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.

Development of the ADFICE_IT clinical decision support system to assist deprescribing of fall-risk increasing drugs: A user-centered design approach.

INTRODUCTION: Deprescribing fall-risk increasing drugs (FRIDs) is promising for reducing the risk of falling in older adults. Applying appropriate deprescribing in practice can be difficult due to the outcome uncertainties associated with stopping FRIDs. The ADFICE_IT intervention addresses this complexity with a clinical decision support system (CDSS) that facilitates optimum deprescribing of FRIDs by using a fall-risk prediction model, aggregation of deprescribing guidelines, and joint medication management. METHODS: The development process of the CDSS is described in this paper. Development followed a user-centered design approach in which users and experts were involved throughout each phase. In phase I, a prototype of the CDSS was developed which involved a literature and systematic review, European survey (n = 581), and semi-structured interviews with clinicians (n = 19), as well as the aggregation and testing of deprescribing guidelines and the development of the fall-risk prediction model. In phase II, the feasibility of the CDSS was tested by means of two usability testing rounds with users (n = 11). RESULTS: The final CDSS consists of five web pages. A connection between the Electronic Health Record allows for the retrieval of patient data into the CDSS. Key design requirements for the CDSS include easy-to-use features for fast-paced clinical environments, actionable deprescribing recommendations, information transparency, and visualization of the patient's fall-risk estimation. Key elements for the software include a modular architecture, open source, and good security. CONCLUSION: The ADFICE_IT CDSS supports physicians in deprescribing FRIDs optimally to prevent falls in older patients. Due to continuous user and expert involvement, each new feedback round led to an improved version of the system. Currently, a cluster-randomized controlled trial with process evaluation at hospitals in the Netherlands is being conducted to test the effect of the CDSS on falls. The trial is registered with ClinicalTrials.gov (date; 7-7-2022, identifier: NCT05449470).

Leptin, ghrelin and high-molecular-weight adiponectin in relation to anxiety in older adults.

BACKGROUND: Leptin and ghrelin have been linked to depressive symptoms in older adults. There is a large overlap between depression and anxiety in this group. It is unclear whether the same associations exist with anxiety. Adiponectin has an inverse association with anxiety in older adults. However, the association between the most biologically active isoform - high-molecular-weight (HMW) adiponectin - and anxiety has not been previously reported. METHODS: We analyzed the association between leptin, ghrelin and HMW adiponectin and general symptoms of anxiety (HADS-A score ≥ 7) at baseline and after three years of follow-up in a population based cohort of older adults in the Netherlands (n = 898) using multivariable logistic regression analyses. RESULTS: For leptin there was significant effect modification by sex. We found a positive association between leptin and general symptoms of anxiety in men at baseline and after three years of follow-up after adjusting for depressive symptoms, when comparing the third to the first leptin tertile (T3 vs T1 OR 3.40, 95 % CI 1.08 - 10.78). We found no significant associations for ghrelin. HMW adiponectin was associated with general symptoms of anxiety at follow up. We found a positive association both before and after adjustment for depressive symptoms (T3 vs T1 OR 3.26, 95 % CI 1.36 - 7.83). CONCLUSIONS: Our results showed significant associations in men only between leptin and HMW adiponectin and general symptoms of anxiety after three years of follow up. Our findings contribute to further insight into the pathophysiology of anxiety in older adults. However, further research is necessary as we show associations.

Joint Trajectories of Performance-Based and Self-Reported Physical Functioning in Older Adults: A 20-Year Longitudinal Study in the Netherlands.

BACKGROUND: The well-known disablement process has been conceptualized as a series of transitions between progressive states of functional decline. We studied joint patterns of change within disablement states defined as walking speed, grip strength, and self-reported disability. METHODS: 1702 participants aged 65 and over were included from the Longitudinal Aging Study Amsterdam, spanning seven waves over 20 years (1996-2016). Group-based multi-trajectory modeling yielded trajectory clusters (TCs) of different patterns of change, further characterized by baseline sociodemographic characteristics, physical and cognitive health, and survival rate. RESULTS: Five TCs were identified, distinguished by increasing baseline age. Walking speed and disability showed generally concomitant trajectories. Women had poorer trajectories in grip strength than men, but not in walking speed and disability. Poor physical health distinguished especially the poorest, and cognitive impairment distinguished especially the one-before-poorest from the better TCs. DISCUSSION: The findings suggest that the disablement states are not generally distinct or sequential.

