Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

PubMed Central

Zhong, W‐P; Wu, H; Chen, J‐Y; Li, X‐X; Lin, H‐M; Zhang, B; Zhang, Z‐W; Ma, D‐L; Sun, S; Li, H‐P; Mai, L‐P; He, G‐D; Wang, X‐P; Lei, H‐P; Zhou, H‐K; Tang, L; Liu, S‐W

2017-01-01

Genetic variants in the pharmacokinetic (PK) mechanism are the main underlying factors affecting the antiplatelet response to clopidogrel. Using a genomewide association study (GWAS) to identify new genetic loci that modify antiplatelet effects in Chinese patients with coronary heart disease, we identified novel variants in two transporter genes (SLC14A2 rs12456693, ATP‐binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reaction unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically improved the predictability of PRU variability to 37.7%. The associations between these loci and PK parameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P < 0.05). Rs2254638 was further identified to exert a marginal risk effect for major adverse cardiac events in an independent cohort. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment. PMID:27981573

Evaluation of Modified Risk Claim Advertising Formats for Camel Snus

ERIC Educational Resources Information Center

Fix, Brian V.; Adkison, Sarah E.; O'Connor, Richard J.; Bansal-Travers, Maansi; Cummings, K. Michael; Rees, Vaughan W.; Hatsukami, Dorothy K.

2017-01-01

Objectives: The US Food and Drug Administration (FDA) has regulatory authority for modified risk tobacco product advertising claims. To guide future regulatory efforts, we investigated how variations in modified risk claim advertisements influence consumer perceptions of product risk claims for Camel Snus. Methods: Young people and adults (15-65),…

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

PubMed

Neuberger, James M; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K; Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L; Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Trunečka, Pavel; Tisone, Giuseppe; van Gelder, Teun

2017-04-01

Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

Identifying and Managing Risk.

ERIC Educational Resources Information Center

Abraham, Janice M.

1999-01-01

The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

Pre-Diabetes Non-Modifiable Risk Factors

MedlinePlus

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pre-diabetes Non-modifiable Risk Factors Updated:Nov 9,2015 ... This content was last reviewed August 2015. Pre-diabetes • Introduction • About Pre-diabetes • What's the Problem? Intro ...

Interventions to modify sexual risk behaviours for preventing HIV in homeless youth.

PubMed

Naranbhai, Vivek; Abdool Karim, Quarraisha; Meyer-Weitz, Anna

2011-01-19

Homeless youth are at high risk for HIV infection as a consequence of risky sexual behaviour. Interventions for homeless youth are challenging. Assessment of the effectiveness of interventions to modify sexual risk behaviours for preventing HIV in homeless youth is needed. To evaluate and summarize the effectiveness of interventions for modifying sexual risk behaviours and preventing transmission of HIV among homeless youth. We searched electronic databases (CENTRAL, MEDLINE, EMBASE, AIDSearch, Gateway, PsycInfo, LILACS), reference lists of eligible articles, international health agency publication lists, and clinical trial registries. The search was updated January 2010. We contacted authors of published reports and other key role players. Randomised studies of interventions to modify sexual risk behaviour (biological, self-reporting of sexual-risk behaviour or health-seeking behaviour) in homeless youth (12-24 years). Data from eligible studies were extracted by two reviewers. We assessed risk of bias per the Cochrane Collaborations tool. None of the eligible studies reported any primary biological outcomes for this review. Reports of self-reporting sexual risk behaviour outcomes varied across studies precluding calculation of summary measures of effect; we present the outcomes descriptively for each study. We contacted authors for missing or ambiguous data. We identified three eligible studies after screening a total of 255 unique records. All three were performed in the United States of America and recruited substance-abusing male and female adolescents (total N=615) through homeless shelters into randomised controlled trials of independent and non-overlapping behavioural interventions. The three trials differed in theoretical background, delivery method, dosage (number of sessions,) content and outcome assessments. Overall, the variability in delivery and outcomes precluded estimation of summary of effect measures. We assessed the risk of bias to be high for

Modifiable risk factors in periodontitis: at the intersection of aging and disease.

PubMed

Reynolds, Mark A

2014-02-01

Chronic inflammation is a prominent feature of aging and of common age-related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

PubMed Central

Vijai, Joseph; Klein, Robert J.; Kirchhoff, Tomas; McGuffog, Lesley; Barrowdale, Daniel; Dunning, Alison M.; Lee, Andrew; Dennis, Joe; Healey, Sue; Dicks, Ed; Soucy, Penny; Sinilnikova, Olga M.; Pankratz, Vernon S.; Wang, Xianshu; Eldridge, Ronald C.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Schmutzler, Rita K.; Nathanson, Katherine L.; Piedmonte, Marion; Singer, Christian F.; Thomassen, Mads; Hansen, Thomas v. O.; Neuhausen, Susan L.; Blanco, Ignacio; Greene, Mark H.; Garber, Judith; Weitzel, Jeffrey N.; Andrulis, Irene L.; Goldgar, David E.; D'Andrea, Emma; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; van Rensburg, Elizabeth J.; Arason, Adalgeir; Rennert, Gad; van den Ouweland, Ans M. W.; van der Hout, Annemarie H.; Kets, Carolien M.; Aalfs, Cora M.; Wijnen, Juul T.; Ausems, Margreet G. E. M.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Jacobs, Chris; Adlard, Julian; Tischkowitz, Marc; Porteous, Mary E.; Damiola, Francesca; Golmard, Lisa; Barjhoux, Laure; Longy, Michel; Belotti, Muriel; Ferrer, Sandra Fert; Mazoyer, Sylvie; Spurdle, Amanda B.; Manoukian, Siranoush; Barile, Monica; Genuardi, Maurizio; Arnold, Norbert; Meindl, Alfons; Sutter, Christian; Wappenschmidt, Barbara; Domchek, Susan M.; Pfeiler, Georg; Friedman, Eitan; Jensen, Uffe Birk; Robson, Mark; Shah, Sohela; Lazaro, Conxi; Mai, Phuong L.; Benitez, Javier; Southey, Melissa C.; Schmidt, Marjanka K.; Fasching, Peter A.; Peto, Julian; Humphreys, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Sawyer, Elinor J.; Burwinkel, Barbara; Guénel, Pascal; Bojesen, Stig E.; Milne, Roger L.; Brenner, Hermann; Lochmann, Magdalena; Aittomäki, Kristiina; Dörk, Thilo; Margolin, Sara; Mannermaa, Arto; Lambrechts, Diether; Chang-Claude, Jenny; Radice, Paolo; Giles, Graham G.; Haiman, Christopher A.; Winqvist, Robert; Devillee, Peter; García-Closas, Montserrat; Schoof, Nils; Hooning, Maartje J.; Cox, Angela; Pharoah, Paul D. P.; Jakubowska, Anna; Orr, Nick; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Hall, Per; Couch, Fergus J.; Simard, Jacques; Altshuler, David; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Offit, Kenneth

2013-01-01

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80–0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical

Modifiable Risk Factors in Primary Joint Arthroplasty Increase 90-Day Cost of Care.

PubMed

Schroer, William C; Diesfeld, Paul J; LeMarr, Angela R; Morton, Diane J; Reedy, Mary E

2018-04-19

Risk factors in demographics and health status have been identified that increase the risk of complications after joint arthroplasty, necessitating additional care and incurring additional charges. The purpose of this study was to identify the number of patients in a hospital network database who had one or more predefined modifiable risk factors and determine their impact on average length of stay, need for additional care during the 90-day postoperative period, and the 90-day charges for care. An electronic hospital record query of 6968 lower extremity joint arthroplasty procedures under Diagnosis-Related Group 469/470 performed in 2014-2015 was reviewed, and total 90-day charges were calculated. The case mean was compared to charges for patients with modifiable risk factors: anemia (Hgb < 10 g/dL), malnutrition (albumin < 3.4 g/dL), obesity (body mass index > 45 kg/m 2 ), uncontrolled diabetes (random glucose >180 mg/dL or A1C > 8), narcotic use (prescription filled), and tobacco use (documented within 30 days before surgery). Length of stay, emergency room visits, and hospital readmission were compared. Mean 90-day charges for Diagnosis-Related Group 469/470 were $36,647. Risk factors were associated with a significant increase in 90-day charges: anemia (+$ 15,869/126 patients), malnutrition (+$9270/592), obesity (+$2048/445), diabetes (+$5074/291), narcotic use (+$1801/1943), and tobacco use (+$2034/1882). Intensive care unit admission rate, emergency department visits, and hospital readmission were significantly increased for patients with each risk factor. Length of stay was higher in patients with anemia, malnutrition, diabetes, and tobacco use. When separated by elective vs fracture admission, 90-day charges were significantly higher for each risk factor. Medical strategies to optimize patients before joint arthroplasty are warranted to improve postoperative outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

PubMed Central

Maas, Paige; Barrdahl, Myrto; Joshi, Amit D.; Auer, Paul L.; Gaudet, Mia M.; Milne, Roger L.; Schumacher, Fredrick R.; Anderson, William F.; Check, David; Chattopadhyay, Subham; Baglietto, Laura; Berg, Christine D.; Chanock, Stephen J.; Cox, David G.; Figueroa, Jonine D.; Gail, Mitchell H.; Graubard, Barry I.; Haiman, Christopher A.; Hankinson, Susan E.; Hoover, Robert N.; Isaacs, Claudine; Kolonel, Laurence N.; Le Marchand, Loic; Lee, I-Min; Lindström, Sara; Overvad, Kim; Romieu, Isabelle; Sanchez, Maria-Jose; Southey, Melissa C.; Stram, Daniel O.; Tumino, Rosario; VanderWeele, Tyler J.; Willett, Walter C.; Zhang, Shumin; Buring, Julie E.; Canzian, Federico; Gapstur, Susan M.; Henderson, Brian E.; Hunter, David J.; Giles, Graham G; Prentice, Ross L.; Ziegler, Regina G.; Kraft, Peter; Garcia-Closas, Montse; Chatterjee, Nilanjan

2017-01-01

were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population. CONCLUSIONS AND RELEVANCE This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation. PMID:27228256

Modifiable risk factors for impaired fertility in women: what nurse practitioners need to know.

PubMed

Kelly-Weeder, Susan; O'Connor, Alane

2006-06-01

To provide an overview of impaired fertility in childbearing-aged women, to review the current research on modifiable lifestyle risk factors implicated in its development, and to suggest strategies for nurse practitioners (NPs) to assist women in behavioral changes that will allow them to protect their fertility. Original research articles and comprehensive review articles identified through Medline, CINAHL, and OVID databases. Research has shown that advancing age, a history of a sexually transmitted infection and/or pelvic inflammatory disease, extremes of body weight, and tobacco and caffeine use are potentially modifiable risk factors in the development of impaired fertility. NPs must be aware of the link between these behaviors and the development of impaired fertility in order to assist women in preserving their fertility. Individual counseling, education, and community-wide education strategies are discussed.

Population attributable risk of key modifiable risk factors associated with non-exclusive breastfeeding in Nigeria.

PubMed

Ogbo, Felix Akpojene; Page, Andrew; Idoko, John; Agho, Kingsley E

2018-02-13

Non-exclusive breastfeeding (non-EBF) is a risk factor for many of the 2300 under-five deaths occurring daily in Nigeria - a developing country with approximately 40 million children. This study aimed to quantify and compare the attributable burden of key modifiable risk factors associated with non-EBF in Nigeria to inform strategic policy responses and initiatives. Relative risk and exposure prevalence for selected modifiable risk factors were used to calculate population attributable fractions based on Nigeria Demographic and Health Surveys data for the period (1999-2013). Scenarios based on feasible impact of community-based interventions in reducing exposure prevalence were also considered to calculate comparative potential impact fractions. In Nigeria, an estimated 22.8% (95% Confidence Interval, CI: 9.2-37.0%) of non-EBF was attributable to primary and no maternal education; 24.7% (95% CI: 9.5-39.5%) to middle and poor household wealth, 9.7% (1.7-18.1%) to lower number (1-3) and no antenatal care visits; 18.8% (95% CI: 6.9-30.8%) to home delivery and 16.6% (95% CI: 3.0-31.3%) to delivery assisted by a non-health professional. In combination, more than half of all cases of non-EBF (64.5%; 95% CI: 50.0-76.4%) could be attributed to those modifiable risk factors. Scenarios based on feasible impacts of community-based approaches to improve health service access and human capacity suggest that an avoidable burden of non-EBF practice of approximately 11% (95% CI: -5.4; 24.7) is achievable. Key modifiable risk factors contribute significantly to non-EBF in Nigerian women. Community-based initiatives and appropriate socio-economic government policies that specifically consider those modifiable risk factors could substantially reduce non-EBF practice in Nigeria.

Aquaculture: Incorporating risk assessment and risk management into public policies on genetically modified finfish and shellfish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallerman, E.M.; Kapuscinski, A.R.

Genetically modified finfish and shellfish pose economic benefits to aquaculture, but also pose ecological and genetic risks to ecosystems receiving such organisms. Realization of benefits with minimization of risks posed by a new technology can be addressed through the processes of risk assessment and risk management. Public policies adopted by individual countries will reflect differences in the outocme of risk assessment and risk management processes resulting from differences among the receiving ecosystems and sets of human values at issue. A number of countries and international institutions have begun development of policies for oversight of genetically modified aquatic organisms. In themore » United States, a working group commissioned by the U.S. Department of Agriculture incorporated risk assessment and risk management principles into draft performance standards for safely conducting research with genetically modified finfish and shellfish. The performance standards address research with a broad range of aquatic GMO`s and compliance is intended to be voluntary. In contrast, the Canadian policy mandates adherence to specified guidelines for experiments with transgenic aquatic organisms; establishment as national policy is expended soon.« less

Identifying risks in the realm of enterprise risk management.

PubMed

Carroll, Roberta

2016-01-01

An enterprise risk management (ERM) discipline is comprehensive and organization-wide. The effectiveness of ERM is governed in part by the strength and breadth of its practices and processes. An essential element in decision making is a thorough process by which organizational risks and value opportunities can be identified. This article will offer identification techniques that go beyond those used in traditional risk management programs and demonstrate how these techniques can be used to identify risks and opportunity in the ERM environment. © 2016 American Society for Healthcare Risk Management of the American Hospital Association.

Interventions to modify sexual risk behaviours for preventing HIV in homeless youth

PubMed Central

Naranbhai, Vivek; Karim, Quarraisha Abdool; Meyer-Weitz, Anna

2013-01-01

Background Homeless youth are at high risk for HIV infection as a consequence of risky sexual behavior. Interventions in homeless youth are challenging. Assessment of the effectiveness of interventions to modify sexual risk behaviours for preventing HIV in homeless youth is needed. Objectives To evaluate and summarize the effectiveness of interventions for modifying sexual risk behaviours and preventing transmission of HIV among homeless youth. Search methods We searched electronic databases (CENTRAL, Medline, EMBASE, AIDSearch, Gateway, PsycInfo, LILACS), reference lists of eligible articles, international health agency publication lists, and clinical trial registries. The search was updated January 2010. We contacted authors of published reports and other key role players. Selection criteria Randomized studies of interventions to modify sexual risk behavior (biological, self-report sexual-risk behavior or health seeking behavior) in homeless youth (12–24 years). Data collection and analysis Data from eligible studies were extracted by two reviewers. We assessed risk of bias per the Cochrane Collaborations tool. None of the eligible studies reported any primary biological outcomes for this review and the reporting of self-report sexual risk behavior outcomes was highly variable across studies precluding calculation of summary measures of effect; we present the outcomes descriptively for each study. We contacted authors for missing or ambiguous data. Results We identified three eligible studies after screening a total of 255 unique records. All three were performed in the United States of America and recruited substance-abusing male and female adolescents (total N=615) through homeless shelters into randomised controlled trials of independent and non-overlapping behavioural interventions. The three trials differed in theoretical background, delivery method, dosage (number of sessions,) content and outcome assessments. Overall, the variability in delivery and

Modifiable risk factors for migraine progression.

PubMed

Bigal, Marcelo E; Lipton, Richard B

2006-10-01

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

NIH Researchers Identify OCD Risk Gene

MedlinePlus

... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers.

PubMed

Wang, Xianshu; Pankratz, V Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D P; Ponder, Bruce A J; Dunning, Alison M; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B L; Hooning, Maartje J; Ligtenberg, Marjolijn J; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Singer, Christian F; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N; Hunter, David J; Chanock, Stephen J; Easton, Douglas F; Antoniou, Antonis C; Couch, Fergus J

2010-07-15

Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 x 10(-3)) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutation carriers from nine centers. Associations with breast cancer risk were assessed using Cox models weighted for penetrance. Eight SNPs in BRCA1 carriers and 12 SNPs in BRCA2 carriers, representing an enrichment over the number expected, were significantly associated with breast cancer risk (P(trend) < 0.01). The minor alleles of rs6138178 in SNRPB and rs6602595 in CAMK1D displayed the strongest associations in BRCA1 carriers (HR = 0.78, 95% CI: 0.69-0.90, P(trend) = 3.6 x 10(-4) and HR = 1.25, 95% CI: 1.10-1.41, P(trend) = 4.2 x 10(-4)), whereas rs9393597 in LOC134997 and rs12652447 in FBXL7 showed the strongest associations in BRCA2 carriers (HR = 1.55, 95% CI: 1.25-1.92, P(trend) = 6 x 10(-5) and HR = 1.37, 95% CI: 1.16-1.62, P(trend) = 1.7 x 10(-4)). The magnitude and direction of the associations were consistent with the original GWAS. In subsequent risk assessment studies, the loci appeared to interact multiplicatively for breast cancer risk in BRCA1 and BRCA2 carriers. Promising candidate SNPs from GWAS were identified as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. Upon further validation, these SNPs together with other genetic and environmental factors may improve breast cancer risk assessment in these populations.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Inventory of Personal Skills for Achievement: Validity and Reliability Study of an Instrument for Identifying Educationally At-Risk Junior [High] School Students.

ERIC Educational Resources Information Center

Leaseburg, Melinda G.; And Others

This paper describes the development and test of an early-warning instrument for identifying at-risk students aged 10-15. A statistically sound test to identify at-risk high school students existed in the Personal Skills Map--Adolescent version (PSMA-A). This study used a modified version of PSM-A , which was renamed Personal Skills for…

Identifying and assessing highly hazardous drugs within quality risk management programs.

PubMed

Sussman, Robert G; Schatz, Anthony R; Kimmel, Tracy A; Ader, Allan; Naumann, Bruce D; Weideman, Patricia A

2016-08-01

Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Modifiable Lifestyle Risk Factors and Incident Diabetes in African Americans.

PubMed

Joseph, Joshua J; Echouffo-Tcheugui, Justin B; Talegawkar, Sameera A; Effoe, Valery S; Okhomina, Victoria; Carnethon, Mercedes R; Hsueh, Willa A; Golden, Sherita H

2017-11-01

The associations of modifiable lifestyle risk factors with incident diabetes are not well investigated in African Americans (AAs). This study investigated the association of modifiable lifestyle risk factors (exercise, diet, smoking, TV watching, and sleep-disordered breathing burden) with incident diabetes among AAs. Modifiable lifestyle risk factors were characterized among 3,252 AAs in the Jackson Heart Study who were free of diabetes at baseline (2000-2004) using baseline questionnaires and combined into risk factor categories: poor (0-3 points), average (4-7 points), and optimal (8-11 points). Incidence rate ratios (IRR) for diabetes (fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or glycosylated hemoglobin A1c ≥6.5%) were estimated using Poisson regression modeling adjusting for age, sex, education, occupation, systolic blood pressure, and BMI. Outcomes were collected 2005-2012 and data analyzed in 2016. Over 7.6 years, there were 560 incident diabetes cases (mean age=53.3 years, 64% female). An average or optimal compared to poor risk factor categorization was associated with a 21% (IRR=0.79, 95% CI=0.62, 0.99) and 31% (IRR=0.69, 95% CI=0.48, 1.01) lower risk of diabetes. Among participants with BMI <30, IRRs for average or optimal compared to poor categorization were 0.60 (95% CI=0.40, 0.91) and 0.53 (95% CI=0.29, 0.97) versus 0.90 (95% CI=0.67, 1.21) and 0.83 (95% CI=0.51, 1.34) among participants with BMI ≥30. A combination of modifiable lifestyle factors are associated with a lower risk of diabetes among AAs, particularly among those without obesity. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Older Americans' risk-benefit preferences for modifying the course of Alzheimer disease.

PubMed

Hauber, A Brett; Johnson, F Reed; Fillit, Howard; Mohamed, Ateesha F; Leibman, Christopher; Arrighi, H Michael; Grundman, Michael; Townsend, Raymond J

2009-01-01

Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative illness affecting millions of patients, families, and caregivers. Effective disease-modifying therapies for AD are desperately needed, but none currently exist on the market. Thus, accelerating the discovery, development, and approval of new disease-modifying drugs for AD is a high priority for individuals, physicians, and medical decision makers. Potentially disease-modifying drugs likely will have significant therapeutic benefits but also may have treatment-related risks. We quantified older Americans' treatment-related risk tolerance by eliciting their willingness to accept the risk of treatment-related death or permanent severe disability in exchange for modifying the course of AD. A stated-choice survey instrument was administered to 2146 American residents 60 years of age and older. On average, subjects were willing to accept a 1-year risk of treatment-related death or permanent severe disability from stroke of over 30% for a treatment that prevents AD from progressing beyond the mild stage. Thus, most people in this age cohort are willing to accept considerable risks in return for disease-modifying benefits of new AD drugs. These results are consistent with other studies indicating that individuals view AD as a serious, life threatening illness that imposes heavy burdens on both patients and caregivers.

Modifiable worker risk factors contributing to workplace absence: a stakeholder-centred best-evidence synthesis of systematic reviews.

PubMed

Wagner, Shannon; White, Marc; Schultz, Izabela; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

2014-01-01

A challenge facing stakeholders is the identification and translation of relevant high quality research to inform policy and practice. This study engaged academic and community stakeholders in conducting a best evidence-synthesis to identify modifiable risk and protective worker factors across health conditions impacting work-related absence. To identify modifiable worker disability risk and protective factors across common health conditions impacting work-related absence. We searched Medline, Embase, CINHAL, The Cochrane Library, PsycINFO, BusinessSourceComplete, and ABI/Inform from 2000 to 2011. Quantitative, qualitative, or mixed methods systematic reviews of work-focused population were considered for inclusion. Two or more reviewers independently reviewed articles for inclusion and methodological screening. The search strategy, expert input and grey literature identified 2,467 unique records. One hundred and forty-two full text articles underwent comprehensive review. Twenty-four systematic reviews met eligibility criteria. Modifiable worker factors found to have consistent evidence across two or more health conditions included emotional distress, negative enduring psychology/personality factors, negative health and disability perception, decreased physical activity, lack of family support, poor general health, increased functional disability, increased pain, increased fatigue and lack of motivation to return to work. Systematic reviews are limited by availability of high quality studies, lack of consistency of methodological screening and reporting, and variability of outcome measures used.

Modifiable Prostate Cancer Risk Reduction and Early Detection Behaviors in Black Men

ERIC Educational Resources Information Center

Odedina, Folakemi T.; Scrivens, John J., Jr.; Larose-Pierre, Margareth; Emanuel, Frank; Adams, Angela Denise; Dagne, Getachew A.; Pressey, Shannon Alexis; Odedina, Oladapo

2011-01-01

Objective: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. Methods: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. Results: Modifiable prostate cancer risk-reduction behavior was found…

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

PubMed Central

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A.M.; Meijers-Heijboer, Hanne E.J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P.G.; Hoogerbrugge, Nicoline; Ausems, Margreet G.E.M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

2014-01-01

Background BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. PMID:25336561

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

PubMed

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B; Rudolph, Anja; Schmutzler, Rita K; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A; Easton, Douglas F; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A; Schmidt, Marjanka K; van der Baan, Frederieke H; Spurdle, Amanda B; Walker, Logan C; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B; Olopade, Olufunmilayo I; Nussbaum, Robert L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Karlan, Beth Y; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K; Miron, Alex; Southey, Melissa C; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E; Blazer, Kathleen R; Weitzel, Jeffrey N; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D Gareth R; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V; Ellis, Steve; Cole, Trevor; Godwin, Andrew K; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L; Rodriguez, Gustavo C; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A M; Meijers-Heijboer, Hanne E J; van der Hout, Annemarie H; Vreeswijk, Maaike P G; Hoogerbrugge, Nicoline; Ausems, Margreet G E M; van Doorn, Helena C; Collée, J Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R; Olswold, Curtis; Couch, Fergus J; Lindor, Noralane M; Wang, Xianshu; Szabo, Csilla I; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C; Friedman, Eitan

2015-01-01

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. ©2014 American Association for Cancer Research.

Awareness of modifiable acute myocardial infarction risk factors has little impact on risk perception for heart attack among vulnerable patients.

