Association of Therapy Time Per Day With Functional Outcomes and Rate of Recovery in Older Adults After Elective Joint Replacement Surgery

ObjectivesTo explore the association between therapy minutes per length of stay (LOS) day (TMLD), functional outcomes, and rate of functional recovery among older adults after elective hip or knee replacement surgery across postacute (PAC) settings.DesignSecondary analysis of data collected for an observational cohort study from 2005 to 2010.SettingFour inpatient rehabilitation facilities (IRF) and 7 skilled nursing facilities (SNF).ParticipantsAdults aged 65 years or older (N=162) with Medicare fee-for-service insurance and a primary diagnosis of elective hip or knee replacement.InterventionsNot applicable.Main Outcome MeasuresFIM mobility and self-care measures at discharge.ResultsThe TMLD was divided into high, medium, and low categories. Participants were grouped into low, medium, and high gain rate groups based on their average change in mobility and self-care FIM measures per LOS day. Gain rate and TMLD groups were crossmapped to create 9 gain-TMLD groups separately for mobility and self-care. There were no significant differences in admission mobility or self-care measures by gain rate and TMLD trajectory or by facility type (IRF or SNF). TMLD was not significantly associated with discharge mobility measures. Participants in high gain trajectories attained independence with mobility and self-care tasks at discharge regardless of TMLD. Those in low gain trajectories needed supervision or assistance on all mobility tasks. Older age and greater pain at discharge were significantly associated with lower odds of being in the medium or high gain rate groups.ConclusionsFor clinicians and facility managers who must care for patients with constrained resources, the shift to value-based reimbursement for rehabilitation services in PAC settings has reinvigorated the question of whether the duration of therapy provided influences patient outcomes. Three hours of daily therapy after joint replacement surgery may exceed what is necessary for recovery. Postsurgical pain management remains a significant challenge in older adults.     

The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster

Background:

Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations.

Objectives:

Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure.

Methods:

To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs.

Results:

We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system.

Conclusions:

Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations.

Citation:

Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124:1062–1070; http://dx.doi.org/10.1289/ehp.1510513     

A priori and a posteriori dietary patterns at the age of 1 year and body composition at the age of 6 years: the Generation R Study

Dietary patterns have been linked to obesity in adults, however, not much is known about this association in early childhood. We examined associations of different types of dietary patterns in 1-year-old children with body composition at school age in 2026 children participating in a population-based cohort study. Dietary intake at the age of 1 year was assessed with a food-frequency questionnaire. At the children’s age of 6 years we measured their body composition with dual-energy X-ray absorptiometry and we calculated body mass index, fat mass index (FMI), and fat-free mass index (FFMI). Three dietary pattern approaches were used: (1) An a priori-defined diet quality score; (2) dietary patterns based on variation in food intake, derived from principal-component-analysis (PCA); and (3) dietary patterns based on variations in FMI and FFMI, derived with reduced-rank-regression (RRR). Both the a priori-defined diet score and a ‘Health-conscious’ PCA-pattern were characterized by a high intake of fruit, vegetables, grains, and vegetable oils, and, after adjustment for confounders, children with higher adherence to these patterns had a higher FFMI at 6 years [0.19 SD (95 % CI 0.08;0.30) per SD increase in diet score], but had no different FMI. One of the two RRR-patterns was also positively associated with FFMI and was characterized by intake of whole grains, pasta and rice, and vegetable oils. Our results suggest that different a priori- and a posteriori-derived health-conscious dietary patterns in early childhood are associated with a higher fat-free mass, but not with fat mass, in later childhood.     

Screening for familial and hereditary prostate cancer

Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome‐wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies.     

