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 is 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.

A European survey of older peoples' preferences, and perceived barriers and facilitators to inform development of a medication-related fall-prevention patient portal.

PURPOSE: Falls are a major and growing health care problem in older adults. A patient portal has the potential to provide older adults with fall-prevention advice to reduce fall-risk. However, to date, the needs and preferences regarding a patient portal in older people who have experienced falls have not been explored. This study assesses content preferences, potential barriers and facilitators with regard to using a patient portal, as perceived by older people who have experienced falls, and explores regional differences between European participants. METHODS: We conducted a survey of older adults attending an outpatient clinic due to a fall or fall-related injury, to explore their content preferences, perceived barriers, and facilitators with respect to a fall-prevention patient portal. Older adults (N = 121, 69.4% female, mean age: 77.9) were recruited from seven European countries. RESULTS: Almost two-thirds of respondents indicated they would use a fall-prevention patient portal. The portal would preferably include information on Fall-Risk-Increasing Drugs (FRIDs), and ways to manage other related/relevant medical conditions. Facilitators included a user-friendly portal, with easily accessible information and physician recommendations to use the portal. The most-commonly-selected barriers were privacy issues and usage fees. A family member's recommendation to use the portal was seemingly more important for Southern and Eastern European participants compared to the other regions. CONCLUSION: The majority of older people with lived falls experience expressed an interest in a fall-prevention patient portal providing personalized treatment advice to prevent further falls. The results will be used to inform the development of a fall-prevention patient portal. The fall-prevention patient portal is intended to be used in addition to a consultation with a physician. Future research is needed to explore how to prevent falls in older patients who are not interested in a fall-prevention patient portal.

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons.

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased ß1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

PURPOSE: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. METHODS: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. RESULTS: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. CONCLUSION: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults.

BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. METHODS: The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. RESULTS: In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00). CONCLUSION: This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults: A Systematic Review.

Importance: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. Objectives: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. Evidence Review: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Findings: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. Conclusions and Relevance: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

Depression, antidepressants and fall risk: therapeutic dilemmas-a clinical review.

PURPOSE: The aim of this clinical review was to summarize the existing knowledge on fall risk associated with antidepressant use in older adults, describe underlying mechanisms, and assist clinicians in decision-making with regard to (de-) prescribing antidepressants in older persons. METHODOLOGY: We comprehensively examined the literature based on a literature search in Pubmed and Google Scholar, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in depression in geriatric patients. We discuss use of antidepressants, potential fall-related side effects, and deprescribing of antidepressants in older persons. RESULTS: Untreated depression and antidepressant use both contribute to fall risk. Antidepressants are equally effective, but differ in fall-related side effect profile. They contribute to (or cause) falling through orthostatic hypotension, sedation/impaired attention, hyponatremia, movement disorder and cardiac toxicity. Falling is an important driver of morbidity and mortality and, therefore, requires prevention. If clinical condition allows, withdrawal of antidepressants is recommended in fall-prone elderly persons. An important barrier is reluctance of prescribers to deprescribe antidepressants resulting from fear of withdrawal symptoms or disease relapse/recurrence, and the level of complexity of deprescribing antidepressants in older persons with multiple comorbidities and medications. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antidepressants. CONCLUSIONS: (De-) prescribing antidepressants in fall-prone older adults is often challenging, but detailed insight in fall-related side effect profile of the different antidepressants and a recently developed expert-based decision aid STOPPFalls assists prescribers in clinical decision-making.

Effect of body surface area and gender on wall thickness thresholds in hypertrophic cardiomyopathy.

