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

A vérnyomáscsökkentő terápiában a családorvosi gyakorlatban megmutatkozó eltérések elemzése érdekében 2543 családorvos bevonásával online kérdőíves felmérést végeztünk különböző karakterisztikájú – esendőség, SBP és CVD tekintetében –, nagyon idős (80 évesnél idősebb) betegek körében. Arra is kerestük a választ, hogy mennyire befolyásolja a kezelési döntésüket az időskori esendőség. A tanulmányunk másik célkitűzése a magyar eredmények összehasonlítása volt a nemzetközi eredményekkel. Országonként összehasonlításra került azon esetek aránya, amelyekben a kezelés mellett döntöttek a családorvosok. A 29 országból 24 országban (83%) a beteg esendő állapotát a családorvosok azzal a döntéssel kapcsolták össze, hogy inkább nem indítanak kezelést. A legalacsonyabb kezelési arány Hollandiában volt, a legmagasabb arány pedig Ukrajnában. Magyarország azon országok közé tartozott, ahol a családorvosok inkább kezelik az esendő pácienseket (a kezelési arány 50–59% között volt). A páciens esendősége nem befolyásolta a terápia megkezdését, sokkal jobban a cardiovascularis megbetegedés és a 160 Hgmm feletti SBP. A vizsgálat fontos üzenete volt, hogy továbbra is szükséges a családorvosok és a családorvos-rezidensek oktatása az idős, esendő hypertoniás betegek kezelésével kapcsolatban.

Background loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. Methods this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60–19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. Results we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1–97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P Conclusions in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.

BackgroundMany older persons use the thyroid hormone levothyroxine which is often continued for life. Scientifically, there is much uncertainty whether simple continuation is the optimal approach. First, the physical need for levothyroxine can decrease with age thereby posing a higher risk of overtreatment and adverse effects. Second, large trials in subclinical hypothyroidism have shown no benefit for the use of levothyroxine. Interestingly, guidelines do not address re-evaluation of the indication. This self-controlled trial aims to determine the effects of discontinuation of levothyroxine treatment in older adults.Methods and analysisParticipants are community-dwelling subjects aged ≥60 years using levothyroxine continuously at a stable dosage of ≤150 µg and a level of thyroid-stimulating hormone (TSH) Ethics and disseminationApproval was obtained from the institutional Medical Ethics Committee. The Older People Advisory Board Health and Well-being has reviewed the research proposal and their comments were used for improvement. In line with the funding policies of the grant organisation funding this study, the study results will be proactively disseminated to the general public and key public health stakeholders.Trial registration numberNL7978;NCT05821881.

To reduce inappropriate polypharmacy, deprescribing should be part of patients' regular care. Yet deprescribing is difficult to implement, as shown in several studies. Understanding patients' attitudes towards deprescribing at the individual and country level may reveal effective ways to involve older adults in decisions about medications and help to implement deprescribing in primary care settings. In this study we aim to investigate older adults' perceptions and views on deprescribing in different European countries. Specific objectives are to investigate the patients' willingness to have medications deprescribed by medication type and to have herbal or dietary supplements reduced or stopped, the role of the Patient Typology (on medication perspectives), and the impact of the patient-GP relationship in these decisions.This cross-sectional survey study has two parts: Part A and Part B. Data collection for Part A will take place in nine countries, in which per country 10 GPs will recruit 10 older patients (≥65 years old) each (n = 900). Part B will be conducted in Switzerland only, in which an additional 35 GPs will recruit five patients each and respond to a questionnaire themselves, with questions about the patients' medications, their willingness to deprescribe those, and their patient-provider relationship. For both Part A and part B, a questionnaire will be used to assess the willingness of older patients with polypharmacy to have medications deprescribed and other relevant information. For Part B, this same questionnaire will have additional questions on the use of herbal and dietary supplements.The international study design will allow comparisons of patient perspectives on deprescribing from different countries. We will collect information about willingness to have medications deprescribed by medication type and regarding herbal and dietary supplements, which adds important information to the literature on patients' preferences. In addition, GPs in Switzerland will also be surveyed, allowing us to compare GPs' and patients' views and preferences on stopping or reducing specific medications. Our findings will help to understand patients' attitudes towards deprescribing, contributing to improvements in the design and implementation of deprescribing interventions that are better tailored to patients' preferences.

Background translation of the available evidence concerning primary cardiovascular prevention into clinical guidance for the heterogeneous population of older adults is challenging. With this review, we aimed to give an overview of the thresholds and targets of antihypertensive drug therapy for older adults in currently used guidelines on primary cardiovascular prevention. Secondly, we evaluated the relationship between the advised targets and guideline characteristics, including guideline quality. Methods we systematically searched PubMed, Embase, Emcare and five guideline databases. We selected guidelines with (i) numerical thresholds for the initiation or target values of antihypertensive drug therapy in context of primary prevention (January 2008–July 2020) and (ii) specific advice concerning antihypertensive drug therapy in older adults. We extracted the recommendations and appraised the quality of included guidelines with the AGREE II instrument. Results thirty-four guidelines provided recommendations concerning antihypertensive drug therapy in older adults. Twenty advised a higher target of systolic blood pressure (SBP) for octogenarians in comparison with the general population and three advised a lower target. Over half of the guidelines (n = 18) recommended to target a SBP Conclusion the ongoing debate concerning targets of antihypertensive treatment in older adults, is reflected in an inconsistency of recommendations across guidelines. Recommended targets are largely set on chronological rather than biological age.