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.

Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models.

BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to €300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393.

The Effect of Genetic Variations in the Vitamin D Receptor Gene on the Course of Depressive Symptoms.

BACKGROUND: Evidence on the association between single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and depressive symptoms is inconclusive. OBJECTIVES: The primary aim of the study was to investigate the association between SNPs in the VDR gene and depressive symptoms. METHODS: In a sample of older adults from the Longitudinal Ageing Study Amsterdam (n = 922), depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale (CES-D scale) at baseline and after 3, 6, and 10 y of follow-up. Blood samples for SNP and serum 25-hydroxyvitamin D3 (25(OH)D3) determination were obtained at baseline. The association between 13 SNPs in the VDR gene and the course of depressive symptoms were evaluated using linear mixed models. The interaction between SNPs and serum 25(OH)D3 in relation to depressive symptoms was evaluated using multiple linear regression. RESULTS: No SNPs were associated with the course of depressive symptoms. Significant interactions between serum 25(OH)D3 and SNPs in the VDR gene were found. Stratified analysis revealed that within the GG genotype strata, 10 nmol/L higher serum 25(OH)D3 was associated with 0.27 (95% CI: -0.50, -0.04) and 0.23 (95% CI: -0.48, 0.02) lower scores on the CES-D scale for Cdx-2 and 1b-G-886A, respectively. This association was not found in persons having the GA or AA genotype. CONCLUSIONS: No SNPs are associated with the course of depressive symptoms. Stratified analysis shows that the effect of serum 25(OH)D3 concentrations on depressive symptoms is different among genotypes of Cdx-2 and 1b-G-886A. Future research should elucidate on the function of Cdx-2 and 1b-G-886A to describe their effect.

Cognitively healthy centenarians are genetically protected against Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians. RESULTS: Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10-71), and 2-fold lower compared to age-matched controls (P = 5.83 × 10-17). DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems. HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.

Long-term trajectories of peak expiratory flow rate in older men and women show linear decline mainly determined by baseline levels.

BACKGROUND: Peak expiratory flow rate (PEFR) predicts mortality and other negative health outcomes. However, little evidence exists on how PEFR changes with ageing and how trajectories of change differ among older people. AIMS: To identify trajectories of PEFR in older men and women, and to study characteristics associated with these trajectories. METHODS: Data from the Longitudinal Aging Study Amsterdam were used, an ongoing cohort study in a representative sample of Dutch older men and women. PEFR was assessed using the Mini-Wright peak flow meter across a 13-year follow-up in 991 men and 1107 women. Trajectories were analyzed using Latent Class Growth Analysis. RESULTS: Mean age was 72.5 (SD 8.4) in men and 72.4 (SD 8.4) in women. In men, three declining trajectories were identified, i.e. high, intermediate and low, with prevalences of 30%, 46% and 24%, respectively. In women, two declining trajectories were identified, i.e. high and low, with prevalences of 62 and 38%. All trajectories showed linear decline and differed mostly with regard to their intercept. Significant differences between trajectories with regard to baseline demographic, health and lifestyle characteristics were observed, e.g., men and women in the low PEFR trajectory were older, had more chronic diseases, and were more often smoker. DISCUSSION AND CONCLUSIONS: Trajectories in both men and women differ mainly in baseline level of PEFR and not in rate of decline over time. Therefore, one PEFR measurement might be sufficient to give an indication of the trajectory that an older adult is likely to follow.

Combining user-centered design and behavioral theory to enhance health technologies: A personas-based approach for a primary-care based multifactorial falls risk assessment tool.

