The effects of diuretic deprescribing in adult patients: A systematic review to inform an evidence-based diuretic deprescribing guideline.

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

Syncope in older adults: challenges, approach and treatment.

Syncope can have devastating consequences, resulting in injuries, accidents or even death. In our ageing society, the subsequent healthcare usage, such as emergency room presentations, surgeries and hospital admissions, forms a significant and growing socioeconomic burden. Causes of syncope in the older adult include orthostatic hypotension, carotid sinus syndrome, vasovagal syncope, structural cardiac abnormalities, cardiac arrhythmias and conduction abnormalities. As stated in the recently published World Falls Guidelines, syncope in older adults often presents as falls, which is either due to amnesia for loss of consciousness, or pre-syncope leading to a fall, especially in those prone to falls with several other risk-factors for falls present. This difference in presentation can hinder the recognition of syncope. In patients with unexplained falls, or in whom the history comprises red flags for potential syncope, special attention to (pre)syncope is therefore warranted. When syncope is mistaken for other causes of a transient loss of consciousness, such as epileptic seizures, or when syncope presents as falls, patients are often referred to multiple specialists, which may in turn lead to excessive and unnecessary diagnostic testing and costs. Specialist services that are able to provide a comprehensive assessment can improve diagnostic yield and minimise diagnostic testing, thus improving patient satisfaction. Comprehensive assessment also leads to reduced length of hospital stay. Increasingly, geriatricians are involved in the assessment of syncope in the older patient, especially given the overlap with falls. Therefore, awareness of causes of syncope, as well as state-of-the-art assessment and treatment, is of great importance.

New horizons in clinical practice guidelines for use with older people.

Globally, more people are living into advanced old age, with age-associated frailty, disability and multimorbidity. Achieving equity for all ages necessitates adapting healthcare systems. Clinical practice guidelines (CPGs) have an important place in adapting evidence-based medicine and clinical care to reflect these changing needs. CPGs can facilitate better and more systematic care for older people. But they can also present a challenge to patient-centred care and shared decision-making when clinical and/or socioeconomic heterogeneity or personal priorities are not reflected in recommendations or in their application. Indeed, evidence is often lacking to enable this variability to be reflected in guidance. Evidence is more likely to be lacking about some sections of the population. Many older adults are at the intersection of many factors associated with exclusion from traditional clinical evidence sources with higher incidence of multimorbidity and disability compounded by poorer healthcare access and ultimately worse outcomes. We describe these challenges and illustrate how they can adversely affect CPG scope, the evidence available and its summation, the content of CPG recommendations and their patient-centred implementation. In all of this, we take older adults as our focus, but much of what we say will be applicable to other marginalised groups. Then, using the established process of formulating a CPG as a framework, we consider how these challenges can be mitigated, with particular attention to applicability and implementation. We consider why CPG recommendations on the same clinical areas may be inconsistent and describe approaches to ensuring that CPGs remain up to date.

Topic evolution before fall incidents in new fallers through natural language processing of general practitioners' clinical notes.

BACKGROUND: Falls involve dynamic risk factors that change over time, but most studies on fall-risk factors are cross-sectional and do not capture this temporal aspect. The longitudinal clinical notes within electronic health records (EHR) provide an opportunity to analyse fall risk factor trajectories through Natural Language Processing techniques, specifically dynamic topic modelling (DTM). This study aims to uncover fall-related topics for new fallers and track their evolving trends leading up to falls. METHODS: This case-cohort study utilised primary care EHR data covering information on older adults between 2016 and 2019. Cases were individuals who fell in 2019 but had no falls in the preceding three years (2016-18). The control group was randomly sampled individuals, with similar size to the cases group, who did not endure falls during the whole study follow-up period. We applied DTM on the clinical notes collected between 2016 and 2018. We compared the trend lines of the case and control groups using the slopes, which indicate direction and steepness of the change over time. RESULTS: A total of 2,384 fallers (cases) and an equal number of controls were included. We identified 25 topics that showed significant differences in trends between the case and control groups. Topics such as medications, renal care, family caregivers, hospital admission/discharge and referral/streamlining diagnostic pathways exhibited a consistent increase in steepness over time within the cases group before the occurrence of falls. CONCLUSIONS: Early recognition of health conditions demanding care is crucial for applying proactive and comprehensive multifactorial assessments that address underlying causes, ultimately reducing falls and fall-related injuries.

A systematic review of fall prediction models for community-dwelling older adults: comparison between models based on research cohorts and models based on routinely collected data.