PubMed

Abed, Mona A; Khalil, Amani A; Moser, Debra K

2015-01-01

Poor awareness of modifiable risks for acute myocardial infarction (AMI) may explain the reported weak relationship between patients' actual and perceived risk for AMI. To assess the level of awareness of modifiable risks and perceived vulnerability for AMI among Jordanian patients, and to determine their independent association. This was a cross-sectional correlational study (N = 231). Perceived risk, awareness of risk factors and risk profile were collected by self-reports and medical chart review. Patients were mostly males (80%) and had a mean of 55.3 ± 12.6 years for age. Perceived and actual AMI risks were not highly congruent even though patients had, on average, two modifiable risks and were knowledgeable of them. Awareness of risk factors independently explained 3.5% of the variance in perceived risk. The risk for developing AMI is underestimated among cardiac patients and it is only weakly linked with their awareness of AMI risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Identifying and managing the risks of medical ionizing radiation in endourology.

PubMed

Yecies, Todd; Averch, Timothy D; Semins, Michelle J

2018-02-01

The risks of exposure to medical ionizing radiation is of increasing concern both among medical professionals and the general public. Patients with nephrolithiasis are exposed to high levels of ionizing radiation through both diagnostic and therapeutic modalities. Endourologists who perform a high-volume of fluoroscopy guided procedures are also exposed to significant quantities of ionizing radiation. The combination of judicious use of radiation-based imaging modalities, application of new imaging techniques such as ultra-low dose computed tomography (CT) scan, and modifying use of current technology such as increasing ultrasound and pulsed fluoroscopy utilization offers the possibility of significantly reducing radiation exposure. We present a review of the literature regarding the risks of medical ionizing radiation to patients and surgeons as it pertains to the field of endourology and interventions that can be performed to limit this exposure. A review of the current state of the literature was performed using MEDLINE and PubMed. Interventions designed to limit patient and surgeon radiation exposure were identified and analyzed. Summaries of the data were compiled and synthesized in the body of the text. While no level 1 evidence exists demonstrating the risk of secondary malignancy with radiation exposure, the preponderance of evidence suggests a dose and age dependent increase in malignancy risk from ionizing radiation. Patients with nephrolithiasis were exposed to an average effective dose of 37mSv over a 2 year period. Multiple evidence-based interventions to limit patient and surgeon radiation exposure and associated risk were identified. Current evidence suggest an age and dose dependent risk of secondary malignancy from ionizing radiation. Urologists must act in accordance with ALARA principles to safely manage nephrolithiasis while minimizing radiation exposure.

Using risk-adjustment models to identify high-cost risks.

PubMed

Meenan, Richard T; Goodman, Michael J; Fishman, Paul A; Hornbrook, Mark C; O'Keeffe-Rosetti, Maureen C; Bachman, Donald J

2003-11-01

We examine the ability of various publicly available risk models to identify high-cost individuals and enrollee groups using multi-HMO administrative data. Five risk-adjustment models (the Global Risk-Adjustment Model [GRAM], Diagnostic Cost Groups [DCGs], Adjusted Clinical Groups [ACGs], RxRisk, and Prior-expense) were estimated on a multi-HMO administrative data set of 1.5 million individual-level observations for 1995-1996. Models produced distributions of individual-level annual expense forecasts for comparison to actual values. Prespecified "high-cost" thresholds were set within each distribution. The area under the receiver operating characteristic curve (AUC) for "high-cost" prevalences of 1% and 0.5% was calculated, as was the proportion of "high-cost" dollars correctly identified. Results are based on a separate 106,000-observation validation dataset. For "high-cost" prevalence targets of 1% and 0.5%, ACGs, DCGs, GRAM, and Prior-expense are very comparable in overall discrimination (AUCs, 0.83-0.86). Given a 0.5% prevalence target and a 0.5% prediction threshold, DCGs, GRAM, and Prior-expense captured $963,000 (approximately 3%) more "high-cost" sample dollars than other models. DCGs captured the most "high-cost" dollars among enrollees with asthma, diabetes, and depression; predictive performance among demographic groups (Medicaid members, members over 64, and children under 13) varied across models. Risk models can efficiently identify enrollees who are likely to generate future high costs and who could benefit from case management. The dollar value of improved prediction performance of the most accurate risk models should be meaningful to decision-makers and encourage their broader use for identifying high costs.

Modifiable risk factors for RA: prevention, better than cure?

PubMed Central

Lahiri, Manjari; Morgan, Catharine; Symmons, Deborah P. M.

2012-01-01

Objective. To perform a meta-synthesis of the evidence for modifiable lifestyle risk factors for inflammatory polyarthritis (IP) and RA. Methods. We performed a MEDLINE literature search. Case–control and cohort studies and systematic reviews published from 1948 through February 2011 and studying modifiable risk factors for RA were retrieved. The main outcome measure was diagnosis of RA according to the standard criteria. Results. Smoking contributes up to 25% of the population burden of RA. The risk is dose related, stronger in males and especially strong for anti-citrullinated peptide antibody positive (ACPA+) RA through an interaction with the shared epitope. After smoking cessation, there is, however, a latency of up to 20 years to return to baseline risk. Other associations are less definitive; however, prospective studies suggest that dietary antioxidants and breastfeeding may be protective and that high coffee consumption may increase RA risk. An inverse association with alcohol intake (especially in smokers) and with education/social class (especially seropositive RA) and an increased risk with obesity (seronegative RA) is also noted. Conclusion. There is a need for further large-scale prospective studies with a consistent definition of RA phenotype (undifferentiated IP through to ACPA+/RF+ disease). This will ultimately afford the opportunity to evaluate preventative population strategies for RA akin to the well-established programmes for cardiovascular disease and cancer, targeting common risk factors. PMID:22120459

[Modifiable risk factors for primary headache. A systematic review].

PubMed

Albers, L; Ziebarth, S; von Kries, R

2014-08-01

Strategies to prevent primary headaches could be very beneficial, especially given that primary headaches can lead to the development of chronic headache. In order to establish headache prevention strategies, the modifiable risk factors for primary headaches need to be identified. A systematic literature search on the risk factors for primary headaches was conducted independently by two persons using the databases MEDLINE and Embase. Further inclusion criteria were observational studies in adult general populations or case-control studies, where the effect sizes were reported as odds ratios or where the odds ratios could be calculated from the given data. In all, 24 studies were included in the analysis. There was a large amount of heterogeneity among the studies concerning headache acquisition, headache classification, and risk factors for headache development. Independent of headache trigger and definition of headache, the association between headache and the risk factor "stress" was very high: The meta-analysis shows an overall effect of 2.26 (odds ratio; 95 %-CI = [1.79; 2.85]). Studies evaluating neck and shoulder pain also report a strong association with headache; however, these results could not be summarized in a meta-analysis. Equally, the overall effects of smoking and coffee consumption on headaches could not be verified because the effect sizes were rather small and predominantly noticeable only at higher doses. A strong association between headache and the risk factors stress and neck and shoulder pain was confirmed. The effect sizes of smoking and coffee consumption on headaches were rather small.

Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal Masses?

PubMed

Saltzman, Amanda F; Carrasco, Alonso; Colvin, Alexandra N; Meyers, Mariana L; Cost, Nicholas G

2018-03-20

We characterize and apply the modified Bosniak classification system to a cohort of children with cystic renal lesions and known surgical pathology. We identified all patients at our institution with cystic renal masses who also underwent surgery for these lesions. Patients without available preoperative imaging or pathology were excluded. All radiological imaging was independently reviewed by a pediatric radiologist blinded to pathological findings. Imaging characteristics (size, border, septations, calcifications, solid components, vascularity) were recorded from the most recent preoperative ultrasounds and computerized tomograms. The modified Bosniak classification system was applied to these scans and then correlated with final pathology. A total of 22 patients met study criteria. Median age at surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%) underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%) laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%) laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%), intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and 8 of 9 benign lesions (89%) were modified class 1 or 2. Cystic renal lesions in children with a modified Bosniak class of 1 or 2 were most often benign, while class 3 or 4 lesions warranted surgical excision since more than 90% of masses harbored intermediate or malignant pathology. The modified Bosniak classification system appears to allow for a reasonable clinical risk stratification of pediatric cystic renal masses. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Interventions for improving modifiable risk factor control in the secondary prevention of stroke.

PubMed

Lager, Kate E; Mistri, Amit K; Khunti, Kamlesh; Haunton, Victoria J; Sett, Aung K; Wilson, Andrew D

2014-05-02

interval (CI) -5.46 to 0.31), mean diastolic blood pressure (MD -0.90 mmHg; 95% CI -2.49 to 0.68), blood pressure target achievement (OR 1.24; 95% CI 0.94 to 1.64) and mean body mass index (MD -0.68 kg/m(2); 95% CI -1.46 to 0.11). There were no significant effects of organisational interventions on lipid profile, HbA1c, medication adherence or recurrent cardiovascular events. Educational and behavioural interventions were not generally associated with clear differences in any of the review outcomes, with only two exceptions. Pooled results indicated that educational interventions were not associated with clear differences in any of the review outcomes. The estimated effects of organisational interventions were compatible with improvements and no differences in several modifiable risk factors. We identified a large number of ongoing studies, suggesting that research in this area is increasing. The use of standardised outcome measures would facilitate the synthesis of future research findings.

DTREEv2, a computer-based support system for the risk assessment of genetically modified plants.

PubMed

Pertry, Ine; Nothegger, Clemens; Sweet, Jeremy; Kuiper, Harry; Davies, Howard; Iserentant, Dirk; Hull, Roger; Mezzetti, Bruno; Messens, Kathy; De Loose, Marc; de Oliveira, Dulce; Burssens, Sylvia; Gheysen, Godelieve; Tzotzos, George

2014-03-25

Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems that can facilitate the risk assessment process. In this paper we describe DTREEv2, a computer-based decision support system for the identification of hazards related to the introduction of GM-crops into the environment. DTREEv2 structures hazard identification and evaluation by means of an Event-Tree type of analysis. The system produces an output flagging identified hazards and potential risks. It is intended to be used for the preparation and evaluation of biosafety dossiers and, as such, its usefulness extends to researchers, risk assessors and regulators in government and industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis

PubMed Central

Lehert, Philippe; Villaseca, Paulina; Hogervorst, Eef; Maki, Pauline M.; Henderson, Victor W.

2016-01-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually-modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For 10 of these, we used PubMed databases for a systematic review of long-duration (at least six months), randomized controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11 to 0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging. PMID:26361790

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.

PubMed

Lehert, P; Villaseca, P; Hogervorst, E; Maki, P M; Henderson, V W

2015-10-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long-duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging.

76 FR 36544 - Scientific Evaluation of Modified Risk Tobacco Product Applications; Public Workshop; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

... appropriate collection of data regarding the use, consumer perception, and health risks of an MRTP? III...] Scientific Evaluation of Modified Risk Tobacco Product Applications; Public Workshop; Request for Comments... obtain input on specific issues associated with the scientific evaluation of modified risk tobacco...

The Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide.

PubMed

Clemens, Kristin K; McArthur, Eric; Dixon, Stephanie N; Fleet, Jamie L; Hramiak, Irene; Garg, Amit X

2015-08-01

The risk for hypoglycemia when taking glyburide compared with modified-release gliclazide remains to be established in older adults in routine care. We investigated the risk of a hospital encounter with hypoglycemia following a new prescription for glyburide compared with modified-release gliclazide. In 2 population-based matched retrospective cohort studies in Ontario, Canada, between 2002 and 2011, we examined older adults who were newly prescribed glyburide or gliclazide as monotherapy or in the presence of metformin. Our primary outcome was a hospital encounter with hypoglycemia assessed within 90 days. The baseline characteristics between matched groups were similar. Initiating glyburide vs. gliclazide as monotherapy was associated with a higher risk for a hospital encounter with hypoglycemia (69 patients of 4374 taking glyburide [1.58%] vs. 8 patients of 4374 taking gliclazide [0.18%], absolute risk increase 1.40% [95% CI 1.01% to 1.79%], number needed to harm 71 [55 to 99], odds ratio 8.63 [95% CI 4.15 to 17.93], p<0.0001). Similar findings were noted when glyburide vs. gliclazide was initiated in the presence of metformin (110 patients of 8038 taking glyburide [1.37%] vs. 19 patients of 8038 taking gliclazide [0.24%], absolute risk increase 1.13% [95% CI 0.86% to 1.40%], number needed to harm 77 [71 to 116], odds ratio 6.06 [95% CI 3.68 to 9.97], p<0.0001). Glyburide was associated with a higher risk for hypoglycemia than modified-release gliclazide. The results of our studies may help to convince healthcare professionals who use glyburide to consider modified-release gliclazide as a safer alternative. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors.

PubMed

Rudolph, Anja; Milne, Roger L; Truong, Thérèse; Knight, Julia A; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Munday, Hannah R; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Olson, Janet; Vachon, Celine M; Hallberg, Emily; Castelao, J Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G; Nielsen, Sune F; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G; Broeks, Annegien; Rutgers, Emiel J; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Arias Perez, José Ignacio; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W; Ekici, Arif B; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J; Lissowska, Jolanta; Sherman, Mark E; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G; Brenner, Hermann; Fasching, Peter A; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E; Easton, Doug F; Schmidt, Marjanka K; Guénel, Pascal; Hall, Per; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chang-Claude, Jenny

2015-03-15

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. © 2014 UICC.

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Modifiable risk factors of hypertension: A hospital-based case-control study from Kerala, India.

PubMed

Pilakkadavath, Zarin; Shaffi, Muhammed

2016-01-01

Hypertension is a major cause of cardiovascular morbidity and mortality in Kerala. Excess dietary salt, low dietary potassium, overweight and obesity, physical inactivity, excess alcohol, smoking, socioeconomic status, psychosocial stressors, and diabetes are considered as modifiable risk factors for hypertension. To estimate and compare the distribution of modifiable risk factors among hypertensive (cases) and nonhypertensive (controls) patients and to estimate the effect relationship of risk factors. Age- and sex-matched case-control study was conducted in a tertiary care hospital in Kerala using a pretested interviewer-administered structured questionnaire based on the WHO STEPS instrument for chronic disease risk factor surveillance. Bivariate and multiple logistic regression analyses were done. A total of 296 subjects were included in the study. The mean age of study sample was 50.13 years. All modifiable risk factors studied vis-ΰ-vis obesity, lack of physical activity, inadequate fruits and vegetable intake, diabetes, smoking, and alcohol use were significantly different in proportion among cases and controls. Obesity, lack of physical activity, smoking, and diabetes were found to be significant risk factors for hypertension after adjusting for other risk factors. Hypertension is strongly driven by a set of modifiable risk factors. Massive public awareness campaign targeting risk factors is essential in controlling hypertension in Kerala, especially focusing on physical exercise and control of diabetes, obesity, and on quitting smoking.

Chronic headache and potentially modifiable risk factors: screening and behavioral management of sleep disorders.

PubMed

Rains, Jeanetta C

2008-01-01

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.

Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

PubMed Central

Cox, David G.; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A.; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S.; Borg, Åke; Karlsson, Per; Stenmark Askmalm, Marie; Barbany Bustinza, Gisela; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Benítez, Javier; Hamann, Ute; Rookus, Matti A.; van den Ouweland, Ans M.W.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; van Asperen, Christi J.; Devilee, Peter; Gille, Hans J.J.P.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Eisinger, François; Bressac de Paillerets, Brigitte; Caron, Olivier; Delnatte, Capucine; Goldgar, David; Miron, Alex; Ozcelik, Hilmi; Buys, Saundra; Southey, Melissa C.; Terry, Mary Beth; Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng; Hansen, Thomas V.O.; Johannsson, Oskar; Piedmonte, Marion; Rodriguez, Gustavo C.; Basil, Jack B.; Blank, Stephanie; Toland, Amanda E.; Montagna, Marco; Isaacs, Claudine; Blanco, Ignacio; Gayther, Simon A.; Moysich, Kirsten B.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Gadzicki, Dorothea; Fiebig, Britta; Caldes, Trinidad; Laframboise, Rachel; Nevanlinna, Heli; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Radice, Paolo; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Sinilnikova, Olga M.

2011-01-01

Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77–0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription. PMID:21890493

Non-modifiable worker and workplace risk factors contributing to workplace absence: A stakeholder-centred synthesis of systematic reviews.

PubMed

White, Marc I; Wagner, Shannon L; Schultz, Izabela Z; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

2015-01-01

Workplace stakeholders report the identification and translation of relevant high quality research to inform workplace disability policy and practice is a challenge. The present study engaged academic and community stakeholders in conducting a best evidence-synthesis to identify non-modifiable risk and protective worker and workplace factors impacting work-related absence across a variety of health conditions. To identify non-modifiable worker and workplace disability risk and protective factors impacting work-related absence across common health conditions. The research team searched Medline, Embase, CINAHL, The Cochrane Library, PsycINFO, BusinessSource-Complete, and ABI/Inform from 2000 to 2011. Quantitative, qualitative, or mixed methods systematic reviews of work-focused population were considered for inclusion. Two or more reviewers independently reviewed articles for inclusion and methodological screening. The search strategy, including expert input and grey literature, led to the identification of 2,467 unique records. From this initial search, 2325 were eliminated by title or abstract review, 142 articles underwent comprehensive review to assess for inclusion, 26 systematic reviews met eligibility criteria for this synthesis. For non-modifiable worker and workplace factors we found consistent evidence across two or more health conditions for increased risk of disability in situations where workers experience lower education, older age, emotional distress, poor personal functioning, decreased physical functioning, psychological symptoms, overweight status, and greater sick leave history. Heterogeneity of existing literature due to differences in outcome measures, definitions and research designs limited ability to assess effect size and results reflect findings limited to English-language papers.

Using Decomposition Analysis to Identify Modifiable Racial Disparities in the Distribution of Blood Pressure in the United States.

PubMed

Basu, Sanjay; Hong, Anthony; Siddiqi, Arjumand

2015-08-15

To lower the prevalence of hypertension and racial disparities in hypertension, public health agencies have attempted to reduce modifiable risk factors for high blood pressure, such as excess sodium intake or high body mass index. In the present study, we used decomposition methods to identify how population-level reductions in key risk factors for hypertension could reshape entire population distributions of blood pressure and associated disparities among racial/ethnic groups. We compared blood pressure distributions among non-Hispanic white, non-Hispanic black, and Mexican-American persons using data from the US National Health and Nutrition Examination Survey (2003-2010). When using standard adjusted logistic regression analysis, we found that differences in body mass index were the only significant explanatory correlate to racial disparities in blood pressure. By contrast, our decomposition approach provided more nuanced revelations; we found that disparities in hypertension related to tobacco use might be masked by differences in body mass index that significantly increase the disparities between black and white participants. Analysis of disparities between white and Mexican-American participants also reveal hidden relationships between tobacco use, body mass index, and blood pressure. Decomposition offers an approach to understand how modifying risk factors might alter population-level health disparities in overall outcome distributions that can be obscured by standard regression analyses. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Modifiable Risk Factors for West Nile Virus Infection during an Outbreak—Arizona, 2010

PubMed Central

Gibney, Katherine B.; Colborn, James; Baty, Steven; Bunko Patterson, Andrean M.; Sylvester, Tammy; Briggs, Graham; Stewart, Tasha; Levy, Craig; Komatsu, Ken; MacMillan, Katherine; Delorey, Mark J.; Mutebi, John-Paul; Fischer, Marc; Staples, J. Erin

2012-01-01

West Nile virus (WNV) is the leading cause of mosquito-borne disease in the United States; however, risk factors for infection are poorly defined. We performed a case-control study to identify modifiable risk factors for WNV infection. Case-patients (N = 49) had laboratory evidence of recent WNV infection, whereas control-subjects (N = 74) had negative WNV serology. We interviewed participants, surveyed households, and assessed environmental data. WNV infection was associated with living in or near Water District X within Gilbert Township (adjusted odds ratio [aOR] 5.2; 95% confidence interval [95% CI] = 1.5–18.1), having water-holding containers in their yard (aOR 5.0; 95% CI = 1.5–17.3), and not working or attending school outside the home (aOR 2.4; 95% CI = 1.1–5.5). During this outbreak, WNV infection was likely primarily acquired peri-domestically with increased risk associated with potential mosquito larval habitats around the home and neighborhood. PMID:22556093

A measurement model of perinatal stressors: identifying risk for postnatal emotional distress in mothers of high-risk infants.

PubMed

DeMier, R L; Hynan, M T; Hatfield, R F; Varner, M W; Harris, H B; Manniello, R L

2000-01-01

A measurement model of perinatal stressors was first evaluated for reliability and then used to identify risk factors for postnatal emotional distress in high-risk mothers. In Study 1, six measures (gestational age of the baby, birthweight, length of the baby's hospitalization, a postnatal complications rating for the infant, and Apgar scores at 1 and 5 min) were obtained from chart reviews of preterm births at two different hospitals. Confirmatory factor analyses revealed that the six measures could be accounted for by three factors: (a) Infant Maturity, (b) Apgar Ratings, and (c) Complications. In Study 2, a modified measurement model indicated that Infant Maturity and Complications were significant predictors of postnatal emotional distress in an additional sample of mothers. This measurement model may also be useful in predicting (a) other measures of psychological distress in parents, and (b) measures of cognitive and motor development in infants.

Modifiable risk and protective factors for depressive symptoms in low-income African American mothers.

PubMed

Siefert, Kristine; Finlayson, Tracy L; Williams, David R; Delva, Jorge; Ismail, Amid I

2007-01-01

Low-income African American mothers of young children experience high rates of depression, but many of the risk factors that have been identified provide little direction for intervention. The authors examined modifiable risk and protective factors for probable depression (Center for Epidemiological Studies Depression Scale >or= 23) in 824 African American mothers living in the 39 poorest census tracts in Detroit. Household food insufficiency and deteriorated housing significantly increased the odds of likely depression, whereas availability of a loan in a crisis, help with childcare, and transportation were protective. However, more frequent experiences of everyday discrimination greatly increased the odds of elevated depressive symptoms. These findings support the need for interventions that operate across individual and societal levels to address the fundamental causes of poor mental health.

Identifying Treatment Effect Modifiers in the STarT Back Trial: A Secondary Analysis.

PubMed

Beneciuk, Jason M; Hill, Jonathan C; Campbell, Paul; Afolabi, Ebenezer; George, Steven Z; Dunn, Kate M; Foster, Nadine E

2017-01-01

Identification of patient characteristics influencing treatment outcomes is a top low back pain (LBP) research priority. Results from the STarT Back trial support the effectiveness of prognostic stratified care for LBP compared with current best care, however, patient characteristics associated with treatment response have not yet been explored. The purpose of this secondary analysis was to identify treatment effect modifiers within the STarT Back trial at 4-month follow-up (n = 688). Treatment response was dichotomized using back-specific physical disability measured using the Roland-Morris Disability Questionnaire (≥7). Candidate modifiers were identified using previous literature and evaluated using logistic regression with statistical interaction terms to provide preliminary evidence of treatment effect modification. Socioeconomic status (SES) was identified as an effect modifier for disability outcomes (odds ratio [OR] = 1.71, P = .028). High SES patients receiving prognostic stratified care were 2.5 times less likely to have a poor outcome compared with low SES patients receiving best current care (OR = .40, P = .006). Education level (OR = 1.33, P = .109) and number of pain medications (OR = .64, P = .140) met our criteria for effect modification with weaker evidence (.20 > P ≥ .05). These findings provide preliminary evidence for SES, education, and number of pain medications as treatment effect modifiers of prognostic stratified care delivered in the STarT Back Trial. This analysis provides preliminary exploratory findings about the characteristics of patients who might least likely benefit from targeted treatment using prognostic stratified care for LBP. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Obesity: The Modifiable Risk Factor in Total Joint Arthroplasty.

PubMed

Bookman, Jared S; Schwarzkopf, Ran; Rathod, Parthiv; Iorio, Richard; Deshmukh, Ajit J

2018-07-01

Obesity is an epidemic in the health care system. Obesity poses several challenges and raises unique issues for the arthroplasty surgeon. Obese patients are at higher risk for infection and dislocation. Additionally, obese patients have poorer implant survivorship and functional scores postoperatively. Obesity is a modifiable risk factor and weight loss preoperatively should be strongly considered. Obese patients must be counseled so that they have realistic expectations after total joint arthroplasty. Copyright © 2018 Elsevier Inc. All rights reserved.

Genome-Wide Association Study to Identify Susceptibility Loci That Modify Radiation-Related Risk for Breast Cancer After Childhood Cancer.

