Revised Recommendations on Methods for Assessing Multimorbidity Changes over Time: Aligning the Method to the Purpose.

BACKGROUND: The rapidly growing field of multimorbidity research demonstrates that changes in multimorbidity in mid- and late-life have far reaching effects on important person-centered outcomes, such as health-related quality of life. However, there are few organizing frameworks and comparatively little work weighing the merits and limitations of various quantitative methods applied to the longitudinal study of multimorbidity. METHODS: We identify and discuss methods aligned to specific research objectives with the goals of 1) establishing a common language for assessing longitudinal changes in multimorbidity, 2) illuminating gaps in our knowledge regarding multimorbidity progression and critical periods of change, and 3) informing research to identify groups that experience different rates and divergent etiological pathways of disease progression linked to deterioration in important health-related outcomes. RESULTS: We review practical issues in the measurement of multimorbidity, longitudinal analysis of health-related data, operationalizing change over time, and discuss methods that align with four general typologies for research objectives in the longitudinal study of multimorbidity: 1) examine individual change in multimorbidity, 2) identify sub-groups that follow similar trajectories of multimorbidity progression, 3) understand when, how, and why individuals or groups shift to more advanced stages of multimorbidity, and 4) examine the co-progression of multimorbidity with key health domains. CONCLUSION: This work encourages a systematic approach to the quantitative study of change in multimorbidity and provides a valuable resource for researchers working to measure and minimize the deleterious effects of multimorbidity on aging populations.

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial.

BACKGROUND: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH). METHODS: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records. RESULTS: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode. CONCLUSIONS: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD.

Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008-2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013-2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cohort Trends in the Burden of Multiple Chronic Conditions Among Aging U.S. Adults.

OBJECTIVES: Multimorbidity, also referred to as multiple chronic conditions (MCCs), is the concurrent presence of 2 or more chronic health conditions. Increasing multimorbidity represents a substantial threat to the health of aging populations. Recent trends suggest greater risk of poor health and mortality among later-born cohorts, yet we are unaware of work examining cohort differences in multimorbidity among aging U.S. adults. METHODS: We examine intercohort variation in MCC burden in adults aged 51 years and older using 20 years (n = 33,598; 1998-2018) of repeated assessment drawn from the Health and Retirement Study. The index of MCCs included 9 chronic conditions (heart disease, hypertension, stroke, diabetes, arthritis, lung disease, cancer excluding skin cancer, high depressive symptoms, and cognitive impairment). We used linear mixed models with various approaches to estimate age/period/cohort effects to model intercohort patterns in MCC burden. We also explored variation in the specific conditions driving cohort differences in multimorbidity. RESULTS: More recent cohorts had greater MCC burden and developed multimorbidity at earlier ages than those born to prior generations. The burden of chronic conditions was patterned by life-course sociodemographic factors and childhood health for all cohorts. Among adults with multimorbidity, arthritis and hypertension were the most prevalent conditions for all cohorts, and there was evidence that high depressive symptoms and diabetes contributed to the observed cohort differences in multimorbidity risk. DISCUSSION: Our results suggest increasing multimorbidity burden among more recently born cohorts of aging U.S. adults and should inform policy to address diminishing health in aging populations.

Early childhood hospitalization and problematic behaviors: A propensity score analysis.

Existing research suggests that children who experience poverty and hospitalization in early childhood are at risk of developing behavior problems. We examined whether the association between early childhood hospitalization and children's internalizing and externalizing behaviors were moderated by family poverty status and child sex. Participants included 224 children from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. There was no direct association between hospitalization and problematic behaviors. Poverty status during early childhood, but not child sex, significantly moderated the association between hospitalization and externalizing problems. Findings support the need for community programs that promote an integrative approach to healthcare for families experiencing poverty.

Expanding the phenotype of SPARC-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in SPARC and literature review.