BACKGROUND: Prediction models can identify fall-prone individuals. Prediction models can be based on either data from research cohorts (cohort-based) or routinely collected data (RCD-based). We review and compare cohort-based and RCD-based studies describing the development and/or validation of fall prediction models for community-dwelling older adults. METHODS: Medline and Embase were searched via Ovid until January 2023. We included studies describing the development or validation of multivariable prediction models of falls in older adults (60+). Both risk of bias and reporting quality were assessed using the PROBAST and TRIPOD, respectively. RESULTS: We included and reviewed 28 relevant studies, describing 30 prediction models (23 cohort-based and 7 RCD-based), and external validation of two existing models (one cohort-based and one RCD-based). The median sample sizes for cohort-based and RCD-based studies were 1365 [interquartile range (IQR) 426-2766] versus 90 441 (IQR 56 442-128 157), and the ranges of fall rates were 5.4% to 60.4% versus 1.6% to 13.1%, respectively. Discrimination performance was comparable between cohort-based and RCD-based models, with the respective area under the receiver operating characteristic curves ranging from 0.65 to 0.88 versus 0.71 to 0.81. The median number of predictors in cohort-based final models was 6 (IQR 5-11); for RCD-based models, it was 16 (IQR 11-26). All but one cohort-based model had high bias risks, primarily due to deficiencies in statistical analysis and outcome determination. CONCLUSIONS: Cohort-based models to predict falls in older adults in the community are plentiful. RCD-based models are yet in their infancy but provide comparable predictive performance with no additional data collection efforts. Future studies should focus on methodological and reporting quality.

Retrospective evaluation of the world falls guidelines-algorithm in older adults.

BACKGROUND: The World Falls Guidelines (WFG) propose an algorithm that classifies patients as low-, intermediate-, and high-risk. We evaluated different operationalizations of the WFG algorithm and compared its predictive performance to other screening tools for falls, namely: the American Geriatrics Society and British Geriatrics Society (AGS/BGS) algorithm, the 3KQ on their own and fall history on its own. METHODS: We included data from 1509 adults aged ≥65 years from the population-based Longitudinal Aging Study Amsterdam. The outcome was ≥1 fall during 1-year follow-up, which was ascertained using fall calendars. The screening tools' items were retrospectively operationalized using baseline measures, using proxies where necessary. RESULTS: Sensitivity ranged between 30.9-48.0% and specificity ranged between 77.0-88.2%. Operationalizing the algorithm with the 3KQ instead of fall history yielded a higher sensitivity but lower specificity, whereas operationalization with the Clinical Frailty Scale (CFS) classification tree instead of Fried's frailty criteria did not affect predictive performance. Compared to the WFG algorithm, the AGS/BGS algorithm and fall history on its own yielded similar predictive performance, whereas the 3KQ on their own yielded a higher sensitivity but lower specificity. CONCLUSION: The WFG algorithm can identify patients at risk of a fall, especially when the 3KQ are included in its operationalization. The CFS and Fried's frailty criteria may be used interchangeably in the algorithm's operationalization. The algorithm performed similarly compared to other screening tools, except for the 3KQ on their own, which have higher sensitivity but lower specificity and lack clinical recommendations per risk category.

A genome-wide association study meta-analysis in a European sample of stage III/IV grade C periodontitis patients ≤35 years of age identifies new risk loci.

AIM: Few genome-wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta-analysis in cases with a diagnosis at ≤35 years of age was performed. MATERIALS AND METHODS: Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age ≤35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data. RESULTS: The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 × 10-9 ), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p < 10-5 , including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 × 10-8 ). CONCLUSIONS: This study expands the set of known genetic loci for severe periodontitis with an age of onset ≤35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health.

The association between adherence to a plant-based diet and cognitive ageing.