PubMed

Morton, Lindsay M; Sampson, Joshua N; Armstrong, Gregory T; Chen, Ting-Huei; Hudson, Melissa M; Karlins, Eric; Dagnall, Casey L; Li, Shengchao Alfred; Wilson, Carmen L; Srivastava, Deo Kumar; Liu, Wei; Kang, Guolian; Oeffinger, Kevin C; Henderson, Tara O; Moskowitz, Chaya S; Gibson, Todd M; Merino, Diana M; Wong, Jeannette R; Hammond, Sue; Neglia, Joseph P; Turcotte, Lucie M; Miller, Jeremy; Bowen, Laura; Wheeler, William A; Leisenring, Wendy M; Whitton, John A; Burdette, Laurie; Chung, Charles; Hicks, Belynda D; Jones, Kristine; Machiela, Mitchell J; Vogt, Aurelie; Wang, Zhaoming; Yeager, Meredith; Neale, Geoffrey; Lear, Matthew; Strong, Louise C; Yasui, Yutaka; Stovall, Marilyn; Weathers, Rita E; Smith, Susan A; Howell, Rebecca; Davies, Stella M; Radloff, Gretchen A; Onel, Kenan; Berrington de González, Amy; Inskip, Peter D; Rajaraman, Preetha; Fraumeni, Joseph F; Bhatia, Smita; Chanock, Stephen J; Tucker, Margaret A; Robison, Leslie L

2017-11-01

Childhood cancer survivors treated with chest-directed radiotherapy have substantially elevated risk for developing breast cancer. Although genetic susceptibility to breast cancer in the general population is well studied, large-scale evaluation of breast cancer susceptibility after chest-directed radiotherapy for childhood cancer is lacking. We conducted a genome-wide association study of breast cancer in female survivors of childhood cancer, pooling two cohorts with detailed treatment data and systematic, long-term follow-up: the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. The study population comprised 207 survivors who developed breast cancer and 2774 who had not developed any subsequent neoplasm as of last follow-up. Genotyping and subsequent imputation yielded 16 958 466 high-quality variants for analysis. We tested associations in the overall population and in subgroups stratified by receipt of lower than 10 and 10 or higher gray breast radiation exposure. We report P values and pooled per-allele risk estimates from Cox proportional hazards regression models. All statistical tests were two-sided. Among survivors who received 10 or higher gray breast radiation exposure, a locus on 1q41 was associated with subsequent breast cancer risk (rs4342822, nearest gene PROX1 , risk allele frequency in control subjects [RAF controls ] = 0.46, hazard ratio = 1.92, 95% confidence interval = 1.49 to 2.44, P = 7.09 × 10 -9 ). Two rare variants also showed potentially promising associations (breast radiation ≥10 gray: rs74949440, 11q23, TAGLN , RAF controls = 0.02, P = 5.84 × 10 -8 ; <10 gray: rs17020562, 1q32.3, RPS6KC1 , RAF controls = 0.0005, P = 6.68 × 10 -8 ). Associations were restricted to these dose subgroups, with consistent findings in the two survivor cohorts. Our study provides strong evidence that germline genetics outside high-risk syndromes could modify the effect of radiation exposure on breast cancer risk after

What Risk Assessments of Genetically Modified Organisms Can Learn from Institutional Analyses of Public Health Risks

PubMed Central

Rajan, S. Ravi; Letourneau, Deborah K.

2012-01-01

The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large. PMID:23193357

What risk assessments of genetically modified organisms can learn from institutional analyses of public health risks.

PubMed

Rajan, S Ravi; Letourneau, Deborah K

2012-01-01

The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.

The Impact of an Incentive-Based Worksite Health Promotion Program on Modifiable Health Risk Factors.

ERIC Educational Resources Information Center

Poole, Kathleen; Kumpfer, Karol; Pett, Marjorie

2001-01-01

Examined the impact of participating in an incentive-based employee health promotion program on modifiable health risk factors over 4 years. Data from physiological and self-report measures indicated that modifiable health risks improved over time (smoking, physical activity, systolic and diastolic blood pressure, and seat belt use). Cholesterol…

Identifying risk event in Indonesian fresh meat supply chain

NASA Astrophysics Data System (ADS)

Wahyuni, H. C.; Vanany, I.; Ciptomulyono, U.

2018-04-01

The aim of this paper is to identify risk issues in Indonesian fresh meat supply chain from the farm until to the “plate”. The critical points for food safety in physical fresh meat product flow are also identified. The paper employed one case study in the Indonesian fresh meat company by conducting observations and in-depth three stages of interviews. At the first interview, the players, process, and activities in the fresh meat industry were identified. In the second interview, critical points for food safety were recognized. The risk events in each player and process were identified in the last interview. The research will be conducted in three stages, but this article focuses on risk identification process (first stage) only. The second stage is measuring risk and the third stage focuses on determining the value of risk priority. The results showed that there were four players in the fresh meat supply chain: livestock (source), slaughter (make), distributor and retail (deliver). Each player has different activities and identified 16 risk events in the fresh meat supply chain. Some of the strategies that can be used to reduce the occurrence of such risks include improving the ability of laborers on food safety systems, improving cutting equipment and distribution processes

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

PubMed

Muranen, Taru A; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Bojesen, Stig E; Nordestgaard, Børge G; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Investigators, Nbcs; Peto, Julian; Dos Santos Silva, Isabel; Couch, Fergus J; Olson, Janet E; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K; Cox, Angela; Cross, Simon S; Sawyer, Elinor J; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W M; Fasching, Peter A; Beckmann, Matthias W; Andrulis, Irene L; Knight, Julia A; Investigators, kConFab/Aocs; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G; Milne, Roger L; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L; Southey, Melissa C; John, Esther M; Whittemore, Alice S; Bolla, Manjeet K; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F; Schmidt, Marjanka K; Nevanlinna, Heli

2017-05-01

CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.

Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

PubMed

Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

2016-08-22

Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

A Modified Delphi to Identify the Significant Works Pertaining to the Understanding of Reading Comprehension and Content Analysis of the Identified Works

ERIC Educational Resources Information Center

Zunker, Norma D.; Pearce, Daniel L.

2012-01-01

The first part of this study explored the significant works pertaining to the understanding of reading comprehension using a Modified Delphi Method. A panel of reading comprehension experts identified 19 works they considered to be significant to the understanding of reading comprehension. The panel of experts identified the reasons they…

Impact of genetically modified organisms on aquatic environments: Review of available data for the risk assessment.

PubMed

Pott, Antonia; Otto, Mathias; Schulz, Ralf

2018-09-01

The aquatic environment is strongly connected to the surrounding agricultural landscapes, which regularly serve as sources of stressors such as agrochemicals. Genetically modified crops, which are cultivated on a large scale in many countries, may also act as stressors. Despite the commercial use of genetically modified organisms (GMOs) for over 20years, their impact on the aquatic environment came into focus only 10years ago. We present the status quo of the available scientific data in order to provide an input for informed aquatic risk assessment of GMOs. We could identify only 39 publications, including 84 studies, dealing with GMOs in the aquatic environment, and our analysis shows substantial knowledge gaps. The available information is restricted to a small number of crop plants, traits, events, and test organisms. The analysis of effect studies reveals that only a narrow range of organisms has been tested and that studies on combinatorial actions of stressors are virtually absent. The analysis of fate studies shows that many aspects, such as the fate of leached toxins, degradation of plant material, and distribution of crop residues in the aquatic habitat, are insufficiently investigated. Together with these research needs, we identify standardization of test methods as an issue of high priority, both for research and risk assessment needed for GMO regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Modifiable Risk Factors for Pneumonia Requiring Hospitalization among Community-Dwelling Older Adults: The Health, Aging, and Body Composition Study

PubMed Central

Juthani-Mehta, Manisha; De Rekeneire, Nathalie; Allore, Heather; Chen, Shu; O’Leary, John R.; Bauer, Douglas C.; Harris, Tamara B.; Newman, Anne B.; Yende, Sachin; Weyant, Robert J.; Kritchevsky, Stephen; Quagliarello, Vincent

2013-01-01

Background Pneumonia requiring hospitalization remains a major public health problem among community-dwelling older adults. Impaired oral hygiene is a modifiable risk factor for healthcare-associated pneumonia, but its role in community-acquired pneumonia is unclear. Objectives To identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization among community-dwelling older adults. Design Prospective observational cohort study Setting Memphis, Tennessee and Pittsburgh, Pennsylvania Participants Of 3075 well-functioning community-dwelling adults aged 70–79 years enrolled in the Health, Aging, and Body Composition Study from 1997–1998, 1441 had complete data, dental exam within six months of baseline, and were eligible for this study. Measurements The primary outcome was pneumonia requiring hospitalization through 2008. Results Of 1441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male gender (HR 2.07, 95%CI 1.51–2.83), white race (HR 1.44, 95%CI 1.03–2.01), history of pneumonia (HR 3.09, 95%CI 1.86–5.14), pack-years of smoking (HR 1.006, 95%CI 1.001–1.011), and percent predicted FEV1 (moderate vs. mild/normal lung function [HR 1.78, 95%CI 1.28–2.48], severe vs. mild/normal lung function [HR 2.90, 95%CI 1.51–5.57]) were non-modifiable risk factors for pneumonia. Incident mobility limitation (HR 1.77, 95%CI 1.32–2.38) and higher mean oral plaque score (HR 1.29, 95%CI 1.02–1.64) were modifiable risk factors for pneumonia. Average Attributable Fractions revealed that 11.5% of pneumonias were attributed to incident mobility limitation and 10.3% to mean oral plaque score ≥1. Conclusion Incident mobility limitation and higher mean oral plaque score were two modifiable risk factors attributable for 22% of pneumonias requiring hospitalization. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults. PMID:23772872

Lack of motivation: a new modifiable risk factor for peritonitis in patients undergoing peritoneal dialysis?

PubMed

Paudel, Klara; Namagondlu, Girish; Samad, Nasreen; McKitty, Khadija; Fan, Stanley L

2015-03-01

Can we identify modifiable risk factors for peritonitis in patients undergoing peritoneal dialysis (PD)? We aimed to determine whether housing standard, PD exchange technique or patient motivation might be modifiable risks for peritonitis. We also explored the relationship between lack of motivation and depression. Nurse home visits assessed PD exchange technique, environment and patient motivation. Motivation scores were correlated separately with an Apathy Evaluation Score and a depression score using PHQ-9 questionnaires. Home hygiene, exchange technique and motivation were above average in 53%, 56% and 60%, respectively in 104 patients undergoing PD. After 15 months, 25.9% patients developed peritonitis but nurses' ratings of homes and exchange techniques were not predictive. Low patient motivation was predictive. Patients rated to have above or below median motivation had significantly different Apathy Scores (p = 0.0002). Unmotivated depressed patients were significantly more likely to develop peritonitis compared to motivated depressed patients. Lack of motivation predicted peritonitis particularly if associated with depression. Further studies are required focusing on specific motivation scoring schemes and the psychosocial support that might lead to better outcomes. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Predicting the unpredictable? Identifying high-risk versus low-risk parents with intellectual disabilities.

PubMed

McGaw, Sue; Scully, Tamara; Pritchard, Colin

2010-09-01

This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates 'high-risk' from 'low-risk' parenting; and (iii) the impact of partner relationships on parental competency and risk status. Secondary data analysis was conducted on data gathered from 101 parents with IDs and 172 of their children, all of whom had been referred to a specialist parenting service over a 5 year period. Cross-tabulations were applied to the data to examine causal processes and to improve general understanding of the risks associated with families. Contrary to popular expectations IQ levels of the main parent, relationship status, parental age, employment, amenities, valued support and parents' perception of need were not identified as contributory factors distinguishing 'high-risk' from 'low-risk' parents. Instead, 'high-risk' parenting associated more with parental reports of childhood trauma (emotional abuse and physical neglect in particular), parents' having additional special needs in addition to their IDs or parents who were raising a child with special needs. Other 'high-risk' factors identified related to the male partners of mothers with IDs, many of whom did not have IDs and/or whose histories included anti-social behaviors or criminality. The study identified some high-risk variables among parents with IDs that can distinguish them from low-risk parents with IDs. These findings generate challenges for agencies who attempt to capture the needs of parents with IDs and who endeavour to provide services to families deemed to be "at risk." These outcomes will be of special interest to the courts, especially when parents with IDs are involved in care proceedings. Copyright © 2010. Published by Elsevier Ltd.

Presenilin-Based Genetic Screens in Drosophila melanogaster Identify Novel Notch Pathway Modifiers

PubMed Central

Mahoney, Matt B.; Parks, Annette L.; Ruddy, David A.; Tiong, Stanley Y. K.; Esengil, Hanife; Phan, Alexander C.; Philandrinos, Panos; Winter, Christopher G.; Chatterjee, Runa; Huppert, Kari; Fisher, William W.; L'Archeveque, Lynn; Mapa, Felipa A.; Woo, Wendy; Ellis, Michael C.; Curtis, Daniel

2006-01-01

Presenilin is the enzymatic component of γ-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for γ-tubulin in the pathway. PMID:16415372

Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers.

PubMed

Mahoney, Matt B; Parks, Annette L; Ruddy, David A; Tiong, Stanley Y K; Esengil, Hanife; Phan, Alexander C; Philandrinos, Panos; Winter, Christopher G; Chatterjee, Runa; Huppert, Kari; Fisher, William W; L'Archeveque, Lynn; Mapa, Felipa A; Woo, Wendy; Ellis, Michael C; Curtis, Daniel

2006-04-01

Presenilin is the enzymatic component of gamma-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for gamma-tubulin in the pathway.

An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

PubMed Central

Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Perez, José Ignacio Arias; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Investigators, kConFab; Group, AOCS; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Chang-Claude, Jenny

2014-01-01

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) <1.1×10−3. None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170cm (OR=1.22, p=0.017), but inversely associated with ER-negative BC risk in women <160cm (OR=0.83, p=0.039, pint=1.9×10−4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR=0.85, p=2.0×10−4), and absent in women who had had just one (OR=0.96, p=0.19, pint = 6.1×10−4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR=0.93, p=2.8×10−5), but no association was observed in current smokers (OR=1.07, p=0.14, pint = 3.4×10−4). In conclusion, recently identified breast cancer susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. PMID:25227710

The use of genetically modified mice in cancer risk assessment: challenges and limitations.

PubMed

Eastmond, David A; Vulimiri, Suryanarayana V; French, John E; Sonawane, Babasaheb

2013-09-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53⁺/⁻, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program's conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals.

The use of genetically modified mice in cancer risk assessment: Challenges and limitations*

PubMed Central

Eastmond, David A.; Vulimiri, Suryanarayana V.; French, John E.; Sonawane, Babasaheb

2015-01-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53+/−, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program’s conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals. PMID:23985072

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior.

PubMed

Bokslag, Anouk; Hermes, Wietske; de Groot, Christianne J M; Teunissen, Pim W

2016-11-01

To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as "chance of health" or "risk of disease". 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence.

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE PAGES

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.; ...

2015-10-21

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Associations between Adolescent Risk Behaviors and Injury: The Modifying Role of Disability

ERIC Educational Resources Information Center

Raman, Sudha R.; Boyce, William F.; Pickett, William

2009-01-01

Background: Adolescents with disabilities are at risk for poor health outcomes including injury. The objective of this study was to examine if disability status modifies the association between risk behavior and injury among adolescents. Methods: The cross-sectional Health Behavior in School-Aged Children Survey was administered to a…

Genetic modifiers of CHEK2*1100delC associated breast cancer risk

PubMed Central

Muranen, Taru A.; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D.P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Bojesen, Stig E.; Nordestgaard, Børge G.; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V.; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Peto, Julian; dos Santos Silva, Isabel; Couch, Fergus J.; Olson, Janet E.; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor J.; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W.M.; Fasching, Peter A.; Beckmann, Matthias W.; Andrulis, Irene L.; Knight, Julia A.; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G.; Milne, Roger L.; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L.; Southey, Melissa C.; John, Esther M.; Whittemore, Alice S.; Bolla, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F.; Schmidt, Marjanka K.; Nevanlinna, Heli

2016-01-01

Purpose CHEK2*1100delC is a founder variant in European populations conferring a 2–3 fold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods With genotype data of 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results The PRS conferred an odds ratio (OR) of 1.59 [95% CI 1.21–2.09] per standard deviation for BC for CHEK2*1100delC carriers and 1.58 [1.55–1.62] for non-carriers. No evidence for deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 [0.86–4.78] for CHEK2*1100delC carriers placing them to the high risk category according to UK NICE guidelines. OR for the lowest quintile was 0.52 [0.16–1.74], indicating life-time risk close to population average. Conclusion Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify the carriers at a high life-time risk for clinical actions. PMID:27711073

The Combined Association of Modifiable Risk Factors with Breast Cancer Risk in the Women's Health Initiative.

PubMed

Arthur, Rhonda; Wassertheil-Smoller, Sylvia; Manson, JoAnn E; Luo, Juhua; Snetselaar, Linda; Hastert, Theresa; Caan, Bette; Qi, Lihong; Rohan, Thomas

2018-06-01

Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women's Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER + /PR + , and HER2 + breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACR See related editorial by Friedenreich and McTiernan, p. 313 . ©2018 American Association for Cancer Research.

Modifying a Risk Assessment Instrument for Youthful Offenders.

PubMed

Shapiro, Cheri J; Malone, Patrick S; Gavazzi, Stephen M

2018-02-01

High rates of incarceration in the United States are compounded by high rates of recidivism and prison return. One solution is more accurate identification of individual prisoner risks and needs to promote offender rehabilitation and successful community re-entry; this is particularly important for youthful offenders who developmentally are in late adolescence or early adulthood, and who struggle to reengage in education and/or employment after release. Thus, this study examined the feasibility of administration and initial psychometric properties of a risk and needs assessment instrument originally created for a juvenile justice population (the Global Risk Assessment Device or GRAD) with 895 male youthful offenders in one adult correctional system. Initial feasibility of implementation within the correctional system was demonstrated; confirmatory factor analyses support the invariance of the modified GRAD factor structure across age and race. Future studies are needed to examine the predictive validity and the sensitivity of the instrument.

Screening for Albuminuria Identifies Individuals at Increased Renal Risk

PubMed Central

van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

2009-01-01

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

Genetically modified crops and aquatic ecosystems: considerations for environmental risk assessment and non-target organism testing.

PubMed

Carstens, Keri; Anderson, Jennifer; Bachman, Pamela; De Schrijver, Adinda; Dively, Galen; Federici, Brian; Hamer, Mick; Gielkens, Marco; Jensen, Peter; Lamp, William; Rauschen, Stefan; Ridley, Geoff; Romeis, Jörg; Waggoner, Annabel

2012-08-01

Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.

Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.

PubMed

Yadav, Pankaj; Ellinghaus, David; Rémy, Gaëlle; Freitag-Wolf, Sandra; Cesaro, Anabelle; Degenhardt, Frauke; Boucher, Gabrielle; Delacre, Myriam; Peyrin-Biroulet, Laurent; Pichavant, Muriel; Rioux, John D; Gosset, Philippe; Franke, Andre; Schumm, L Philip; Krawczak, Michael; Chamaillard, Mathias; Dempfle, Astrid; Andersen, Vibeke

2017-08-01

The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients and in mouse models of IBD. We used 55 Immunochip-wide datasets that included 19,735 IBD cases (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta-analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never vs ever smokers, never vs current smokers, and never vs former smokers. We studied the effects of exposure to cigarette smoke in Il10 -/- and Nod2 -/- mice, as well as in Balb/c mice without disruption of these genes (wild-type mice). Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8 weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta-analysis Wald test P < 5.0 × 10 -5 ; heterogeneity Cochrane Q test P > .05). Twenty of these variants were located within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from SNP genotypes) revealed an interaction with smoking. We replicated the interaction of a variant in NOD2 with current smoking in relation to the risk for CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the same genomic region (rs2270368 and rs17221417) that interact with smoking in relation to CD risk. Approximately 45% of the SNPs that interact with smoking were in close vicinity (≤1 Mb) to SNPs previously associated with IBD; many were located near or within genes that regulate mucosal barrier function and immune tolerance. Smoking modified the disease risk of some variants in opposite directions

Identifying Children At Risk for Being Bullies in the US

PubMed Central

Shetgiri, Rashmi; Lin, Hua; Flores, Glenn

2012-01-01

Objective To identify risk factors associated with the highest and lowest prevalence of bullying perpetration among US children. Methods Using the 2001–2002 Health Behavior in School-Aged Children, a nationally-representative survey of US children in 6th–10th grades, bivariate analyses were conducted to identify factors associated with any (≥ once or twice), moderate (≥ two-three times/month), and frequent (≥ weekly) bullying. Stepwise multivariable analyses identified risk factors associated with bullying. Recursive partitioning analysis (RPA) identified risk factors which, in combination, identify students with the highest and lowest bullying prevalence. Results The prevalence of any bullying in the 13,710 students was 37.3%, moderate bullying was 12.6%, and frequent bullying was 6.6%. Characteristics associated with bullying were similar in the multivariable analyses and RPA clusters. In RPA, the highest prevalence of any bullying (67%) accrued in children with a combination of fighting and weapon-carrying. Students who carry weapons, smoke, and drink alcohol more than 5–6 days weekly were at highest risk for moderate bullying (61%). Those who carry weapons, smoke, drink > once daily, have above-average academic performance, moderate/high family affluence, and feel irritable or bad-tempered daily were at highest risk for frequent bullying (68%). Conclusions Risk clusters for any, moderate, and frequent bullying differ. Children who fight and carry weapons are at highest risk of any bullying. Weapon-carrying, smoking, and alcohol use are included in the highest risk clusters for moderate and frequent bullying. Risk-group categories may be useful to providers in identifying children at highest risks for bullying and in targeting interventions. PMID:22989731

Fetal alcohol-spectrum disorders: identifying at-risk mothers

PubMed Central

Montag, Annika C

2016-01-01

Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

Clustering of modifiable biobehavioral risk factors for chronic disease in US adults: a latent class analysis.

PubMed

Leventhal, Adam M; Huh, Jimi; Dunton, Genevieve F

2014-11-01

Examining the co-occurrence patterns of modifiable biobehavioral risk factors for deadly chronic diseases (e.g. cancer, cardiovascular disease, diabetes) can elucidate the etiology of risk factors and guide disease-prevention programming. The aims of this study were to (1) identify latent classes based on the clustering of five key biobehavioral risk factors among US adults who reported at least one risk factor and (2) explore the demographic correlates of the identified latent classes. Participants were respondents of the National Epidemiologic Survey of Alcohol and Related Conditions (2004-2005) with at least one of the following disease risk factors in the past year (N = 22,789), which were also the latent class indicators: (1) alcohol abuse/dependence, (2) drug abuse/dependence, (3) nicotine dependence, (4) obesity, and (5) physical inactivity. Housing sample units were selected to match the US National Census in location and demographic characteristics, with young adults oversampled. Participants were administered surveys by trained interviewers. Five latent classes were yielded: 'obese, active non-substance abusers' (23%); 'nicotine-dependent, active, and non-obese' (19%); 'active, non-obese alcohol abusers' (6%); 'inactive, non-substance abusers' (50%); and 'active, polysubstance abusers' (3.7%). Four classes were characterized by a 100% likelihood of having one risk factor coupled with a low or moderate likelihood of having the other four risk factors. The five classes exhibited unique demographic profiles. Risk factors may cluster together in a non-monotonic fashion, with the majority of the at-risk population of US adults expected to have a high likelihood of endorsing only one of these five risk factors. © Royal Society for Public Health 2013.

Personally Modifiable Risk Factors Associated with Pediatric Hearing Loss: A Systematic Review

PubMed Central

Vasconcellos, Adam P.; Kyle, Meghann E.; Gilani, Sapideh; Shin, Jennifer J.

2015-01-01

Background Pediatric hearing loss is an increasingly recognized problem with significant implications. Increasing our quantitative understanding of potentially modifiable environmental risk factors for hearing loss may form the foundation for prevention and screening programs. Objective To determine whether specific threshold exposure levels of personally modifiable risk factors for hearing loss have been defined, with the overarching goal of providing actionable guidance for the prevention of pediatric hearing loss. Data Sources A systematic review was performed. Computerized searches of PubMed, EMBASE, and the Cochrane Library were completed and supplemented with manual searches. Review Methods Inclusion/exclusion criteria were designed to determine specific threshold values of personally modifiable risk factors on hearing loss in the pediatric population. Searches and data extraction were performed by independent reviewers. Results There were 38 criterion-meeting studies, including a total of 50,651 subjects. Threshold noise exposures significantly associated with hearing loss in youth included: (1) more than 4 hours per week or more than 5 years of personal headphone usage, (2) more than 4 visits per month to a discotheque, and (3) working on a mechanized farm. Quantified tobacco levels of concern included any level of in utero smoke exposure as well as secondhand exposure sufficient to elevate serum cotinine. Conclusions Specific thresholds analyses are limited. Future studies would ideally focus on stratifying risk according to clearly defined levels of exposure, in order to provide actionable guidance for children and families. PMID:24671457

A conceptual framework for managing modifiable risk factors for cardiovascular diseases in Fiji.

PubMed

Witter, Trevor; Poudevigne, Melanie; Lambrick, Danielle M; Faulkner, James; Lucero, Adam A; Page, Rachel; Perry, Lane G; Tarrant, Michael A; Stoner, Lee

2015-03-01

The current review will look at modifiable lifestyle (physical inactivity, poor nutrition, risky alcohol behavior and cigarette smoking) and cardio-metabolic (obesity, diabetes mellitus, high cholesterol and high blood pressure) cardiovascular disease (CVD) risk factors among Indigenous-Fijian and Indo-Fijian subgroups. A framework for monitoring and managing these risk factors will be presented. National health surveys were identified where available. Electronic databases identified sources for filling missing data. The most relevant data were identified, organized and synthesized. Compared to Indo-Fijians, Indigenous-Fijians have higher rates of obesity (17% vs 11%) and hypertension (21% vs 16%), but lower rates of diabetes mellitus (12% vs 21%) and high cholesterol (33% vs 39%). Indigenous-Fijians report higher rates of prescribed physical activity (25% vs 21%), but poorer recommended vegetable intake (48% vs 56%), greater risky alcohol behavior (17% vs 15%) and a much greater prevalence of cigarette smoking (45% vs 24%). Both Indigenous-Fijians and Indo-Fijians report a low prevalence of recommended fruit intake (17% vs 15%). Fiji is progressing through demographic and epidemiological transitions, including a decline in infectious diseases and improved life expectancy. However, in concert with other developing nations, 'modernization' is accompanied by increased mortality from non-communicable diseases, with CVD being the most prevalent. This transition has been associated with changes to socio-cultural aspects of Fiji, including poor lifestyle choices that may contribute to a cluster of cardio-metabolic conditions which precede CVD. © Royal Society for Public Health 2013.