Background Observational studies have reported an inverse association between ultraviolet (UV) radiation and hypertension. The aim of this study was to assess differences in blood pressure changes between persons with dementia receiving UV light versus vitamin D (VD) supplementation. Methods Post-hoc analysis of randomized controlled trial data concerning nursing home residents with dementia (N = 61; 41 women, mean age 84.8 years). The participants received half-body UV irradiation, twice weekly over 6 months, at one standard erythema dose (UV group, n = 22) or 5600 international units of cholecalciferol once a week (VD group, n = 39). Short-term effects were evaluated after 1 month and long-term effects after 3 and 6 months. Differences in blood pressure changes were assessed using linear mixed models. Results With the VD group as a reference, the estimated difference in mean change of systolic blood pressure was − 26.0 mmHg [95% confidence interval (CI) -39.9, − 12.1, p = .000] at 1 month, 4.5 mmHg (95% CI -6.8, 15.9, p = 0.432) at 3 months, and 0.1 (95% CI -14.1, 14.3, p = 0.83) at 6 months. The estimated difference in diastolic blood pressure was − 10.0 mmHg (95% CI -19.2, − 0.7, p = 0.035) at 1 month, 3.6 mmHg (95% CI -4.1, 11.2, p = 0.358) at 3 months, and 2.7 (95% CI -6.8, 12.1, p = 0.580) at 6 months. Conclusions UV light had only a short-term effect but not a long-term effect on blood pressure reduction compared to VD use in this sample of normotensive to mild hypertensive nursing home residents with dementia. Future studies will be needed to determine the effect of UV light in different samples of the population and especially in a population with hypertension.

PURPOSE: Hypertension trials often exclude patients with complex health problems and lack generalizability. We aimed to determine if systolic blood pressure (SBP) in patients undergoing antihypertensive treatment is associated with 1-year changes in cognitive/daily functioning or quality of life (QoL) in persons aged ≥75 years with or without complex health problems. METHODS: We analyzed data from a population-based prospective cohort study (Integrated Systematic Care for Older Persons [ISCOPE]) with a 1-year follow-up. Stratified by SBP level in the year before baseline, we used mixed-effects linear regression models to evaluate the change from baseline to 1-year follow-up in outcome measures (Mini-Mental State Examination [MMSE], Groningen Activity Restriction Scale [GARS], and EQ-5D-3L). We adjusted for age, sex, and baseline MMSE/GARS/EQ-5D-3L scores and stratified for complex health problems as a proxy for frailty. RESULTS: Participant (n = 1,266) age averaged 82.4 (SD 5) years, and 874 (69%) were women. For participants undergoing antihypertensive therapy (1,057; 83.5%) and with SBP 150 mm Hg, it was 0.14 points MMSE (ie, 0.76-point less decline; P for trend = .013). Complex health problems modified the association of SBP with cognition; the association was seen in those with antihypertensive treatment (P for trend

BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism – a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7–81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (pConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT01660126] (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+).

Background General practitioners (GPs) should regularly review patients’ medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients’ health. However, deprescribing can be challenging for physicians. This study investigates GPs’ deprescribing decisions in 31 countries. Methods In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs’ deprescribing decisions. Results Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). Interpretation The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD.