BACKGROUND: Secreted protein, acidic, cysteine rich (SPARC)-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report of this form of OI. SPARC is located on chromosome 5 between bands q31 and q33. The encoded protein is necessary for calcification of the collagen in bone, synthesis of extracellular matrix and the promotion of changes to cell shape. METHODS: We describe a further two patients with previously unreported homozygous SPARC variants with OI: one splice site; one nonsense pathogenic variant. We present detailed information on the clinical and radiological phenotype and correlate this with their genotype. There are only two previous reports by Mendozo-Londono et al and Hayat et al with clinical descriptions of patients with SPARC variants. RESULTS: From the data we have obtained, common clinical features in individuals with OI type XVII caused by SPARC variants include scoliosis (5/5), vertebral compression fractures (5/5), multiple long bone fractures (5/5) and delayed motor development (3/3). Interestingly, 2/4 patients also had abnormal brain MRI, including high subcortical white matter changes, abnormal fluid-attenuated inversion in the para-atrial white matter and a large spinal canal from T10 to L1. Of significance, both patients reported here presented with significant neuromuscular weakness prompting early workup. CONCLUSION: Common phenotypic expressions include delayed motor development with neuromuscular weakness, scoliosis and multiple fractures. The data presented here broaden the phenotypic spectrum establishing similar patterns of neuromuscular presentation with a presumed diagnosis of 'myopathy'.

Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial.

BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and ß-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. RESULTS: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 µg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 µg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: ß = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

Dietary quality modifies the association between multimorbidity and change in mobility limitations among older Americans.

To identify potentially modifiable risk-factors in the age-related disablement process, we examined the association between change in mobility limitations and multimorbidity and how dietary quality moderates this association. Information from 3320 adults aged 65 and older in 2012 was drawn from the Health and Retirement Study and the Health Care and Nutrition Study. Mobility limitations reported in 2012 and change in mobility limitations from 2012 to 2014 were regressed on multimorbidity measured as number of chronic conditions in 2012, dietary quality measured in 2013 using the Alternative Healthy Eating Index-2010 (AHEI-2010), and their interaction term using Poisson regression. Respondents reported an average of 2.9 (SD, 2.9) mobility limitations in 2012 and 3.1 (SD, 3.0) mobility limitations in 2014, an average of 2.64 (SD, 1.4) chronic conditions in 2012, and mean AHEI-2010 score in 2013 of 57.1 (SD, 10.9). Greater AHEI-2010 scores were associated with fewer mobility limitations at baseline (p < .001) and slower progression of mobility limitations over the two-year observational window (p < .001). For those with AHEI-2010 scores ≥48.4, dietary quality appeared to moderate the association between multimorbidity and change in mobility limitations. These results suggest that improving dietary quality may be an effective means of reducing the progression of mobility limitations among older adults and that dietary quality may modify the effect of multimorbidity on progressive disablement. Our work adds to research supporting dietary quality as a potentially intervenable factor in the reduction of disablement in aging populations.

eHealth Literacy and Caregiver Burden Among Chinese Caregivers of Older Adults With Cognitive Impairment: Does Education Matter?

eHealth literacy is a critical factor that influences caregivers' well-being. The purpose of this study is to examine the association between eHealth literacy, education, and caregiver burden among Chinese caregivers of older adults with cognitive impairment. Data came from structured interviews with 300 primary family caregiver-care recipient dyads in Wuhan, China. We used logistic regression to examine the association between eHealth literacy, education, and caregiver burden. An interaction effect between eHealth literacy and education on caregiver burden was identified. eHealth literacy was positively associated with caregiver burden among caregivers with less than a high school education, but not among those with a high school education or above. eHealth literacy is salient in the burden experienced by caregivers with low education. eHealth literacy needs to be enhanced with health information verification from health professionals and programs to support caregiving efficacy to realize its positive impact on caregivers' mental health.

Investigating walnut consumption and cognitive trajectories in a representative sample of older US adults.