Identification of prostate cancer modifier pathways using parental strain expression mapping

PubMed Central

Xu, Qing; Majumder, Pradip K.; Ross, Kenneth; Shim, Yeonju; Golub, Todd R.; Loda, Massimo; Sellers, William R.

2007-01-01

Inherited genetic risk factors play an important role in cancer. However, other than the Mendelian fashion cancer susceptibility genes found in familial cancer syndromes, little is known about risk modifiers that control individual susceptibility. Here we developed a strategy, parental strain expression mapping, that utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses to directly identify candidate germ-line modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and, specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with the findings in the murine models, in multiple human prostate expression data set, we found that enrichment of glycolysis pathways in normal tissues was associated with decreased rates of cancer recurrence after prostatectomy. Together, these data suggest that parental strain expression mapping can directly identify germ-line modifier pathways of relevance to human disease. PMID:17978178

Modifiable Midlife Risk Factors for Late-Life Cognitive Impairment and Dementia

PubMed Central

Hughes, Tiffany F.; Ganguli, Mary

2009-01-01

The baby boom generation is approaching the age of greatest risk for cognitive impairment and dementia. There is growing interest in strategies to modify the environment in midlife to increase the probability of maintaining cognitive health in late life. Several potentially modifiable risk factors have been studied in relation to cognitive impairment and dementia in late life, but methodological limitations of observational research have resulted in some inconsistencies across studies. The most promising strategies are maintaining cardiovascular health, engagement in mental, physical, and social activities, using alcohol in moderation, abstaining from tobacco use, and following a heart-healthy diet. Other factors that may influence cognitive health are occupational attainment, depression, personality, exposure to general anesthesia, head injury, postmenopausal hormone therapy, non-steroidal anti-inflammatory medications, and nutritional supplements such as antioxidants. Some long-term observational studies initiated in midlife or earlier, and some randomized controlled trials, have examined the effects of specific cognitive health promotion behaviors in midlife on the risk of cognitive impairment in late life. Overall, these studies provide limited support for risk reduction at this time. Recommendations and challenges for developing effective strategies to reduce the burden of cognitive impairment and dementia in the future are discussed. PMID:19946443

The media and genetically modified foods: evidence in support of social amplification of risk.

PubMed

Frewer, Lynn J; Miles, Susan; Marsh, Roy

2002-08-01

Empirical examinations of the "social amplification of risk" framework are rare, partly because of the difficulties in predicting when conditions likely to result in amplification effects will occur. This means that it is difficult to examine changes in risk perception that are contemporaneous with increases and/or decreases in social or media discussion of the risks associated with a particular risk event. However, the collection of attitude data before, during, and after the increased reporting of the risks of genetically modified food in the United Kingdom (spring 1999) has demonstrated that people's risk perceptions do increase and decrease in line with what might be expected upon examination of the amplification and attenuation mechanisms integral to the framework. Perceptions of benefit, however, appeared to be permanently depressed by negative reporting about genetically modified food. Trust in regulatory institutions with responsibility for protecting the public was not affected. It was concluded that the social amplification of risk framework is a useful framework for beginning to explain the potential impact on risk perceptions of a risk event, particularly if that risk event is presented to the public as a new hazard occurring in a crisis context.

41 CFR 102-80.50 - Are Federal agencies responsible for identifying/estimating risks and for appropriate risk...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identify and estimate safety and environmental management risks and appropriate risk reduction strategies... responsible for identifying/estimating risks and for appropriate risk reduction strategies? 102-80.50 Section... Environmental Management Risks and Risk Reduction Strategies § 102-80.50 Are Federal agencies responsible for...

Nutritional markers may identify patients with greater risk of re-admission after geriatric hip fractures.

PubMed

Stone, Austin V; Jinnah, Alexander; Wells, Brian J; Atkinson, Hal; Miller, Anna N; Futrell, Wendell M; Lenoir, Kristin; Emory, Cynthia L

2018-02-01

Osteoporotic hip fractures are increasing in prevalence with the growing elderly population. Morbidity and mortality remain high following osteoporotic hip fractures despite advances in medical and surgical treatments. The associated costs and medical burdens are increased with a re-admission following hip fracture treatment. This study sought to identify demographic and clinical values that may be a predictive model for 30-day re-admission risk following operative management of an isolated hip fracture. Between January 1, 2013 and April 30, 2015 all patients admitted to a single academic medical centre for treatment of a hip fracture were reviewed. Candidate variables included standard demographics, common laboratory values, and markers of comorbid conditions and nutrition status. A 30-day, all-cause re-admission model was created utilizing multivariate logistic regression. A total of 607 patients with hip fractures were identified and met the inclusion criteria; of those patients, 67 were re-admitted within 30 days. Univariate analysis indicates that the re-admission group had more comorbidities (p < 0.001) and lower albumin (p = 0.038) and prealbumin (p < 0.001). The final, reduced model contained 12 variables and incorporated four out of five nutritional makers with an internally, cross-validated C-statistic of 0.811 (95% CI: 0.754, 0.867). Our results indicate that specific nutritional laboratory markers at the index admission may identify patients that have a greater risk of re-admission after hip fracture. This model identifies potentially modifiable risk factors and may allow orthogeriatricians to better educate patients and better treat post-operative nutritional status and care.

A Retrospective Analysis of Pressure Ulcer Incidence and Modified Braden Scale Score Risk Classifications.

PubMed

Chen, Hong-Lin; Cao, Ying-Juan; Wang, Jing; Huai, Bao-Sha

2015-09-01

The Braden Scale is the most widely used pressure ulcer risk assessment in the world, but the currently used 5 risk classification groups do not accurately discriminate among their risk categories. To optimize risk classification based on Braden Scale scores, a retrospective analysis of all consecutively admitted patients in an acute care facility who were at risk for pressure ulcer development was performed between January 2013 and December 2013. Predicted pressure ulcer incidence first was calculated by logistic regression model based on original Braden score. Risk classification then was modified based on the predicted pressure ulcer incidence and compared between different risk categories in the modified (3-group) classification and the traditional (5-group) classification using chi-square test. Two thousand, six hundred, twenty-five (2,625) patients (mean age 59.8 ± 16.5, range 1 month to 98 years, 1,601 of whom were men) were included in the study; 81 patients (3.1%) developed a pressure ulcer. The predicted pressure ulcer incidence ranged from 0.1% to 49.7%. When the predicted pressure ulcer incidence was greater than 10.0% (high risk), the corresponding Braden scores were less than 11; when the predicted incidence ranged from 1.0% to 10.0% (moderate risk), the corresponding Braden scores ranged from 12 to 16; and when the predicted incidence was less than 1.0% (mild risk), the corresponding Braden scores were greater than 17. In the modified classification, observed pressure ulcer incidence was significantly different between each of the 3 risk categories (P less than 0.05). However, in the traditional classification, the observed incidence was not significantly different between the high-risk category and moderate-risk category (P less than 0.05) and between the mild-risk category and no-risk category (P less than 0.05). If future studies confirm the validity of these findings, pressure ulcer prevention protocols of care based on Braden Scale scores can

Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers

PubMed Central

Stevens, Kristen N.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Greene, Mark H.; Andrulis, Irene L.; Thomassen, Mads; Caligo, Maria; Nathanson, Katherine L.; Jakubowska, Anna; Osorio, Ana; Hamann, Ute; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Southey, Melissa; Buys, Saundra S.; Singer, Christian F.; Hansen, Thomas V.O.; Arason, Adalgeir; Offit, Kenneth; Piedmonte, Marion; Montagna, Marco; Imyanitov, Evgeny; Tihomirova, Laima; Sucheston, Lara; Beattie, Mary; Neuhausen, Susan L.; Szabo, Csilla I.; Simard, Jacques; Spurdle, Amanda B.; Healey, Sue; Chen, Xiaoqing; Rebbeck, Timothy R.; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C; Couch, Fergus J.

2012-01-01

Several common germline variants identified through genome-wide association studies of breast cancer risk in the general population have recently been shown to be associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. When combined, these variants can identify marked differences in the absolute risk of developing breast cancer for mutation carriers, suggesting that additional modifier loci may further enhance individual risk assessment for BRCA1 and BRCA2 mutation carriers. Recently, a common variant on 6p22 (rs9393597) was found to be associated with increased breast cancer risk for BRCA2 mutation carriers [Hazard ratio (HR)=1.55, 95% CI 1.25–1.92, p=6.0×10−5]. This observation was based on data from GWAS studies in which, despite statistical correction for multiple comparisons, the possibility of false discovery remains a concern. Here we report on an analysis of this variant in an additional 6,165 BRCA1 and 3,900 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). In this replication analysis, rs9393597 was not associated with breast cancer risk for BRCA2 mutation carriers [HR=1.09, 95% CI 0.96–1.24, p=0.18]. No association with ovarian cancer risk for BRCA1 or BRCA2 mutation carriers or with breast cancer risk for BRCA1 mutation carriers was observed. This follow-up study suggests that, contrary to our initial report, this variant is not associated with breast cancer risk among individuals with germline BRCA2 mutations. PMID:23011509

Operating Room Traffic as a Modifiable Risk Factor for Surgical Site Infection.

PubMed

Wanta, Brendan T; Glasgow, Amy E; Habermann, Elizabeth B; Kor, Daryl J; Cima, Robert R; Berbari, Elie F; Curry, Timothy B; Brown, Michael J; Hyder, Joseph A

2016-12-01

Surgical site infections (SSI) contribute to surgical patients' morbidity and costs. Operating room traffic may be a modifiable risk factor for SSI. We investigated the impact of additional operating room personnel on the risk of superficial SSI (sSSI). In this matched case-control study, cases included patients in whom sSSI developed in clean surgical incisions after elective, daytime operations. Control subjects were matched by age, gender, and procedure. Operating room personnel were classified as (1) surgical scrubbed, (2) surgical non-scrubbed, or (3) anesthesia. We used conditional logistic regression to test the extent to which additional personnel overall and from each work group were associated with infection. In total, 474 patients and 803 control subjects were identified. Each additional person among total personnel and personnel from each work group was significantly associated with greater odds of infection (all personnel, odds ratio [OR] = 1.082, 95% confidence interval [CI] 1.031-1.134, p = 0.0013; surgical scrubbed OR = 1.132, 95% CI 1.029-1.245, p = 0.0105; surgical non-scrubbed OR = 1.123, 95% CI 1.008-1.251, p = 0.0357; anesthesia OR = 1.153, 95% CI 1.031-1.290, p = 0.0127). After adjusting for operative duration, body mass index, diabetes mellitus, and vascular disease, additional personnel and sSSI were no longer associated overall or for any work groups (total personnel OR = 1.033, 95% CI 0.974-1.095, p = 0.2746; surgical scrubbed OR = 1.060, 95% CI 0.952-1.179, p = 0.2893; surgical non-scrubbed OR = 1.023 95% CI 0.907-1.154, p = 0.7129; anesthesia OR = 1.051, 95% CI 0.926-1.193, p = 0.4442). The presence of additional operating room personnel was not independently associated with increased odds of sSSI. Efforts dedicated to sSSI reduction should focus on other modifiable risk factors.

Identifying the Risk of Swallowing-Related Pulmonary Complications in Older Patients With Hip Fracture.

PubMed

Meals, Clifton; Roy, Siddharth; Medvedev, Gleb; Wallace, Matthew; Neviaser, Robert J; O'Brien, Joseph

2016-01-01

To identify and potentially modify the risk of pulmonary complications in a group of older patients with hip fracture, the authors obtained speech and language pathology consultations for these patients. Then they performed a retrospective chart review of all patients 65 years and older who were admitted to their institution between June 2011 and July 2013 with acute hip fracture, were treated surgically, and had a speech and language pathology evaluation in the immediate perioperative period. The authors identified 52 patients who met the study criteria. According to the American Society of Anesthesiologists (ASA) classification system, at the time of surgery, 1 patient (2%) was classified as ASA I, 12 patients (23%) were ASA II, 26 (50%) were ASA III, and 12 (23%) were ASA IV. Based on a speech and language pathology evaluation, 22 patients (42%) were diagnosed with dysphagia. Statistical analysis showed that ASA III status and ASA IV status were meaningful predictors of dysphagia and that dysphagia itself was a strong risk factor for pulmonary aspiration, pneumonia, and aspiration pneumonitis. Evaluation by a speech and language pathologist, particularly of patients classified as ASA III or ASA IV, may be an efficient means of averting pulmonary morbidity that is common in older patients with hip fracture. Copyright 2016, SLACK Incorporated.

A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication

PubMed Central

Dahmen, Norbert; Beckmann, Lars; Lindström, Sara; Schoof, Nils; Czene, Kamila; Mittelstraß, Kirstin; Illig, Thomas; Seibold, Petra; Behrens, Sabine; Humphreys, Keith; Li, Jingmei; Liu, Jianjun; Olson, Janet E.; Wang, Xianshu; Hankinson, Susan E.; Truong, Thérèse; Menegaux, Florence; dos Santos Silva, Isabel; Johnson, Nichola; Chen, Shou-Tung; Yu, Jyh-Cherng; Ziogas, Argyrios; Kataja, Vesa; Kosma, Veli-Matti; Mannermaa, Arto; Anton-Culver, Hoda; Shen, Chen-Yang; Brauch, Hiltrud; Peto, Julian; Guénel, Pascal; Kraft, Peter; Couch, Fergus J.; Easton, Douglas F.; Hall, Per; Chang-Claude, Jenny

2013-01-01

Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10−6 for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10−7) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women. PMID:23423446

Multiple Changes to Reusable Solid Rocket Motors, Identifying Hidden Risks

NASA Technical Reports Server (NTRS)

Greenhalgh, Phillip O.; McCann, Bradley Q.

2003-01-01

The Space Shuttle Reusable Solid Rocket Motor (RSRM) baseline is subject to various changes. Changes are necessary due to safety and quality improvements, environmental considerations, vendor changes, obsolescence issues, etc. The RSRM program has a goal to test changes on full-scale static test motors prior to flight due to the unique RSRM operating environment. Each static test motor incorporates several significant changes and numerous minor changes. Flight motors often implement multiple changes simultaneously. While each change is individually verified and assessed, the potential for changes to interact constitutes additional hidden risk. Mitigating this risk depends upon identification of potential interactions. Therefore, the ATK Thiokol Propulsion System Safety organization initiated the use of a risk interaction matrix to identify potential interactions that compound risk. Identifying risk interactions supports flight and test motor decisions. Uncovering hidden risks of a full-scale static test motor gives a broader perspective of the changes being tested. This broader perspective compels the program to focus on solutions for implementing RSRM changes with minimal/mitigated risk. This paper discusses use of a change risk interaction matrix to identify test challenges and uncover hidden risks to the RSRM program.

Panel 2: anticipatory risk assessment: identifying, assessing, and mitigating exposure risks before they occur.

PubMed

Guidotti, Tee L; Pacha, Laura

2011-07-01

Health threats place the military mission and deployed service members at risk. A commander's focus is on preventing acute health risks, such as diarrhea, because these quickly compromise the mission. However, in recent conflicts chronic and long-term illness risks have emerged as concerns. Department of Defense and Joint Chiefs of Staff mandates require documentation of exposures and environmental conditions to reconstruct exposures and evaluate future health risks. Current processes for identifying and assessing hazards, including identification and assessment before deployment and in time to take action to prevent or reduce exposures, when followed, are generally adequate for known hazards. Identifying and addressing novel, unexpected risks remain challenges. Armed conflicts are associated with rapidly changing conditions, making ongoing hazard identification and assessment difficult. Therefore, surveillance of the environment for hazards and surveillance of personnel for morbidity must be practiced at all times. Communication of risk information to decision makers is critical but problematic. Preventive Medicine (PM) personnel should take responsibility for communicating this information to non-PM military medical people and to military commanders. Communication of risks identified and lessons learned between PM personnel of different military units is extremely important when one military unit replaces another in a deployed environment.

Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data.

PubMed

Yelland, Lisa N; Salter, Amy B; Ryan, Philip

2011-10-15

Modified Poisson regression, which combines a log Poisson regression model with robust variance estimation, is a useful alternative to log binomial regression for estimating relative risks. Previous studies have shown both analytically and by simulation that modified Poisson regression is appropriate for independent prospective data. This method is often applied to clustered prospective data, despite a lack of evidence to support its use in this setting. The purpose of this article is to evaluate the performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data, by using generalized estimating equations to account for clustering. A simulation study is conducted to compare log binomial regression and modified Poisson regression for analyzing clustered data from intervention and observational studies. Both methods generally perform well in terms of bias, type I error, and coverage. Unlike log binomial regression, modified Poisson regression is not prone to convergence problems. The methods are contrasted by using example data sets from 2 large studies. The results presented in this article support the use of modified Poisson regression as an alternative to log binomial regression for analyzing clustered prospective data when clustering is taken into account by using generalized estimating equations.

Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable.

PubMed

Broderick, Joseph P; Viscoli, Catherine M; Brott, Thomas; Kernan, Walter N; Brass, Lawrence M; Feldmann, Edward; Morgenstern, Lewis B; Wilterdink, Janet Lee; Horwitz, Ralph I

2003-06-01

To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.

Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.

PubMed

Winter, Jean M; Curry, Natasha L; Gildea, Derek M; Williams, Kendra A; Lee, Minnkyong; Hu, Ying; Crawford, Nigel P S

2018-06-11

It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain. The relevance of germline modifiers of aggressive PC identified in these mice was extensively correlated in human PC datasets and functionally validated in cell lines. Aggressive PC traits were quantified in a population of 30 week old (TRAMP x WSB) F2 mice (n = 307). Correlation of germline genotype with aggressive disease phenotype revealed seven modifier loci that were significantly associated with aggressive disease. RNA-seq were analyzed using cis-eQTL and trait correlation analyses to identify candidate genes within each of these loci. Analysis of 92 (TRAMP x WSB) F2 prostates revealed 25 candidate genes that harbored both a significant cis-eQTL and mRNA expression correlations with an aggressive PC trait. We further delineated these candidate genes based on their clinical relevance, by interrogating human PC GWAS and PC tumor gene expression datasets. We identified four genes (CCDC115, DNAJC10, RNF149, and STYXL1), which encompassed all of the following characteristics: 1) one or more germline variants associated with aggressive PC traits; 2) differential mRNA levels associated with aggressive PC traits; and 3) differential mRNA expression between normal and tumor tissue. Functional validation studies of these four genes using the human LNCaP prostate adenocarcinoma cell line revealed ectopic overexpression of CCDC115 can significantly impede cell growth in vitro and tumor growth in vivo. Furthermore, CCDC115 human prostate tumor expression was associated with better survival

GAB2 Alleles Modify Alzheimer’s Risk in APOE ε4 Carriers

PubMed Central

Reiman, Eric M.; Webster, Jennifer A.; Myers, Amanda J.; Hardy, John; Dunckley, Travis; Zismann, Victoria L.; Joshipura, Keta D.; Pearson, John V.; Hu-Lince, Diane; Huentelman, Matthew J.; Craig, David W.; Coon, Keith D.; Liang, Winnie S.; Herbert, RiLee H.; Beach, Thomas; Rohrer, Kristen C.; Zhao, Alice S.; Leung, Doris; Bryden, Leslie; Marlowe, Lauren; Kaleem, Mona; Mastroeni, Diego; Grover, Andrew; Heward, Christopher B.; Ravid, Rivka; Rogers, Joseph; Hutton, Michael L.; Melquist, Stacey; Petersen, Ron C.; Alexander, Gene E.; Caselli, Richard J.; Kukull, Walter; Papassotiropoulos, Andreas; Stephan, Dietrich A.

2008-01-01

SUMMARY The apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for late-onset Alzheimer’s disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In ε4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB-associated binding protein 2 (GAB2) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 × 10−11) was associated with an odds ratio of 4.06 (confidence interval 2.81–14.69), which interacts with APOE ε4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE ε4 carriers and influences Alzheimer’s neuropathology. PMID:17553421

Quantifying the risk-reduction potential of new Modified Risk Tobacco Products.

PubMed

Martin, Florian; Vuillaume, Gregory; Baker, Gizelle; Sponsiello-Wang, Zheng; Ricci, Paolo F; Lüdicke, Frank; Weitkunat, Rolf

2018-02-01

Quantitative risk assessment of novel Modified Risk Tobacco Products (MRTP) must rest on indirect measurements that are indicative of disease development prior to epidemiological data becoming available. For this purpose, a Population Health Impact Model (PHIM) has been developed to estimate the reduction in the number of deaths from smoking-related diseases following the introduction of an MRTP. One key parameter of the model, the F-factor, describes the effective dose upon switching from cigarette smoking to using an MRTP. Biomarker data, collected in clinical studies, can be analyzed to estimate the effects of switching to an MRTP as compared to quitting smoking. Based on transparent assumptions, a link function is formulated that translates these effects into the F-factor. The concepts of 'lack of sufficiency' and 'necessity' are introduced, allowing for a parametrization of a family of link functions. These can be uniformly sampled, thus providing different 'scenarios' on how biomarker-based evidence can be translated into the F-factor to inform the PHIM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Identifying children at risk for being bullies in the United States.

PubMed

Shetgiri, Rashmi; Lin, Hua; Flores, Glenn

2012-01-01

To identify risk factors associated with the greatest and lowest prevalence of bullying perpetration among U.S. children. Using the 2001-2002 Health Behavior in School-Aged Children, a nationally representative survey of U.S. children in 6th-10th grades, bivariate analyses were conducted to identify factors associated with any (once or twice or more), moderate (two to three times/month or more), and frequent (weekly or more) bullying. Stepwise multivariable analyses identified risk factors associated with bullying. Recursive partitioning analysis (RPA) identified risk factors which, in combination, identify students with the highest and lowest bullying prevalence. The prevalence of any bullying in the 13,710 students was 37.3%, moderate bullying was 12.6%, and frequent bullying was 6.6%. Characteristics associated with bullying were similar in the multivariable analyses and RPA clusters. In RPA, the highest prevalence of any bullying (67%) accrued in children with a combination of fighting and weapon-carrying. Students who carry weapons, smoke, and drink alcohol more than 5 to 6 days/week were at greatest risk for moderate bullying (61%). Those who carry weapons, smoke, have more than one alcoholic drink per day, have above-average academic performance, moderate/high family affluence, and feel irritable or bad-tempered daily were at greatest risk for frequent bullying (68%). Risk clusters for any, moderate, and frequent bullying differ. Children who fight and carry weapons are at greatest risk of any bullying. Weapon-carrying, smoking, and alcohol use are included in the greatest risk clusters for moderate and frequent bullying. Risk-group categories may be useful to providers in identifying children at the greatest risk for bullying and in targeting interventions. Copyright © 2012 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

RAD51 135G→C Modifies Breast Cancer Risk among BRCA2 Mutation Carriers: Results from a Combined Analysis of 19 Studies

PubMed Central

Antoniou, Antonis C. ; Sinilnikova, Olga M. ; Simard, Jacques ; Léoné, Mélanie ; Dumont, Martine ; Neuhausen, Susan L. ; Struewing, Jeffery P. ; Stoppa-Lyonnet, Dominique ; Barjhoux, Laure ; Hughes, David J. ; Coupier, Isabelle ; Belotti, Muriel ; Lasset, Christine ; Bonadona, Valérie ; Bignon, Yves-Jean ; Rebbeck, Timothy R. ; Wagner, Theresa ; Lynch, Henry T. ; Domchek, Susan M. ; Nathanson, Katherine L. ; Garber, Judy E. ; Weitzel, Jeffrey ; Narod, Steven A. ; Tomlinson, Gail ; Olopade, Olufunmilayo I. ; Godwin, Andrew ; Isaacs, Claudine ; Jakubowska, Anna ; Lubinski, Jan ; Gronwald, Jacek ; Górski, Bohdan ; Byrski, Tomasz ; Huzarski, Tomasz ; Peock, Susan ; Cook, Margaret ; Baynes, Caroline ; Murray, Alexandra ; Rogers, Mark ; Daly, Peter A. ; Dorkins, Huw ; Schmutzler, Rita K. ; Versmold, Beatrix ; Engel, Christoph ; Meindl, Alfons ; Arnold, Norbert ; Niederacher, Dieter ; Deissler, Helmut ; Spurdle, Amanda B. ; Chen, Xiaoqing ; Waddell, Nicola ; Cloonan, Nicole ; Kirchhoff, Tomas ; Offit, Kenneth ; Friedman, Eitan ; Kaufmann, Bella ; Laitman, Yael ; Galore, Gilli ; Rennert, Gad ; Lejbkowicz, Flavio ; Raskin, Leon ; Andrulis, Irene L. ; Ilyushik, Eduard ; Ozcelik, Hilmi ; Devilee, Peter ; Vreeswijk, Maaike P. G. ; Greene, Mark H. ; Prindiville, Sheila A. ; Osorio, Ana ; Benítez, Javier ; Zikan, Michal ; Szabo, Csilla I. ; Kilpivaara, Outi ; Nevanlinna, Heli ; Hamann, Ute ; Durocher, Francine ; Arason, Adalgeir ; Couch, Fergus J. ; Easton, Douglas F. ; Chenevix-Trench, Georgia 

2007-01-01

RAD51 is an important component of double-stranded DNA–repair mechanisms that interacts with both BRCA1 and BRCA2. A single-nucleotide polymorphism (SNP) in the 5′ untranslated region (UTR) of RAD51, 135G→C, has been suggested as a possible modifier of breast cancer risk in BRCA1 and BRCA2 mutation carriers. We pooled genotype data for 8,512 female mutation carriers from 19 studies for the RAD51 135G→C SNP. We found evidence of an increased breast cancer risk in CC homozygotes (hazard ratio [HR] 1.92 [95% confidence interval {CI} 1.25–2.94) but not in heterozygotes (HR 0.95 [95% CI 0.83–1.07]; P=.002, by heterogeneity test with 2 degrees of freedom [df]). When BRCA1 and BRCA2 mutation carriers were analyzed separately, the increased risk was statistically significant only among BRCA2 mutation carriers, in whom we observed HRs of 1.17 (95% CI 0.91–1.51) among heterozygotes and 3.18 (95% CI 1.39–7.27) among rare homozygotes (P=.0007, by heterogeneity test with 2 df). In addition, we determined that the 135G→C variant affects RAD51 splicing within the 5′ UTR. Thus, 135G→C may modify the risk of breast cancer in BRCA2 mutation carriers by altering the expression of RAD51. RAD51 is the first gene to be reliably identified as a modifier of risk among BRCA1/2 mutation carriers. PMID:17999359

A risk-based classification scheme for genetically modified foods. III: Evaluation using a panel of reference foods.