Importance Previous trials on the effect of levothyroxine on depressive symptom scores in patients with subclinical hypothyroidism were limited by small sample sizes (N = 57 to 94) and potential biases. Objective To assess the effect of levothyroxine on the development of depressive symptoms in older adults with subclinical hypothyroidism in the largest trial on this subject and to update a previous meta-analysis including the results from this study. Design, Setting, and Participants This predefined ancillary study analyzed data from participants in the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism (TRUST) trial, a double-blind, randomized, placebo-controlled, parallel-group clinical trial conducted from April 2013 to October 31, 2016. The TRUST trial included adults aged 65 years or older diagnosed with subclinical hypothyroidism, defined as the presence of persistently elevated thyroid-stimulating hormone (TSH) levels (4.6-19.9 mIU/L) with free thyroxine (T4) within the reference range. Participants were identified from clinical and general practitioner laboratory databases and recruited from the community in Switzerland, the Netherlands, Ireland, and the UK. This ancillary study included a subgroup of 472 participants from the Netherlands and Switzerland; after exclusions, a total of 427 participants (211 randomized to levothyroxine and 216 to placebo) were analyzed. This analysis was conducted from December 1, 2019, to September 1, 2020. Interventions Randomization to either levothyroxine or placebo. Main Outcomes and Measures Depressive symptom scores after 12 months measured with the Geriatric Depression Scale (GDS-15), with higher scores indicating more depressive symptoms (minimal clinically important difference = 2). Results A total of 427 participants with subclinical hypothyroidism (mean [SD] age, 74.52 [6.29] years; 239 women [56%]) were included in this analysis. The mean (SD) TSH level was 6.57 (2.22) mIU/L at baseline and decreased after 12 months to 3.83 (2.29) mIU/L in the levothyroxine group; in the placebo group, it decreased from 6.55 (2.04) mIU/L to 5.91 (2.66) mIU/L. At baseline, the mean (SD) GDS-15 score was 1.26 (1.85) in the levothyroxine group and 0.96 (1.58) in the placebo group. The mean (SD) GDS-15 score at 12 months was 1.39 (2.13) in the levothyroxine and 1.07 (1.67) in the placebo group with an adjusted between-group difference of 0.15 for levothyroxine vs placebo (95% CI, -0.15 to 0.46; P = .33). In a subgroup analysis including participants with a GDS-15 of at least 2, the adjusted between-group difference was 0.61 (95% CI, -0.32 to 1.53; P = .20). Results did not differ according to age, sex, or TSH levels. A previous meta-analysis (N = 278) on the association of levothyroxine with depressive symptoms was updated to include these findings, resulting in an overall standardized mean difference of 0.09 (95% CI, -0.05 to 0.22). Conclusions and Relevance This ancillary study of a randomized clinical trial found that depressive symptoms did not differ after levothyroxine therapy compared with placebo after 12 months; thus, these results do not provide evidence in favor of levothyroxine therapy in older persons with subclinical hypothyroidism to reduce the risk of developing depressive symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT01853579.

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

Objectives Neuropsychiatric symptoms (NPS) are very common in older patients with dementia. There is increasing evidence that hypoperfusion of the brain plays a role in the development of NPS. The aim of this study is to assess whether there is an association between low systolic blood pressure (SBP) and NPS and if NPS are more prevalent in older people with dementia using antihypertensive medication. Methods We studied the baseline data from participants in the Communication, Systematic pain treatment, Medication review, Organized activities and Safety study, a multicenter clustered trial with 765 participants from 72 nursing home units from 37 nursing homes in Norway. SBP (lowest quartile vs rest) and use of antihypertensive medication were predictors and Neuropsychiatric Inventory—Nursing Home version (NPI-NH) score (total and clusters) was the outcome. Missing data were imputed, except for missing data in predictors. We used a mixed model analysis adjusted for age, sex and Minimal Mental State Examination (MMSE) score. In a sensitivity analysis, continuous SBP values were used. Results In total, 412 patients were included with a mean age of 86.9 years, 53.9% had a MMSE score of

Background Levothyroxine is one of the most commonly prescribed drugs. A common reason for levothyroxine treatment on patients with subclinical hypothyroidism are depressive symptoms. A meta-analysis of four RCTs (n = 278) found no benefit of levothyroxine therapy on depressive symptoms. However, the confidence interval does not exclude a small clinical benefit. We aim to assess the effect of levothyroxine therapy for depressive symptoms in patients with subclinical hypothyroidism using data from a RCT with more than 400 adults. Methods The TRUST trial was a double-blind, randomized, placebo-controlled trial involving adults aged ≥65y with subclinical hypothyroidism (elevated TSH levels (4.6-19.9 mU/L) and free thyroxine within the reference range). The outcome was depressive symptoms after 12 months based on the Geriatric Depression Scale (GDS-15), a 15-item questionnaire (range: 0 to 15, higher scores indicate more depressive symptoms, minimal clinical important difference: 2). The multivariable linear regression model was adjusted for levothyroxine starting dose, sex, site, and GDS-15 baseline score. Results 425 Swiss and Dutch adults with subclinical hypothyroidism were randomised (mean age 75y, 56% female). The mean (SD) TSH was 6.6 (2.1) mU/L at baseline and after 12 months decreased to 3.8 (2.3) mU/L in the levothyroxine group vs 5.9 (2.7) mU/L in the placebo group. At baseline, the mean GDS-15 score was 1.3 (1.9) in the levothyroxine group and 1.0 (1.6) in the placebo group. The mean GDS-15 score at 12 months was 1.4 (2.1) in the levothyroxine and 1.1 (1.7) in the placebo group with an adjusted between-group difference of 0.2 for levothyroxine vs. placebo (95% CI:-0.1 to 0.5; p = 0.29). Conclusions In this by far largest RCT on the topic, levothyroxine therapy did not confer a benefit for depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine for depressive symptoms when they co-occur with subclinical hypothyroidism. Key messages Levothyroxine has no benefit on depressive symptoms in patients with subclinical hypothyroidism. Levothyroxine prescription to patients with subclinical hypothyroidism and depressive symptoms should be reconsidered.

