those receiving L-thyroxine (mean within-group change, -8.9 [CI, -14.5 to -3.3]) and those receiving placebo (mean within-group change, -10.9 [CI, -16.0 to -5.8]); the adjusted between-group difference was 0.0 (CI, -4.1 to 4.0; P = 0.99). There was no evidence that baseline Hypothyroid Symptoms score or Tiredness score modified the effects of L-thyroxine versus placebo (P for interaction = 0.20 and 0.82, respectively).Limitation: Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data.Conclusion: In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo. Show less
Background The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An... Show moreBackground The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection. Methods/design The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score >= 3 on 0-10 numerical rating scale; 0 = no knee pain) will be included. Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area. The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients' reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle. Discussion This study will evaluate non-inferiority of intramuscular glucocorticoid injection compared to intra-articular glucocorticoid injection for knee osteoarthritis symptoms. Trial sponsor Erasmus MC University Medical Center Rotterdam. PO-box 2040. 3000 CA Rotterdam. The Netherlands. Show less
BACKGROUND Urgency triage in the emergency department (ED) is important for early identification of potentially lethal conditions and extensive resource utilization. However, in older patients,... Show moreBACKGROUND Urgency triage in the emergency department (ED) is important for early identification of potentially lethal conditions and extensive resource utilization. However, in older patients, urgency triage systems could be improved by taking geriatric vulnerability into account. We investigated the association of geriatric vulnerability screening in addition to triage urgency levels with 30-day mortality in older ED patients.DESIGN Secondary analysis of the observational multicenter Acutely Presenting Older Patient (APOP) study.SETTING EDs within four Dutch hospitals.PARTICIPANTS Consecutive patients, aged 70 years or older, who were prospectively included.MEASUREMENTS Patients were triaged using the Manchester Triage System (MTS). In addition, the APOP screener was used as a geriatric screening tool. The primary outcome was 30-day mortality. Comparison was made between mortality within the geriatric high- and low-risk screened patients in every urgency triage category. We calculated the difference in explained variance of mortality by adding the geriatric screener (APOP) to triage urgency (MTS) by calculating Nagelkerke R-2.RESULTS We included 2,608 patients with a median age of 79 (interquartile range = 74-84) years, of whom 521 (20.0%) patients were categorized as high risk according to geriatric screening. Patients were triaged on urgency as standard (27.2%), urgent (58.5%), and very urgent (14.3%). In total, 132 (5.1%) patients were deceased within a period of 30 days. Within every urgency triage category, 30-day mortality was threefold higher in geriatric high-risk compared to low-risk patients (overall = 11.7% vs 3.4%; P < .001). The explained variance of 30-day mortality with triage urgency was 1.0% and increased to 6.3% by adding the geriatric screener.CONCLUSION Combining triage urgency with geriatric screening has the potential to improve triage, which may help clinicians to deliver early appropriate care to older ED patients. Show less
With increasing age, associations between traditional risk factors (TRFs) and cardiovascular disease (CVD) shift. It is unknown which mid-life risk factors remain relevant predictors for CVD in... Show moreWith increasing age, associations between traditional risk factors (TRFs) and cardiovascular disease (CVD) shift. It is unknown which mid-life risk factors remain relevant predictors for CVD in older people.We systematically searched PubMed and EMBASE on August 16th 2019 for studies assessing predictive ability of > 1 of fourteen TRFs for fatal and non-fatal CVD, in the general population aged 60 + .We included 12 studies, comprising 11 unique cohorts. TRF were evaluated in 2 to 11 cohorts, and retained in 0-70% of the cohorts: age (70%), diabetes (64%), male sex (57%), systolic blood pressure (SBP) (50%), smoking (36%), high-density lipoprotein cholesterol (HDL) (33%), left ventricular hypertrophy (LVH) (33%), total cholesterol (22%), diastolic blood pressure (20%), antihypertensive medication use (AHM) (20%), body mass index (BMI) (0%), hypertension (0%), low-density lipoprotein cholesterol (0%). In studies with low to moderate risk of bias, systolic blood pressure (SBP) (80%), smoking (80%) and HDL cholesterol (60%) were more often retained. Model performance was moderate with C-statistics ranging from 0.61 to 0.77.Compared to middle-aged adults, in people aged 60 + different risk factors predict CVD and current prediction models perform only moderate at best. According to most studies, age, sex and diabetes seem valuable predictors of CVD in old-age. SBP, HDL cholesterol and smoking may also have predictive value. Other blood pressure and cholesterol related variables, BMI, and LVH seem of very limited or no additional value. Without competing risk analysis, predictors are overestimated. Show less
Background: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely... Show moreBackground: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group.Methods: Patients aged >= 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk >= 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation.Results: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients (5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients.Conclusion: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients. Show less