INTRODUCTION: Multifactorial falls risk assessment tools (FRATs) can be an effective falls prevention method for older adults, but are often underutilized by health care professionals (HCPs). This study aims to enhance the use and implementation of multifactorial FRATs by combining behavioral theory with the user-centered design (UCD) method of personas construction. Specifically, the study aimed to (1) construct personas that are based on external (i.e., needs, preferences) and intrinsic user characteristics (i.e., behavioral determinants); and (2) use these insights to inform requirements for optimizing an existing Dutch multifactorial FRAT (i.e., the 'Valanalyse'). METHODS: Survey data from HCPs (n = 31) was used to construct personas of the 'Valanalyse.' To examine differences between clusters on 68 clustering variables, a multivariate cluster analysis technique with non-parametric analyses and computational methods was used. The aggregated external and intrinsic user characteristics of personas were used to inform key design and implementation requirements for the 'Valanalyse,' respectively, whereby intrinsic user characteristics were matched with appropriate behavior change techniques to guide implementation. RESULTS: Significant differences between clusters were observed in 20 clustering variables (e.g., behavioral beliefs, situations for use). These variables were used to construct six personas representing users of each cluster. Together, the six personas helped operationalize four key design requirements (e.g., guide treatment-related decision making) and 14 implementation strategies (e.g., planning coping responses) for optimizing the 'Valanalyse' in Dutch geriatric, primary care settings. CONCLUSION: The findings suggest that theory- and evidence-based personas that encompass both external and intrinsic user characteristics are a useful method for understanding how the use and implementation of multifactorial FRATs can be optimized with and for HCPs, providing important implications for developers and eHealth interventions with regards to encouraging technology adoption.

Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

BACKGROUND: Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies. OBJECTIVE: This study aimed to compare more frequently dosed vitamin D2 and vitamin D3 in improving total 25(OH)D and determine the concomitant effect of response modifiers on heterogeneity, and secondly, to compare the vitamin D2-associated change in 25(OH)D2 with the vitamin D3-associated change in 25(OH)D3. METHODS: PubMed, EMBASE, Cochrane, and the Web of Science Core collection were searched for randomized controlled trials of vitamin D2 compared with vitamin D3, daily or once/twice weekly dosed. After screening for eligibility, relevant data were extracted for meta-analyses to determine the standardized mean difference when different methods of 25(OH)D analyses were used. Otherwise, the weighted mean difference (WMD) was determined. RESULTS: Overall, the results based on 20 comparative studies showed vitamin D3 to be superior to vitamin D2 in raising total 25(OH)D concentrations, but vitamin D2 and vitamin D3 had a similar positive impact on their corresponding 25(OH)D hydroxylated forms. The WMD in change in total 25(OH)D based on 12 daily dosed vitamin D2-vitamin D3 comparisons, analyzed using liquid chromatography-tandem mass spectrometry, was 10.39 nmol/L (40%) lower for the vitamin D2 group compared with the vitamin D3 group (95% confidence interval: -14.62, -6.16; I2 = 64%; P < 00001). Body mass index (BMI) appeared to be the strongest response modifier, reducing heterogeneity to 0% in both subgroups. The vitamin D2- and vitamin D3-induced change in total 25(OH)D lost significance predominantly in subjects with a BMI >25 kg/m2 (P = 0.99). However, information on BMI was only available in 13/17 daily dosed comparisons. CONCLUSIONS: Vitamin D3 leads to a greater increase of 25(OH)D than vitamin D2, even if limited to daily dose studies, but vitamin D2 and vitamin D3 had similar positive impacts on their corresponding 25(OH)D hydroxylated forms. Next to baseline 25(OH)D concentration, BMI should be considered when comparing the effect of daily vitamin D2 and vitamin D3 supplementation on total 25(OH)D concentration. This study was registered in PROSPERO as CRD42021272674.

The phenotypic and genotypic association of grip strength with frailty, physical performance and functional limitations over time in older adults.

OBJECTIVES: To replicate the phenotypic associations of grip strength with frailty, physical performance and functional limitations in older adults for longer follow-up periods and to examine whether these associations are due to shared genetic factors. METHODS: In total 2,262 participants 55 years and older with follow-up data up to 23 years (Nobservations = 8,262) from the Longitudinal Aging Study Amsterdam were included. Weighted polygenic risk scores for grip strength (PRS-GS) were built using the genome-wide meta-analysis results from UK Biobank as reference. Grip strength was measured two times on each hand using a dynamometer. Frailty index (FI) and frailty phenotype were operationalised following standard procedures. Performance tests included a timed walk test, a repeated chair stands test and put on-take off cardigan test. Functional limitations were assessed using a questionnaire with six items. RESULTS: Higher grip strength was phenotypically associated with lower FI (b = -0.013, 95% CI (-0.016, -0.009)), better physical performance (b = 0.040, 95% CI (0.026, 0.054)) and less functional limitations (OR = 0.965, 95% CI (0.954, 0.977)) over time for follow-up periods up to 23 years. However, PRS-GS was not associated with any of the traits. CONCLUSION: The phenotypic associations between grip strength, frailty, physical performance and functional limitations were replicated for follow-up periods up to 23 years. However, the associations between the traits could not be explained by shared genetics potentially indicating a more relevant involvement of non-genetic factors.