Background:\ud L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit.\ud \ud Objective:\ud To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden.\ud \ud Design:\ud Secondary analysis of the randomized, placebo-controlled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126)\ud \ud Setting:\ud Switzerland, Ireland, the Netherlands, and Scotland.\ud \ud Participants:\ud 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.\ud \ud Intervention:\ud L-thyroxine or matching placebo with mock dose titration.\ud \ud Measurements:\ud 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.\ud \ud Results:\ud \ud 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).\ud \ud Limitation:\ud Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data.\ud \ud Conclusion:\ud In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo.\ud \ud Primary Funding Source:\ud European Union FP7.

Contains fulltext : 218901.pdf (Publisher’s version ) (Open Access) 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 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.

ObjectivesTo 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.DesignCross-validated prospective cohort study. The models were tested in the BELFRAIL Study and externally validated in the Leiden 85-plus Study.SettingGeneral practice, Belgium and The Netherlands.ParticipantsThe 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 measuresThe 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.ResultsTraditional 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)).ConclusionsThis 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.

Objective: The objective of this study was to identify key features to be addressed in the reporting of deprescribing trials and to elab-orate and explain CONSORT items in this regard.Study Design and Setting: As a first step in a multistage process and based on a systematic review of deprescribing trials, we elab-orated variation in design, intervention, and reporting of the included trials of the review. We identified items that were missed or insufficiently described, using the CONSORT and TIDieR checklists. The resulting list of items, which we considered relevant to be reported in deprescribing trials, were discussed in a single-round Delphi exercise and subsequently in a full-day face-to-face meeting with an international panel of 14 experts. We agreed on CONSORT items for further elaboration with regard to design and reporting of deprescribing trials.Results: We identified seven CONSORT items on trial design, participants, intervention, outcomes, flowchart, and harms, where the investigators of deprescribing trials should take into consideration specific aspects, such as whether or not to use placebo or how to inform participants.Conclusion: This article presents an elaboration to the CONSORT statement for the reporting of deprescribing trials. It may also support investigators in motivated design choices. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Clinical trials have demonstrated that antihypertensive treatment (AHT) in older adults is beneficial. Longitudinal studies, in contrast, have shown that low blood pressure is associated with higher all-cause mortality, especially in frail older adults. Despite the high quality of the available evidence, its translation into clinical guidance for the heterogeneous older population is challenging. To give a systematic overview of blood pressure targets for older adults recommended in clinical guidelines, we searched PubMed, Embase, Emcare, and five guideline databases. We selected guidelines with numerical thresholds for the initiation or the goal of non-disease-specific AHT (January 2008-October 2019). Guidelines with advices concerning AHT in older adults were analyzed. We appraised the guideline quality with the AGREEII-instrument. Of the 44 guidelines containing a numerical threshold for the initiation or the goal of AHT, 33 (75%) provided recommendations concerning AHT for older adults. Nineteen advised a higher target of systolic blood pressure (SBP) for older adults in comparison with the middle-aged population and 3 more recent advised a lower target. Over half (19/33) recommended to treat hypertension in the oldest old to a SBP

Clare H Luymes,1 Nelleke J Boelhouwer,1 Rosalinde KE Poortvliet,1 Wouter de Ruijter,1 Ria Reis,1–3 Mattijs E Numans1 1Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2Amsterdam Institute for Social Science Research, University of Amsterdam, Amsterdam, the Netherlands; 3The Children’s Institute, University of Cape Town, Cape Town, South Africa Background: Patients with low cardiovascular disease (CVD) risk potentially use preventive cardiovascular medication unnecessarily. Our aim was to identify various viewpoints and beliefs concerning the preventive CVD management of patients with low CVD risk using preventive cardiovascular medication. Furthermore, we investigated whether certain viewpoints were related to a preference for deprescription or the continuation of preventive cardiovascular medication.Methods: In 2015, we purposively sampled patients from the intervention arm of the Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care (ECSTATIC) trial in the Netherlands for this study. Participants made Q-sorts by ranking 43 statements concerning preventive CVD management from “totally disagree” to “totally agree”. These Q-sorts were analyzed using PQMethod 2.35 software. A varimax procedure presented the distinguishing viewpoints that were favored by our participants. We used group discussion quotations to underline our findings. For validation purposes, we asked participants how well each viewpoint fitted them.Results: Of 291 invited patients, 33 participated. Thirty-one Q-sorts were analyzed. The following three viewpoints were found: 1) a controlling viewpoint, in which patients held the belief that monitoring blood pressure and cholesterol levels is important (n=13, of which seven had their medication deprescribed and six continued their medication); 2) an autonomous viewpoint, in which patients showed a dislike of medication (n=8, of which seven had their medication deprescribed and one had it continued); and 3) an afraid viewpoint, in which patients were fearful of developing CVD (n=8, of which two had their medication deprescribed and six had it continued). Seventy-four percent of the participants believed that the viewpoint to which they were assigned was a good fit.Conclusion: Three well-discriminating viewpoints about preventive CVD management were determined. Knowing and recognizing these viewpoints is effective for general practitioners when discussing the deprescribing of preventive cardiovascular medications with patients and may be used to promote implementation of deprescription. Keywords: general practice, preventive medicine, cardiovascular diseases, antihypertensive agents, anticholesteremic agents, inappropriate prescribing

