Pent-up demand for care among dual-eligible victims of elder financial exploitation in Maine.

Elder financial exploitation (EFE), the misuse of a vulnerable adult's property or resources for personal gain, is a form of elder abuse. This study addresses whether dual-eligible EFE victims were experiencing pent-up demand for health services alleviated through investigation by Adult Protective Services (APS). A quasi-experimental design addressed health service utilization and costs for 131 dual-eligible Maine APS clients over age 60 with substantiated allegations of EFE relative to comparable non-APS controls. APS case files spanning 2007-2012 were linked to 2006-2014 Medicare and Medicaid claims data. Service utilization and costs were analyzed 1 year prior, during, and 2 years after the initial APS investigation. Difference in differences logistic regression and generalized linear models addressed the likelihood of incurring costs and expenditure levels relative to matched controls, respectively. Victims of EFE had higher overall odds of using inpatient and long-term services and supports (LTSS) and higher odds of using LTSS post-investigation than controls. Higher overall levels of outpatient and prescriptions expenditures and higher inpatient expenditures during the APS event year contributed toward APS clients incurring $1,142 higher PMPM total costs than controls. Victims of EFE were experiencing significant pent-up demand for health services post-APS involvement.

Characterising radium-226 particles from legacy contamination to support radiation dose assessments.

Radioactive particles are physically discrete sources of radioactivity that have been released into the environment as a result of past emergencies, events and practices. As the release of radioactive particles is often unplanned, the source term has not been characterised, and the potential radiation doses have not been prospectively assessed. If a plausible exposure pathway exists, radioactive particles in the environment may present a hazard to the public depending on their radiological, physical and chemical characteristics. Given their physically discrete nature, standard assessment approaches such as dispersion and transfer modelling of liquid and gaseous radioactive releases, are not appropriate for radioactive particles. The challenge for national regulatory authorities is to calculate potential radiation doses from unplanned releases of radioactive particles into the environment, assess whether the doses are relevant to radiological protection and decide whether actions are required to reduce potential doses. To address this challenge, this paper presents the approach being adopted to radiologically, physically and chemically characterise Ra-226 particles from a contaminated legacy site using gamma spectrometry, optical macroscopy and SEM-EDS. The use of particle characterisation data to support radiation dose assessments is discussed and consideration is given to radioactive particles in the context of radiological protection.

Validity of the activPAL3 activity monitor in people moderately affected by Multiple Sclerosis.

Walking is the primary form of physical activity performed by people with Multiple Sclerosis (MS), therefore it is important to ensure the validity of tools employed to measure walking activity. The aim of this study was to assess the criterion validity of the activPAL3 activity monitor during overground walking in people with MS. Validity of the activPAL3 accelerometer was compared to video observation in 20 people moderately affected by MS. Participants walked 20-30m twice along a straight quiet corridor at a comfortable speed. Inter-rater reliability of video observations was excellent (all intraclass correlations >0.99). The mean difference (activPAL3- mean of raters) was -4.70±9.09, -4.55s±10.76 and 1.11s±1.11 for steps taken, walking duration and upright duration respectively. These differences represented 8.7%, 10.0% and 1.8% of the mean for each measure respectively. The activPAL3 tended to underestimate steps taken and walking duration in those who walked at cadences of ≤38 steps/min by 60% and 47%, respectively. The activPAL3 is valid for measuring walking activity in people moderately affected by MS. It is accurate for upright duration regardless of cadence. In participants with slow walking cadences, outcomes of steps taken and walking duration should be interpreted with caution.

Facilitators and barriers to the increased supervisory role of senior charge nurses: a qualitative study.