BACKGROUND: Family screening for hypertrophic cardiomyopathy (HCM) is based on genetic testing and clinical evaluation (maximal left ventricular wall thickness (MWT) ≥15 mm, or ≥13 mm in first-degree relatives of HCM patients). The aim of this study was to assess the effect of gender and body size on diagnosis of HCM and prediction of clinical outcome. METHODS: This study includes 199 genotype-positive subjects (age 44 ± 15 years, 50% men) referred for cardiac screening. Gender-specific reference values for MWT indexed by body surface area (BSA), height and weight were derived from 147 healthy controls. Predictive accuracy of each method for HCM-related events was assessed by comparing areas under the receiver operating characteristic curves (AUC). RESULTS: Men had a higher absolute, but similar BSA- and weight-indexed MWT compared with women (14.0 ± 3.9 mm vs 11.5 ± 3.8 mm, p < 0.05; 6.8 ± 2.1 mm/m2 vs 6.6 ± 2.4 mm/m2; 0.17 ± 0.06 mm/kg vs 0.17 ± 0.06 mm/kg, both p > 0.05). Applying BSA- and weight-indexed cut-off values decreased HCM diagnoses in the study group (48% vs 42%; 48% vs 39%, both p < 0.05), reclassified subjects in the largest, lightest and heaviest tertiles (≥2.03 m2: 58% vs 45%; ≤70 kg: 37% vs 46%; ≥85 kg: 53% vs 25%, all p < 0.05) and improved predictive accuracy (AUC 0.76 [95% CI 0.69-0.82] vs 0.78 [0.72-0.85]; and vs 0.80 [0.74-0.87]; both p < 0.05). CONCLUSIONS: In genotype-positive subjects referred for family screening, differences in MWT across gender are mitigated after indexation by BSA or weight. Indexation decreases the prevalence of HCM, particularly in larger men, and improves the predictive accuracy for HCM-related events.

Effectiveness of Cardiovascular Evaluations and Interventions on Fall Risk: A Scoping Review.

OBJECTIVE: Cardiovascular abnormalities are consistently associated with fall risk in older people. However, little research has been done to assess the effect of cardiovascular interventions on fall risk. The aim of this scoping review is to explore the current literature on the effectiveness of cardiovascular evaluations and interventions in reducing fall risk in older people. DESIGN: Scoping review. DATA SOURCES: Medline, Cochrane Library, and WHO ICTRP Search Portal were systematically searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) and intervention studies of community-dwelling adults aged ≥50 years or with a mean age of >60 years that assessed the effect of a cardiovascular assessment and interventions in reducing fall risk. Key search concepts were "falls" and "aged", and terms for different cardiovascular evaluations and interventions were included. The Cochrane Checklist for risk of bias and the ROBINS-I tool were used to assess the quality of the studies. RESULTS: Seven studies were included. The majority showed a reduction in falls after cardiovascular evaluation and intervention. Two out of four studies that focused on carotid sinus hypersensitivity (CSH) as a modifiable cardiovascular risk factor for falls, showed a significant reduction in falls after pacemaker implantation. Two studies that looked at sinus node dysfunction (SND) both showed a significant reduction in falls after pacemaker implantation. One study showed that 33% of the patients experienced a fall after cardiovascular evaluation and intervention, whereas all patients fell before assessment. CONCLUSIONS: The majority of the included studies showed a reduction in falls after the intervention. However, the number of published papers regarding the effect of cardiovascular assessment and interventions on falls is small. A standardized assessment of cardiovascular risk factors may be essential in preventing falls in older adults and could consequently reduce injuries, loss of quality of life, deaths, and fall-related expenditures.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Age modifies the association between apathy and recurrent falling in Dutch ambulant older persons with a high fall risk: Recurrent falling in Dutch outpatients, does apathy play a role?

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number of falls in the past 12 months in 243 outpatients aged ≥65 years with ≥3 fall risk-factors visiting a fall-clinic after a fall. We calculated Odds Ratio's (ORs), Incidence Rate Ratio's (IRRs) and their 95% Confidential Intervals (CI95) using multivariable regression and negative binomial regression analyses. We adjusted for cognitive functioning, depression, the use of fall risk increasing drugs, visual impairment, urine incontinence, comorbidity, smoking, use of alcohol, body mass index (BMI), and the number of months between assessment of fall risk and of apathy. We assessed effect modification by age and gender. In our study, apathy was independently associated with recurrent falling in patients aged 65-75 years: OR 2.8 (CI95 1.0-7.7). Overall, patients with apathy experienced 1.46 times as many falls in the past 12 months compared to patients without apathy (IRR 1.46 (CI95 1.0-2.1). To conclude, in high fall-risk older outpatients, apathy was cross-sectionally associated with recurrent falling in patients aged 65-75 years and the number of falls. Apathy appeared to be especially relevant in relation to falling in this age group. Whether apathy predicts recurrent falling is yet to be determined.

[The associations between God representations and suicidality among Christian patients with a major depressive disorder]. / De relatie tussen godsrepresentaties en suïcidaliteit bij christelijke patiënten met een depressieve stoornis.