PURPOSE: While the benefits of adopting a more plant-based diet for sustainability and animal welfare are clear, its long-term health impacts, including the impact on cognitive ageing, are limited studied. Therefore, we investigated the associations between plant-based diet adherence and cognitive ageing. METHODS: Data from a previous intervention study involving community-dwelling adults aged ≥ 65 years were analysed at baseline (n = 658) and after 2-year follow-up (n = 314). Global and domain-specific cognitive functioning were assessed at both timepoints. Overall, healthful and unhealthful plant-based dietary indices were calculated from a 190-item food frequency questionnaire. Multivariate-adjusted linear regression models were applied to test for associations. RESULTS: After full-adjustment, higher overall adherence to a plant-based diet was not associated with global cognitive function (difference in Z-score, tertile 1 versus 3 [95% CI]: 0.04 [- 0.05, 0.13] p = 0.40) or cognitive change (- 0.04 [- 0.11, 0.04], p = 0.35). Similarly, healthful and unhealthful plant-based diet indices were not associated with cognitive functioning (respectively p = 0.48; p = 0.87) or change (respectively p = 0.21, p = 0.33). Interestingly, we observed fish consumption to influence the association between plant-based diet adherence and cognitive functioning (p-interaction = 0.01), with only individuals with a fish consumption of ≥ 0.93 portion/week benefitting from better overall plant-based diet adherence (ß per 10-point increment [95% CI]: 0.12 [0.03, 0.21] p = 0.01). CONCLUSION: We did not demonstrate associations of a more plant-based diet with cognitive ageing. However, possibly such association exists in a subpopulation with higher fish intake. This would be in line with earlier observations that diets rich in plant foods and fish, such as the Mediterranean diet, may be beneficial for cognitive ageing. TRIAL REGISTRATION: Registered at clinicaltrials.gov (NCT00696514) on June 12, 2008.

Predicting future falls in older people using natural language processing of general practitioners' clinical notes.

BACKGROUND: Falls in older people are common and morbid. Prediction models can help identifying individuals at higher fall risk. Electronic health records (EHR) offer an opportunity to develop automated prediction tools that may help to identify fall-prone individuals and lower clinical workload. However, existing models primarily utilise structured EHR data and neglect information in unstructured data. Using machine learning and natural language processing (NLP), we aimed to examine the predictive performance provided by unstructured clinical notes, and their incremental performance over structured data to predict falls. METHODS: We used primary care EHR data of people aged 65 or over. We developed three logistic regression models using the least absolute shrinkage and selection operator: one using structured clinical variables (Baseline), one with topics extracted from unstructured clinical notes (Topic-based) and one by adding clinical variables to the extracted topics (Combi). Model performance was assessed in terms of discrimination using the area under the receiver operating characteristic curve (AUC), and calibration by calibration plots. We used 10-fold cross-validation to validate the approach. RESULTS: Data of 35,357 individuals were analysed, of which 4,734 experienced falls. Our NLP topic modelling technique discovered 151 topics from the unstructured clinical notes. AUCs and 95% confidence intervals of the Baseline, Topic-based and Combi models were 0.709 (0.700-0.719), 0.685 (0.676-0.694) and 0.718 (0.708-0.727), respectively. All the models showed good calibration. CONCLUSIONS: Unstructured clinical notes are an additional viable data source to develop and improve prediction models for falls compared to traditional prediction models, but the clinical relevance remains limited.

The association between hyperkyphosis and fall incidence among community-dwelling older adults.

Hyperkyphosis, an increased kyphosis angle of the thoracic spine, was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Hyperkyphosis could serve as an indicator of an increased fall risk as well as a treatable condition. INTRODUCTION: Hyperkyphosis is frequently found in adults aged 65 years and older and may be associated with falls. We aimed to investigate prospectively in community-dwelling older adults whether hyperkyphosis or change in the kyphosis angle is associated with fall incidence. METHODS: Community-dwelling older adults (n = 1220, mean age 72.9 ± 5.7 years) reported falls weekly over 2 years. We measured thoracic kyphosis through the Cobb angle between the fourth and 12th thoracic vertebra on DXA-based vertebral fracture assessments and defined hyperkyphosis as a Cobb angle ≥ 50°. The change in the Cobb angle during follow-up was dichotomized (< 5 or ≥ 5°). Through multifactorial regression analysis, we investigated the association between the kyphosis angle and falls. RESULTS: Hyperkyphosis was present in 15% of the participants. During follow-up, 48% of the participants fell at least once. In the total study population, hyperkyphosis was not associated with the number of falls (adjusted IRR 1.12, 95% CI 0.91-1.39). We observed effect modification by age (p = 0.002). In the oldest quartile, aged 77 years and older, hyperkyphosis was prospectively associated with a higher number of falls (adjusted IRR 1.67, 95% CI 1.14-2.45). Change in the kyphosis angle was not associated with fall incidence. CONCLUSIONS: Hyperkyphosis was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Because hyperkyphosis is a partially reversible condition, we recommend investigating whether hyperkyphosis is one of the causes of falls and whether a decrease in the kyphosis angle may contribute to fall prevention.

Clinical validation of clinical decision support systems for medication review: A scoping review.

