Health care providers acceptance of default prescribing of TB preventive treatment for people living with HIV in Malawi: a qualitative study.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) substantially reduces the risk of developing active TB for people living with HIV (PLHIV). We utilized a novel implementation strategy based on choice architecture (CAT) which makes TPT prescribing the default option. Through CAT, health care workers (HCWs) need to "opt-out" when choosing not to prescribe TPT to PLHIV. We assessed the prospective, concurrent, and retrospective acceptability of TPT prescribing among HCWs in Malawi who worked in clinics participating in a cluster randomized trial of the CAT intervention. METHODS: 28 in-depth semi-structured interviews were conducted with HCWs from control (standard prescribing approach) and intervention (CAT approach) clinics. The CAT approach was facilitated in intervention clinics using a default prescribing module built into the point-of-care HIV Electronic Medical Record (EMR) system. An interview guide for the qualitative CAT assessment was developed based on the theoretical framework of acceptability and on the normalization process theory. Thematic analysis was used to code the data, using NVivo 12 software. RESULTS: We identified eight themes belonging to the three chronological constructs of acceptability. HCWs expressed no tension for changing the standard approach to TPT prescribing (prospective acceptability); however, those exposed to CAT described several advantages, including that it served as a reminder to prescribe TPT and routinized TPT prescribing (concurrent acceptability). Some felt that CAT may reduce HCW´s autonomy and might lead to inappropriate TPT prescribing (retrospective acceptability). CONCLUSIONS: The default prescribing module for TPT has now been incorporated into the point-of-care EMR system nationally in Malawi. This seems to fit the acceptability of the HCWs. Moving forward, it is important to train HCWs on how the EMR can be leveraged to determine who is eligible for TPT and who is not, while acknowledging the autonomy of HCWs.

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.

Malnutrition risk and oropharyngeal dysphagia in the chronic post-stroke phase.

Background: Oropharyngeal dysphagia (OD) and malnutrition are associated with poor clinical outcomes after stroke. The present study evaluated (1) malnutrition risk and OD-related characteristics in patients with chronic post-stroke OD, and (2) the relationship between on the one hand OD severity and on the other hand functional oral intake and dysphagia-specific quality of life. Methods: A cross-sectional study was conducted in a Dutch interdisciplinary outpatient clinic for OD. The standardized examination protocol comprised: clinical ear, nose, and throat examination, body mass index, the short nutritional assessment questionnaire (SNAQ), a standardized fiberoptic endoscopic evaluation of swallowing (FEES), the functional oral intake scale (FOIS), and the MD Anderson dysphagia inventory (MDADI). Results: Forty-two consecutive patients with chronic post-stroke OD were included. Mean (±SD) age and BMI of the population were 69.1 (±8.7) years and 26.8 (±4.1) kg/m2 respectively. Seventeen (40.4%) patients presented a moderate to high risk of malnutrition (SNAQ score≥2). The FEES examination showed moderate to severe OD in 28 (66.7%) patients. The severity of OD was significantly related to the FOIS score but not to the MDADI scores. Conclusion: In this specific sample of referred stroke patients, moderate to severe OD and moderate to high risk of malnutrition were common. Despite the use of clinical practice guidelines on stroke and a normal nutritional status at first sight, repeated screening for malnutrition and monitoring the severity and management of OD remain important elements in the care of patients with chronic post-stroke OD.

[Dairy products help aged care residents to maintain strong bones]. / Zuivel kan botten verzorgingshuisbewoner sterk houden.

A well-performed and large intervention study by Iuliano et al. showed that protein and calcium supplementation via regular dairy products reduces the risk of fractures and falls in vitamin D replete older adults in aged care facilities. The study was performed in Australia, which raises the question whether their intervention might also be effective in aged care facilities in the Netherlands. Intake levels of protein and calcium are comparable between Australian and Dutch older adults. A higher protein intake, for example from dairy, is associated with higher muscle mass, muscle strength and bone density. Iuliano et al. showed that with accessible, regular food products, relevant health outcomes can be improved. These results are relevant for Dutch older adults as well. Future research should investigate whether sustainable dairy substitutes can be just as successful.