BACKGROUND: Depression strongly increases the risk of suicide. Religion is described as a protective factor against suicide. Considering the emotional blunting associated with depression, it is important to investigate the affective dimension of religion. This dimension is conveyed in God representations.
AIM: To describe what types of God representation occur among Christian patients with major depressive disorder and to determine whether there is a relationship between types of God representation and suicide.
METHOD: Clinical and outpatients with a major depressive disorder (n=155) completed the Questionnaire God Representations and the Paykel Suicide Items. A k-means cluster analysis is applied to examine which types of God representations occur among depressed patients. Whether there is a relationship between the different God representations and suicide is examined by applying a linear regression analysis.
RESULTS: Depressed patients uphold two types of God representation: a positive type (n=82) with positive feelings towards God and where God was experienced as supportive, and a negative type (n=73) with anger and anxiety towards God and where God was experienced as passive. Patients with a negative type of God representation scored significantly higher on suicidality. The severity of depression was the main predictor of suicidality, but God representations were also related with a 4% increase in the explained variance.
CONCLUSION: In Christian patients with major depressive disorder a negative and a positive God representation emerged. Patients with a negative God representation mainly seem to feel abandoned by God. The suicidality is significantly increased in patients with a negative God representation, however, the increase in the proportion of the explained variance is small.

Integration of Murine and Human Studies for Mapping Periodontitis Susceptibility.

Periodontitis is one of the most common inflammatory human diseases with a strong genetic component. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWASs) of chronic periodontitis (CP) have largely been unsuccessful in identifying common susceptibility factors. A combination of quantitative trait loci (QTL) mapping in mice with association studies in humans has the potential to discover novel risk loci. To this end, we assessed alveolar bone loss in response to experimental periodontal infection in 25 lines (286 mice) from the Collaborative Cross (CC) mouse population using micro-computed tomography (µCT) analysis. The orthologous human chromosomal regions of the significant QTL were analyzed for association using imputed genotype data (OmniExpress BeadChip arrays) derived from case-control samples of aggressive periodontitis (AgP; 896 cases, 7,104 controls) and chronic periodontitis (CP; 2,746 cases, 1,864 controls) of northwest European and European American descent, respectively. In the mouse genome, QTL mapping revealed 2 significant loci (-log P = 5.3; false discovery rate = 0.06) on chromosomes 1 ( Perio3) and 14 ( Perio4). The mapping resolution ranged from ~1.5 to 3 Mb. Perio3 overlaps with a previously reported QTL associated with residual bone volume in F2 cross and includes the murine gene Ccdc121. Its human orthologue showed previously a nominal significant association with CP in humans. Use of variation data from the genomes of the CC founder strains further refined the QTL and suggested 7 candidate genes ( CAPN8, DUSP23, PCDH17, SNORA17, PCDH9, LECT1, and LECT2). We found no evidence of association of these candidates with the human orthologues. In conclusion, the CC populations enabled mapping of confined QTL that confer susceptibility to alveolar bone loss in mice and larger human phenotype-genotype samples and additional expression data from gingival tissues are likely required to identify true positive signals.

Prevalence of iron deficiency in a Dutch geriatric migrant population.

BACKGROUND: The prevalence of iron deficiency anaemia (IDA) rises with age. Migrants are potentially at higher risk for IDA because of differences in intake and uptake as well as their higher comorbid status. We assessed whether geriatric Turkish and Moroccan migrants have a higher prevalence of low iron status and IDA. METHODS: Retrospective case-control study in a geriatric outpatient clinic (2012-2015). In total, 188 consecutive Turkish and Moroccan migrants aged ≥ 65 years were included and matched with 188 Dutch controls. Matching was based on the visiting date of the patients. Main outcome measures were serum ferritin level (below 15 µg/l) and IDA. IDA was defined as anaemia according to the WHO definition, with a serum ferritin level below 15 µg/l and serum CRP below 10 mg/l. Multivariate logistic regression was performed to correct for confounders. RESULTS: Mean serum ferritin level was significantly lower in migrants (83.46 µg/l, SD 106.8 vs. 164.94 µg/l, SD 160.1, (p < 0.05)). In total, 7.4% met the IDA criteria, of these 5.6% were migrants and 1.8% were Dutch (p < 0.05). After correction for age, gender, BMI, and use of NSAIDs, a low ferritin level was associated with migrant status (OR 3.0, 95% CI 1.0-8.9) as was IDA (OR 2.9, 95% CI 1.2-7.2). CONCLUSION: Prevalence of low serum ferritin and IDA is increased in the first-generation Turkish and Moroccan geriatric migrant population. This might be caused by differences in iron intake or uptake from nutrition between the populations or because of gastrointestinal pathology; further study is warranted.