Managing the growing number of oldest-old patients with multimorbidity and polypharmacy in primary health care poses an increasing public health challenge. Since inappropriate polypharmacy can harm patients’ health, general practitioners (GPs) should regularly review patients’ medications and, if necessary, deprescribe. This case vignette study evaluates the deprescribing decisions of GPs from 31 countries and compares the factors influencing GPs’ deprescribing decisions. We invited GPs to participate in an online survey, containing a) three cases of increasingly dependent oldest-old multimorbid patients with potentially inappropriate polypharmacy and b) Likert-scale questions assessing the importance of factors influencing deprescribing. We presented each case with and without history of cardiovascular disease (CVD). For each case, we asked whether GPs would deprescribe any medication and, if so, which one(s). We calculated percentages of GPs deprescribing at least one medication in each case, compared cases with/without CVD history and different levels of dependency in activities of daily living, and calculated the percentage of factors rated as important or very important. Of 3175 invited GPs from 31 countries, 53% responded (N = 1’706) with a mean age of 50 years and 60% females. Results are preliminary, but despite some differences across GP characteristics (male/female, age) and across countries, GPs generally showed a high willingness to deprescribe in oldest-old patients (>80 years) with polypharmacy. GPs were more likely to deprescribe in patients with a higher level of dependency, in the absence of history of CVD, and when patients are on statins, proton-pump inhibitors or potentially inappropriate pain medication. Factors GPs rated as important or very important for the deprescribing decision were patients’ quality of life, risks and benefits of medications, patients’ life expectancy, and potential negative health outcomes resulting from deprescribing. Key messages Despite international differences, most GPs report they would deprescribe in older multimorbid patients with polypharmacy. The results will facilitate the development of interventions supporting general practitioners to deprescribe.

Importance It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. Objective To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. Design, Setting, and Participants Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. Exposures Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). Main Outcomes and Measures Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). Results Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). Conclusions and Relevance In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. Trial Registration ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.

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 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. J Am Geriatr Soc 68:417-425, 2020.

[This corrects the article DOI: 10.1371/journal.pone.0166857.].

Physicians are confronted with dilemma’s on cardiovascular preventive medication for older people with complex health problems. With accumulation of diseases, limitations and shortening life expectancy, questions arise for whom cardiovascular preventive treatment is still appropriate (the expected benefits of treatment exceeds the negative consequences by a sufficiently wide margin resulting that treatment is worth doing). There is a need for more guidance in clinical situations. With the RAND/UCLA appropriateness method (RUAM), we investigated the appropriateness of cardiovascular preventive medication in adults ≥ 75 years. The RUAM is a systematic, formalized method, to combine available scientific evidence with the collective judgment of experts. Fourteen interdisciplinary panelists (9 physicians representing 6 medical disciplines, 1 medical ethics expert, 1 pharmacist and 3 older adults [lay man]), discussed and rated the appropriateness of starting and stopping of three medication groups (cholesterol lowering, blood pressure lowering and thrombocyte aggregation inhibitors) for different clinical scenarios (combinations of cardiovascular history, systolic blood pressure, complexity of health problems, age, life-expectancy, side-effects). Depending on the medication group, different patterns of appropriateness judgments across the clinical scenarios were found. In general, absence of cardiovascular disease, presence of complex health problems, a short life-expectancy or hindering side-effects were important factors to judge cardiovascular preventive medication as inappropriate. Results were summarized into colored reading maps. These findings can offer more guidance in clinical decision making about cardiovascular preventive treatment for adults ≥ 75 years.

Background: The use of preventive cardiovascular medication by patients with low cardiovascular disease (CVD) risk is potentially inappropriate. Objective: The aim of this study was to identify barriers to and enablers of deprescribing potentially inappropriate preventive cardiovascular medication experienced by patients and general practitioners (GPs). Methods: A total of 10 GPs participating in the ECSTATIC trial (Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care) audiotaped deprescribing consultations with low-CVD-risk patients. After initial conventional content analysis, 2 researchers separately coded all barriers to and enablers of deprescribing medication using framework analysis. We performed a within-case and cross-case analysis to explore barriers and enablers among both patients and GPs. Results: Patients (n = 49) and GPs (n = 10) expressed barriers and enablers with regard to the appropriateness of the medication and the deprescribing process. A family history for CVD was identified as a barrier to deprescribing medication for both patients and GPs. Patients feared possible consequences of deprescribing and were influenced by the opinion of their GP. Additionally, a presumed disapproving opinion from specialists influenced the GPs’ willingness to deprescribe medication. Conclusions: Patients appreciated discussing their doubts regarding deprescribing potentially inappropriate preventive cardiovascular medication. Furthermore, they acknowledged their GP’s expertise and took their opinion toward deprescribing into consideration. The GPs’ decisions to deprescribe were influenced by the low CVD risk of the patients, additional risk factors, and the alleged specialist’s opinion toward deprescribing. We recommend deprescribing consultations to be patient centered, with GPs addressing relevant themes and probable consequences of deprescribing preventive cardiovascular medication.