Effects of a clinical decision support system and patient portal for preventing medication-related falls in older fallers: Protocol of a cluster randomized controlled trial with embedded process and economic evaluations (ADFICE_IT).

BACKGROUND: Falls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs. METHODS: A multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient's consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression. DISCUSSION: The findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449470 (7-7-2022).

Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.

Changes in physical performance according to job demands across three cohorts of older workers in the Longitudinal Aging Study Amsterdam.

This study set out to evaluate the association between job demands at baseline and physical performance over a six-year period across three cohorts of older Dutch workers examined 10 years apart. Data were drawn from three cohorts (1992-1999, 2002-2009 and 2012-2019) of the Longitudinal Aging Study Amsterdam. Individuals aged 55-65 years from each cohort who worked for pay were included (n = 274, n = 416, n = 618, respectively). Physical performance was measured using gait speed and chair stand performance. A population-based job exposure matrix was used to indicate levels of exposure probability of physical (use of force and repetitive movements) and psychosocial (cognitive demands and time pressure) job demands. We found that psychosocial job demands increased and physical demands decreased across the three cohorts. No between cohort differences were found for how job demands affected changes in physical performance over follow-up. For men, faster decline in gait speed was observed when comparing higher and lower use of force at baseline (ß -0.012, 95% CI -0.021, -0.004). Greater use of force and repetitive movements were associated with faster decline in chair stand performance (ß -0.012, 95% CI -0.020, -0.004 and ß -0.009, 95% CI -0.017, -0.001, respectively). In women, no association of job demands on change in physical performance was observed. The study concluded that higher physical job demands were associated with stronger decline in physical performance across six years for men in all cohorts, while no associations were found among women.

Methodological aspects of in vivo axial loading in rodents: a systematic review.

Axial loading in rodents provides a controlled setting for mechanical loading, because load and subsequent strain, frequency, number of cycles and rest insertion between cycles, are precisely defined. These methodological aspects as well as factors, such as ovariectomy, aging, and disuse may affect the outcome of the loading test, including bone mass, structure, and bone mineral density. This review aims to overview methodological aspects and modifying factors in axial loading on bone outcomes. A systematic literature search was performed in bibliographic databases until December 2021, which resulted in 2183 articles. A total of 144 articles were selected for this review: 23 rat studies, 74 mouse studies, and 47 knock out (KO) mouse studies. Results indicated that peak load, frequency, and number of loading cycles mainly affected the outcomes of bone mass, structure, and density in both rat and mouse studies. It is crucial to consider methodological parameters and modifying factors such as age, sex-steroid deficiency, and disuse in loading protocols for the prediction of loading-related bone outcomes.

Validation of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Geriatric Outpatients.

OBJECTIVES: Before being used in clinical practice, a prediction model should be tested in patients whose data were not used in model development. Previously, we developed the ADFICE_IT models for predicting any fall and recurrent falls, referred as Any_fall and Recur_fall. In this study, we externally validated the models and compared their clinical value to a practical screening strategy where patients are screened for falls history alone. DESIGN: Retrospective, combined analysis of 2 prospective cohorts. SETTING AND PARTICIPANTS: Data were included of 1125 patients (aged ≥65 years) who visited the geriatrics department or the emergency department. METHODS: We evaluated the models' discrimination using the C-statistic. Models were updated using logistic regression if calibration intercept or slope values deviated significantly from their ideal values. Decision curve analysis was applied to compare the models' clinical value (ie, net benefit) against that of falls history for different decision thresholds. RESULTS: During the 1-year follow-up, 428 participants (42.7%) endured 1 or more falls, and 224 participants (23.1%) endured a recurrent fall (≥2 falls). C-statistic values were 0.66 (95% CI 0.63-0.69) and 0.69 (95% CI 0.65-0.72) for the Any_fall and Recur_fall models, respectively. Any_fall overestimated the fall risk and we therefore updated only its intercept whereas Recur_fall showed good calibration and required no update. Compared with falls history, Any_fall and Recur_fall showed greater net benefit for decision thresholds of 35% to 60% and 15% to 45%, respectively. CONCLUSIONS AND IMPLICATIONS: The models performed similarly in this data set of geriatric outpatients as in the development sample. This suggests that fall-risk assessment tools that were developed in community-dwelling older adults may perform well in geriatric outpatients. We found that in geriatric outpatients the models have greater clinical value across a wide range of decision thresholds compared with screening for falls history alone.

Development and validation of an intrinsic capacity composite score in the Longitudinal Aging Study Amsterdam: a formative approach.

BACKGROUND: Intrinsic capacity (IC) defined by the WHO refers to the composite of five domains of capacities. So far, developing and validating a standardized overall score of the concept have been challenging partly because its conceptual framework has been unclear. We consider that a person's IC is determined by its domain-specific indicators suggesting a formative measurement model. AIMS: To develop an IC score applying a formative approach and assess its validity. METHODS: The study sample (n = 1908) consisted of 57-88-year-old participants from the Longitudinal Aging Study Amsterdam (LASA). We used logistic regression models to select the indicators to the IC score with 6-year functional decline as an outcome. An IC score (range 0-100) was constructed for each participant. We examined the known-groups' validity of the IC score by comparing groups based on age and number of chronic diseases. The criterion validity of the IC score was assessed with 6-year functional decline and 10-year mortality as outcomes. RESULTS: The constructed IC score included seven indicators covering all five domains of the construct. The mean IC score was 66.7 (SD 10.3). The scores were higher among younger participants and those who had lower number of chronic diseases. After adjustment for sociodemographic indicators, chronic diseases, and BMI, a one-point higher IC score was associated with a 7% decreased risk for 6-year functional decline and a 2% decreased risk for 10-year mortality. CONCLUSIONS: The developed IC score demonstrated discriminative ability according to age and health status and is associated with subsequent functional decline and mortality.

External validation of the Johns Hopkins Fall Risk Assessment Tool in older Dutch hospitalized patients.

PURPOSE: Fall prevention is a safety goal in many hospitals. The performance of the Johns Hopkins Fall Risk Assessment Tool (JHFRAT) in older inpatients is largely unknown. We aimed to assess the JHFRAT performance in a large sample of Dutch older inpatients, including its trend over time. METHODS: We used an Electronic Health Records (EHR) dataset with hospitalized patients (≥ 70), admitted for ≥ 24 h between 2016 and 2021. Inpatient falls were extracted from structured and free-text data. We assessed the association between JHFRAT and falls using logistic regression. For test accuracy, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Discrimination was measured by the AUC. For calibration, we plotted the predicted fall probability with the actual probability of falls. For time-related effects, we calculated the AUC per 6 months (using data of patients admitted during the 6 months' time interval) and plotted these different AUC values over time. Furthermore, we compared the model (JHFRAT and falls) with and without adjusting for seasonal influenza, COVID-19, spring, summer, fall or winter periods. RESULTS: Data included 17,263 admissions with at least 1 JHFRAT measurement, a median age of 76 and a percentage female of 47%. The in-hospital fall prevalence was 2.5%. JHFRAT [OR = 1.11 (1.03-1.20)] and its subcategories were significantly associated with falls. For medium/high risk of falls (JHFRAT > 5), sensitivity was 73%, specificity 51%, PPV 4% and NPV 99%. The overall AUC was 0.67, varying over time between 0.62 and 0.71 (for 6 months' time intervals). Seasonal influenza did affect the association between JHFRAT and falls. COVID-19, spring, summer, fall or winter did not affect the association. CONCLUSIONS: Our results show an association between JHFRAT and falls, a low discrimination by JHFRAT for older inpatients and over-prediction in the calibration. Improvements in the fall-risk assessment are warranted to improve efficiency.