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.

The Effect of Food Odor Exposure on Appetite and Nutritional Intake of Older Adults with Dementia.

OBJECTIVES: Dementia can lead to decreased appetite and nutritional intake. Food odor exposure has been shown to increase appetite and nutritional intake in young healthy adults. This study investigates the effect of food odor exposure on appetite, nutritional intake and body weight of Dutch nursing home residents with dementia. DESIGN: This was a one-armed, non-randomized, non-blinded intervention study consisting of a four-week control period followed by a twelve-week intervention period. SETTING: Four nursing homes in the Netherlands. PARTICIPANTS: Forty-five nursing home residents with dementia. INTERVENTION: During the intervention period, odors were dispersed prior to the main meals. MEASUREMENTS: General and specific appetite for sweet and savory foods was measured weekly. Nutritional intake was measured once during the control period and three times during the intervention period through a 3-day food record. Body weight was assessed at the start and end of the control period and at the start, end and halfway the intervention period. Data were analyzed with linear mixed models. RESULTS: Small changes in general and specific appetite were observed after odor exposure. Overall energy intake did not change during the first four intervention weeks, but increased during the second and third (+118kcal/d, p=0.003 and +122kcal/d, p=0.004). Protein intake and body weight did not significantly change during the study. CONCLUSION: In this study, no clinically relevant changes in appetite, nutritional intake and body weight were observed after food odor exposure. Future studies should assess the effect of natural food odors and/or meal-tailored odors on nutritional intake of older adults with dementia.

Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial.

OBJECTIVE: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. DESIGN: Two year cluster randomised controlled trial. SETTING: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. PARTICIPANTS: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). INTERVENTION: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). MAIN OUTCOME MEASURES: Group differences in incidence of fractures, falls, and all cause mortality. RESULTS: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08). CONCLUSIONS: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000228785.

A Propensity Score Matched Approach to Assess the Associations of Commonly Prescribed Medications with Fall Risk in a Large Harmonized Cohort of Older Ambulatory Persons.

INTRODUCTION: Several medication classes are considered to present risk factors for falls. However, the evidence is mainly based on observational studies that often lack adequate adjustment for confounders. Therefore, we aimed to assess the associations of medication classes with fall risk by carefully selecting confounders and by applying propensity score matching (PSM). METHODS: Data from several European cohorts, harmonized into the ADFICE_IT cohort, was used. Our primary outcome was time until the first fall within 1-year follow-up. The secondary outcome was a fall in the past year. Our exposure variables were commonly prescribed medications. We used 1:1 PSM to match the participants with reported intake of specific medication classes with participants without. We constructed Cox regression models stratified by the pairs matched on the propensity score for our primary outcome and conditional logistic regression models for our secondary outcome. RESULTS: In total, 32.6% of participants fell in the 1-year follow-up and 24.4% reported falling in the past year. ACE inhibitor users (prevalence of use 15.3%) had a lower fall risk during follow-up when matched to non-users, with a hazard ratio (HR) of 0.82 (95% CI 0.68-0.98). Also, statin users (prevalence of use 20.1%) had a lower risk, with an HR of 0.76 (95% CI 0.65-0.90). Other medication classes showed no association with risk of first fall. Also, in our secondary outcome analyses, statin users had a significantly lower risk. Furthermore, ß-blocker users had a lower fall risk and proton pump inhibitor use was associated with a higher risk in our secondary outcome analysis. CONCLUSION: Many commonly prescribed medication classes showed no associations with fall risk in a relatively healthy population of community-dwelling older persons. However, the treatment effects and risks can be heterogeneous between individuals. Therefore, focusing on identification of individuals at risk is warranted to optimize personalized falls prevention.

Joint action malnutrition in the elderly (MaNuEL) knowledge hub: summary of project findings.