The aim of this scoping review is to summarize approaches and outcomes of clinical validation studies of clinical decision support systems (CDSSs) to support (part of) a medication review. A literature search was conducted in Embase and Medline. In total, 30 articles validating a CDSS were ultimately included. Most of the studies focused on detection of adverse drug events, potentially inappropriate medications and drug-related problems. We categorized the included articles in three groups: studies subjectively reviewing the clinical relevance of CDSS's output (21/30 studies) resulting in a positive predictive value (PPV) for clinical relevance of 4-80%; studies determining the relationship between alerts and actual events (10/30 studies) resulting in a PPV for actual events of 5-80%; and studies comparing output of CDSSs to chart/medication reviews in the whole study population (10/30 studies) resulting in a sensitivity of 28-85% and specificity of 42-75%. We found heterogeneity in the methods used and in the outcome measures. The validation studies did not report the use of a published CDSS validation strategy. To improve the effectiveness and uptake of CDSSs supporting a medication review, future research would benefit from a more systematic and comprehensive validation strategy.

Does Late-Life Depression Counteract the Beneficial Effect of Physical Activity on Cognitive Decline? Results From the NESDO Study.

OBJECTIVES: Depression both affects physical activity (PA) and cognition in older persons, yet its impact on the association between PA and cognitive decline is to be determined. We aimed to investigate the association between baseline PA and cognitive functioning over time, stratified for depression. METHODS: We used data of the Netherlands Study of Depression in Older persons (NESDO), a multi-site cohort study with 6-years follow-up. Patients with complete data on PA and cognitive functioning at baseline were included, yielding 394 participants for the analyses of whom 297 were depressed and 97 non-depressed. PA (continuous) was measured with the International Physical Activity Questionnaire. Linear mixed models were used to determine differential effects of baseline PA on the rate of decline of 5 standardized outcomes of cognitive functioning over 6-year follow-up. For this purpose, we examined the significance of the interaction-term (PA*time) in both basic and adjusted models. We also assessed the association between time and cognitive functioning. All analyses were stratified for depression. RESULTS: In both groups, no robust significant interactions of PA with time were found. Furthermore, only decline in working memory was significantly worse in the depressed compared to the non-depressed. CONCLUSION: At older age, the impact of a more inactive lifestyle on cognitive decline was shown to be limited, irrespective of depression that appeared to worsen age-related decline of working memory only. As a higher PA-level at older age has a positive effect on a multitude of other health outcomes, PA should still be encouraged in this population.

How to tackle the global challenge of falls?

Worldwide, falls and accompanying injuries are increasingly common, making their prevention and management a critical global challenge. The wealth of evidence to support interventions to prevent falls has recently (2022) been distilled in the first World Falls Guideline for Prevention and Management for Older Adults. The core of falls prevention includes (i) risk assessment and stratification; (ii) general recommendations on optimising physical function and mobility for all and (iii) offering a holistic, multidomain intervention to older adults at high risk of falls, in which the older adult's priorities, beliefs and resources are carefully considered. In recent decades, sustainable and adequately resourced falls prevention has proved challenging, although evidence suggests that suboptimal implementation of falls prevention is ineffective. Future research should focus on understanding the most successful approaches for implementation. To further optimise falls prevention, recent developments include technological innovation to identify and prevent falls, including exergaming. Further work is warranted to understand how to best incorporate the concepts of frailty and sarcopenia in falls prevention and management. This themed collection includes key articles in the field of falls prevention, covering several topics including risk factors, effective interventions, older adult's views, implementation issues and future perspectives.

Potentially inappropriate medications and their effect on falls during hospital admission.

OBJECTIVE: to investigate the effect of potentially inappropriate medications (PIMs) on inpatient falls and to identify whether PIMs as defined by STOPPFall or the designated section K for falls of STOPP v2 have a stronger association with inpatient falls when compared to the general tool STOPP v2. METHODS: a retrospective observational matching study using an electronic health records dataset of patients (≥70 years) admitted to an academic hospital (2015-19), including free text to identify inpatient falls. PIMs were identified using the STOPP v2, section K of STOPP v2 and STOPPFall. We first matched admissions with PIMs to those without PIMs on confounding factors. We then applied multinomial logistic regression analysis and Cox proportional hazards analysis on the matched datasets to identify effects of PIMs on inpatient falls. RESULTS: the dataset included 16,678 hospital admissions, with a mean age of 77.2 years. Inpatient falls occurred during 446 (2.7%) admissions. Adjusted odds ratio (OR) (95% confidence interval (CI)) for the association between PIM exposure and falls were 7.9 (6.1-10.3) for STOPP section K, 2.2 (2.0-2.5) for STOPP and 1.4 (1.3-1.5) for STOPPFall. Adjusted hazard ratio (HR) (95% CI) for the effect on time to first fall were 2.8 (2.3-3.5) for STOPP section K, 1.5 (1.3-1.6) for STOPP and 1.3 (1.2-1.5) for STOPPFall. CONCLUSIONS: we identified an independent association of PIMs on inpatient falls for all applied (de)prescribing tools. The strongest effect was identified for STOPP section K, which is restricted to high-risk medication for falls. Our results suggest that decreasing PIM exposure during hospital stay might benefit fall prevention, but intervention studies are warranted.

Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis.

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. DESIGN: systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. ELIGIBILITY CRITERIA: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. STUDY RECORDS: title/abstract and full-text screening by two reviewers. RISK OF BIAS: Cochrane Collaboration revised tool. DATA SYNTHESIS: results reported separately for different settings and sufficiently comparable studies meta-analysed. RESULTS: forty-nine heterogeneous studies were included. COMMUNITY: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85-1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70-1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69-1.14, I2 = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74-1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07-3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively. LONG-TERM CARE: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72-1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64-1.35, I2 = 92%, 7 s) for number of falls. CONCLUSIONS: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls.PROSPERO registration number: CRD42020218231.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Patterns of discordance of physical functioning in older persons; different associations for apathy and depression? Results from the NESDO-study.

OBJECTIVES: Discordance between self-reported functional limitations and performance-based physical functioning may have a negative impact in functional independence in older adults. We longitudinally examined baseline apathy- and depressive symptomatology as associates of discordance. METHOD: 469 participants from the multi-site cohort study NESDO were included. Self-reported functional limitations were assessed by two items derived from the WHO-Disability Assessment Schedule. Performance-based physical functioning included walking speed and handgrip-strength. Both measures were rescaled, with final sum-scores ranging from 0 to 6. Discordance-scores were computed by subtracting sum-scores on performance-based measures from self-reported functional limitations. Using latent growth curve analysis, we estimated individual trajectories of discordance at baseline, 2-and 6-years follow-up, consisting of the baseline discordance-score (intercept) and the yearly change of discordance-score (slope). We then estimated associations with apathy and depression indicators. RESULTS: At baseline, persons (mean age 70.48 years, 65% female, 73% depressed) on average overestimated their daily functioning compared to performance tests (b = 0.77, p < 0.001). The average discordance-scores yearly increased by 0.15 (p < 0.001). Only in models adjusted for several demographic and clinical characteristics, depression severity was negatively associated with discordance-scores at baseline (b=-0.01, p = 0.02), while apathy was not (b=-0.02, p = 0.21). No associations with change over time were found. CONCLUSION: In older persons, not indifference and diminished goal-directed activity, but negative emotions appear to underlie underestimation of one's physical capacity. Further research is needed to determine (1) to what extent targeting discordance results in actual preservation of physical functioning and (2) whether older persons with apathy and/or depression need different approaches for this purpose.

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Potentially inappropriate prescribing in older hospitalized Dutch patients according to the STOPP/START criteria v2: a longitudinal study.

PURPOSE: To investigate prevalence, independent associations, and variation over time of potentially inappropriate prescriptions in a population of older hospitalized patients. METHODS: A longitudinal study using a large dataset of hospital admissions of older patients (≥ 70 years) based on an electronic health records cohort including data from 2015 to 2019. Potentially inappropriate medication (PIM) and potential prescribing omission (PPO) prevalence during hospital stay were identified based on the Dutch STOPP/START criteria v2. Univariate and multivariate logistic regression were used for analyzing associations and trends over time. RESULTS: The data included 16,687 admissions. Of all admissions, 56% had ≥ 1 PIM and 58% had ≥ 1 PPO. Gender, age, number of medications, number of diagnoses, Charlson score, and length of stay were independently associated with both PIMs and PPOs. Additionally, number of departments and number of prescribing specialties were independently associated with PIMs. Over the years, the PIM prevalence did not change (OR = 1.00, p = .95), whereas PPO prevalence increased (OR = 1.08, p < .001). However, when corrected for changes in patient characteristics such as number of diagnoses, the PIM (aOR = 0.91, p < .001) and PPO prevalence (aOR = 0.94, p < .001) decreased over the years. CONCLUSION: We found potentially inappropriate prescriptions in the majority of admissions of older patients. Prescribing relatively improved over time when considering complexity of the admissions. Nevertheless, the high prevalence shows a clear need to better address this issue in clinical practice. Studies seeking effective (re)prescribing interventions are warranted.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.