Background Many oldest-old (> 80-years) with multimorbidity and polypharmacy are at high risk of inappropriate use of medication, but we know little about whether and how GPs would deprescribe, especially in the frail oldest-old. We aimed to determine whether, how, and why Swiss GPs deprescribe for this population. Methods GPs took an online survey that presented case-vignettes of a frail oldest-old patient with and without history of cardiovascular disease (CVD) and asked if they would deprescribe any of seven medications. We calculated percentages of GPs willing to deprescribe at least one medication in the case with CVD and compared these with the case without CVD using paired t-tests. We also included open-ended questions to capture reasons for deprescribing and asked which factors could influence their decision to deprescribe by asking for their agreement on a 5-point-Likert-scale. Results Of the 282 GPs we invited, 157 (56%) responded: 73% were men; mean age was 56. In the case-vignette without CVD, 98% of GPs deprescribed at least one medication (usually cardiovascular preventive medications) stating it had no indication nor benefit. They would lower the dose or prescribe pain medication as needed to reduce side effects. Their response was much the same when the patient had a history of CVD. GPs reported they were influenced by ‘risk’ and ‘benefit’ of medications, ‘quality of life’, and ‘life expectancy’, and prioritized the patient’s wishes and priorities when deprescribing. Conclusion Swiss GPs were willing to deprescribe cardiovascular preventive medication when it lacked indication but tended to retain pain medication. Developing tools for GPs to assist them in balancing the risks and benefits of medication in the context of patient values may improve deprescribing activities in practice. Electronic supplementary material The online version of this article (10.1186/s12875-018-0856-9) contains supplementary material, which is available to authorized users.

Background the appropriateness of lowering systolic blood pressure remains controversial in the oldest-old. We tested whether systolic blood pressure is associated with all-cause mortality and change in cognitive function for patients prescribed antihypertensive treatment and those without treatment. Methods we studied participants in the population-based Leiden 85-plus cohort study. Baseline systolic blood pressure and use of antihypertensive treatment were predictors; all-cause mortality and change in cognitive function measured using the Mini-Mental State Examination were the outcomes. Grip strength was measured as a proxy for physical frailty. We used Cox proportional hazards and mixed-effects linear regression models to analyse the relationship between systolic blood pressure and both time to death and change in cognitive function. In sensitivity analyses, we excluded deaths within 1 year and restricted analyses to participants without a history of cardiovascular disease. Results of 570 participants, 249 (44%) were prescribed antihypertensive therapy. All-cause mortality was higher in participants with lower blood pressure prescribed antihypertensive treatment (HR 1.29 per 10 mmHg lower systolic blood pressure, 95% CI 1.15-1.46, P < 0.001). Participants taking antihypertensives showed an association between accelerated cognitive decline and lower blood pressure (annual mean change -0.35 points per 10 mmHg lower systolic blood pressure, 95% CI -0.60, -0.11, P = 0.004); decline in cognition was more rapid in those with lower hand grip strength. In participants not prescribed antihypertensive treatment, no significant associations were seen between blood pressure and either mortality or cognitive decline. Conclusions lower systolic blood pressure in the oldest-old taking antihypertensives was associated with higher mortality and faster decline in cognitive function.

BACKGROUND: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.METHODS: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure.DISCUSSION: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.TRIAL REGISTRATION: Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).

ObjectivesTo estimate and compare the prevalence and type of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) among community-dwelling older adults (≥65 years) enrolled to a clinical trial in three European countries.DesignA secondary analysis of the Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial dataset.ParticipantsA subset of 48/80 PIP and 22/34 PPOs indicators from the Screening Tool of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) V2 criteria were applied to prescribed medication data for 532/737 trial participants in Ireland, Switzerland and the Netherlands.ResultsThe overall prevalence of PIP was lower in the Irish participants (8.7%) compared with the Swiss (16.7%) and Dutch (12.5%) participants (P=0.15) and was not statistically significant. The overall prevalence of PPOs was approximately one-quarter in the Swiss (25.3%) and Dutch (24%) participants and lower in the Irish (14%) participants (P=0.04) and the difference was statistically significant. The hypnotic Z-drugs were the most frequent PIP in Irish participants, (3.5%, n=4), while it was non-steroidal anti-inflammatory drug and oral anticoagulant combination, sulfonylureas with a long duration of action, and benzodiazepines (all 4.3%, n=7) in Swiss, and benzodiazepines (7.1%, n=18) in Dutch participants. The most frequent PPOs in Irish participants were vitamin D and calcium in osteoporosis (3.5%, n=4). In the Swiss and Dutch participants, they were bone antiresorptive/anabolic therapy in osteoporosis (9.9%, n=16, 8.6%, n=22) respectively. The odds of any PIP after adjusting for age, sex, multimorbidity and polypharmacy were (adjusted OR (aOR)) 3.04 (95% CI 1.33 to 6.95, PConclusionsThis study has estimated and compared the prevalence and type of PIP and PPOs among this cohort of community-dwelling older people. It demonstrated a significant difference in the prevalence of PPOs between the three populations. Further research is urgently needed into the impact of system level factors as this has important implications for patient safety, healthcare provision and economic costs.