PubMed

Chao, Eunice; Krewski, Daniel

2008-12-01

This paper presents an exploratory evaluation of four functional components of a proposed risk-based classification scheme (RBCS) for crop-derived genetically modified (GM) foods in a concordance study. Two independent raters assigned concern levels to 20 reference GM foods using a rating form based on the proposed RBCS. The four components of evaluation were: (1) degree of concordance, (2) distribution across concern levels, (3) discriminating ability of the scheme, and (4) ease of use. At least one of the 20 reference foods was assigned to each of the possible concern levels, demonstrating the ability of the scheme to identify GM foods of different concern with respect to potential health risk. There was reasonably good concordance between the two raters for the three separate parts of the RBCS. The raters agreed that the criteria in the scheme were sufficiently clear in discriminating reference foods into different concern levels, and that with some experience, the scheme was reasonably easy to use. Specific issues and suggestions for improvements identified in the concordance study are discussed.

Do not fear the Framingham: Practical application to properly evaluate and modify cardiovascular risk in commercial divers.

PubMed

Suresh, Rahul; Pavela, James; Kus, Marcus S; Alleman, Tony; Sanders, Robert

2018-01-01

In April 2016 the Association of Diving Contractors International (ADCI) consensus guidelines began recommending annual cardiovascular risk stratification of commercial divers using the Framingham Risk Score (FRS). For those at elevated risk, further testing is recommended. This approach has raised concerns about potential operational and financial impacts. However, the prevalence of elevated cardiovascular risk and need for additional testing among commercial divers is not known. Clinical data required to calculate the FRS was abstracted for 190 commercial divers in two cohorts. Population demographics, FRS distribution, contributions of risk factors and effect of interventions on reducing risk-factor burden were assessed. Mean FRS score was 1.68 ± 6.35 points, with 13 divers (6.8%) at intermediate risk and none at high 10-year risk. In these 13 divers, the mean contributions to the FRS were from age (6.5 points), cholesterol (3.1 pts.), smoking (1.3 pts.), highdensity lipoprotein (1 pt.), and systolic blood pressure (0.8 pts). The youngest age group had a significantly higher modifiable risk core than the oldest age group (5.87 vs. 1.2 points, P ⟨ 0.001). All 13 intermediate risk divers could have been reclassified as low-risk with successful treatment of modifiable risk factors. The prevalence of elevated cardiovascular risk among commercial divers is low, and treatment of modifiable risk factors could reclassify those at intermediate risk to low risk. Therefore, FRS implementation coupled with intensive risk-reduction strategies for at risk-divers may help improve diver health and prolong the careers of divers while limiting the need for additional testing and adverse operational impact. Copyright© Undersea and Hyperbaric Medical Society.

Predicting the Unpredictable? Identifying High-Risk versus Low-Risk Parents with Intellectual Disabilities

ERIC Educational Resources Information Center

McGaw, Sue; Scully, Tamara; Pritchard, Colin

2010-01-01

Objectives: This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates "high-risk"…

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

PubMed

Yamada, Shunsuke; Taniguchi, Masatomo; Tokumoto, Masanori; Yoshitomi, Ryota; Yoshida, Hisako; Tatsumoto, Narihito; Hirakata, Hideki; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. Cross-sectional study and prospective longitudinal cohort study. An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. Bone fracture at any site. In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients. Copyright © 2017

The association between modifiable well-being risks and productivity: a longitudinal study in pooled employer sample.

PubMed

Shi, Yuyan; Sears, Lindsay E; Coberley, Carter R; Pope, James E

2013-04-01

To examine the longitudinal relationship between modifiable well-being risks and productivity. A total of 19,121 employees from five employers participated in baseline and follow-up well-being assessment surveys. Multivariate regressions assessed whether changes in absenteeism, presenteeism, and job performance were associated with changes in 19 modifiable well-being risks. Over time, a 5% reduction in total count of well-being risks was significantly associated with 0.74% decrease in absenteeism, 2.38% decrease in presenteeism, and 0.24% increase in performance. High blood pressure, recurring pain, unhealthy diet, inadequate exercise, poor emotional health, poor supervisor relationship, not utilizing strengths doing job, and organization unsupportive of well-being had greater independent contributions in explaining productivity impairment. The often-ignored well-being risks such as work-related and financial health risks provided incremental explanation of longitudinal productivity variations beyond traditional measures of health-related risks.

Which modifiable health risks are associated with changes in productivity costs?

PubMed

Kirkham, Heather S; Clark, Bobby L; Bolas, Cheryl A; Lewis, Geraint Hywel; Jackson, Allison S; Fisher, Don; Duncan, Ian

2015-02-01

The purpose of this retrospective, longitudinal study was to assess longitudinal associations between modifiable health risks and workplace absenteeism and presenteeism and to estimate lost productivity costs. Across the 4-year study period (2007-2010), 17,089 unique employees from a large US computer manufacturer with a highly technical workforce completed at least 1 health risk assessment. Generalized estimating equation models were used to estimate the mean population-level absenteeism and presenteeism for 11 modifiable health risks and adjust for 9 sociodemographic and employment-related factors. Because patient age was highly correlated with several other variables, the analysis was stratified by age (<45 vs. ≥45 years). For all ages, poor emotional health, inadequate exercise, tobacco use, and having a body mass index (BMI) greater than 35 (all P<.05) were consistently associated with both absenteeism and presenteeism. Having a BMI over 35 and poor emotional health were associated with the largest impact in absenteeism (0.46 days) and presenteeism (4.03 days), respectively. Younger and older workers had similar associations between health risks and presenteeism; however, hypertension, blood sugar, inadequate exercise, and alcohol were associated (P⋜.01) with greater absenteeism among older but not younger workers. The results suggest that productivity loss is strongly related to emotional health and obesity-related health risks (eg, BMI, exercise) but differs by age. These findings could help prioritize preventive health programs offered by employers at their worksite health centers. Given the aging of the US workforce, keeping older workers healthy and productive will be crucial to remaining competitive in the global economy. (Population Health Management 2015;18:30-38).

High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance.

PubMed

Hudson, Melissa M; Mulrooney, Daniel A; Bowers, Daniel C; Sklar, Charles A; Green, Daniel M; Donaldson, Sarah S; Oeffinger, Kevin C; Neglia, Joseph P; Meadows, Anna T; Robison, Leslie L

2009-05-10

Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

Identifying nursing home residents at risk for falling.

PubMed

Kiely, D K; Kiel, D P; Burrows, A B; Lipsitz, L A

1998-05-01

To develop a fall risk model that can be used to identify prospectively nursing home residents at risk for falling. The secondary objective was to determine whether the nursing home environment independently influenced the development of falls. A prospective study involving 1 year of follow-up. Two hundred seventy-two nursing homes in the state of Washington. A total of 18,855 residents who had a baseline assessment in 1991 and a follow-up assessment within the subsequent year. Baseline Minimum Data Set items that could be potential risk factors for falling were considered as independent variables. The dependent variable was whether the resident fell as reported at the follow-up assessment. We estimated the extrinsic risk attributable to particular nursing home environments by calculating the annual fall rate in each nursing home and grouping them into tertiles of fall risk according to these rates. Factors associated independently with falling were fall history, wandering behavior, use of a cane or walker, deterioration of activities of daily living performance, age greater than 87 years, unsteady gait, transfer independence, wheelchair independence, and male gender. Nursing home residents with a fall history were more than three times as likely to fall during the follow-up period than residents without a fall history. Residents in homes with the highest tertile of fall rates were more than twice as likely to fall compared with residents of homes in the lowest tertile, independent of resident-specific risk factors. Fall history was identified as the strongest risk factor associated with subsequent falls and accounted for the vast majority of the predictive strength of the model. We recommend that fall history be used as an initial screener for determining eligibility for fall intervention efforts. Studies are needed to determine the facility characteristics that contribute to fall risk, independent of resident-specific risk factors.

Identifying Older Adults at Risk of Delirium Following Elective Surgery: A Systematic Review and Meta-Analysis.

PubMed

Watt, Jennifer; Tricco, Andrea C; Talbot-Hamon, Catherine; Pham, Ba'; Rios, Patricia; Grudniewicz, Agnes; Wong, Camilla; Sinclair, Douglas; Straus, Sharon E

2018-04-01

Postoperative delirium is a common preventable complication experienced by older adults undergoing elective surgery. In this systematic review and meta-analysis, we identified prognostic factors associated with the risk of postoperative delirium among older adults undergoing elective surgery. Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. A total of 5692 titles and abstracts were screened in duplicate for possible inclusion. Studies using any method for diagnosing delirium were eligible. Two reviewers independently completed all data extraction and quality assessments using the Cochrane Risk-of-Bias Tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random effects meta-analysis models were used to derive pooled effect estimates. Forty-one studies (9384 patients) reported delirium-related prognostic factors. Among our included studies, the pooled incidence of postoperative delirium was 18.4% (95% confidence interval [CI] 14.3-23.3%, number needed to follow [NNF] = 6). Geriatric syndromes were important predictors of delirium, namely history of delirium (odds ratio [OR] 6.4, 95% CI 2.2-17.9), frailty (OR 4.1, 95% CI 1.4-11.7), cognitive impairment (OR 2.7, 95% CI 1.9-3.8), impairment in activities of daily living (ADLs; OR 2.1, 95% CI 1.6-2.6), and impairment in instrumental activities of daily living (IADLs; OR 1.9, 95% CI 1.3-2.8). Potentially modifiable prognostic factors such as psychotropic medication use (OR 2.3, 95% CI 1.4-3.6) and smoking status (OR 1.8 95% CI 1.3-2.4) were also identified. Caregiver support was associated with lower odds of postoperative delirium (OR 0.69, 95% CI 0.52-0.91). Though caution must be used in interpreting meta-analyses of non-randomized studies due to the potential influence of unmeasured confounding, we identified potentially modifiable prognostic factors including

Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age.

PubMed

Shi, Zumin; Johnstone, Daniel; Talseth-Palmer, Bente A; Evans, Tiffany-Jane; Spigelman, Allan D; Groombridge, Claire; Milward, Elizabeth A; Olynyk, John K; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; Scott, Rodney J

2009-07-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.

"Obesity-Associated" Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk.

PubMed

Denis, Gerald V; Palmer, Julie R

2017-05-01

Why is obesity only weakly associated with certain "obesity-driven" cancers? Recent population studies identify cohorts of high body mass index (BMI) subjects with unexpectedly reduced risk for breast and colon cancer, and normal BMI subjects with unexpectedly elevated risk for breast cancer, provoking hard thinking about cellular and molecular mechanisms that most strongly couple obesity to cancer occurrence or progression. Emerging work suggests that abnormal metabolism and its associated chronic inflammation make the difference. Type II diabetes, for example, is a chronic inflammatory disease with specific imbalances in T-cell and myeloid-origin cytokines. Inflammation is elevated systemically, measured through blood biomarkers, and locally in adipose tissue. Here, cytokines and chemokines likely modify tumor microenvironments in dangerous ways. High BMI subjects with low inflammation and less disturbed metabolism appear to have reduced risk for certain obesity-associated cancers, whereas lean or slightly overweight subjects with high inflammation and metabolic abnormalities have elevated risk. This latter phenotype is prevalent among South Asian adults and suggests we are not monitoring certain normal weight adults sufficiently for risks of "obesity-associated" cancers. Profiling of patient metabolism and inflammation should accompany measures of body composition when considering cancer risk; the evidence base for these refinements must be extended through new, prospective observational studies. Cancer Prev Res; 10(5); 267-9. ©2017 AACR See related article by Iyengar et al., Cancer Prev Res 2017;10(4):235-43 . ©2017 American Association for Cancer Research.

African genetic ancestry interacts with body mass index to modify risk for uterine fibroids

PubMed Central

Hartmann, Katherine E.; Torstenson, Eric S.; Wellons, Melissa; Schreiner, Pamela J.; Velez Edwards, Digna R.

2017-01-01

Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an

A comparative analysis of media reporting of perceived risks and benefits of genetically modified crops and foods in Kenyan and international newspapers.

PubMed

DeRosier, Christopher; Sulemana, Iddisah; James, Harvey S; Valdivia, Corinne; Folk, William; Smith, Randall D

2015-07-01

We empirically examine the reporting on biotechnology in Kenyan and international newspapers between 2010 and early 2014. We identify news articles that reported on biotechnology and analyze their use of words to determine whether there is a balance in the reporting of perceived risks and benefits. We also consider how the sources used in news articles and how the publication of the Séralini study of rats fed genetically modified maize affect the balance of reporting of perceived risks and benefits. We find that in Kenyan news reporting, more articles mention perceived benefits than risks, but when risks are mentioned, new articles contain more references to risks than to benefits. We also find that sources affect the reporting of perceived risks and benefits and that the Séralini study increased the likelihood that perceived risks are reported in Kenyan news reporting, but not in international newspapers. © The Author(s) 2015.

Modified Sainsbury tool: an initial risk assessment tool for primary care mental health and learning disability services.

PubMed

Stein, W

2005-10-01

Risk assessments by health and social care professionals must encompass risk of suicide, of harm to others, and of neglect. The UK's National Confidential Inquiry into Homicide and Suicide paints a picture of failure to predict suicides and homicides, failure to identify opportunities for prevention and a failure to manage these opportunities. Assessing risk at 'first contact' with the mental health service assumes a special place in this regard. The initial opportunity to be alerted to, and thus to influence, risk, usually falls to the general psychiatric service (as opposed to forensic specialists) or to a joint health and local authority community mental health team. The Mental Health and Learning Disabilities Directorate of Renfrewshire & Inverclyde Primary Care NHS Trust, Scotland, determined to standardize their approach to risk assessment and selected a modified version of the Sainsbury Risk Assessment Tool. A year-long pilot revealed general support for its service-wide introduction but also some misgivings to address, including: (i) rejection of the tool by some medical staff; (ii) concerns about limited training; and (iii) a perceived failure on the part of the management to properly resource its use. The tool has the potential to fit well with the computer-networked needs assessment system used in joint-working with partner local authorities to allocate care resources.

Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis.

PubMed

Sørensen, Per Soelberg

2011-12-01

Balancing efficacy versus burden of therapy is essential for the choice of disease-modifying therapy in every MS patient. The first-line therapies, interferon-? and glatiramer acetate, have well-established efficacy and present no major safety concerns. Certain second-line therapies, such as natalizumab, offer potentially greater efficacy, but are associated with an increased level of risk. Over the last year, the first two oral treatments of relapsing-remitting multiple sclerosis, cladribine and fingolimod, have been marketed in certain countries, although cladribine was subsequently withdrawn. In the Phase III clinical development programme, both drugs appeared effective and reasonably safe. However, there were cases of serious adverse events (malignancies and fatal infections) whose relationship with treatment was unclear. Specific postmarketing studies will be necessary to assess the risks of these new oral therapies. Indeed, both natalizumab and mitoxantrone are known today to be associated with rare adverse drug reactions (progressive multifocal leukoencephalopathy for natalizumab and treatment-related leukaemia for mitoxantrone), which were not identified before the treatments were approved. The use of therapies carrying potential serious risks is justified in patients who cannot be treated effectively with safe first-line therapies, but probably not in the average relapsing-remitting multiple sclerosis or clinical isolated syndrome patient. Pivotal Phase III clinical trials, on which basis drug approval is generally granted, are designed to demonstrate clinical efficacy and reveal frequently occurring adverse effects of a new drug. However, post-approval trials with extensive patient exposure are needed to generate knowledge of more patient-specific clinical effectiveness and long-term safety, in particular with respect to rare adverse reactions. Other post-approval measures, such as risk management programmes, pharmacovigilance studies, or phased launch of

Modifying Risk Factors in the Management of Erectile Dysfunction: A Review

PubMed Central

DeLay, Kenneth J; Haney, Nora

2016-01-01

Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patient's overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process. PMID:27574592

Prevalence of modifiable cardiovascular risk factors among tea garden and general population in Dibrugarh, Assam, India.

PubMed

Mahanta, Tulika G; Joshi, Rajnish; Mahanta, Bhupendra N; Xavier, Denis

2013-09-01

Risk factors for cardiovascular disease (CVD) are multifactorial. Previous research has reported a high prevalence of CVD risk factors in tea-garden workers. This study was conducted to assess prevalence and level of modifiable cardiovascular risk factors among tea-garden and general population in Dibrugarh, Assam. A community-based cross-sectional study using the World Health Organization's (WHO) Stepwise methodology was conducted in Dibrugarh District of Assam. A multistep random sampling was done to include adults aged 35 years and above, with an intended equal sampling from tea-garden and general population. INTERHEART modifiable non-laboratory based risk score was estimated. Salt consumption was estimated using questionnaire-based methods in both subgroups. A total of 2826 individuals participated in the study (1231 [43.6%] tea-garden workers; 1595 [56.4%] general population). Tobacco consumption was higher in tea-garden workers as compared with general population (85.2% vs. 41.7% (p < 0.0001). Mean daily per-capita salt consumption was also significantly higher among tea-garden workers (29.60 vs. 22.89 g, p = 0.0001). Overall prevalence of hypertension was similar (44.4% vs. 45.2%), but among those who had hypertension, prevalence of undiagnosed hypertension was higher in tea-garden workers (82.8% vs. 74.4%, p < 0.0001). Tea-garden workers had lower BMI, were more physically active, and had a lower prevalence of diabetes mellitus and metabolic syndrome. Their INTERHEART modifiable risk score was also lower (1.44 [2.5] vs. 1.79 [2.8], p = 0.001). High prevalence of modifiable risk factors like tobacco consumption, high salt intake and high prevalence of hypertension indicates the need for early implementation of preventive actions in this population. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Incidence and risk factors for oxygen desaturation during recovery from modified electroconvulsive therapy: A prospective observational study.

PubMed

Surve, Rohini; Bansal, Sonia; Sriganesh, Kamath; Subbakrishna, Doddaballapur Kumaraswamy; Thirthalli, Jagadisha; Umamaheswara Rao, Ganne Sesha

2015-01-01

Electroconvulsive therapy (ECT) is an established modality of treatment for severe psychiatric illnesses. Among the various complications associated with ECT, oxygen desaturation is often under reported. None of the previous studies has evaluated the predictive factors for oxygen desaturation during ECT. The objective of this study was to evaluate the incidence of oxygen desaturation during recovery from anesthesia for modified ECT and evaluate its risk factors in a large sample. All patients aged above 15 years who were prescribed a modified ECT for their psychiatric illness over 1 year were prospectively included in this observational study. The association between age, body mass index (BMI), doses of thiopentone and suxamethonium, stimulus current, ECT session number, pre- and post-ECT heart rate and mean arterial pressure, seizure duration, and pre- and post ECT oxygen saturation, was systematically studied. The incidence of oxygen desaturation was 29% (93/316 patients). Seizure duration and BMI were found to be significantly correlated with post ECT desaturation. In this prospective observational study, the incidence of oxygen desaturation during recovery from anesthesia for ECT was high. The study identified obesity and duration of seizure as the independent predictors of this complication. This knowledge is likely to help in identifying and optimizing such patients before subsequent ECT sessions.

Modifiable Risk Factors for Attempted Suicide in Australian Clinical and Community Samples

ERIC Educational Resources Information Center

Carter, Gregory L.; Page, Andrew; Clover, Kerrie; Taylor, Richard

2007-01-01

Modifiable risk factors for suicide attempt require identification in clinical and community samples. The aim of this study was to determine if similar social and psychiatric factors are associated with suicide attempts in community and clinical settings and whether the magnitude of effect is greater in clinical populations. Two case-control…

Identifying Causal Risk Factors for Violence among Discharged Patients

PubMed Central

Coid, Jeremy W.; Kallis, Constantinos; Doyle, Mike; Shaw, Jenny; Ullrich, Simone

2015-01-01

Background Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. Methods We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. Results In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85–12.65, P<0.001), instability (OR 5.41, 95% CI 3.44–8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21–16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08–0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. Conclusions Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors

The contribution of recently identified adult BMI risk loci to paediatric obesity in a Singaporean Chinese childhood dataset.

PubMed

Dorajoo, R; Ong, R T-H; Sim, X; Wang, L; Liu, W; Tai, E S; Liu, J; Saw, S-M

2017-12-01

Recent genome-wide association studies have identified 103 adult obesity risk loci; however, it is unclear if these findings are relevant to East-Asian childhood body mass index (BMI) levels. We evaluated for paediatric obesity associations at these risk loci utilizing genome-wide data from Chinese childhood subjects in the Singapore Cohort study Of the Risk factors for Myopia study (N = 1006). A weighted gene-risk score of all adult obesity risk loci in the Singapore Cohort study Of the Risk factors for Myopia study showed strong associations with BMI at age 9 (p-value = 3.40 × 10 -12 ) and 4-year average BMI (age 9 to 12, p-value = 6.67 × 10 -8 ). Directionally consistent nominal associations for 15 index single nucleotide polymorphisms (SNPs) (p-value < 0.05) were observed. Pathway analysis with genes from these 15 replicating loci revealed over-representation for the G-protein-coupled receptor (GPCR)-mediated integration of entero-endocrine signalling pathway exemplified by L-cell (adjusted p-value = 0.018). Evaluations of birth weight to modify the effects of BMI risk SNPs in paediatric obesity did not reveal significant interactions, and these SNPs were generally not associated with birth weight. At least some common adult BMI risk variants predispose to paediatric obesity risk in East-Asians. © 2016 World Obesity Federation.

Modifiable risk factors of ecstasy use: risk perception, current dependence, perceived control, and depression

PubMed Central

Leung, Kit Sang; Ben Abdallah, Arbi; Cottler, Linda B.

2009-01-01

Risk perception, perceived behavioral control of obtaining ecstasy (PBC-obtaining), current ecstasy dependence, and recent depression have been associated with past ecstasy use, however, their utility in predicting ecstasy use has not been demonstrated. This study aimed to determine whether these four modifiable risk factors could predict ecstasy use after controlling for socio-demographic covariates and recent polydrug use. Data from 601 ecstasy users in the National Institute on Drug Abuse funded TriCity Study of Club Drug Use, Abuse and Dependence were analyzed using multivariate logistic regression. Participants were interviewed twice within a 2-week period using standardized instruments. Thirteen percent (n=80) of the participants reported using ecstasy between the two interviews. Low risk perception, high PBC-obtaining (an estimated ecstasy procurement time < 24 hours), and current ecstasy dependence were statistically associated with ecstasy use between the two interviews. Recent depression was not a significant predictor. Despite not being a target predictor, recent polydrug use was also statistically associated with ecstasy use. The present findings may inform the development of interventions targeting ecstasy users. PMID:19880258

Regulating genetically modified food. Policy trajectories, political culture, and risk perceptions in the U.S., Canada, and EU.

PubMed

Wohlers, Anton E

2010-09-01

This paper examines whether national differences in political culture add an explanatory dimension to the formulation of policy in the area of biotechnology, especially with respect to genetically modified food. The analysis links the formulation of protective regulatory policies governing genetically modified food to both country and region-specific differences in uncertainty tolerance levels and risk perceptions in the United States, Canada, and European Union. Based on polling data and document analysis, the findings illustrate that these differences matter. Following a mostly opportunistic risk perception within an environment of high tolerance for uncertainty, policymakers in the United States and Canada modified existing regulatory frameworks that govern genetically modified food in their respective countries. In contrast, the mostly cautious perception of new food technologies and low tolerance for uncertainty among European Union member states has contributed to the creation of elaborate and stringent regulatory policies governing genetically modified food.