AIMS: To explore the experiences of senior charge nurses provided with 'increased supervisory hours'. BACKGROUND: Designated supervisory time is essential for senior charge nurses to provide effective clinical leadership. It is important to explore the impact arises of such an increase. METHODS: An online questionnaire collected exploratory data from senior charge nurses (n = 60). Semi-structured interviews gathered in-depth qualitative data (n = 12). Findings were analysed for common themes associated with implementation of the increased senior charge nurse supervisory role. RESULTS: The majority of senior charge nurses were unable to use their full allocation of supervisory time. They struggled to accomplish leadership goals because of managing staffing levels, increased workload, time constraints and limited support. Factors that facilitated the role included preparation and support, adequate staff capacity, effective leadership skills and availability of supervisory time. The senior charge nurses took pride in providing clinical leadership, promoting staff development and delivering patient care. Support, in terms of preparation, capacity building and ongoing mentoring, was a key factor for achieving senior charge nurse goals. CONCLUSION: Senior charge nurses should be supported to maximise supervisory time through the provision of an induction programme, formal coaching and ongoing training and development. IMPLICATIONS FOR NURSING MANAGEMENT: Preparation and support is essential for senior charge nurses to deliver enhanced clinical leadership through increased supervisory time.

The radium legacy: Contaminated land and the committed effective dose from the ingestion of radium contaminated materials.

The manufacture and use of radium in the early to mid-20th century within industrial, medicinal and recreational products have resulted in a large number of contaminated sites across a number of countries with notable examples in the USA and Europe. These sites, represent a significant number of unregulated sources of potential radiological exposure that have collectively and hitherto not been well characterised. In 2007, the Radioactive Contaminated Land (RCL) Regulations came into force in the UK, providing the statutory guidance for regulators to classify and deal with RCL. Here we report on results derived from digestion experiments to estimate committed effective dose, a key aspect of the RCL Regulations, from the ingestion of radium contaminated sources that can be found in the environment. This case study includes particles, clinker and artefacts that arise from past military activities on a site that was once an airfield at Dalgety Bay on the Firth of Forth, UK. Since 2011 the number of radium contaminated finds has increased by one order of magnitude on the foreshore areas of Dalgety Bay. The increase in finds may in large part be attributed to a change in monitoring practice. A subsample of sixty sources was selected, on the basis of their activity and dimensions, and subjected to digestion in simulated stomach and lower intestine solutions. The study demonstrated that more radium-226 ((226)Ra) and lead-210 ((210)Pb; driven by Polonium solubility) are dissolved from sources in artificial 'stomach' solutions compared with 'lower intestine' solutions. The combined 'gut' solubility for (226)Ra and apparent (210)Pb varied from less than 1% to up to 35% ICRP 72 conversion factors were used to convert the activities measured in solution to committed effective dose. A little over 10% of the sources tested dissolved sufficient radioactivity to result in 100mSv committed effective dose to an infant. Using the solubility of 35% as a worst case, minimum source activities necessary to deliver 100mSv to the full age range of users of the foreshore were estimated. All the estimated activities have been detected and recovered through routine monitoring.

In vitro diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions.

BACKGROUND: Previous reports have suggested that drug-specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed-type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting. METHODS: A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug-specific proliferation, and interferon (IFN)-γ and interleukin (IL)-4 production. RESULTS: Healthy controls showed negative drug-specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN-γ) and 92% (IL-4). The sensitivity of combined measurement of drug-specific IFN-γ and IL-4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN-γ assays was strong (r = 0·7, P < 0·0001), whereas the IL-4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme-linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication. CONCLUSIONS: In vitro assays of drug-specific IFN-γ and IL-4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.

Primary paratesticular seminoma - A case report.

INTRODUCTION: Paratesticular tumours are rare. Rhabdomyosarcomas are the commonest malignant paratesticular tumours although tumours can arise from any paratesticular structure. Here we report a case of a primary paratesticular seminoma and a review of the literature. PRESENTATION OF CASE: A 42 year old man presented with a right scrotal mass. Histology revealed a paratesticular seminoma. Following a radical orchidectomy, there was no evidence of testicular seminoma. DISCUSSION: Primary paratesticular seminoma in the absence of testicular seminoma is extremely rare. CONCLUSION: After a thorough review of the literature, this is, to our knowledge only the second reported case of a primary paratesticular seminoma.

A genome-wide admixture scan for ancestry-linked genes predisposing to sarcoidosis in African-Americans.

Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multiorgan granulomatous inflammatory disease. African ancestry may influence disease pathogenesis, as African-Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1384 highly ancestry-informative single-nucleotide polymorphisms genotyped on 1357 sarcoidosis cases and 703 unaffected controls self-identified as African-American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)=1.90; P=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; P=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12, which had the most significant association with European ancestry (aRR=0.65; P=0.002), and markers on chromosomes 5p13 (aRR=1.46; P=0.005) and 5q31 (aRR=0.67; P=0.005), which correspond to regions we previously identified through sib-pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; P=2 × 10(-5)), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis.

Evaluation of C1q genomic region in minority racial groups of lupus.

Complement cascade plasma proteins play a complex role in the etiopathogenesis of systemic lupus erythematosus (SLE). Hereditary C1q deficiency has been strongly related to SLE; however, there are very few published SLE studies that evaluate the polymorphisms of genes encoding for C1q (A, B and C). In this study, we evaluated 17 single nucleotide polymorphisms (SNPs) across 37 kb of C1QA, C1QB and C1QC in a lupus cohort of individuals of the African-American and Hispanic origin. In a case-only analysis, a significant association at multiple SNPs in the C1QA gene was detected in African Americans with kidney nephritis (best P=4.91 x 10(-6)). In addition, C1QA was associated with SLE in African Americans with a lack of nephritis and accompanying photosensitivity when compared with that in normal controls (P=6.80 x 10(-6)). A similar trend was observed in the Hispanic subjects (P=0.003). Quantitative analysis showed that some SNPs in C1q genes might be correlated with C3 complement levels in an additive model among African Americans (best P=0.0001). The C1QA gene is associated with subphenotypes of lupus in the African-American and Hispanic subjects. Further studies with higher SNP densities in this region and other complement components are necessary to elucidate the complex genetics and phenotypic interactions between complement components and SLE.

Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations.

TNFAIP3 encodes the ubiquitin-modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus (SLE). To further localize the risk variant(s), we performed a meta-analysis using genetic data available from two Caucasian case-control datasets (1453 total cases, 3381 total control subjects) and 713 SLE trio families. The best result was found at rs5029939 (P=1.67 x 10(-14), odds ratio=2.09, 95% confidence interval 1.68-2.60). We then imputed single nucleotide polymorphisms (SNPs) from the CEU Phase II HapMap using genotypes from 431 SLE cases and 2155 control subjects. Imputation identified 11 SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk allele was associated with SLE clinical manifestations, we observed that heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a twofold increased risk of developing renal or hematologic manifestations compared to homozygous non-risk subjects. In summary, our study strengthens the genetic evidence that variants in the region of TNFAIP3 influence risk for SLE, particularly in patients with renal and hematologic manifestations, and narrows the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.

VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo.

Von Hippel-Lindau (VHL) disease is caused by germline mutations in the VHL tumor suppressor gene, with Type 2B missense VHL mutations predisposing to renal cell carcinoma, hemangioblastoma and pheochromocytoma. Type 2B mutant pVHL is predicted to be defective in hypoxia inducible factor (HIF)-alpha regulation. Murine embryonic stem (ES) cells in which the endogenous wild-type Vhl gene was replaced with the representative Type 2B VHL hotspot mutation R167Q (Vhl(2B/2B)) displayed preserved physiological regulation of both HIF factors with slightly greater normoxic dysregulation of HIF-2alpha. Differentiated Vhl(2B/2B)-derived teratomas overexpressed joint HIF targets Vegf and EglN3 but not the HIF-1alpha-specific target Pfk1. Vhl(2B/2B) teratomas additionally displayed a growth advantage over Vhl(-/-)-derived teratomas, suggestive of a tight connection between perturbations in the degree and ratio of HIF-1alpha and HIF-2alpha stabilization and cell growth. Vhl(2B/2B) mice displayed mid-gestational embryonic lethality, whereas adult Vhl(2B/+) mice exhibited susceptibility to carcinogen-promoted renal neoplasia compared with wild-type littermates at 12 months. Our experiments support a model in which the representative Type 2B R167Q mutant pVhl produces a unique profile of HIF dysregulation, thereby promoting tissue-specific effects on cell growth, development and tumor predisposition.

Doctors' attitudes about prescribing and knowledge of the costs of common medications.

INTRODUCTION: Compliance with medical therapy may be compromised because of the affordability of medications. Inadequate physician knowledge of drug costs may unwittingly contribute to this problem. METHODS: We measured attitudes about prescribing and knowledge of medication costs by written survey of medical and surgical non consultant hospital doctors and consultants in two University teaching hospitals (n = 102). Sixty-eight percent felt the cost of medicines was an important consideration in the prescribing decision, however, 88% often felt unaware of the actual costs. Only 33% had easy access to drug cost data, and only 3% had been formally educated about drug costs. Doctors' estimates of the cost of a supply of ten commonly used medications were accurate in only 12% of cases, too low for 50%, and too high for 38%. CONCLUSIONS: Interventions are needed to educate doctors about drug costs and provide them with reliable, easily accessible cost information in real-world practice.

Using linkage analysis to identify quantitative trait loci for sleep apnea in relationship to body mass index.

To understand the genetics of sleep apnea, we evaluated the relationship between the apnea hypopnea index (AHI) and body mass index (BMI) through linkage analysis to identify genetic loci that may influence AHI and BMI jointly and AHI independent of BMI. Haseman-Elston sibling regression was conducted on AHI, AHI adjusted for BMI and BMI in African-American and European-American pedigrees. A comparison of the magnitude of linkage peaks was used to assess the relationship between AHI and BMI. In EAs, the strongest evidence for linkage to AHI was on 6q23-25 and 10q24-q25, both decreasing after BMI adjustment, suggesting loci with pleiotropic effects. Also, a promising area of linkage to AHI but not BMI was observed on 6p11-q11 near the orexin-2 receptor, suggesting BMI independent pathways. In AAs the strongest evidence of linkage for AHI after adjusting for BMI was on chromosome 8p21.3 with linkage increasing after BMI adjustment and on 8q24.1 with linkage decreasing after BMI adjustment. Novel linkage peaks were also observed in AAs to both BMI and AHI on chromosome 13 near the serotonin-2a receptor. These analyses suggest genetic loci for sleep apnea that operate both independently of BMI and through BMI-related pathways.

Genetic linkage analysis of sarcoidosis phenotypes: the sarcoidosis genetic analysis (SAGA) study.

The sarcoidosis genetic analysis (SAGA) study previously identified eight chromosomal regions with suggestive evidence for linkage to sarcoidosis susceptibility in African-American sib pairs. Since the clinical course of sarcoidosis is variable and likely under genetic control, we used the affected relative pair portion of the SAGA sample (n=344 pairs) to perform multipoint linkage analyses with covariates based on pulmonary and organ involvement phenotypes. Chest radiographic resolution was the pulmonary phenotype with the highest LOD (logarithm of the backward odds, or likelihood ratio) score of 5.11 at D1S3720 on chromosome 1p36 (P=4 x 10(-5)). In general, higher LOD scores were attained for covariates that modeled clustered organ system involvement rather than individual organ systems, with the cardiac/renal group having the highest LOD score of 6.65 at chromosome 18q22 (P=2 x 10(-5)). The highest LOD scores for the other three organ involvement groups of liver/spleen/bone marrow, neuro/lymph and ocular/skin/joint were 3.72 at 10p11 (P=0.0004), 5.16 at 7p22 (P=4 x 10(-5)) and 2.93 at 10q26 (P=0.001), respectively. Most of the phenotype linkages did not overlap with the regions previously found linked to susceptibility. Our results suggest that genes influencing clinical presentation of sarcoidosis in African Americans are likely to be different from those that underlie disease susceptibility.

Familial aggregation and linkage analysis of autoantibody traits in pedigrees multiplex for systemic lupus erythematosus.

Autoantibodies are clinically relevant biomarkers for numerous autoimmune disorders. The genetic basis of autoantibody production in systemic lupus erythematosus (SLE) and other autoimmune diseases is poorly understood. In this study, we characterized autoantibody profiles in 1,506 individuals from 229 multiplex SLE pedigrees. There was strong familial aggregation of antinuclear antibodies (ANAs), anti-double-stranded DNA (dsDNA), anti-La/SSB, anti-Ro/SSA, anti-Sm, anti-nRNP (nuclear ribonucleoprotein), IgM antiphospholipid (aPL) antibodies (Abs) and rheumatoid factor (RF) across these families enriched for lupus. We performed genome-wide linkage analyses in an effort to map genes that contribute to the production of the following autoantibodies: Ro/SSA, La/SSB, nRNP, Sm, dsDNA, RF, nuclear and phospholipids. Using an approach to minimize false positives and adjust for multiple comparisons, evidence for linkage was found to anti-La/SSB Abs on chromosome 3q21 (adjusted P=1.9 x 10(-6)), to anti-nRNP and/or anti-Sm Abs on chromosome 3q27 (adjusted P=3.5 x 10(-6)), to anti-Ro/SSA and/or anti-La/SSB Abs on chromosome 4q34-q35 (adjusted P=3.4 x 10(-4)) and to anti-IgM aPL Abs on chromosome 13q14 (adjusted P=2.3 x 10(-4)). These results support the hypothesis that autoantibody production is a genetically complex trait. Identification of the causative alleles will advance our understanding of critical molecular mechanisms that underlie SLE and perhaps other autoimmune diseases.

Genome-wide search for sarcoidosis susceptibility genes in African Americans.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Outcomes of the peer-taught 12-week family-to-family education program for severe mental illness.

OBJECTIVE: Family-to-Family Education Program (FFEP) is a 12-week course for family members of adults with serious mental illness (SMI). This study evaluates the effectiveness of FFEP for several family member outcomes. METHOD: The FFEP enrollees on a > or =3-month waiting list were eligible; 95 consenting family members agreed to four interviews (waitlist, pre-FFEP, post-FFEP, and 6 months post-FFEP) regarding subjective and objective burden, empowerment, and depression. Mixed effects ANOVA models tested hypotheses of decreased burden and increased empowerment after FFEP. RESULTS: The FFEP was associated with reduced subjective burden (P < 0.01) and increased empowerment (P < 0.01) without changes in objective burden. Knowledge about SMI, understanding the mental health system, and self-care also improved. There was no significant decay at 6-month followup. CONCLUSION: This study provides evidence that FFEP is helpful to relatives of persons with SMI by reducing subjective burden and worry, and increasing empowerment, knowledge about SMI, understanding the mental health system, and self-care.

A comparative study of neurogenesis in the retinal ciliary marginal zone of homeothermic vertebrates.

The retina of many fish and amphibians grows throughout life, roughly matching the overall growth of the animal. The new retinal cells are continually added at the anterior margin of the retina, in a circumferential zone of cells, known as the ciliary marginal zone, or CMZ. Recently, Fischer and Reh [Dev. Biol. 220 (2000) 197] have found that new neurons are added to the retina of the chicken via proliferation and subsequent differentiation of neurons and glia at the retinal margin in a zone highly reminiscent of the CMZ of lower vertebrates. In addition, other groups have reported that putative retinal stem cells could be isolated from the ciliary margin of the adult mouse. In light of these findings, we have re-investigated the eyes of three additional species to determine whether other homeothermic vertebrates also possess CMZ cells and whether we could detect evidence for addition of neurons at the retinal margin in mature animals. We examined one additional avian species, the quail, one marsupial, the opposum, and one mammal, the mouse. We find that the CMZ cells have been gradually diminished during vertebrate evolution. The quail has a reduced CMZ as compared to the chicken, while the opposum has only a few cells likely related to the CMZ and we failed to find evidence of CMZ cells at the margin of the mouse retina.