OBJECTIVE: Existing research suggests walnut intake may be associated with better cognitive function in older adults, yet few studies utilise longitudinal data from observational studies of ageing populations. Our objective was to estimate the association between whole walnut intake and cognitive change in a representative sample of older Americans. DESIGN: Secondary analysis of the Health and Retirement Study and Health Care and Nutrition Study. Walnut consumption was defined as a categorical measure (none, low intake (0·01-0·08 1 oz. servings per day) and moderate intake (>0·08 1 oz. servings per day)) and cognitive function was measured using the Telephone Interview for Cognitive Status. Latent growth modelling estimated the association between walnut consumption and trajectories of cognitive status over a 4-year observational period. Sensitivity analyses assessing non-random dropout and Monte Carlo power analyses were conducted to contextualise results. SETTING: The USA. PARTICIPANTS: A sample of 3632 US adults aged 65 years and older. RESULTS: Those reporting any walnut consumption had greater cognitive scores at baseline than those not consuming walnuts (low walnut consumption, b = 1·53, se = 0·21, P < 0·001; moderate walnut consumption, b = 2·22, se = 0·27, P < 0·001), but walnut consumption was not associated with cognitive change. Walnut consumption was positively associated with socioeconomic status and health behaviours as well as intake of nutrients identified to have neuroprotective benefits. CONCLUSIONS: We identified an association between walnut consumption and cognitive function in older adults, although we did not find that walnut consumption was protective against age-related cognitive decline.

Dietary lutein and zeaxanthin are associated with working memory in an older population.

OBJECTIVE: The purpose of the study was to examine the association between dietary lutein and zeaxanthin (L + Z) intake and immediate word recall (IWR) and delayed word recall (DWR), and to identify the major contributors to dietary L + Z intake in a recent and representative sample of the older US population. DESIGN: In this cross-sectional analysis, multivariate path analytic models estimated the association between L + Z consumption and cognitive performance while adjusting for covariates. SETTING: Observations were drawn from the 2014 Health and Retirement Study, a nationally representative panel study of older US adults, and the 2013 Health Care and Nutrition Study, which assessed dietary intake via FFQ in a subsample of respondents. PARTICIPANTS: The analytic sample included 6390 respondents aged ≥50 years. RESULTS: L + Z intake was 2·44 ± 2·32 mg/d on average, and L + Z intake differed significantly across quartiles (P < 0·001). For example, average L + Z intake in Q1 was 0·74 ± 0·23 mg/d and in Q4 was 5·46 ± 2·88 mg/d. In covariate adjusted models, older adults in the highest quartiles of L + Z intake had significantly greater IWR and DWR scores than those in the lowest quartile. Leafy vegetables, cruciferous vegetables, dark yellow vegetables, fish and seafood, legumes, eggs and fruit were significant and meaningful predictors of dietary L + Z intake. CONCLUSION: A high consumption of vegetables, fish and seafood, legumes, eggs and fruit is associated with a higher intake of L + Z and greater word recall among older adults.

Socioeconomic correlates of adherence to mineral intake recommendations among pregnant women in north China: Findings from a cross-sectional study.