Nest predation risk modifies nestlings' immune function depending on the level of threat.

PubMed

Roncalli, Gianluca; Colombo, Elisa; Soler, Manuel; Tieleman, B Irene; Versteegh, Maaike A; Ruiz-Raya, Fran; Gómez Samblas, Mercedes; Ibáñez-Álamo, Juan Diego

2018-05-20

Predation risk is thought to modify the physiology of prey mainly through the stress response. However, little is known about its potential effects on the immunity of animals, particularly in young individuals, despite the importance of overcoming wounding and pathogen aggression following a predator attack. We investigated the effect of four progressive levels of nest predation risk on several components of the immune system in common blackbird ( Turdus merula ) nestlings by presenting them with four different calls during 1 h: non-predator calls, predator calls, parental alarm calls and conspecific distress calls to induce a null, moderate, high and extreme level of risk, respectively. Nest predation risk induced an increase in ovotransferrin, immunoglobulin and the number of lymphocytes and eosinophils. Thus, the perception of a potential predator per se could stimulate the mobilization of a nestling's immune function and enable the organism to rapidly respond to the immune stimuli imposed by a predator attack. Interestingly, only high and extreme levels of risk caused immunological changes, suggesting that different immunological parameters are modulated according to the perceived level of threat. We also found a mediator role of parasites (i.e. Leucocytozoon ) and the current health status of the individual, as only nestlings not parasitized or in good body condition were able to modify their immune system. This study highlights a previously unknown link between predation risk and immunity, emphasizing the complex relationship among different selective pressures (predation, parasitism) in developing organisms and accentuating the importance of studying predation from a physiological point of view. © 2018. Published by The Company of Biologists Ltd.

A comparison of two prospective risk analysis methods: Traditional FMEA and a modified healthcare FMEA.

PubMed

Rah, Jeong-Eun; Manger, Ryan P; Yock, Adam D; Kim, Gwe-Ya

2016-12-01

To examine the abilities of a traditional failure mode and effects analysis (FMEA) and modified healthcare FMEA (m-HFMEA) scoring methods by comparing the degree of congruence in identifying high risk failures. The authors applied two prospective methods of the quality management to surface image guided, linac-based radiosurgery (SIG-RS). For the traditional FMEA, decisions on how to improve an operation were based on the risk priority number (RPN). The RPN is a product of three indices: occurrence, severity, and detectability. The m-HFMEA approach utilized two indices, severity and frequency. A risk inventory matrix was divided into four categories: very low, low, high, and very high. For high risk events, an additional evaluation was performed. Based upon the criticality of the process, it was decided if additional safety measures were needed and what they comprise. The two methods were independently compared to determine if the results and rated risks matched. The authors' results showed an agreement of 85% between FMEA and m-HFMEA approaches for top 20 risks of SIG-RS-specific failure modes. The main differences between the two approaches were the distribution of the values and the observation that failure modes (52, 54, 154) with high m-HFMEA scores do not necessarily have high FMEA-RPN scores. In the m-HFMEA analysis, when the risk score is determined, the basis of the established HFMEA Decision Tree™ or the failure mode should be more thoroughly investigated. m-HFMEA is inductive because it requires the identification of the consequences from causes, and semi-quantitative since it allows the prioritization of high risks and mitigation measures. It is therefore a useful tool for the prospective risk analysis method to radiotherapy.

Genetically Modified Foods: A Brief Overview of the Risk Assessment Process.

PubMed

Finkelstein, Paige E

2016-02-18

Billions of people worldwide are unable to meet their daily micro nutritional needs. Genetically modified (GM) foods, while initially developed to tolerate herbicides and resist disease and insects, have the potential to help alleviate this issue that is currently posing a serious public health concern. However, there is a negative public perception surrounding GM foods, calling for more research regarding the risks that GM foods could pose to the public, specifically on the topics of allergenicity and gene transfer. The risk assessments of GM foods should be performed on a case-by-case basis, by a process outlined by the WHO. The goal of determining food safety is to obtain reasonable certainty that under normal levels of consumption, there will be no harm to people. Current research has shown that GM foods do not cause increased allergenicity or have a meaningful risk of gene transfer to people. GM foods should become publicly accepted products that can bring significant benefit to people at risk of under nutrition.

Procedure to select test organisms for environmental risk assessment of genetically modified crops in aquatic systems.

PubMed

Hilbeck, Angelika; Bundschuh, Rebecca; Bundschuh, Mirco; Hofmann, Frieder; Oehen, Bernadette; Otto, Mathias; Schulz, Ralf; Trtikova, Miluse

2017-11-01

For a long time, the environmental risk assessment (ERA) of genetically modified (GM) crops focused mainly on terrestrial ecosystems. This changed when it was scientifically established that aquatic ecosystems are exposed to GM crop residues that may negatively affect aquatic species. To assist the risk assessment process, we present a tool to identify ecologically relevant species usable in tiered testing prior to authorization or for biological monitoring in the field. The tool is derived from a selection procedure for terrestrial ecosystems with substantial but necessary changes to adequately consider the differences in the type of ecosystems. By using available information from the Water Framework Directive (2000/60/EC), the procedure can draw upon existing biological data on aquatic systems. The proposed procedure for aquatic ecosystems was tested for the first time during an expert workshop in 2013, using the cultivation of Bacillus thuringiensis (Bt) maize as the GM crop and 1 stream type as the receiving environment in the model system. During this workshop, species executing important ecological functions in aquatic environments were identified in a stepwise procedure according to predefined ecological criteria. By doing so, we demonstrated that the procedure is practicable with regard to its goal: From the initial long list of 141 potentially exposed aquatic species, 7 species and 1 genus were identified as the most suitable candidates for nontarget testing programs. Integr Environ Assess Manag 2017;13:974-979. © 2017 SETAC. © 2017 SETAC.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

PubMed

Blein, Sophie; Bardel, Claire; Danjean, Vincent; McGuffog, Lesley; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B; Soucy, Penny; Terry, Mary Beth; Chung, Wendy K; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C; Hansen, Thomas Vo; Osorio, Ana; Benitez, Javier; Conejero, Raquel Andrés; Segota, Ena; Weitzel, Jeffrey N; Thelander, Margo; Peterlongo, Paolo; Radice, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Bonanni, Bernardo; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush; Varesco, Liliana; Capone, Gabriele L; Papi, Laura; Ottini, Laura; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brady, Angela; Brewer, Carole; Foo, Claire; Evans, D Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Cook, Jackie; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Tischkowitz, Marc; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Cole, Trevor; Godwin, Andrew K; Isaacs, Claudine; Claes, Kathleen; De Leeneer, Kim; Meindl, Alfons; Gehrig, Andrea; Wappenschmidt, Barbara; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Schmutzler, Rita K; Preisler-Adams, Sabine; Markov, Nadja Bogdanova; Wang-Gohrke, Shan; de Pauw, Antoine; Lefol, Cédrick; Lasset, Christine; Leroux, Dominique; Rouleau, Etienne; Damiola, Francesca; Dreyfus, Hélène; Barjhoux, Laure; Golmard, Lisa; Uhrhammer, Nancy; Bonadona, Valérie; Sornin, Valérie; Bignon, Yves-Jean; Carter, Jonathan; Van Le, Linda; Piedmonte, Marion; DiSilvestro, Paul A; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Aittomäki, Kristiina; Jager, Agnes; van den Ouweland, Ans Mw; Kets, Carolien M; Aalfs, Cora M; van Leeuwen, Flora E; Hogervorst, Frans Bl; Meijers-Heijboer, Hanne Ej; Oosterwijk, Jan C; van Roozendaal, Kees Ep; Rookus, Matti A; Devilee, Peter; van der Luijt, Rob B; Olah, Edith; Diez, Orland; Teulé, Alex; Lazaro, Conxi; Blanco, Ignacio; Del Valle, Jesús; Jakubowska, Anna; Sukiennicki, Grzegorz; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Agnarsson, Bjarni A; Maugard, Christine; Amadori, Alberto; Montagna, Marco; Teixeira, Manuel R; Spurdle, Amanda B; Foulkes, William; Olswold, Curtis; Lindor, Noralane M; Pankratz, Vernon S; Szabo, Csilla I; Lincoln, Anne; Jacobs, Lauren; Corines, Marina; Robson, Mark; Vijai, Joseph; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Tchatchou, Sandrine; Toland, Amanda Ewart; Pedersen, Inge Sokilde; Thomassen, Mads; Kruse, Torben A; Jensen, Uffe Birk; Caligo, Maria A; Friedman, Eitan; Zidan, Jamal; Laitman, Yael; Lindblom, Annika; Melin, Beatrice; Arver, Brita; Loman, Niklas; Rosenquist, Richard; Olopade, Olufunmilayo I; Nussbaum, Robert L; Ramus, Susan J; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Orsulic, Sandra; Stoppa-Lyonnet, Dominique; Thomas, Gilles; Simard, Jacques; Couch, Fergus J; Offit, Kenneth; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Mazoyer, Sylvie; Phelan, Catherine M; Sinilnikova, Olga M; Cox, David G

2015-04-25

Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

Population attributable risk of modifiable risk factors associated with invasive breast cancer in women aged 45-69 years in Queensland, Australia.

PubMed

Wilson, Louise F; Page, Andrew N; Dunn, Nathan A M; Pandeya, Nirmala; Protani, Melinda M; Taylor, Richard J

2013-12-01

To quantify the population attributable risk of key modifiable risk factors associated with breast cancer incidence in Queensland, Australia. Population attributable fractions (PAFs) for high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity were calculated, using prevalence data from a representative survey of women attending mammographic screening at BreastScreen Queensland in 2008 and relative risk estimates sourced from published literature. Attributable cancers were calculated using 'underlying' breast cancer incidence data for 2008 based on Poisson regression models, adjusting for the inflation of incidence due to the effects of mammographic screening. Attributable burden of breast cancer due to high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity. In Queensland women aged 45-69 years, an estimated 12.1% (95% CI: 11.6-12.5%) of invasive breast cancers were attributable to high BMI in post-menopausal women who have never used HRT; 2.8% (95% CI: 2.7-2.9%) to alcohol consumption; 7.6% (95% CI: 7.4-7.9%) to inadequate physical activity in post-menopausal women and 6.2% (95% CI: 5.5-7.0%) to current use of HRT after stratification by BMI and type of HRT used. Combined, just over one quarter (26.0%; 95% CI: 25.4-26.6%) of all invasive breast cancers in Queensland women aged 45-69 years in 2008 were attributable to these modifiable risk factors. There is benefit in targeting prevention strategies to modify lifestyle behaviours around BMI, physical activity, HRT use and alcohol consumption, as a reduction in these risk factors could decrease invasive breast cancer incidence in the Queensland population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

PubMed

Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

2015-12-01

The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

Suicide Risk Screening in Healthcare Settings: Identifying Males and Females at Risk

PubMed Central

King, Cheryl A.; Horwitz, Adam; Czyz, Ewa; Lindsay, Rebecca

2017-01-01

Suicide is the 10th leading cause of death in the United States, accounting for more than 42,000 deaths in 2014. Although this tragedy cuts across groups defined by age, sex, race/ethnicity, and geographic location, it is striking that nearly four times as many males as females die by suicide in the U.S. We describe the current regulations and recommendations for suicide risk screening in healthcare systems and also describe the aspirational goal of “Zero Suicide,” put forth by the National Action Alliance for Suicide Prevention. We then provide information about suicide risk screening tools and steps to take when a patient screens positive for suicide risk. Given the substantially higher suicide rate among males than females, we argue that it is important to consider how we could optimize suicide risk screening strategies to identify males and females at risk. Further research is needed to accomplish this. It is recommended that we consider multi-factorial suicide risk screens that incorporate risk factors known to be particularly important for males as well computerized, adaptive screens that are tailored for the specific risk considerations of the individual patient, male or female. These strategies are not mutually exclusive. Finally, universal suicide risk screening in healthcare settings, especially primary care, specialty medical care, and emergency department settings, is recommended. PMID:28251427

BCL-2 system analysis identifies high-risk colorectal cancer patients.

PubMed

Lindner, Andreas U; Salvucci, Manuela; Morgan, Clare; Monsefi, Naser; Resler, Alexa J; Cremona, Mattia; Curry, Sarah; Toomey, Sinead; O'Byrne, Robert; Bacon, Orna; Stühler, Michael; Flanagan, Lorna; Wilson, Richard; Johnston, Patrick G; Salto-Tellez, Manuel; Camilleri-Broët, Sophie; McNamara, Deborah A; Kay, Elaine W; Hennessy, Bryan T; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Prehn, Jochen H M

2017-12-01

The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Genetically modified foods: safety, risks and public concerns-a review.

PubMed

Bawa, A S; Anilakumar, K R

2013-12-01

Genetic modification is a special set of gene technology that alters the genetic machinery of such living organisms as animals, plants or microorganisms. Combining genes from different organisms is known as recombinant DNA technology and the resulting organism is said to be 'Genetically modified (GM)', 'Genetically engineered' or 'Transgenic'. The principal transgenic crops grown commercially in field are herbicide and insecticide resistant soybeans, corn, cotton and canola. Other crops grown commercially and/or field-tested are sweet potato resistant to a virus that could destroy most of the African harvest, rice with increased iron and vitamins that may alleviate chronic malnutrition in Asian countries and a variety of plants that are able to survive weather extremes. There are bananas that produce human vaccines against infectious diseases such as hepatitis B, fish that mature more quickly, fruit and nut trees that yield years earlier and plants that produce new plastics with unique properties. Technologies for genetically modifying foods offer dramatic promise for meeting some areas of greatest challenge for the 21st century. Like all new technologies, they also pose some risks, both known and unknown. Controversies and public concern surrounding GM foods and crops commonly focus on human and environmental safety, labelling and consumer choice, intellectual property rights, ethics, food security, poverty reduction and environmental conservation. With this new technology on gene manipulation what are the risks of "tampering with Mother Nature"?, what effects will this have on the environment?, what are the health concerns that consumers should be aware of? and is recombinant technology really beneficial? This review will also address some major concerns about the safety, environmental and ecological risks and health hazards involved with GM foods and recombinant technology.

Informed Consent in Implantable BCI Research: Identifying Risks and Exploring Meaning.

PubMed

Klein, Eran

2016-10-01

Implantable brain-computer interface (BCI) technology is an expanding area of engineering research now moving into clinical application. Ensuring meaningful informed consent in implantable BCI research is an ethical imperative. The emerging and rapidly evolving nature of implantable BCI research makes identification of risks, a critical component of informed consent, a challenge. In this paper, 6 core risk domains relevant to implantable BCI research are identified-short and long term safety, cognitive and communicative impairment, inappropriate expectations, involuntariness, affective impairment, and privacy and security. Work in deep brain stimulation provides a useful starting point for understanding this core set of risks in implantable BCI. Three further risk domains-risks pertaining to identity, agency, and stigma-are identified. These risks are not typically part of formalized consent processes. It is important as informed consent practices are further developed for implantable BCI research that attention be paid not just to disclosing core research risks but exploring the meaning of BCI research with potential participants.

Geographic Mapping as a Tool for Identifying Communities at High Risk for Fires.

PubMed

Fahey, Erin; Lehna, Carlee; Hanchette, Carol; Coty, Mary-Beth

2016-01-01

The purpose of this study was to evaluate whether the sample of older adults in a home fire safety (HFS) study captured participants living in the areas at highest risk for fire occurrence. The secondary aim was to identify high risk areas to focus future HFS interventions. Geographic information systems software was used to identify census tracts where study participants resided. Census data for these tracts were compared with participant data based on seven risk factors (ie, age greater than 65 years, nonwhite race, below high school education, low socioeconomic status, rented housing, year home built, home value) previously identified in a fire risk model. The distribution of participants and census tracts among risk categories determined how well higher risk census tracts were sampled. Of the 46 census tracts where the HFS intervention was implemented, 78% (n = 36) were identified as high or severe risk according to the fire risk model. Study participants' means for median annual family income (P < .0001) and median home value (P < .0001) were significantly lower than the census tract means (n = 46), indicating participants were at higher risk of fire occurrence. Of the 92 census tracts identified as high or severe risk in the entire county, the study intervention was implemented in 39% (n = 36), indicating 56 census tracts as potential areas for future HFS interventions. The Geographic information system-based fire risk model is an underutilized but important tool for practice that allows community agencies to develop, plan, and evaluate their outreach efforts and ensure the most effective use of scarce resources.

Modifiable Disease Risk, Readiness to Change, and Psychosocial Functioning Improve With Integrative Medicine Immersion Model

PubMed Central

Wolever, Ruth Q.; Webber, Daniel M.; Meunier, Justin P.; Greeson, Jeffrey M.; Lausier, Evangeline R.; Gaudet, Tracy W.

2013-01-01

Background Stroke, diabetes, and coronary heart disease (CHD) remain leading causes of death in the United States and are largely attributable to lifestyle behaviors. Integrative medicine can provide a supportive partnership that focuses on improving health by identifying and implementing lifestyle changes based upon personal values and goals. Objective This prospective observational study was designed to assess the effectiveness of an integrative medicine intervention on modifiable disease risk, patient activation, and psychosocial risk factors for stroke, diabetes, and CHD. Design Sixty-three adults participated in a 3-day comprehensive, multimodal health immersion program at Duke Integrative Medicine, Duke University Medical Center, Durham, North Carolina. Participants received follow-up education, physician support, and telephonic health coaching between the immersion program and the endpoint 7 to 9 months later. Primary Outcome Measures Psychosocial functioning, read iness to change health behaviors, and risk of developing diabetes, stroke, and CHD were assessed at baseline and endpoint. Results Although cardiac risk remained unchanged (P = .19) during the study period, risk of diabetes (P = .02) and stroke (P < .01) decreased significantly. Perceived stress remained unchanged, but improvements were seen in mood (P < .05) and relationship satisfaction (P < .004). Patients became more activated towards self-management of health (P <.001), endorsed greater readiness to change health behaviors (P <.01), and reported increased aerobic exercise (P <.001) and stretching (P = .006) following the intervention. Conclusion An integrative health model can help patients become more engaged in self-management of health and support them in making and maintaining healthy lifestyle changes. These findings provide support for use of an integrative health model in adult disease risk reduction. PMID:22314632

Detection of Genetically Modified Food: Has Your Food Been Genetically Modified?

ERIC Educational Resources Information Center

Brandner, Diana L.

2002-01-01

Explains the benefits and risks of genetically-modified foods and describes methods for genetically modifying food. Presents a laboratory experiment using a polymerase chain reaction (PCR) test to detect foreign DNA in genetically-modified food. (Contains 18 references.) (YDS)

A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.

PubMed

Lee, Alice W; Bomkamp, Ashley; Bandera, Elisa V; Jensen, Allan; Ramus, Susan J; Goodman, Marc T; Rossing, Mary Anne; Modugno, Francesmary; Moysich, Kirsten B; Chang-Claude, Jenny; Rudolph, Anja; Gentry-Maharaj, Aleksandra; Terry, Kathryn L; Gayther, Simon A; Cramer, Daniel W; Doherty, Jennifer A; Schildkraut, Joellen M; Kjaer, Susanne K; Ness, Roberta B; Menon, Usha; Berchuck, Andrew; Mukherjee, Bhramar; Roman, Lynda; Pharoah, Paul D; Chenevix-Trench, Georgia; Olson, Sara; Hogdall, Estrid; Wu, Anna H; Pike, Malcolm C; Stram, Daniel O; Pearce, Celeste Leigh

2016-12-15

Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non-users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (p int  = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users of 10+ years (OR = 1.85, 95% CI 1.28-2.66, p int  = 0.034). Non-users showed essentially no association (OR = 1.08, 95% CI 0.96-1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (p int  = 0.021 and p int  = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci. © 2016 UICC.

What are the real risks of sport-related concussion, and are they modifiable?

PubMed

Randolph, Christopher; Kirkwood, Michael W

2009-07-01

Over the past two decades, the management of sport-related concussion has been the topic of increased attention in the scientific literature and in the popular media. Despite a proliferation of competing guidelines for concussion management, the widespread use of neuropsychological "baseline" testing designed to monitor postinjury recovery, and several prospective controlled studies of the natural history of concussion, there has been virtually no attempt to quantify the risks associated with sport-related concussion or to determine whether these risks are modifiable via management strategies. Using American football as a model, the short- and long-term risks of sport-related concussion are reviewed. It is concluded that serious short-term consequences of sport-related concussion are extremely rare and unlikely to be significantly modified via management strategies that rely on baseline testing. Other less serious short-term adverse outcomes are also quite rare, transient, and not likely to be altered by specific management guidelines. The long-term consequences of multiple sport-related head trauma remain unclear but are potentially of greater public health concern and should be the focus of increased research. Based on available evidence, there is little rationale for the use of rigid strategies or guidelines in the place of individual clinical decision-making in the management of these injuries.

Identifying Objective Physiological Markers and Modifiable Behaviors for Self-Reported Stress and Mental Health Status Using Wearable Sensors and Mobile Phones: Observational Study.

PubMed

Sano, Akane; Taylor, Sara; McHill, Andrew W; Phillips, Andrew Jk; Barger, Laura K; Klerman, Elizabeth; Picard, Rosalind

2018-06-08

Wearable and mobile devices that capture multimodal data have the potential to identify risk factors for high stress and poor mental health and to provide information to improve health and well-being. We developed new tools that provide objective physiological and behavioral measures using wearable sensors and mobile phones, together with methods that improve their data integrity. The aim of this study was to examine, using machine learning, how accurately these measures could identify conditions of self-reported high stress and poor mental health and which of the underlying modalities and measures were most accurate in identifying those conditions. We designed and conducted the 1-month SNAPSHOT study that investigated how daily behaviors and social networks influence self-reported stress, mood, and other health or well-being-related factors. We collected over 145,000 hours of data from 201 college students (age: 18-25 years, male:female=1.8:1) at one university, all recruited within self-identified social groups. Each student filled out standardized pre- and postquestionnaires on stress and mental health; during the month, each student completed twice-daily electronic diaries (e-diaries), wore two wrist-based sensors that recorded continuous physical activity and autonomic physiology, and installed an app on their mobile phone that recorded phone usage and geolocation patterns. We developed tools to make data collection more efficient, including data-check systems for sensor and mobile phone data and an e-diary administrative module for study investigators to locate possible errors in the e-diaries and communicate with participants to correct their entries promptly, which reduced the time taken to clean e-diary data by 69%. We constructed features and applied machine learning to the multimodal data to identify factors associated with self-reported poststudy stress and mental health, including behaviors that can be possibly modified by the individual to improve

Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide—An Overview

PubMed Central

Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

2017-01-01

People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment tools. PMID:28257103

Framing alters risk-taking behavior on a modified Balloon Analogue Risk Task (BART) in a sex-specific manner.

PubMed

Gabriel, Kara I; Williamson, Ashley

2010-12-01

Framing uncertain scenarios to emphasize potential positive or negative elements influences decision making and behavior. The current experiment investigated sex differences in framing effects on risk-taking propensity in a modified version of the Balloon Analogue Risk Task (BART). Male and female undergraduates completed questionnaires on sensation seeking, impulsiveness, and risk and benefit perception prior to viewing one of three framing conditions for the BART: (1) positively-framed instructions emphasizing the ability to earn money if balloons were inflated to large size; (2) negatively framed instructions emphasizing the possibility that money could be lost if balloons were inflated to bursting; and (3) completely framed instructions noting both possible outcomes. Results revealed correlations between BART performance and impulsiveness for both sexes. Compared to positive and complete framing, negatively framed instructions decreased balloon inflation time in women but not men, indicating sex differences in response to treatments designed to alter risk-taking behavior.

Modified creatinine index and risk for cardiovascular events and all-cause mortality in patients undergoing hemodialysis: The Q-Cohort study.