Objectives To explore general practitioners’ (GPs) routines and considerations on (de)prescribing antihypertensive medication (AHM) in older patients, their judgement on usability of the current guideline and needs for future support. Design Semistructured interviews. Setting Dutch general practice. Participants Fifteen GPs were purposively sampled based on level of experience and practice characteristics until saturation was reached. Results GPs appeared reluctant to start AHM, especially in patient >80 years. High systolic blood pressure and history of cardiovascular disease or diabetes were enablers to start or intensify treatment. Reasons to refrain from this were frailty and patient preference. GPs described a tendency to continue AHM regimens unchanged, influenced by daily time constraints, automated prescription routines and anticipating discomfort when disturbing patients’ delicate balance. GPs were only inclined to deprescribe AHM in terminally ill patients or after prolonged achievement of target levels in combination with side effects or patient preference. Deprescription was facilitated when GPs had experience with patients showing increased quality of life after deprescription and was withheld by anticipated regret (ie, GPs’ fear of a stroke after deprescribing). GPs felt insufficient guidance from current guidelines, especially on deprescription. Conclusions GPs are reluctant to start or deprescribe AHM in older people and have a propensity to continue AHM within a daily routine that insufficiently supports critical medication review. (De)prescription is influenced by patient preferences and anticipated regret and current guidelines provide insufficient guidance.

Background the impact of renal function and its changes and the occurrence of cardiovascular events on changes in N-terminal pro-brain natriuretic peptide levels (NT-proBNP) is unknown in very old age. Objective to assess whether increase in NT-proBNP levels over time is still associated with cardiac disease and mortality in very old age, independent of renal function. Methods changes in NT-proBNP levels between age 85 and 90 years and their associations with incident cardiac disease, (cardiovascular) mortality and renal function were assessed in 252 nonagenarian participants from a population-based sample of the Leiden 85-plus Study. Results median NT-proBNP increase over 5 years was 154 pg/ml (inter-quartile range: 29-549), while in the same period estimated glomerular filtration rate (eGFR) decreased by 5.8 ml/min/1.73 m(2) (standard deviation 7.5). Participants with increasing NT-proBNP levels more frequently developed heart failure and atrial fibrillation (odds ratio 2.79, 95% confidence interval (CI) 1.11-7.02 and 2.63, 95% CI 1.02-6.79, respectively, adjusted for eGFR at age 85 and change in eGFR) between age 85 and 90 years. Increasing NT-proBNP levels between age 85 and 90 years were associated with an increased cardiovascular mortality risk after age 90 years compared with not-increasing NT-proBNP levels (hazard ratio 1.62, 95% CI 1.04-2.51, adjusted for eGFR at age 90 years and change in eGFR). Conclusion in the oldest old, increase in NT-proBNP is associated with incident heart failure and atrial fibrillation and risk for cardiovascular mortality, independent of decreasing renal function.

Background The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. Methods In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40–70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. Results Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P

Background In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision. Methods Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP. Results The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs’ decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48–0.59; ORs per country 0.11–1.78). Conclusions Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making. Electronic supplementary material The online version of this article (doi:10.1186/s12877-017-0486-4) contains supplementary material, which is available to authorized users.

Background: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH.Methods: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients.Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture.Discussion: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition.Trial registration: Clinicaltrials.gov NCT01660126; registered 8th June 2012.

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 "highest tertile of NT-proBNP and the lowest tertile of systolic BP" had a 3.7-point-lower MMSE score at baseline (p0.001) and a 0.49-point-steeper decline in MMSE score per year (p0.001) 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.

Objective Elevated levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) are associated with cognitive impairment, which might be explained by cardiovascular diseases or risk factors. The aim of this study was to investigate the association of NT-proBNP with cognitive function and decline in older adults at high risk of cardiovascular disease. Methods We studied 5,205 men and women (mean age = 75 years) who were recruited into the PROspective Study of Pravastatin in the Elderly at Risk. All participants had pre-existing cardiovascular disease or risk factors thereof. Four domains of cognitive function were tested at baseline and repeated during a follow-up period of 3.2 years. Results Participants with higher NT-proBNP (≥450ng/l) had worse baseline cognitive function, including reaction time (mean difference high vs low group = 3.07 seconds, 95% confidence interval [CI] = 0.83 to 5.32), processing speed (−1.02 digits coded, 95% CI = −1.65 to −0.39), and immediate memory (−0.13 pictures remembered, 95% CI = −0.29 to 0.04). There was no significant difference in delayed memory (−0.14, 95% CI = −0.38 to 0.10) between the NT-proBNP groups. Participants with higher NT-proBNP had a steeper cognitive decline, including reaction time (mean annual change high vs low group = 0.60 seconds, 95% CI = 0.14 to 1.07), processing speed (−0.15 digits coded, 95% CI = −0.25 to −0.05), immediate memory (−0.05 pictures remembered, 95% CI = −0.09 to 0.00), and delayed memory (−0.05 pictures remembered, 95% CI = −0.11 to 0.01). Associations were independent of cardiovascular diseases and risks. Interpretation Higher NT-proBNP associates with worse cognitive function and steeper cognitive decline, independent of cardiovascular diseases and risks. Further studies to unravel the underlying mechanisms are warranted. Ann Neurol 2014;76:213–222

