Declining daily functioning as a prelude to a hip fracture in older persons-an individual patient data meta-analysis

Background Daily functioning is known to decline after a hip fracture, but studies of self-reported functioning before the fracture suggest this decline begins before the fracture. Objective Determine whether change in functioning in the year before a hip fracture in very old (80+) differs from change in those without a hip fracture. Design Two-stage individual patient data meta-analysis including data from the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium. Setting Four population-based longitudinal cohorts from the Netherlands, New Zealand and the UK. Subjects Participants aged 80+ years. Methods Participants were followed for 5 years, during which (instrumental) activities of daily living [(I)ADL] scores and incident hip fractures were registered at regular intervals. Z-scores of the last (I)ADL score and the change in (I)ADL in the year before a hip fracture were compared to the scores of controls, adjusted for age and sex. Results Of the 2,357 participants at baseline, the 161 who sustained a hip fracture during follow-up had a worse (I)ADL score before the fracture (0.40 standard deviations, 95% CI 0.19 to 0.61, P = 0.0002) and a larger decline in (I)ADL in the year before fracture (-0.11 standard deviations, 95% CI -0.22 to 0.004, P = 0.06) compared to those who did not sustain a hip fracture. Conclusions In the very old a decline in daily functioning already starts before a hip fracture. Therefore, a hip fracture is a sign of ongoing decline and what full recovery is should be seen in light of the pre-fracture decline.Clinical epidemiolog

The role of a composite fitness score in the association between low-density cholesterol and all-cause mortality in older adults: an individual patient data meta-analysis

BackgroundIn the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score.MethodsA 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score.ResultsComposite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80–0.94]; p p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83–1.15]; p = .78), the test for subgroups differences was not significant.ConclusionsIn this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Emerging application of stereotactic body radiation therapy for gynecologic malignancies

10.1586/era.11.81Expert Review of Anticancer Therapy1171069-1075ERAT

How Long Does It Take to Read a Mammogram? Investigating the Reading Time of Digital Breast Tomosynthesis and Digital Mammography

PurposeTo analyse digital breast tomosynthesis (DBT) reading times in the screening setting, compared to 2D full-field digital mammography (FFDM), and investigate the impact of reader experience and professional group on interpretation times.MethodReading time data were recorded in the PROSPECTS Trial, a prospective randomised trial comparing DBT plus FFDM or synthetic 2D mammography (S2D) to FFDM alone, in the National Health Service (NHS) breast screening programme, from January 2019-February 2023. Time to read DBT+FFDM or DBT+S2D and FFDM alone was calculated per case and reading times were compared between modalities using dependent T-tests. Reading times were compared between readers from different professional groups (radiologists and radiographer readers) and experience levels using independent T-tests. The learning curve effect of using DBT in screening on reading time was investigated using a Kruskal-Wallis test.ResultsForty-eight readers interpreted 1,242 FFDM batches (34,210 FFDM cases) and 973 DBT batches (13,983 DBT cases). DBT reading time was doubled compared to FFDM (2.09 ± 0.64 min vs. 0.98 ± 0.30 min; p < 0.001), and DBT+S2D reading was longer than DBT + FFDM (2.24 ± 0.62 min vs. 2.04 ± 0.46 min; p = 0.006). No difference was identified in reading time between radiologists and radiographers (2.06 ± 0.71 min vs. 2.14 ± 0.46 min, respectively; p = 0.71). Readers with five or more years of experience reading DBT were quicker than those with less experience (1.86 ± 0.56 min vs. 2.37 ± 0.65 min; p = 0.008), and DBT reading time decreased after less than 9 months accrued screening experience (p = 0.01).ConclusionsDBT reading times were double those of FFDM in the screening setting, but there was a short learning curve effect with readers showing significant improvements in reading times within the first nine months of DBT experience