BACKGROUND AND OBJECTIVES: The purpose of the present study is to examine the socioeconomic correlates of adherence to minimum mineral intake recommended by the Chinese Dietary Guidelines during each trimester of pregnancy among Chinese women. METHODS AND STUDY DESIGN: A total of 567 pregnant women with foetal age of 6 - 12 weeks were recruited from nine community health centres and three hospitals. Cross-sectional survey data were collected using structured interviews and questionnaires. Mineral intake was calculated from food consumption reported on 24-hour dietary reviews using the Chinese Food Composition Metrics. Logistic regression models were estimated to assess the relationship between sociodemographic factors and adherence to mineral intake recommendations for each trimester. RESULTS: Significant predictors of adherence to mineral intake recommendations include: (1) age (zinc: OR=1.09, p<0.05; copper: OR=1.11, p<0.05), having bachelor's degree (copper: OR=2.23, p<0.05; phosphorus: OR=2.23, p<0.01), and household income ≥5,000RMB (potassium: OR=2.51, p<0.001; phosphorus: OR=1.91, p<0.05) during the first trimester, (2) being employed (zinc: OR=0.54, p<0.001; selenium: OR=0.53, p<0.05) and household income ≥5,000 RMB (zinc: OR=1.86, p<0.05) during the second trimester, and (3) husband/partner with associate degree or vocational school education (selenium: OR=3.26, p<0.01) and household income of 3,000-4,999 RMB (potassium: OR=1.71, p<0.05; zinc: OR=1.48, p<0.05) during the third trimester. CONCLUSIONS: To our knowledge, this is the first study that examines the relationship between socioeconomic factors and mineral intake among Chinese pregnant women at three trimesters. Findings highlight the importance of considering individuals' socioeconomic status to develop personalized interventions to prevent undernutrition among this population.

Latent profile analysis of dietary intake in a community-dwelling sample of older Americans.

OBJECTIVE: To estimate latent dietary profiles in a community-dwelling sample of older Americans and identify associations between dietary profile membership and individual demographic, socio-economic and health characteristics. DESIGN: Secondary analysis of the 2012 Health and Retirement Study (HRS) and linked 2013 Health Care and Nutrition Study (HCNS). Latent profile analysis identified mutually exclusive subgroups of dietary intake and bivariate analyses examined associations between dietary profile membership, participant characteristics and nutrient intakes. SETTING: USA. PARTICIPANTS: An analytic sample of 3558 adults aged 65 years or older. RESULTS: Four dietary profiles were identified with 15·5 % of the sample having a 'Healthy' diet, 42·0 % consuming a 'Western' diet, 29·7 % having a diet consisting of high intake of all food groups and 12·7 % reporting relatively low intake of all food groups. Members of the 'Healthy' profile reported the greatest socio-economic resources and health, and members of the 'Low Intake' profile had the fewest resources and worst health outcomes. Macronutrient and micronutrient intakes varied across profile although inadequate and excessive intakes of selected nutrients were observed for all profiles. CONCLUSIONS: We identified dietary patterns among older Americans typified by either selective intake of foods or overall quantity of foods consumed, with those described as 'Low Intake' reporting the fewest socio-economic resources, greatest risk of food insecurity and the worst health outcomes. Limitations including the presence of measurement error in dietary questionnaires are discussed. The causes and consequences of limited dietary intake among older Americans require further study and can be facilitated by the HRS and HCNS.

Egg Consumption, Multi-Domain Cognitive Performance, and Short-Term Cognitive Change in a Representative Sample of Older U.S. Adults.

Objective: Existing research supports a positive relationship between egg intake and cognitive function in older populations, although the impact of whole egg consumption on multi-domain cognitive function and cognitive decline in representative samples of older adults has not been described. We examined the association between egg consumption, cognitive performance, and cognitive change in a representative sample of U.S. adults aged 65 and older. Methods: We drew observations from the 2012 and 2014 Health and Retirement Study and the recently released 2013 Health Care and Nutrition Study. The analytic sample contained 3835 respondents, representing a weighted population of 37,806,082 community-dwelling adults aged 65 and older in 2013. Multivariate path analytic models were used to estimate the association between egg consumption groups (none, ≤ 1 serving per week, 2-6 servings per week, ≥ 7 servings per week) and cognitive performance across domains of working memory, executive function, and global mental status. First-order autoregressive models were used to estimate cognitive change over the 2-year observational period. Follow-up analyses examined associations between egg consumption group, dietary patterns, and nutrient intake. Results: On average, older adults consumed 0.34 eggs per day (SD = 0.36). Although bivariate analyses suggested that moderate egg consumers had the best cognitive performance at baseline assessment, egg consumption was not associated with cognitive performance or cognitive change when adjusting models for covariates known to have a robust association with cognitive health. Conclusions: Our results suggest that egg consumption does not benefit, nor is detrimental to, the cognitive health of older adults. Further studies of whole egg consumption and cognitive performance would benefit from controlled experimental settings, longer follow-up periods to measure cognitive change, and assessment of both community-dwelling and institutionalized older adults.