Vitamin B12 Intake and Related Biomarkers: Associations in a Dutch Elderly Population.

BACKGROUND: Vitamin B12 status is measured by four plasma/ serum biomarkers: total vitamin B12 (total B12), holotranscobalamin (holoTC), methylmalonic acid (MMA) and homocysteine (tHcy). Associations of B12 intake with holoTC and tHcy and associations between all four biomarkers have not been extensively studied. A better insight in these associations may contribute to an improved differentiation between vitamin B12 deficiency and a normal vitamin B12 status. OBJECTIVE: This study investigates associations between vitamin B12 intake and biomarkers and associations between biomarkers. DESIGN: In this cross-sectional observational study, levels of total B12, HoloTC, MMA and tHcy were determined in participants of the B-PROOF study: 2919 elderly people (≥65 years, with a mean age of 74.1 years, a mean BMI of 27.1 and 50% women) with elevated tHcy levels (≥12 µmol/L). B12 intake was assessed in a subsample. We assessed the association between intake and status with multivariate regression analysis. We explored the dose-response association between B12 intake and biomarkers and the association of total B12 and holoTC with tHcy and MMA with restricted cubic spline plots. RESULTS: A doubling of B12 intake was associated with 9% higher total B12, 15% higher HoloTC, 9% lower MMA and 2% lower tHcy. Saturation of biomarkers occurs with dietary intakes of >5 µg B12. Spline regression showed that levels of MMA and tHcy started to rise when vitamin B12 levels fall below 330 pmol/L and with HoloTC levels below 100 pmol/L, with a sharp increase with levels of B12 and HoloTC below 220 and 50 pmol/L respectively. CONCLUSIONS: In this study we observed a significant association between vitamin B12 intake and vitamin B12 biomarkers and between the biomarkers. The observed inflections for total B12 and holoTC with MMA and tHcy could indicate cut-off levels for further testing for B12 deficiency and determining subclinical B12 deficiency.

Food sources of vitamin D and their association with 25-hydroxyvitamin D status in Dutch older adults.

Various populations are at increased risk of developing a low vitamin D status, in particular older adults. Whereas sun exposure is considered the main source of vitamin D, especially during summer, dietary contributions should not be underestimated. This study aims to identify food sources of vitamin D that associate most strongly with serum vitamin D concentration. Data of 595 Dutch adults, aged ≥65 years, were analysed. Vitamin D intake was assessed with a food frequency questionnaire and 25-hydroxyvitamin D (25(OH)D) was determined in serum. Associations of total vitamin D intake and vitamin D intake from specific food groups with serum 25(OH)D status were examined by P-for trend analyses over tertiles of vitamin D intake, prevalence ratios (PRs), and spline regression. The prevalence of vitamin D deficiency was high, with 36% of the participants having a 25(OH)D status <50nmol/L. Participants with adequate 25(OH)D concentrations were more likely to be men and more likely to be younger than participants with vitamin D deficiency. Total median vitamin D intake was 4.3µg/day, of which 4.0µg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8µg/day, followed by the intake of fish and shellfish with 0.56µg/day. Participants with higher intakes of butter and margarine were 21% more likely to have a sufficient 25(OH)D status after adjustment for covariates (T1 vs. T3: PR 1.0 vs. 1.21 (95%CI: 1.03-1.42), P-for trend 0.02). None of the other food groups showed a significant association with the probability of having a sufficient 25(OH)D status. This study shows that vitamin D intake was positively associated with total serum 25(OH)D concentration, with butter and margarine being the most important contributors to total vitamin D intake.

A Comprehensive Fracture Prevention Strategy in Older Adults: The European Union Geriatric Medicine Society (EUGMS) Statement.

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

A comprehensive fracture prevention strategy in older adults: the European Union Geriatric Medicine Society (EUGMS) statement.

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society, in collaboration with the International Association of Gerontology and Geriatrics for the European Region, the European Union of Medical Specialists, and the International Osteoporosis Foundation-European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.