PURPOSE: The Joint Action Malnutrition in the Elderly (MaNuEL) Knowledge Hub was established to extend scientific knowledge, strengthen evidence-based practice, build a sustainable, transnational network of experts and harmonize research and clinical practice in the field of protein-energy malnutrition in older persons. This paper aims to summarize the main scientific results achieved during the 2-year project and to outline the recommendations derived. METHODS: 22 research groups from seven countries (Austria, France, Germany, Ireland, Spain, The Netherlands and New Zealand) worked together on 6 relevant domains of malnutrition-i.e. prevalence, screening, determinants, treatment, policy measures and education for health care professionals-making use of existing datasets, evidence and expert knowledge. RESULTS: Four systematic reviews, six secondary data analyses of existing cohort and intervention studies, two web-based surveys and one Delphi study were performed. In addition, a scoring system to rate malnutrition screening tools and a theoretical framework on the aetiology of malnutrition in older persons were developed. Based on these activities and taking existing evidence into consideration, 13 clinical practice, 9 research and 4 policy recommendations were developed. The MaNuEL Toolbox was created and made available to effectively distribute and disseminate the MaNuEL results and recommendations. CONCLUSIONS: The MaNuEL Knowledge Hub successfully achieved its aims. Results and recommendations will support researchers, healthcare professionals, policy-makers as well as educational institutes to advance their efforts in tackling the increasing problem of protein-energy malnutrition in the older population.

Gaze direction affects walking speed when using a self-paced treadmill with a virtual reality environment.

BACKGROUND: In a previous study it was observed that participants increase their walking speed during a dual task while walking on a self-paced treadmill in a virtual reality (VR) environment (Gait Real time Analysis Interactive Lab (GRAIL)). This observation is in contrast with the limited resources hypothesis, which suggests walking speed of healthy persons to decrease when performing a cognitive dual task. AIM: The aim of the present study was therefore to determine whether the cognitive demand of the task, an aroused feeling, discrepancy in optic flow or a change in gaze direction caused participants to walk faster in this computer assisted rehabilitation environment. MATERIALS: The GRAIL included a self-paced treadmill, a motion-capture system and synchronized VR environments. METHODS: Thirteen healthy young adults (mean age 21.6 ±â€¯2.5) were included in this study. Participants walked on the self-paced treadmill while seven different intervention conditions (IC) were offered. Prior to each IC, a control condition (CC) was used to determine the natural self-selected walking speed. Walking speed during the last 30 s of each IC was compared with the walking speed during the last 30 s of the preceding CC. RESULTS: Results show that the height on which a visual task was presented in the VR environment, influenced walking speed. Participants walked faster when gaze was directed above the focus of expansion. SIGNIFICANCE: These findings contribute to a further understanding of the differences between walking in a real life environment or computer assisted rehabilitation environment. When analyzing gait on a self-paced treadmill in the future, one must be attentive where to place a visual stimulus in the VR environment.

Muscle mass and strength gains following 6 months of resistance type exercise training are only partly preserved within one year with autonomous exercise continuation in older adults.

INTRODUCTION: Although resistance type exercise training (RT) effectively increases muscle mass and strength in older individuals, it remains unclear whether gains in muscle mass and strength are maintained without continued supervised training. We assessed the capacity of older individuals to maintain muscle mass and strength gains one year after partaking in a successful RT program. METHODS: Fifty-three healthy older adults performed a 24-wk supervised RT program. Upon the cessation of the training program, participants were not provided with any advice or incentives to continue exercise training. One year after completion of the training program, all participants were contacted and invited back to the laboratory to assess anthropometrics, body composition (DXA), quadriceps muscle cross-sectional area (CSA) (CT-scan), muscle strength (1RM knee extension/leg press), and muscle fiber characteristics (muscle biopsy). Following primary analyses on all participants that responded to the invitation (n = 35), participants were divided into two groups: individuals who had continued to perform exercise training on an individual basis (EXER group; n = 16) and individuals who had not continued to perform any regular exercise (STOP group; n = 19) after completing the RT program. RESULTS: The initial increases in quadriceps CSA (+506 ±â€¯209 and +584 ±â€¯287 mm2) and knee extension strength (+32 ±â€¯12 vs +34 ±â€¯10 kg) after the 24-wk RT program did not differ between the STOP and EXER group (all P > 0.05). One year after discontinuation of the RT program, participants had lost muscle mass (P < 0.01), with a greater decline in quadriceps CSA in the STOP vs EXER group (-579 ±â€¯268 vs -309 ±â€¯253 mm2, respectively; P < 0.05). Muscle strength had decreased significantly compared to values after completing the RT program (P < 0.01), with no differences observed between the STOP vs EXER group (knee extension: -21 ±â€¯8 vs -18 ±â€¯8 kg, respectively; P > 0.05), yet remained higher compared with values before the RT program (P < 0.05). CONCLUSION: Though prolonged RT can effectively increase muscle mass and strength in the older population, muscle mass gains are lost and muscle strength gains are only partly preserved within one year if the supervised exercise program is not continued.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Association between Oropharyngeal Dysphagia and Malnutrition in Dutch Nursing Home Residents: Results of the National Prevalence Measurement of Quality of Care.

OBJECTIVES: Nursing home residents often suffer from multi-morbidities and geriatric syndromes leading to lower quality of life or mortality. Oropharyngeal dysphagia (OD) and malnutrition are profound conditions in this complex profile of multi-morbidities and are associated with deprived mental -and physical health status, e.g. aspiration pneumonia or dehydration. This study aimed to assess the association between OD and malnutrition in Dutch nursing home residents. DESIGN: Data for this cross-sectional study were obtained from the annual National Prevalence Measurement of Quality of Care (LPZ). SETTING: The National Prevalence Measurement of Quality of Care was conducted in Nursing Homes in The Netherlands. PARTICIPANTS: Participants were nursing home residents age 65 or older and admitted to psychogeriatric- or somatic wards. MEASUREMENTS: The measurements were taken by trained nurses from the participating nursing homes. Anthropometric measurements and unintended weight loss (%) were assessed to determine nutritional status (malnutrition). OD was assessed by means of a standardized questionnaire assessing clinically relevant symptoms of OD such as swallowing problems or sneezing/coughing while swallowing. Cox regression was applied to assess the association between malnutrition and clinically relevant symptoms of OD in older Dutch nursing home residents. RESULTS: Approximately 12% of the residents suffered from swallowing problems and 7% sneezed/coughed while swallowing liquids or solid foods. Approximately 10% of the residents was malnourished. Residents with OD symptoms were more often malnourished compared to residents without OD symptoms. Approximately 17% of the problematic swallowers were concurrently malnourished. Increased risk for malnutrition was found in residents suffering from swallowing problems (PR 1.5, 95%CI 1.2-1.9), as well as in residents that sneezed/coughed while swallowing (PR 1.3, 95%CI 1.0-1.7). Stratification based on wards revealed that problematic swallowers from somatic wards were at a high risk of malnutrition (PR 1.9, 95%CI 1.3-2.8). CONCLUSION: Clinically relevant symptoms of oropharyngeal dysphagia, such as swallowing problems and sneezing/coughing while swallowing are associated with increased risk of malnutrition in psychogeriatric and somatic Dutch nursing home residents.

Mediterranean diet and hip fracture incidence among older adults: the CHANCES project.

The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk. INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults. METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis. RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence. CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

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.

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.

The Impact of Dietary Protein or Amino Acid Supplementation on Muscle Mass and Strength in Elderly People: Individual Participant Data and Meta-Analysis of RCT's.