Gestational Vitamin D Supplementation Leads to Reduced Perinatal RXRA DNA Methylation: Results From the MAVIDOS Trial.

We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. In this study, we used an existing randomized trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicenter, double-blind, randomized, placebo-controlled trial of 1000 IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at -80°C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significantly lower in the umbilical cord from offspring of cholecalciferol-supplemented mothers, reaching statistical significance at four CpG sites, represented by CpG5: mean difference in % methylation between the supplemented and placebo groups was -1.98% (95% CI, -3.65 to -0.32, p = 0.02). ENCODE (Encyclopedia of DNA Elements) evidence supports the functionality of this locus with strong DNase hypersensitivity and enhancer chromatin within biologically relevant cell types including osteoblasts. Enrichment of the enhancer-related H3K4me1 histone mark is also seen in this region, as are binding sites for a range of transcription factors with roles in cell proliferation, response to stress, and growth factors. Our findings are consistent with previous observational results and provide new evidence that maternal gestational supplementation with cholecalciferol leads to altered perinatal epigenetic marking, informing mechanistic understanding of early life mechanisms related to maternal vitamin D status, epigenetic marks, and bone development. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

New diagnostic modalities and emerging treatments for neonatal bone disease.

Bone disease in the neonatal period has often been regarded as an issue affecting premature infants, or a collection of rare and ultra-rare disorders that most neonatologists will see only once or twice each year, or possibly each decade. The emergence of targeted therapies for some of these rare disorders means that neonatologists may be faced with diagnostic dilemmas that need a rapid solution in order to access management options that did not previously exist. The diagnostic modalities available to the neonatologist have not changed a great deal in recent years; blood tests and radiographs still form the mainstays with other techniques usually reserved for research studies, but rapid access to genomic testing is emergent. This paper provides an update around diagnosis and management of bone problems likely to present to the neonatologist.

Food insecurity, comorbidity, and mobility limitations among older U.S. adults: Findings from the Health and Retirement Study and Health Care and Nutrition Study.

Both food insecurity and comorbidity have been identified as precursors to functional limitation in older adults, yet whether food insecurity modifies the progression from chronic disease to disability has not been assessed. We examined 5986 respondents age 50 and older drawn from the 2012-2014 Health and Retirement Study (HRS) and 2013 Health Care and Nutrition Study (HCNS). Mobility limitations reported in 2014 and change in mobility limitations from 2012 to 2014 were regressed on measures of food insecurity, number of chronic conditions, and their interaction terms using Poisson regression. Around 17.3% of the sample was identified as food insecure. In 2012, respondents reported an average of 1.9 (SD = 1.5) chronic conditions and 2.4 mobility limitations (SD = 3.0). In 2014, individuals reported an average of 2.5 (SD = 3.1) mobility limitations. Food insecurity was associated with a greater number of mobility limitations (IRR = 1.20, 95% CI: 1.11-1.29, p < .001) and more rapid increase in mobility limitations over the two-year observational period (IRR = 1.06, 95% CI: 1.00-1.11, p = .047). Food security status also modified the association between comorbidity and both mobility limitation outcomes, with the food secure exhibiting a stronger positive association between chronic conditions and mobility limitations than the food insecure. The food insecure tended to have more mobility limitations than the food secure when few chronic conditions were reported. Our results suggest that food insecurity is associated with prevalence and change in mobility limitations among older adults.

Autism and heritable bone fragility: A true association?