PubMed

Arase, Hokuto; Yamada, Shunsuke; Yotsueda, Ryusuke; Taniguchi, Masatomo; Yoshida, Hisako; Tokumoto, Masanori; Nakano, Toshiaki; Tsuruya, Kazuhiko; Kitazono, Takanari

2018-06-02

The modified creatinine (Cr) index, calculated by age, sex, pre-dialysis serum Cr levels, and Kt/V for urea, reflects skeletal muscle mass in patients on hemodialysis. Whether the modified Cr index is associated with cardiovascular events and all-cause mortality remains unknown. A total of 3027 patients registered in the Q-Cohort Study, a multicenter, prospective study of patients on hemodialysis in Japan, were analyzed. The main outcomes were cardiovascular events and all-cause mortality. Associations between sex-specific quartiles of the modified Cr index and outcomes were analyzed by the Cox proportional hazard models and the Fine-Gray proportional subdistribution hazards model. The modified Cr index was correlated with known nutritional and inflammatory markers. During a 4-year follow-up, 499 patients died of any cause, 372 experienced heart disease, and 194 developed stroke. The risk for all-cause mortality was significantly higher in the lower quartiles (Q1 and Q2) than in the highest quartile (Q4) as the reference group (hazard ratios and 95% confidence intervals: Q1, 2.65 [1.69-4.25], Q2, 1.92 [1.27-2.94], and Q3, 1.31 [0.87-2.02]). The risk of heart disease was significantly higher in Q1 than in Q4 (hazard ratios and 95% confidence intervals: Q1, 1.64 [1.04-2.61], Q2, 1.34 [0.91-2.00], and Q3, 1.04 [0.71-1.52]). The risk of stroke was not associated with the modified Cr index. A lower modified Cr index is associated with an increased risk for heart disease and all-cause mortality, but not with the risk for stroke in patients on hemodialysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Unconventional P-35S sequence identified in genetically modified maize

PubMed Central

Al-Hmoud, Nisreen; Al-Husseini, Nawar; Ibrahim-Alobaide, Mohammed A; Kübler, Eric; Farfoura, Mahmoud; Alobydi, Hytham; Al-Rousan, Hiyam

2014-01-01

The Cauliflower Mosaic Virus 35S promoter sequence, CaMV P-35S, is one of several commonly used genetic targets to detect genetically modified maize and is found in most GMOs. In this research we report the finding of an alternative P-35S sequence and its incidence in GM maize marketed in Jordan. The primer pair normally used to amplify a 123 bp DNA fragment of the CaMV P-35S promoter in GMOs also amplified a previously undetected alternative sequence of CaMV P-35S in GM maize samples which we term V3. The amplified V3 sequence comprises 386 base pairs and was not found in the standard wild-type maize, MON810 and MON 863 GM maize. The identified GM maize samples carrying the V3 sequence were found free of CaMV when compared with CaMV infected brown mustard sample. The data of sequence alignment analysis of the V3 genetic element showed 90% similarity with the matching P-35S sequence of the cauliflower mosaic virus isolate CabbB-JI and 99% similarity with matching P-35S sequences found in several binary plant vectors, of which the binary vector locus JQ693018 is one example. The current study showed an increase of 44% in the incidence of the identified 386 bp sequence in GM maize sold in Jordan’s markets during the period 2009 and 2012. PMID:24495911

Identifying Home Care Clinicians’ Information Needs for Managing Fall Risks

PubMed Central

Alhuwail, Dari

2016-01-01

Summary Objectives To help manage the risk of falls in home care, this study aimed to (i) identify home care clinicians’ information needs and how they manage missing or inaccurate data, (ii) identify problems that impact effectiveness and efficiency associated with retaining, exchanging, or processing information about fall risks in existing workflows and currently adopted health information technology (IT) solutions, and (iii) offer informatics-based recommendations to improve fall risk management interventions. Methods A case study was carried out in a single not-for-profit suburban Medicare-certified home health agency with three branches. Qualitative data were collected over a six month period through observations, semi-structured interviews, and focus groups. The Framework method was used for analysis. Maximum variation sampling was adopted to recruit a diverse sample of clinicians. Results Overall, the information needs for fall risk management were categorized into physiological, care delivery, educational, social, environmental, and administrative domains. Examples include a brief fall-related patient history, weight-bearing status, medications that affect balance, availability of caregivers at home, and the influence of patients’ cultures on fall management interventions. The unavailability and inaccuracy of critical information related to fall risks can delay necessary therapeutic services aimed at reducing patients’ risk for falling and thereby jeopardizing their safety. Currently adopted IT solutions did not adequately accommodate data related to fall risk management. Conclusion The results highlight the essential information for fall risk management in home care. Home care workflows and health IT solutions must effectively and efficiently retain, exchange, and process information necessary for fall risk management. Interoperability and integration of the various health IT solutions to make data sharing accessible to all clinicians is critical

Diastolic blood pressure is a potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes.

PubMed

Nørgaard, Sidse Kjærhus; Vestgaard, Marianne Jenlev; Jørgensen, Isabella Lindegaard; Ásbjörnsdóttir, Björg; Ringholm, Lene; McIntyre, Harold David; Damm, Peter; Mathiesen, Elisabeth Reinhardt

2018-04-01

To identify early clinical, modifiable risk factors for preeclampsia present at first antenatal visit and assess the prevalence of pregnancy-related hypertensive disorders in women with pre-existing diabetes treated with tight glycemic and blood pressure (BP) control. A population-based cohort study of 494 women with pre-existing diabetes (307 and 187 women with type 1 and type 2 diabetes, respectively), included at their first antenatal visit from 2012 to 2016. The prevalence of chronic hypertension (without diabetic nephropathy or microalbuminuria), gestational hypertension and preeclampsia was recorded. Diabetic microangiopathy included presence of nephropathy, microalbuminuria and/or retinopathy. Treatment target was BP <135/85 mmHg. HbA1c was 6.9 ± 2.4% (50 ± 12 mmol/mol) at first antenatal visit and 6.0 ± 0.6% (43 ± 6 mmol/mol) before delivery with no differences between women with type 1 and type 2 diabetes. At the first antenatal visit, the prevalence of microalbuminuria was 6% (6% vs. 6%), nephropathy 2% (1% vs. 2%) and chronic hypertension 6% (3% vs. 10%, p = 0.03). Gestational hypertension developed in 8% (9% vs. 6%) and preeclampsia developed in 8% (9% vs. 7%). Presence of diabetic microangiopathy (adjusted odds ratio (OR) 4.35 (confidence interval 2.12-8.93)) and diastolic BP (adjusted OR 1.72 per 10 mmHg (1.05-2.82)) at the first antenatal visit were independent risk factors for preeclampsia. At the first antenatal visit, diastolic BP was the only independent, potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes in the context of tight glycemic and BP control. One out of four women had hypertensive disorders during pregnancy. Copyright © 2018 Elsevier B.V. All rights reserved.

Periodontitis as a Modifiable Risk Factor for Dementia: A Nationwide Population-Based Cohort Study.

PubMed

Lee, Yao-Tung; Lee, Hsin-Chien; Hu, Chaur-Jongh; Huang, Li-Kai; Chao, Shu-Ping; Lin, Chia-Pei; Su, Emily Chia-Yu; Lee, Yi-Chen; Chen, Chu-Chieh

2017-02-01

To determine whether periodontitis is a modifiable risk factor for dementia. Prospective cohort study. National Health Insurance Research Database in Taiwan. Individuals aged 65 and older with periodontitis (n = 3,028) and an age- and sex-matched control group (n = 3,028). Individuals with periodontitis were compared age- and sex-matched controls with for incidence density and hazard ratio (HR) of new-onset dementia. Periodontitis was defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 diagnosed by dentists. To ensure diagnostic validity, only those who had concurrently received antibiotic therapies, periodontal treatment other than scaling, or scaling more than twice per year performed by certified dentists were included. Dementia was defined according to ICD-9-CM codes 290.0-290.4, 294.1, 331.0-331.2. After adjustment for confounding factors, the risk of developing dementia was calculated to be higher for participants with periodontitis (HR = 1.16, 95% confidence interval = 1.01-1.32, P = .03) than for those without. Periodontitis is associated with greater risk of developing dementia. Periodontal infection is treatable, so it might be a modifiable risk factor for dementia. Clinicians must devote greater attention to this potential association in an effort to develop new preventive and therapeutic strategies for dementia. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Trends in Modifiable Risk Factors Are Associated With Declining Incidence of Hospitalized and Nonhospitalized Acute Coronary Heart Disease in a Population.

PubMed

Mannsverk, Jan; Wilsgaard, Tom; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Rasmussen, Knut; Thelle, Dag S; Njølstad, Inger; Hopstock, Laila Arnesdatter; Bønaa, Kaare Harald

2016-01-05

Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors. We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48-97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively. We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events. © 2015 American Heart Association, Inc.

Incidence of neonatal hypoglycemia in babies identified as at risk.

PubMed

Harris, Deborah L; Weston, Philip J; Harding, Jane E

2012-11-01

Routine blood glucose screening is recommended for babies at risk of neonatal hypoglycemia. However, the incidence of hypoglycemia in those screened is not well described. We sought to determine the incidence of hypoglycemia in babies identified as being at risk, and also to determine differences in incidence between at risk groups. Infants (n = 514) were recruited who were born in a tertiary hospital, ≥35 weeks gestation and identified as at risk of hypoglycemia (small, large, infant of a diabetic, late-preterm, and other). Blood glucose screening used a standard protocol and a glucose oxidase method of glucose measurement in the first 48 hours after birth. One-half of the babies (260/514, 51%) became hypoglycemic (<2.6 mM), 97 (19%) had severe hypoglycemia (≤2.0 mM), and 98 (19%) had more than 1 episode. The mean duration of an episode was 1.4 hours. Most episodes (315/390, 81%) occurred in the first 24 hours. The median number of blood glucose measurements for each baby was 9 (range 1-22). The incidence and timing of hypoglycemia was similar in all at risk groups, but babies with a total of 3 risk factors were more likely to have severe hypoglycemia. Hypoglycemia is common amongst babies recommended for routine blood glucose screening. We found no evidence that screening protocols should differ in different at risk groups, but multiple risk factors may increase severity. The significance of these hypoglycemic episodes for long-term outcome remains undetermined. Copyright © 2012 Mosby, Inc. All rights reserved.

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

PubMed

Fox, A S; Bonacci, J; McLean, S G; Saunders, N

2017-05-01

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In Search of Black Swans: Identifying Students at Risk of Failing Licensing Examinations.

PubMed

Barber, Cassandra; Hammond, Robert; Gula, Lorne; Tithecott, Gary; Chahine, Saad

2018-03-01

To determine which admissions variables and curricular outcomes are predictive of being at risk of failing the Medical Council of Canada Qualifying Examination Part 1 (MCCQE1), how quickly student risk of failure can be predicted, and to what extent predictive modeling is possible and accurate in estimating future student risk. Data from five graduating cohorts (2011-2015), Schulich School of Medicine & Dentistry, Western University, were collected and analyzed using hierarchical generalized linear models (HGLMs). Area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of predictive models and determine whether they could be used to predict future risk, using the 2016 graduating cohort. Four predictive models were developed to predict student risk of failure at admissions, year 1, year 2, and pre-MCCQE1. The HGLM analyses identified gender, MCAT verbal reasoning score, two preclerkship course mean grades, and the year 4 summative objective structured clinical examination score as significant predictors of student risk. The predictive accuracy of the models varied. The pre-MCCQE1 model was the most accurate at predicting a student's risk of failing (AUC 0.66-0.93), while the admissions model was not predictive (AUC 0.25-0.47). Key variables predictive of students at risk were found. The predictive models developed suggest, while it is not possible to identify student risk at admission, we can begin to identify and monitor students within the first year. Using such models, programs may be able to identify and monitor students at risk quantitatively and develop tailored intervention strategies.

Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015.

PubMed

Bulage, Lilian; Masiira, Ben; Ario, Alex R; Matovu, Joseph K B; Nsubuga, Peter; Kaharuza, Frank; Nankabirwa, Victoria; Routh, Janell; Zhu, Bao-Ping

2017-09-25

Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (OR adj  = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (OR adj  = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (OR adj  = 9.0, 95%CI = 1.1-78). Delay in seeking treatment increased the risk of TIPs

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

PubMed Central

Feldman, Amy S.; He, Yuan; Moore, Martin L.; Hershenson, Marc B.

2015-01-01

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts. PMID:25369458

Food Allergy - Basic Mechanisms and Applications to Identifying Risks Associated with Plant Incorporated Pesticides and Other Genetically Modified Crops

EPA Science Inventory

Food allergy is a relatively new concern for toxicologists as a result of the incorporation of novel proteins into food crops in order to promote resistance to pests and other stresses, improve nutrition, or otherwise modify the phenotype. Food allergy can manifest as inflammatio...

Characterizing Stressors and Modifiable Health Risk Factors among Homeless Smokers: An Exploratory Pilot Study

ERIC Educational Resources Information Center

Kendzor, Darla E.; Reitzel, Lorraine R.; Businelle, Michael S.

2015-01-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were…

Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

PubMed

Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

2017-03-01

To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely

Trends in major modifiable risk factors for severe perineal trauma, 1996-2006.

PubMed

Kudish, Bela; Sokol, Robert J; Kruger, Michael

2008-08-01

To examine what effect the major modifiable risk factors for severe perineal trauma have had on the rates of this trauma over time. A retrospective observational cohort study of singleton vaginal deliveries taken from a perinatal database for the period 1996 through 2006. A total of 46,239 singleton vertex vaginal deliveries met the inclusion criteria. Major risk factors for severe perineal trauma were increased maternal age (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.1-1.5), non-African American ethnicity (OR 1.5, 95% CI 1.3-1.7), nulliparity (OR 4.8, 95% CI 4.11-5.6), fetal birth weight (OR 2.2, 95% CI 1.9-2.4), forceps (OR 8.3, 95% CI 5.4-10.8), vacuum (OR 2.9, 95% CI 1.9-4.4), and midline episiotomy (OR 5.7, 95% CI 5.0-6.4). Evaluation of the changes in rates of these factors over the study period revealed that the decline in the rates of episiotomy and the use of forceps accounted for a reduction in severe lacerations of more than 50%. Reduction of severe perineal trauma by restricted use of the 2 modifiable clinical variables, episiotomy and forceps, is evident over time.

Prioritizing stream types according to their potential risk to receive crop plant material--A GIS-based procedure to assist in the risk assessment of genetically modified crops and systemic insecticide residues.

PubMed

Bundschuh, Rebecca; Kuhn, Ulrike; Bundschuh, Mirco; Naegele, Caroline; Elsaesser, David; Schlechtriemen, Ulrich; Oehen, Bernadette; Hilbeck, Angelika; Otto, Mathias; Schulz, Ralf; Hofmann, Frieder

2016-03-15

Crop plant residues may enter aquatic ecosystems via wind deposition or surface runoff. In the case of genetically modified crops or crops treated with systemic pesticides, these materials may contain insecticidal Bt toxins or pesticides that potentially affect aquatic life. However, the particular exposure pattern of aquatic ecosystems (i.e., via plant material) is not properly reflected in current risk assessment schemes, which primarily focus on waterborne toxicity and not on plant material as the route of uptake. To assist in risk assessment, the present study proposes a prioritization procedure of stream types based on the freshwater network and crop-specific cultivation data using maize in Germany as a model system. To identify stream types with a high probability of receiving crop materials, we developed a formalized, criteria-based and thus transparent procedure that considers the exposure-related parameters, ecological status--an estimate of the diversity and potential vulnerability of local communities towards anthropogenic stress--and availability of uncontaminated reference sections. By applying the procedure to maize, ten stream types out of 38 are expected to be the most relevant if the ecological effects from plant-incorporated pesticides need to be evaluated. This information is an important first step to identifying habitats within these stream types with a high probability of receiving crop plant material at a more local scale, including accumulation areas. Moreover, the prioritization procedure developed in the present study may support the selection of aquatic species for ecotoxicological testing based on their probability of occurrence in stream types having a higher chance of exposure. Finally, this procedure can be adapted to any geographical region or crop of interest and is, therefore, a valuable tool for a site-specific risk assessment of crop plants carrying systemic pesticides or novel proteins, such as insecticidal Bt toxins, expressed

Development of a claims-based risk score to identify obese individuals.

PubMed

Clark, Jeanne M; Chang, Hsien-Yen; Bolen, Shari D; Shore, Andrew D; Goodwin, Suzanne M; Weiner, Jonathan P

2010-08-01

Obesity is underdiagnosed, hampering system-based health promotion and research. Our objective was to develop and validate a claims-based risk model to identify obese persons using medical diagnosis and prescription records. We conducted a cross-sectional analysis of de-identified claims data from enrollees of 3 Blue Cross Blue Shield plans who completed a health risk assessment capturing height and weight. The final sample of 71,057 enrollees was randomly split into 2 subsamples for development and validation of the obesity risk model. Using the Johns Hopkins Adjusted Clinical Groups case-mix/predictive risk methodology, we categorized study members' diagnosis (ICD) codes. Logistic regression was used to determine which claims-based risk markers were associated with a body mass index (BMI) > or = 35 kg/m(2). The sensitivities of the scores > or =90(th) percentile to detect obesity were 26% to 33%, while the specificities were >90%. The areas under the receiver operator curve ranged from 0.67 to 0.73. In contrast, a diagnosis of obesity or an obesity medication alone had very poor sensitivity (10% and 1%, respectively); the obesity risk model identified an additional 22% of obese members. Varying the percentile cut-point from the 70(th) to the 99(th) percentile resulted in positive predictive values ranging from 15.5 to 59.2. An obesity risk score was highly specific for detecting a BMI > or = 35 kg/m(2) and substantially increased the detection of obese members beyond a provider-coded obesity diagnosis or medication claim. This model could be used for obesity care management and health promotion or for obesity-related research.

Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies.

PubMed

Sharpe, Richard A; Cocq, Kate Le; Nikolaou, Vasilis; Osborne, Nicholas J; Thornton, Christopher R

2016-01-01

The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of diet- and lifestyle-based metabolic risk-modifying interventions on preeclampsia: a meta-analysis.

PubMed

Allen, Rebecca; Rogozinska, Ewelina; Sivarajasingam, Priya; Khan, Khalid S; Thangaratinam, Shakila

2014-10-01

To evaluate the effect of dietary and lifestyle interventions with the potential to modify metabolic risk factors on the risk of preeclampsia. We searched MEDLINE, EMBASE and Cochrane from inception until February 2013. Randomized trials in pregnant women evaluating the effect of dietary and lifestyle interventions with the potential to modify metabolic risks such as obesity, hyperlipidemia, hyperglycemia and hypertension on the risk of preeclampsia were included. Two independent reviewers selected studies, extracted data and assessed quality. Results were summarized as pooled relative risks (RR) for dichotomous data. Eighteen studies (8712 women) met our search criteria for inclusion. Six studies evaluated diet (2695 women), six studied mixed interventions with diet, physical activity and lifestyle (1438 women) and six assessed essential fatty acid supplementation (4579 women). The interventions overall reduced the risk of preeclampsia (RR 0.81, 95% CI 0.69-0.94; p = 0.006 I(2) = 0%) compared with the control group. Dietary interventions reduced the risk of preeclampsia by 33% (RR 0.67, 95% CI 0.53-0.85; p = 0.001; I(2) = 0%). There was no reduction in the risk of preeclampsia with mixed interventions (RR 0.93, 95% CI 0.66-1.32, p = 0.68, I(2) = 0%) or fatty acid supplementation (RR 0.92, 95% CI 0.71-1.18; p = 0.49, I(2) = 15%). Meta-regression showed a borderline impact of gestational diabetes status (p = 0.05) on the observed effect. Dietary and lifestyle interventions have the potential to reduce the risk of preeclampsia. The effect of additional therapeutic interventions in women with gestational diabetes mellitus on preeclampsia is not known. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

PubMed

Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

2017-01-01

Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10 -6 ). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

Can subsyndromal manifestations of major depression be identified in children at risk?

PubMed

Uchida, M; Fitzgerald, M; Lin, K; Carrellas, N; Woodworth, H; Biederman, J

2017-02-01

Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder. The sample was derived from two previously conducted longitudinal case-control family studies of psychiatrically and pediatrically referred youth and their families. For this study, probands were stratified based on the presence or absence of a parental mood disorder. Subsyndromal scores on the CBCL Anxiety/Depression scale significantly separated the children at high risk for pediatric MDD from those at low risk in a variety of functional areas, including social and academic functioning. Additionally, children at genetic risk without elevated CBCL Anxiety/Depression scale scores were largely indistinguishable from controls. These results suggest that the CBCL Anxiety/Depression scale can help identify children at highest risk for pediatric MDD. If implemented clinically, this scale would cost-effectively screen children and identify those most in need of early intervention resources to impede the progression of depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modifiable Risk Factors for Marijuana Use Among Adolescents in a Youth Development Program

DTIC Science & Technology

2010-01-08

including: demographics, drug knowledge, cigarette smoking , alcohol use, access to marijuana and alcohol, disapproval of substance use, friends’ substance...strongest association with marijuana use was “ever smoked cigarettes ,” or lifetime cigarette use (OR = 30.17). After Modifiable Risk Factors for...most strongly associated with lifetime marijuana use (OR = 19.69) (Table 1). This result indicates that having ever smoked cigarettes greatly

Clinical tests performed in acute stroke identify the risk of falling during the first year: postural stroke study in Gothenburg (POSTGOT).

PubMed

Persson, Carina U; Hansson, Per-Olof; Sunnerhagen, Katharina S

2011-03-01

To assess the likelihood of clinical tests for postural balance, walking and motor skills, performed during the first week after stroke, identifying the risk of falling. Prospective study. Patients with first stroke. Assessments were carried out during the first week, and the occurrence of falls was recorded 3, 6 and 12 months after stroke onset. The tests used were: 10-Metre Walking Test (10MWT), Timed Up & Go, Swedish Postural Assessment Scale for Stroke Patients, Berg Balance Scale and Modified Motor Assessment Scale. Cut-off levels were obtained by receiver operation characteristic curves, and odds ratios were used to assess cut-off levels for falling. The analyses were based on 96 patients. Forty-eight percent had at least one fall during the first year. All tests were associated with the risk of falling. The highest predictive values were found for the 10MWT (positive predictive value 64%, negative predictive value 76%). Those subjects who were unable to perform the 10MWT had the highest odds ratio, 6.06 (95% confidence interval 2.66-13.84, p<0.001) of falling. Clinical tests used during the first week after stroke onset can, to some extent, identify those patients at risk of falling during the first year after stroke.

Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-03-01

While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major

Modifiable workplace risk factors contributing to workplace absence across health conditions: A stakeholder-centered best-evidence synthesis of systematic reviews.

PubMed

White, Marc; Wagner, Shannon; Schultz, Izabela Z; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

2013-01-01

A challenge facing stakeholders is the identification and translation of relevant high quality research to inform policy and practice. This study engaged academic and community stakeholders in conducting a best evidence-synthesis to enhance knowledge use. To identify modifiable workplace disability risk and protective factors across common health conditions impacting work-related absence. We searched MEDLINE, Embase, CINHAL, The Cochrane Library, PsycINFO, BusinessSourceComplete, and ABI/Inform from 2000 to 2011. Systematic reviews that employed quantitative, qualitative, or mixed methods of work-focused population were considered for inclusion. Two or more independent reviewers reviewed titles only, titles and abstracts, and/or full articles when assessing eligibility for inclusion. Selected articles underwent methodological screening. The search strategy, expert input and grey literature identified 2,467 unique records from which 142 full text articles underwent comprehensive review. Twenty-seven systematic reviews met eligibility criteria. Modifiable work factors found to have consistent evidence across two or more health conditions included lack of social support, increased physical demands at work, job strain, lack of supervisory support, increased psychological demands, low job satisfaction, low worker control of job, and poor leadership quality. The active engagement of stakeholders led to greater understanding of relevance of the study findings for community stakeholders and appreciation of the mutual benefits of collaboration.

The MAT-sf: identifying risk for major mobility disability.

PubMed

Rejeski, W Jack; Rushing, Julia; Guralnik, Jack M; Ip, Edward H; King, Abby C; Manini, Todd M; Marsh, Anthony P; McDermott, Mary M; Fielding, Roger A; Newman, Anne B; Tudor-Locke, Catrine; Gill, Thomas M

2015-05-01

The assessment of mobility is essential to both aging research and clinical geriatric practice. A newly developed self-report measure of mobility, the mobility assessment tool-short form (MAT-sf), uses video animations as an innovative method to improve measurement accuracy/precision. The primary aim of the current study was to evaluate whether MAT-sf scores can be used to identify risk for major mobility disability (MMD). This article is based on data collected from the Lifestyle Interventions and Independence for Elders study and involved 1,574 older adults between the ages of 70-89. The MAT-sf was administered at baseline; MMD, operationalized as failure to complete the 400-m walk ≤ 15 minutes, was evaluated at 6-month intervals across a period of 42 months. The outcome of interest was the first occurrence of MMD or incident MMD. After controlling for age, sex, clinic site, and treatment arm, baseline MAT-sf scores were found to be effective in identifying risk for MMD (p < .0001). Partitioning the MAT-sf into four groups revealed that persons with scores <40, 40-49, 50-59, and 60+ had failure rates across 42 months of follow-up of 66%, 52%, 35%, and 22%, respectively. The MAT-sf is a quick and efficient way of identifying older adults at risk for MMD. It could be used to clinically identify older adults that are in need of intervention for MMD and provides a simple means for monitoring the status of patients' mobility, an important dimension of functional health. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A modified Leslie-Gower predator-prey interaction model and parameter identifiability

NASA Astrophysics Data System (ADS)

Tripathi, Jai Prakash; Meghwani, Suraj S.; Thakur, Manoj; Abbas, Syed

2018-01-01

In this work, bifurcation and a systematic approach for estimation of identifiable parameters of a modified Leslie-Gower predator-prey system with Crowley-Martin functional response and prey refuge is discussed. Global asymptotic stability is discussed by applying fluctuation lemma. The system undergoes into Hopf bifurcation with respect to parameters intrinsic growth rate of predators (s) and prey reserve (m). The stability of Hopf bifurcation is also discussed by calculating Lyapunov number. The sensitivity analysis of the considered model system with respect to all variables is performed which also supports our theoretical study. To estimate the unknown parameter from the data, an optimization procedure (pseudo-random search algorithm) is adopted. System responses and phase plots for estimated parameters are also compared with true noise free data. It is found that the system dynamics with true set of parametric values is similar to the estimated parametric values. Numerical simulations are presented to substantiate the analytical findings.