Item does not contain fulltext OBJECTIVE: To evaluate the independent contributions of both the trend in SBP and the SBP value at age 90 to the prediction of mortality in nonagenarians. METHODS: The trend in SBP between 85 and 90 years and SBP at age 90 years were assessed in a population-based sample of 271 participants (74 men and 197 women) aged 90 years of the Leiden 85-plus Study, an observational population-based prospective follow-up study (started 1997). Primary endpoint, followed up over 5 years (median 3.6 years), was all-cause mortality. RESULTS: A decreasing trend in SBP between 85 and 90 years (decline >/=2.9 mmHg/year) was associated with increased mortality compared to an average SBP trend (hazard ratio 1.45, 95% confidence interval 1.02-2.06), independent of SBP at age 90. The effect was stronger in institutionalized participants compared to those living independently [hazard ratio 1.87 (1.10-3.19) and hazard ratio 1.30 (0.81-2.09)]. After analysis with a fully adjusted model, the estimate approached unity [hazard ratio 1.08 (0.60-1.86)]. Overall, 90-year-old participants with SBP of 150 mmHg or less had a 1.62 times increased mortality risk compared to those with SBP more than 150 mmHg (1.21-2.20), independent of the SBP trend in preceding years. This applied to those with and without antihypertensive drugs and those with and without history of cardiovascular disease or noncardiovascular disease. In the fully adjusted model, the estimate was 1.47 (0.90-2.40). CONCLUSION: In very old age, both decreasing trend in SBP over the previous 5 years and the current SBP value independently contribute to prediction of all-cause mortality. Therefore, in individual patients, all available preceding SBP measurements should be taken into account.

Background: Impairment in orientation to time and place is commonly observed in community-dwelling older individuals. Nevertheless, the clinical significance of this has been not fully explored. In this study, we investigated the link between performance in orientation domains and future risk of cardiovascular events and mortality in a non-hospital setting of the oldest old adults.Methods: We included 528 subjects free of myocardial infarction (Group A), 477 individuals free of stroke/transient ischemic attack (Group B), and 432 subjects free of both myocardial infarction and stroke/transient ischemic attack (Group C) at baseline from the population-based Leiden 85-plus cohort study. Participants were asked to answer five questions related to orientation to time and five questions related to orientation to place. 5-year risks of first-time fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, as well as cardiovascular and non-cardiovascular mortality, were estimated using the multivariate Cox regression analysis.Results: In the multivariable analyses, adjusted for sociodemographic characteristics and cardiovascular risk factors, each point lower performance in “orientation to time” was significantly associated with higher risk of first-time myocardial infarction (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.09–1.67, P = 0.007), first-time stroke (HR 1.35, 95% CI 1.12–1.64, P = 0.002), cardiovascular mortality (HR 1.28, 95% CI 1.06–1.54, P = 0.009) and non-cardiovascular mortality (HR 1.37, 95% CI 1.20–1.56, P < 0.001). Similarly, each point lower performance in “orientation to place” was significantly associated with higher risk of first-time myocardial infarction (HR 1.67, 95% CI 1.25–2.22, P = 0.001), first-time stroke (HR 1.39, 95% CI 1.05–1.82, P = 0.016), cardiovascular mortality (HR 1.35, 95% CI 1.00–1.82, P = 0.054) and non-cardiovascular mortality (HR 1.45, 95% CI 1.20–1.77, P < 0.001).Conclusions: Lower performance in orientation to time and place in advanced age is independently related to higher risk of myocardial infarction, stroke and mortality. Impaired orientation might be an early sign of covert vascular injuries, putting subjects at greater risk of cardiovascular events and mortality.

Background To date, no validated risk scores exist for prediction of recurrence risk or potential treatment effect for older people with a history of a cardiovascular event. Therefore, we assessed predictive values for recurrent cardiovascular disease of models with age and sex, traditional cardiovascular risk markers, and ‘SMART risk score’, all with and without addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment effect of pravastatin was assessed across low and high risk groups identified by the best performing models.\ud Design and methods Post-hoc analysis in 2348 participants (age 70–82 years) with a history of cardiovascular disease within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Composite endpoint was a recurrent cardiovascular event/cardiovascular mortality.\ud Results The models with age and sex, traditional risk markers and SMART risk score had comparable predictive values (area under the curve (AUC) 0.58, 0.61 and 0.59, respectively). Addition of NT-proBNP to these models improved AUCs with 0.07 (p for difference ((pdiff)) = 0.003), 0.05 (pdiff = 0.009) and 0.06 (pdiff