Objectives To test new cardiovascular (CV) risk models in very old adults with and without a history of CV disease (CVD), based on traditional risk factors and biomarkers.Design Cross-validated... Show moreObjectives To test new cardiovascular (CV) risk models in very old adults with and without a history of CV disease (CVD), based on traditional risk factors and biomarkers.Design Cross-validated prospective cohort study. The models were tested in the BELFRAIL Study and externally validated in the Leiden 85-plus Study.Setting General practice, Belgium and The Netherlands.Participants The BELFRAIL cohort consisted of 266 patients aged 80 years or older without a history of CVD and 260 with a history of CVD. The Leiden 85-plus Study consisted of 264 patients aged 85 years without a history of CVD and 282 with a history of CVD.Outcome measures The model with traditional risk factors and biomarkers, as well as the model using only biomarkers, was compared with the model with only traditional risk factors to predict 3-year CV morbidity and mortality. A competing-risk analysis was performed, and the continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI) and net benefit were used to compare the predictive value of the different models.Results Traditional risk factors poorly predicted CV mortality and morbidity. In participants without a history of CVD, adding N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) improved the prediction (NRI 0.56 (95% CI 0.16 to 0.99) and relative IDI 4.01 (95% CI 2.19 to 6.28)). In participants with a history of CVD, the NRI with the addition of NT-pro-BNP and high-sensitivity C reactive protein was 0.38 (95% CI 0.09 to 0.70), and the relative IDI was 0.53 (95% CI 0.23 to 0.90). Moreover, in participants without a history of CVD, NT-pro-BNP performed well as a stand-alone predictor (NRI 0.32 (95% CI -0.12 to 0.74) and relative IDI 3.44 (95% CI 1.56 to 6.09)).Conclusions This study tested new risk models to predict CV morbidity and mortality in very old adults. Especially, NT-pro-BNP showed a strong added predictive value. This opens perspectives for clinicians who are in need of an easily applicable strategy for CV risk prediction in very old adults. Show less
Rodriguez, E.G.; Stuber, M.; Giovane, C. del; Feller, M.; Collet, T.H.; Lowe, A.L.; ... ; Rodondi, N. 2020
Context: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded... Show moreContext: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results.Objective: To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo.Design and Intervention: Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration.Setting and Participants: 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment.Main Outcome Measures: One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed.Results: Mean age was 74.3 years +/- 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex.Conclusions: Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. Show less
Mooijaart, S.P.; Puy, R.S. du; Stott, D.J.; Kearney, P.M.; Rodondi, N.; Westendorp, R.G.J.; ... ; Gussekloo, J. 2019
OBJECTIVES As a person's age increases and his/her health status declines, new challenges arise that may lead physicians to consider deprescribing statins. We aimed to provide insight into... Show moreOBJECTIVES As a person's age increases and his/her health status declines, new challenges arise that may lead physicians to consider deprescribing statins. We aimed to provide insight into recommendations available in international cardiovascular disease prevention guidelines regarding discontinuation of statin treatment applicable to older adults. DESIGN We systematically searched PubMed, EMBASE, EMCARE, and the websites of guideline development organizations and online guideline repositories for cardiovascular disease prevention guidelines aimed at the general population. We selected all guidelines with recommendations (instructions and suggestions) on discontinuation of statin treatment applicable to older adults, published between January 2009 and April 2019. In addition, we performed a synthesis of information from all other recommendations for older adults regarding statin treatment. Methodological quality of the included guidelines was appraised using the appraisal of guidelines for research & evaluation II (AGREE II) instrument. RESULTS Eighteen international guidelines for cardiovascular disease prevention in the general adult population provided recommendations for statin discontinuation that were applicable to older adults. We identified three groups of instructions for statin discontinuation related to statin intolerance, and none was specifically aimed at older adults. Three guidelines also included suggestions to consider statin discontinuation in patients with poor health status. Of the 18 guidelines included, 16 made recommendations regarding statin treatment in older adults, although details on how to implement these recommendations in practice were not provided. CONCLUSION Current international cardiovascular disease prevention guidelines provide little specific guidance for physicians who are considering statin discontinuation in older adults in the context of declining health status and short life expectancy. Show less
Ploeg, M.A. van der; Floriani, C.; Achterberg, W.P.; Bogaerts, J.M.K.; Gussekloo, J.; Mooijaart, S.P.; ... ; Drewes, Y.M. 2019