The fracture and osteoporosis outpatient clinic: an effective strategy for improving implementation of an osteoporosis guideline

BACKGROUND: Clinical screening for osteoporosis in women aged over 50 years following a fracture is advocated by all guidelines on osteoporosis, but such attitude is widely reported to be inadequate. The aim of this study was to evaluate the effect of a strategy comparing referral for a dual-energy X-ray absorptiometry (DXA) scan as part of the osteoporosis guideline by a dedicated osteoporosis nurse with referral in hospitals without the presence of an osteoporosis nurse. METHODS: We retrospectively compared one reference hospital with five surrounding hospitals in the Netherlands. During a 2-week period, all female patients aged over 50 years who presented with a fracture at the emergency department of the six hospitals were included. Follow-up was minimal 11 weeks. The primary outcome was the referral for DXA measurement. RESULTS: In total, 135 patients were included, of whom 33 were seen in the reference hospital and 102 in the surrounding hospitals. In both groups, mean age and fracture location were similar. In the reference hospital, 14 patients qualified for DXA measurement, of whom 10 patients effectively underwent a DXA scan (71%). In the surrounding hospitals, 78 patients qualified for DXA measurement, of whom only three effectively underwent a DXA scan (4%). Taking into account a refusal percentage for DXA of 33% as was found in the reference centre, 47 patients in the surrounding hospitals should have been qualified for DXA measurement. Thus, successful referral in the surrounding hospitals was three out of 47 (6%) patients. The presence of an osteoporosis nurse did have a significant influence on the amount of DXA scans after fractures [RR 11 (95% CI: 3.6-35.1)]. CONCLUSIONS: This study indicates that referral for DXA is low in surrounding hospitals, and suggests that the presence of an osteoporosis nurse in the reference hospital significantly increased the number of patients receiving adequate osteoporosis screening with DXA measurement after a recent fracture. With this strategy patients who are at risk of osteoporosis are identified effectively, after which treatment can be started, in order to reduce the risk of future fractures.     

Properties of the Plasma Very Low and Low Density Lipoproteins in Tangier Disease

The absence of normal high density lipoproteins (HDL) in Tangier disease is well established, but the properties of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in this disorder have not been well defined. The profiles obtained by analytic ultracentrifugation and the chemical composition, morphology, and electrophoretic mobility of Tangier and normal VLDL and LDL were compared. Apolipoproteins were fractionated by gel chromatography and characterized by amino acid analysis, polyacrylamide-gel electrophoresis, and immunochemical reactivity.Concentrations of low density lipoproteins of S(f) (o) 0-12 were reduced in three of six Tangier plasmas studied by analytic ultracentrifugation. Accumulation of intermediate density lipoproteins (S(f) (o) 12-20) was not observed. Two subjects with hypertriglyceridemia had normal VLDL (S(f) (o) 20-400) levels, suggesting that abnormalities of chylomicron metabolism probably account for the hypertriglyceridemia frequently observed in this disorder.Tangier VLDL migrate more slowly than normal VLDL on paper electrophoresis, yet their morphology, gross chemical composition, and qualitative apolipoprotein content are similar. Quantitative abnormalities in C-apolipoproteins, however, were observed in Tangier VLDL. When patients were consuming unrestricted diets, C apoproteins accounted for 19-49% of the protein in lipoproteins of d < 1.006 g/ml. Ingestion of low-fat, high-carbohydrate diets reduced the VLDL-C-apoprotein content in all Tangier patients (mean = 17% of VLDL protein vs. 43% in controls). These findings suggested that a major proportion of the C apoproteins in Tangier plasma is associated with chylomicrons or their remnants, perhaps because the C-apoprotein reservoir normally provided by HDL is absent. This secondary mechanism for C-apoprotein conservation is lost when dietary fat is withdrawn.LDL-2 (1.035 < d < 1.063) from Tangier and control plasma had identical electrophoretic mobilities. Tangier LDL-2 had slightly smaller median diameters (210-225 A vs. 230-240 A in controls) and a quite different composition than normal LDL-2. Triglyceride accounted for a mean of 29% of Tangier LDL-2 mass (control = 6%) and the cholesteryl ester content was reduced by about 50%. Thus, HDL may be required for the generation of chemically normal LDL. Alternatively, the fundamental defect in Tangier disease may involve all lipoprotein classes.     

Transport of Apolipoproteins A-I and A-II by Human Thoracic Duct Lymph

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in two subjects before and three subjects after renal transplantation. Lymph triglyceride transport was ~83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659±578 mg/d for apolipoprotein A-I and 109±59 mg/d for apolipoprotein A-II among the five subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine.