Hearing and Vision Screening Tools for Long-Term Care Residents with Dementia: Protocol for a Scoping Review

Introduction: Hearing and vision loss among longterm care (LTC) residents with dementia frequently goes unnoticed and untreated. Despite negative consequences for these residents, there is little information available about their sensory abilities and care assessments and practices seldom take these abilities or accessibility needs into account. Without adequate knowledge regarding such sensory loss, it is difficult for LTC staff to determine the level of an individual’s residual basic competence for communication and independent functioning. We will conduct a scoping review to identify the screening measures used in research and clinical contexts that test hearing and vision in adults aged over 65 years with dementia, aiming to: (1) provide an overview of hearing and vision screening in older adults with dementia; and (2) evaluate the sensibility of the screening tools. Methods and analysis: This scoping review will be conducted using the framework by Arksey and O’Malley and furthered by methodological enhancements from cited researchers. We will conduct electronic database searches in CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We will also carry out a ‘grey literature’ search for studies or materials not formally published, both online and through interview discussions with healthcare professionals and research clinicians working in the field. Our aim is to find new and existing hearing and vision screening measures used in research and by clinical professionals of optometry and audiology. Abstracts will be independently reviewed twice for acceptance by a multidisciplinary team of researchers and research clinicians. Ethics and dissemination: This review will inform health professionals working with this growing population. With the review findings, we aim to develop a toolkit and an algorithmic process to select the most appropriate hearing and vision screening assessments for LTC residents with dementia that will facilitate accurate testing and can inform care planning, thereby improving residents’ quality of life

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Risk of breast cancer following exposure to tetrachloroethylene-contaminated drinking water in Cape Cod, Massachusetts: reanalysis of a case-control study using a modified exposure assessment

<p>Abstract</p> <p>Background</p> <p>Tetrachloroethylene (PCE) is an important occupational chemical used in metal degreasing and drycleaning and a prevalent drinking water contaminant. Exposure often occurs with other chemicals but it occurred alone in a pattern that reduced the likelihood of confounding in a unique scenario on Cape Cod, Massachusetts. We previously found a small to moderate increased risk of breast cancer among women with the highest exposures using a simple exposure model. We have taken advantage of technical improvements in publically available software to incorporate a more sophisticated determination of water flow and direction to see if previous results were robust to more accurate exposure assessment.</p> <p>Methods</p> <p>The current analysis used PCE exposure estimates generated with the addition of water distribution modeling software (EPANET 2.0) to test model assumptions, compare exposure distributions to prior methods, and re-examine the risk of breast cancer. In addition, we applied data smoothing to examine nonlinear relationships between breast cancer and exposure. We also compared a set of measured PCE concentrations in water samples collected in 1980 to modeled estimates.</p> <p>Results</p> <p>Thirty-nine percent of individuals considered unexposed in prior epidemiological analyses were considered exposed using the current method, but mostly at low exposure levels. As a result, the exposure distribution was shifted downward resulting in a lower value for the 90th percentile, the definition of "high exposure" in prior analyses. The current analyses confirmed a modest increase in the risk of breast cancer for women with high PCE exposure levels defined by either the 90th percentile (adjusted ORs 1.0-1.5 for 0-19 year latency assumptions) or smoothing analysis cut point (adjusted ORs 1.3-2.0 for 0-15 year latency assumptions). Current exposure estimates had a higher correlation with PCE concentrations in water samples (Spearman correlation coefficient = 0.65, p < 0.0001) than estimates generated using the prior method (0.54, p < 0.0001).</p> <p>Conclusions</p> <p>The incorporation of sophisticated flow estimates in the exposure assessment method shifted the PCE exposure distribution downward, but did not meaningfully affect the exposure ranking of subjects or the strength of the association with the risk of breast cancer found in earlier analyses. Thus, the current analyses show a slightly elevated breast cancer risk for highly exposed women, with strengthened exposure assessment and minimization of misclassification by using the latest technology.</p

Influence of obesity-related risk factors in the aetiology of glioma

BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

Peripheral Blood Signatures of Lead Exposure

BACKGROUND: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway

Impact of atopy on risk of glioma: a Mendelian randomisation study.

Background An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Methods Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.Results Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).Conclusions Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions

Influence of obesity-related risk factors in the aetiology of glioma.

BackgroundObesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation.MethodsGenetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship.ResultsNo convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours.ConclusionsThis study provides no evidence to implicate obesity-related factors as causes of glioma