OBJECTIVES: Increasing protein or amino acid intake has been promoted as a promising strategy to increase muscle mass and strength in elderly people, however, long-term intervention studies show inconsistent findings. Therefore, we aim to determine the impact of protein or amino acid supplementation compared to placebo on muscle mass and strength in older adults by combining the results from published trials in a meta-analysis and pooled individual participant data analysis. DESIGN: We searched Medline and Cochrane databases and performed a meta-analysis on eight available trials on the effect of protein or amino acid supplementation on muscle mass and strength in older adults. Furthermore, we pooled individual data of six of these randomized double-blind placebo-controlled trials. The main outcomes were change in lean body mass and change in muscle strength for both the meta-analysis and the pooled analysis. RESULTS: The meta-analysis of eight studies (n=557) showed no significant positive effects of protein or amino acid supplementation on lean body mass (mean difference: 0.014 kg: 95% CI -0.152; 0.18), leg press strength (mean difference: 2.26 kg: 95% CI -0.56; 5.08), leg extension strength (mean difference: 0.75 kg: 95% CI: -1.96, 3.47) or handgrip strength (mean difference: -0.002 kg: 95% CI -0.182; 0.179). Likewise, the pooled analysis showed no significant difference between protein and placebo treatment on lean body mass (n=412: p=0.78), leg press strength (n=121: p=0.50), leg extension strength (n=121: p=0.16) and handgrip strength (n=318: p=0.37). CONCLUSIONS: There is currently no evidence to suggest that protein or amino acid supplementation without concomitant nutritional or exercise interventions increases muscle mass or strength in predominantly healthy elderly people.

[Amyloidosis despite normal ESR]. / Niet-verhoogde BSE, maar toch amyloïdose.

BACKGROUND: Amyloidosis is a clinical picture brought on by extracellular deposits of insoluble, non-degradable proteins. The clinical presentation of amyloidosis depends upon the type of protein and the organ afflicted. CASE DESCRIPTION: A 65-year-old woman had stiffness of the locomotor apparatus, recurrent carpal tunnel syndrome and problems with swallowing. Laboratory and urine investigations initially showed no abnormalities, but histopathological investigation of a synovial biopsy revealed amyloidosis with light-chain deposits. This turned out to be due to multiple myeloma. CONCLUSION: Amyloidosis can present with atypical symptoms, such as stiffness. Normal erythrocyte sedimentation rate (ESR) and normal urine analysis do not exclude this diagnosis. When there are clinical indications of amyloidosis further analysis for free-light chains should be performed, even when ESR is normal.

Protein Enrichment of Familiar Foods as an Innovative Strategy to Increase Protein Intake in Institutionalized Elderly.

OBJECTIVE: To increase the protein intake of older adults, protein enrichment of familiar foods and drinks might be an effective and attractive alternative for oral nutritional supplements (ONS). We performed a pilot study to test whether these products could help institutionalized elderly to reach a protein intake of 1.2 gram per kg body weight per day (g/kg/d). DESIGN: Intervention study with one treatment group (no control group). Dietary assessment was done before and at the end of a 10-day intervention. SETTING: Two care facilities in Gelderland, the Netherlands: a residential care home and a rehabilitation center. PARTICIPANTS: 22 elderly subjects (13 women, 9 men; mean age 83.0±9.4 years). INTERVENTION: We used a variety of newly developed protein enriched regular foods and drinks, including bread, soups, fruit juices, and instant mashed potatoes. MEASUREMENTS: Dietary intake was assessed on two consecutive days before and at the end of the intervention, using food records filled out by research assistants. Energy and macronutrient intake was calculated using the 2013 Dutch food composition database. Changes in protein intake were evaluated using paired t-tests. RESULTS: Protein intake increased by 11.8 g/d (P=0.003); from 0.96 to 1.14 g/kg/d (P=0.002). This increase is comparable to protein provided by one standard portion of ONS. The intake of energy and other macronutrients did not change significantly. At the end of the intervention more elderly reached a protein intake level of 1.2 g/kg/d than before (9 vs 4). Protein intake significantly increased during breakfast (+3.7 g) and during the evening (+2.2 g). CONCLUSION: Including familiar protein enriched foods and drinks in the menu helped to meet protein recommendations in institutionalized elderly.