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an 'Autism Spectrum Disorder'. A joint genetics and psychology research study was undertaken to identify these patients using 'Gold Standard' research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them. METHOD: A cohort of n = 7 children with autistic traits and severe/complex OI were recruited to the study. The study was set-up to explore whether there was a genetic link between bone fragility and autism in a sub-set of patients with bone fragility identified with autism traits in our complex/severe OI clinic. This was not set-up as a prevalence study but rather an exploration of genetics in association with ADI/ADOS confirmed ASD and bone fragility. ADI& ADOS: Standardised tools were used to confirm autism diagnosis. ADI and ADOS were completed by the Clinical Psychologist; ADI comprises a 93 item semi-structured clinical review with a diagnostic algorithm diagnosing Autism; ADOS is a semi-structured assessment of socialisation, communication and play/imagination which also provides a diagnostic algorithm. EXOME SEQUENCING: In patients recruited, those that fulfilled research criteria for diagnosis of autism using above tools were recruited to trio whole exome sequencing (WES). RESULTS: one patient had compound heterozygous variants in NBAS; one patient had a variant in NRX1; one patient had a maternally inherited PLS3 variant; all the other patients in this cohort had pathogenic variants in COL1A1/COL1A2. CONCLUSIONS: Although, not set out as an objective, we were able to establish that identifying autism had important clinical and social benefits for patients and their families in ensuring access to services, appropriate schooling, increased understanding of behaviour and support. LAY SUMMARY: It is important for clinicians looking after children with brittle bone disease, also referred to as Osteogenesis Imperfecta (OI) to be aware of early features of developmental delay/autistic traits especially with severe forms of OI as the emphasis is on their mobility and bone health. Ensuring appropriate assessment and access to services early-on will enable these patients to achieve their potential. Further investigations of genomics in bone fragility in relation to autism are required and dual diagnosis is essential for high quality clinical and educational provision.

Novel PLS3 variants in X-linked osteoporosis: Exploring bone material properties.

BACKGROUND: Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone-mass. METHODS: Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients. RESULTS: Patient 1: 40-year old adult male diagnosed with IJO in childhood who re-presented with a hip fracture as an adult. Genetic analysis identified a pathogenic PLS3 hemizygous variant, c.1765del in exon 16. Patient 2: 15-year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited PLS3 pathogenic c.1295T>A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation. DISCUSSION: We propose that genetic testing for PLS3 should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype. CONCLUSION: This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for PLS3. Through analysis of bone material properties in Patient 2, we can conclude that PLS3 does have a role in bone mineralisation.

Recent cancer treatment and memory decline in older adults: An analysis of the 2002-2012 Health and Retirement Study.

OBJECTIVE: Few studies have examined the impact of cancer treatment on cognitive trajectories in the growing population of older adults diagnosed with and surviving cancer. This study examined whether recent cancer and its treatment accelerated memory decline in older adults. MATERIALS AND METHODS: We conducted a secondary analysis of observations drawn from the Health and Retirement Study (2002-2012), a population-based sample of older adults in the United States. Changes in immediate (IWR) and delayed word recall (DWR) scores were estimated by latent growth modeling in individuals who never had cancer (n=10,939) or had been diagnosed with cancer between 2000 and 2002 and received treatment with some combination of radiation and/or surgery (n=240), chemotherapy only (n=34), or chemotherapy and some combination of radiation and/or surgery (n=64). RESULTS: In the period immediately following treatment, individuals reporting a recent cancer treated with chemotherapy and surgery/radiation experienced significantly more rapid decline in IWR (b =-0.34, SE =0.17, p=0.047) and DWR (b=-0.38, SE=0.19, p=0.049) than the non-cancer group. Sensitivity analyses addressing mortality selection and memory-related disease at baseline attenuated the strength of these associations. There were no other statistically significant differences in estimated linear or quadratic slope by cancer status or treatment. CONCLUSION: Our results support a potential association between recent cancer treatment and trajectories of memory decline in older adults and provide guidance on the interpretation of statistical estimates from panel studies of health and aging.