Genetic ancestry modifies the association between genetic risk variants and breast cancer risk among Hispanic and non-Hispanic white women

PubMed Central

Fejerman, Laura

2013-01-01

Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case–control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50–1.15] for low IA ancestry and 1.38 (95% CI = 1.04–1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59–1.29) and 1.69 (95% CI = 1.04–2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42–1.31) and 1.73 (95% CI = 1.19–2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations. PMID:23563089

Identifying environmental risk factors and mapping the risk of human West Nile virus in South Dakota.

NASA Astrophysics Data System (ADS)

Hess, A.; Davis, J. K.; Wimberly, M. C.

2017-12-01

Human West Nile virus (WNV) first arrived in the USA in 1999 and has since then spread across the country. Today, the highest incidence rates are found in the state of South Dakota. The disease occurrence depends on the complex interaction between the mosquito vector, the bird host and the dead-end human host. Understanding the spatial domain of this interaction and being able to identify disease transmission hotspots is crucial for effective disease prevention and mosquito control. In this study we use geospatial environmental information to understand what drives the spatial distribution of cases of human West Nile virus in South Dakota and to map relative infection risk across the state. To map the risk of human West Nile virus in South Dakota, we used geocoded human case data from the years 2004-2016. Satellite data from the Landsat ETM+ and MODIS for the years 2003 to 2016 were used to characterize environmental patterns. From these datasets we calculated indices, such as the normalized differenced vegetation index (NDVI) and the normalized differenced water index (NDWI). In addition, datasets such as the National Land Data Assimilation System (NLDAS), National Land Cover Dataset (NLCD), National Wetland inventory (NWI), National Elevation Dataset (NED) and Soil Survey Geographic Database (SSURGO) were utilized. Environmental variables were summarized for a buffer zone around the case and control points. We used a boosted regression tree model to identify the most important variables describing the risk of WNV infection. We generated a risk map by applying this model across the entire state. We found that the highest relative risk is present in the James River valley in northeastern South Dakota. Factors that were identified as influencing the transmission risk include inter-annual variability of vegetation cover, water availability and temperature. Land covers such as grasslands, low developed areas and wetlands were also found to be good predictors for human

Identifying At-Risk Students in General Chemistry via Cluster Analysis of Affective Characteristics

ERIC Educational Resources Information Center

Chan, Julia Y. K.; Bauer, Christopher F.

2014-01-01

The purpose of this study is to identify academically at-risk students in first-semester general chemistry using affective characteristics via cluster analysis. Through the clustering of six preselected affective variables, three distinct affective groups were identified: low (at-risk), medium, and high. Students in the low affective group…

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

PubMed

Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

2011-06-01

Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts

PubMed Central

Casso, David J.; Liu, Songmei; Iwaki, D. David; Ogden, Stacey K.; Kornberg, Thomas B.

2008-01-01

Signaling by Hedgehog (Hh) proteins shapes most tissues and organs in both vertebrates and invertebrates, and its misregulation has been implicated in many human diseases. Although components of the signaling pathway have been identified, key aspects of the signaling mechanism and downstream targets remain to be elucidated. We performed an enhancer/suppressor screen in Drosophila to identify novel components of the pathway and identified 26 autosomal regions that modify a phenotypic readout of Hh signaling. Three of the regions include genes that contribute constituents to the pathway—patched, engrailed, and hh. One of the other regions includes the gene microtubule star (mts) that encodes a subunit of protein phosphatase 2A. We show that mts is necessary for full activation of Hh signaling. A second region includes the gene second mitotic wave missing (swm). swm is recessive lethal and is predicted to encode an evolutionarily conserved protein with RNA binding and Zn+ finger domains. Characterization of newly isolated alleles indicates that swm is a negative regulator of Hh signaling and is essential for cell polarity. PMID:18245841

Sleep Duration Modifies the Association of Overtime Work With Risk of Developing Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

PubMed

Kuwahara, Keisuke; Imai, Teppei; Miyamoto, Toshiaki; Kochi, Takeshi; Eguchi, Masafumi; Nishihara, Akiko; Nakagawa, Tohru; Yamamoto, Shuichiro; Honda, Toru; Kabe, Isamu; Mizoue, Tetsuya; Dohi, Seitaro

2018-02-03

Evidence linking working hours and the risk of type 2 diabetes mellitus (T2DM) is limited and inconsistent in Asian populations. No study has addressed the combined association of long working hours and sleep deprivation on T2DM risk. We investigated the association of baseline overtime work with T2DM risk and assessed whether sleep duration modified the effect among Japanese. Participants were Japanese employees (28,489 men and 4,561 women) aged 30-64 years who reported overtime hours and had no history of diabetes at baseline (mostly in 2008). They were followed up until March 2014. New-onset T2DM was identified using subsequent checkup data, including measurement of fasting/random plasma glucose, glycated hemoglobin, and self-report of medical treatment. Hazard ratios (HRs) of T2DM were estimated using Cox regression analysis. The combined association of sleep duration and working hours was examined in a subgroup of workers (n = 27,590). During a mean follow-up period of 4.5 years, 1,975 adults developed T2DM. Overtime work was not materially associated with T2DM risk. In subgroup analysis, however, long working hours combined with insufficient sleep were associated with a significantly higher risk of T2DM (HR 1.42; 95% CI, 1.11-1.83), whereas long working hours with sufficient sleep were not (HR 0.99; 95% CI, 0.88-1.11) compared with the reference (<45 hours of overtime with sufficient sleep). Sleep duration modified the association of overtime work with the risk of developing T2DM. Further investigations to elucidate the long-term effect of long working hours on glucose metabolism are warranted.

Identifying children at risk for type 2 diabetes in underserved communities.

PubMed

Vivian, Eva M; Carrel, Aaron L; Becker, Tara

2011-01-01

The purpose of this study was to identify and assess health behaviors among ethnic minority children at high risk for type 2 diabetes. Diabetes screenings were conducted at community centers, churches, and local neighborhood health fairs in Madison, Wisconsin. During these events, diabetes risk assessment surveys were given to parents of children between the ages of 10 to 19 years. Parents who identified their children as having 2 or more risk factors for type 2 diabetes were invited to have their child screened for type 2 diabetes. A total of 86 children between the ages of 10 to 19 years (mean age = 13; 58% male) were screened for diabetes. Fifty-one percent of the children were overweight or obese with 38% having >3 risk factors for type 2 diabetes. While there was no significant difference in the nutritional habits reported between normal, overweight, or obese children, fewer overweight and obese children reported exercising at least 30 minutes 5 to 7 days a week compared to children with a normal weight (P = .033). Prevention of diabetes is a powerful public health intervention. Targeted diabetes screening in disadvantaged, underserved communities is an effective way to identify families with children at risk for type 2 diabetes. In addition, information obtained from these screenings can assist researchers and clinicians in designing accessible and affordable health promotion interventions that are culturally relevant to the youth and families within the community.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

PubMed Central

McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

2011-01-01

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

Modifiable risk factor levels of coronary heart disease survivors in a middle-aged workforce.

PubMed

Metcalf, P A; Scragg, R K; Swinburn, B

1999-06-01

Coronary heart disease (CHD) is common in New Zealand. Risk factors for CHD are modifiable or non-modifiable. Modifiable risk factor levels of CHD survivors were compared with those without such a history (non-CHD). Participants were from a cross-sectional survey of 5,656 workers aged > or = 40. CHD survivors were 73 general practitioner (GP)-confirmed participants with a history of hospitalisation for CHD. There were no significant differences in mean blood pressure levels between CHD survivors and non-CHD workers after adjusting for age, gender and ethnicity, but current use of antihypertensive medications was higher in CHD survivors (34.2%) than non-CHD workers (8.1%); p < 0.001. CHD survivors had higher, similarly adjusted, mean serum total cholesterol, triglyceride and lower HDL-cholesterol levels, and their reported carbohydrate, fibre, polyunsaturated fat intakes and ratio of polyunsaturated to saturated fat intakes were higher and total fat, saturated fat and monounsaturated fat intakes were lower. CHD survivors ate fewer servings of red meats per month and more servings of fruit, and cereal, and number of cups of milk. Salt added to meals was lower and margarine use higher in CHD survivors. There were no significant differences in the proportions of those who exercised regularly, or were current cigarette smokers. However, more CHD survivors (57.5%) than non-CHD workers (33.1%) were ex-smokers p < 0.001, who had stopped smoking at a higher mean (se) age (41.1 (1.36) vs 37.6 (0.20) years respectively; p = 0.012). A large proportion of CHD survivors were dyslipidaemic, despite consuming a lower fat, higher fibre and carbohydrate diet. More than 50% of CHD survivors were ex-cigarette smokers, who had given up smoking at a later age than non-CHD workers. These high-risk CHD survivors would benefit from more aggressive measures aimed at correcting their dyslipidaemias.

Selection of focal earthworm species as non-target soil organisms for environmental risk assessment of genetically modified plants.

PubMed

van Capelle, Christine; Schrader, Stefan; Arpaia, Salvatore

2016-04-01

By means of a literature survey, earthworm species of significant relevance for soil functions in different biogeographical regions of Europe (Atlantic, Boreal, Mediterranean) were identified. These focal earthworm species, defined here according to the EFSA Guidance Document on the environmental risk assessment (ERA) of genetically modified plants, are typical for arable soils under crop rotations with maize and/or potatoes within the three regions represented by Ireland, Sweden and Spain, respectively. Focal earthworm species were selected following a matrix of four steps: Identification of functional groups, categorization of non-target species, ranking species on ecological criteria, and final selection of focal species. They are recommended as appropriate non-target organisms to assess environmental risks of genetically modified (GM) crops; in this case maize and potatoes. In total, 44 literature sources on earthworms in arable cropping systems including maize or potato from Ireland, Sweden and Spain were collected, which present information on species diversity, individual density and specific relevance for soil functions. By means of condensed literature data, those species were identified which (i) play an important functional role in respective soil systems, (ii) are well adapted to the biogeographical regions, (iii) are expected to occur in high abundances under cultivation of maize or potato and (iv) fulfill the requirements for an ERA test system based on life-history traits. First, primary and secondary decomposers were identified as functional groups being exposed to the GM crops. In a second step, anecic and endogeic species were categorized as potential species. In step three, eight anecic and endogeic earthworm species belonging to the family Lumbricidae were ranked as relevant species: Aporrectodea caliginosa, Aporrectodea rosea, Aporrectodea longa, Allolobophora chlorotica, Lumbricus terrestris, Lumbricus friendi, Octodrilus complanatus and

Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism.

PubMed

Bi, Yufang; Wang, Weiqing; Xu, Min; Wang, Tiange; Lu, Jieli; Xu, Yu; Dai, Meng; Chen, Yuhong; Zhang, Di; Sun, Wanwan; Ding, Lin; Chen, Ying; Huang, Xiaolin; Lin, Lin; Qi, Lu; Lai, Shenghan; Ning, Guang

2016-01-01

Epidemiology studies showed inconsistent results regarding the relationship between bisphenol A (BPA) exposure and risk of type 2 diabetes (T2D). This study sought to prospectively investigate associations of BPA with incident T2D risk and the longitudinal changes in glycemic traits, particularly examining the interaction between gene and BPA exposure on the associations. A community-based study was conducted at baseline in 2009, including 2209 nondiabetic middle-age and elderly subjects followed for 4 y. Urinary BPA levels were measured at baseline. A genetic risk score (GRS) based on 34 T2D common variants that identified and validated in East Asians was created. Incident T2D was defined according to the 1999 World Health Organization criteria. Fasting (FPG) and 2-h post-loading plasma glucose were measured at baseline and followup. Multivariable logistic regression analysis demonstrated no significant association of risk of incident T2D with BPA while with increase in the weighted T2D-GRS (odds ratio, 1.89; 95% confidence interval, 1.31-2.72 for each 10-point increment). Similar results were found in 4-y changes of FPG and 2-h post-loading plasma glucose. The GRS modified the effect of BPA exposure on 4-y changes in FPG (P for interaction = .01). Each 1 unit of Log_BPA was associated with 0.1 mmol/L increase in FPG (P = .007) in the highest quartile of GRS; no associations were found in the lower three quartiles of GRS. The T2D genetic susceptibility significantly modulated the association of BPA exposure with longitudinal increase in FPG levels.

Risk assessment of soils identified on firefighter turnout gear.

PubMed

Easter, Elizabeth; Lander, Deborah; Huston, Tabitha

2016-09-01

The purpose of this research was to identify the composition of soils on firefighter turnout gear and to determine the dermal exposure risks associated with the soils. Nine used Nomex hoods from the Philadelphia fire department were analyzed for the presence of trace metals and seven sets of used turnout gear were analyzed for semi-volatile organics. Turnout gear samples were removed from areas of the gear known to have high levels of dermal absorption including the collar, armpit, wrist, and crotch areas, from either the outer shell or thermal liner layers. The following compounds were detected: polycyclic aromatic hydrocarbons (PAHs), phthalate plasticizers, and polybrominated diphenyl ether flame retardants (PBDEs). A screening risk assessment was conducted by converting the measured concentrations to an estimated dermally absorbed dose based on estimates for the permeation coefficient (Kp) and an assumed firefighting exposure scenario. Benzo(a) pyrene had the highest dermal exposure risk based on carcinogenic effects and PBDE-99 had the highest dermal exposure risk based on non-carcinogenic effects. For the metals, arsenic had the highest dermal exposure risk for the use hoods.

Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharpe, Richard A.; Cocq, Kate Le; Nikolaou, Vasilis

The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing ofmore » the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. - Highlights: • Monoclonal antibodies were used to track culturable allergenic moulds in homes. • Allergenic moulds were recovered from 82% of swabs from contaminated surfaces. • The mAbs were highly specific with 100% agreement to PCR of recovered fungi. • Improvements to

Modeling Success: Using Preenrollment Data to Identify Academically At-Risk Students

ERIC Educational Resources Information Center

Gansemer-Topf, Ann M.; Compton, Jonathan; Wohlgemuth, Darin; Forbes, Greg; Ralston, Ekaterina

2015-01-01

Improving student success and degree completion is one of the core principles of strategic enrollment management. To address this principle, institutional data were used to develop a statistical model to identify academically at-risk students. The model employs multiple linear regression techniques to predict students at risk of earning below a…

Advantage of the modified Lunn-McNeil technique over Kalbfleisch-Prentice technique in competing risks

NASA Astrophysics Data System (ADS)

Lukman, Iing; Ibrahim, Noor A.; Daud, Isa B.; Maarof, Fauziah; Hassan, Mohd N.

2002-03-01

Survival analysis algorithm is often applied in the data mining process. Cox regression is one of the survival analysis tools that has been used in many areas, and it can be used to analyze the failure times of aircraft crashed. Another survival analysis tool is the competing risks where we have more than one cause of failure acting simultaneously. Lunn-McNeil analyzed the competing risks in the survival model using Cox regression with censored data. The modified Lunn-McNeil technique is a simplify of the Lunn-McNeil technique. The Kalbfleisch-Prentice technique is involving fitting models separately from each type of failure, treating other failure types as censored. To compare the two techniques, (the modified Lunn-McNeil and Kalbfleisch-Prentice) a simulation study was performed. Samples with various sizes and censoring percentages were generated and fitted using both techniques. The study was conducted by comparing the inference of models, using Root Mean Square Error (RMSE), the power tests, and the Schoenfeld residual analysis. The power tests in this study were likelihood ratio test, Rao-score test, and Wald statistics. The Schoenfeld residual analysis was conducted to check the proportionality of the model through its covariates. The estimated parameters were computed for the cause-specific hazard situation. Results showed that the modified Lunn-McNeil technique was better than the Kalbfleisch-Prentice technique based on the RMSE measurement and Schoenfeld residual analysis. However, the Kalbfleisch-Prentice technique was better than the modified Lunn-McNeil technique based on power tests measurement.

Modifying the risk of atypical antipsychotics in the treatment of juvenile-onset schizophrenia.

PubMed

Townsend, Lisa; Findling, Robert L

2010-02-01

This review summarizes the evidence for use of typical and atypical antipsychotic medications for the treatment of juvenile-onset schizophrenia. We highlight the risks and benefits of antipsychotic agents for youth with this disorder, paying special attention to weight gain and metabolic effects, an area of specific concern within child and adolescent psychiatry. We describe the seriousness of juvenile-onset schizophrenia and its impact on long-term functioning, noting that pharmacological treatment remains the standard of care for this disorder. We focus on weight gain and metabolic effects associated with atypical agents and review strategies to modify risks associated with these agents. We summarize strategies for attenuating the risk of weight gain for youth on atypical antipsychotics, including what is known about nutritional counseling and exercise programs as well as pharmacotherapy with adjunctive weight loss agents. Given the negative consequences associated with untreated schizophrenia, it appears that the most effective way to improve the risk:benefit ratio in the treatment of adolescents with schizophrenia is to reduce the risks associated with pharmacological treatment.

Identifying Patients With Vesicovaginal Fistula at High Risk of Urinary Incontinence After Surgery

PubMed Central

Bengtson, Angela M.; Kopp, Dawn; Tang, Jennifer H.; Chipungu, Ennet; Moyo, Margaret; Wilkinson, Jeffrey

2016-01-01

Objective To develop a risk score to identify women with vesicovaginal fistula at high risk of residual urinary incontinence after surgical repair. Methods We conducted a prospective cohort study among 401 women undergoing their first vesicovaginal fistula repair at a referral fistula repair center in Lilongwe, Malawi, between September 2011 and December 2014, who returned for follow-up within 120 days of surgery. We used logistic regression to develop a risk score to identify women with high likelihood of residual urinary incontinence, defined as incontinence grade 2-5 within 120 days of vesicovaginal fistula repair, based on preoperative clinical and demographic characteristics (age, number of years with fistula, HIV status, body mass index, previous repair surgery at an outside facility, revised Goh Classification, Goh vesicovaginal fistula size, circumferential fistula, vaginal scaring, bladder size, and urethral length). The sensitivity, specificity, positive and negative predictive values of the risk score at each cut-point were assessed. Results Overall, 11 (3%) women had unsuccessful fistula closure. Of those with successful fistula closure (n=372), 85 (23%) experienced residual incontinence. A risk score cut-point of 20 had sensitivity 82% (95% CI 72%, 89%) and specificity 63% (95% CI 57%, 69%) to potentially identify women with residual incontinence. In our population, the positive predictive value for a risk score cut-point of _20 or higher was 43% (95% CI 36%, 51%) and the negative predictive value was 91% (95% CI 86%, 94%). Forty-eight percent of our study population had a risk score ≥20 and therefore, would have been identified for further intervention. Conclusions A risk score 20 or higher was associated with an increased likelihood of residual incontinence, with satisfactory sensitivity and specificity. If validated in alternative settings, the risk score could be used to refer women with high likelihood of postoperative incontinence to more

Body mass index cut-points to identify cardiometabolic risk in black South Africans.

PubMed

Kruger, H Salome; Schutte, Aletta E; Walsh, Corinna M; Kruger, Annamarie; Rennie, Kirsten L

2017-02-01

To determine optimal body mass index (BMI) cut-points for the identification of cardiometabolic risk in black South African adults. We performed a cross-sectional study of a weighted sample of healthy black South Africans aged 25-65 years (721 men, 1386 women) from the North West and Free State Provinces. Demographic, lifestyle and anthropometric measures were taken, and blood pressure, fasting serum triglycerides, high-density lipoprotein (HDL) cholesterol and blood glucose were measured. We defined elevated cardiometabolic risk as having three or more risk factors according to international metabolic syndrome criteria. Receiver operating characteristic curves were applied to identify an optimal BMI cut-point for men and women. BMI had good diagnostic performance to identify clustering of three or more risk factors, as well as individual risk factors: low HDL-cholesterol, elevated fasting glucose and triglycerides, with areas under the curve >.6, but not for high blood pressure. Optimal BMI cut-points averaged 22 kg/m 2 for men and 28 kg/m 2 for women, respectively, with better sensitivity in men (44.0-71.9 %), and in women (60.6-69.8 %), compared to a BMI of 30 kg/m 2 (17-19.1, 53-61.4 %, respectively). Men and women with a BMI >22 and >28 kg/m 2 , respectively, had significantly increased probability of elevated cardiometabolic risk after adjustment for age, alcohol use and smoking. In black South African men, a BMI cut-point of 22 kg/m 2 identifies those at cardiometabolic risk, whereas a BMI of 30 kg/m 2 underestimates risk. In women, a cut-point of 28 kg/m 2 , approaching the WHO obesity cut-point, identifies those at risk.

Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa.

PubMed

Sartorius, Benn; Cohen, C; Chirwa, T; Ntshoe, G; Puren, A; Hofman, K

2013-03-01

To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011. Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV) infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012. A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring) areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken. The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage), high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.

The relationship between modifiable health risks and group-level health care expenditures. Health Enhancement Research Organization (HERO) Research Committee.

PubMed

Anderson, D R; Whitmer, R W; Goetzel, R Z; Ozminkowski, R J; Dunn, R L; Wasserman, J; Serxner, S

2000-01-01

To assess the relationship between modifiable health risks and total health care expenditures for a large employee group. Risk data were collected through voluntary participation in health risk assessment (HRA) and worksite biometric screenings and were linked at the individual level to health care plan enrollment and expenditure data from employers' fee-for-service plans over the 6-year study period. The setting was worksite health promotion programs sponsored by six large private-sector and public-sector employers. Of the 50% of employees who completed the HRA, 46,026 (74.7%) met all inclusion criteria for the analysis. Eleven risk factors (exercise, alcohol use, eating, current and former tobacco use, depression, stress, blood pressure, cholesterol, weight, and blood glucose) were dichotomized into high-risk and lower-risk levels. The association between risks and expenditures was estimated using a two-part regression model, controlling for demographics and other confounders. Risk prevalence data were used to estimate group-level impact of risks on expenditures. Risk factors were associated with 25% of total expenditures. Stress was the most costly factor, with tobacco use, overweight, and lack of exercise also being linked to substantial expenditures. Modifiable risk factors contribute substantially to overall health care expenditures. Health promotion programs that reduce these risks may be beneficial for employers in controlling health care costs.

Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study.

PubMed

Wijnands, José Maria Andreas; Zhu, Feng; Kingwell, Elaine; Fisk, John David; Evans, Charity; Marrie, Ruth Ann; Zhao, Yinshan; Tremlett, Helen

2018-03-30

Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters. Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996-2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. Results were reported as adjusted HRs (aHRs). Of 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02), nor was exposure to these drug classes when assessed separately. Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon. Exposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights

Modifiable risk factors for chronic back pain: insights using the co-twin control design.

PubMed

Suri, Pradeep; Boyko, Edward J; Smith, Nicholas L; Jarvik, Jeffrey G; Williams, Frances M K; Jarvik, Gail P; Goldberg, Jack

2017-01-01

Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP. This is a cross-sectional co-twin control study in a nationwide sample of male twin members of the Vietnam Era Twin Registry. The sample is composed of 7,108 participants, including 1,308 monozygotic (MZ) pairs and 793 dizygotic pairs. The outcome measure is the self-reported lifetime history of CBP. Lifestyle factors included body mass index (BMI), smoking history, alcohol consumption, habitual physical activity, and typical sleep duration. Psychological factors included depression (Patient Health Questionnaire-9) and posttraumatic stress disorder (PTSD) symptoms (PTSD Checklist). Covariates included age, race, education, and income. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the association of risk factors with lifetime CBP when considering twins as individuals, and a within-pair co-twin control analysis that accounted for familial and genetic factors. Funding was through VA Grant 5IK2RX001515; there were no study-specific conflicts of interest. The mean age of respondents was 62 years and the prevalence of lifetime CBP was 28%. All lifestyle factors were associated with CBP in the individual level analysis. However, none of these persisted in the within-pair analyses, except for severe obesity (BMI ≥35.0), which was associated with lifetime CBP in both individual-level (OR=1.6, 95% CI: 1.3-1.9) and within-pair analyses (MZ analysis: OR=3.7, 95% CI: 1.2-11.4). Symptoms of PTSD and depression were strongly associated with

Physical Activity Modifies the Effect of LPL, LIPC and CETP polymorphisms on HDL-C Levels and the Risk of Myocardial Infarction in Caucasian Women

PubMed Central

Ahmad, Tariq; Chasman, Daniel I.; Buring, Julie E.; Lee, I-Min; Ridker, Paul M; Everett, Brendan M.

2010-01-01

Background Recent genome-wide association studies have identified common variants associated with high-density lipoprotein cholesterol (HDL-C). Whether these associations are modified by physical activity, which increases HDL-C levels and reduces the risk of cardiovascular disease (CVD), is uncertain. Methods and Results In a prospective cohort study of 22,939 apparently healthy Caucasian US women, we selected 58 single nucleotide polymorphisms (SNPs) in 9 genes that demonstrated genome-wide association (P<5×10−8) with HDL-C levels and sought evidence of effect modification according to levels of physical activity (PA). PA modified the effects on HDL-C of 7 SNPs at 3 loci, and the strongest evidence of effect was observed for rs10096633 at LPL, rs1800588 at LIPC and rs1532624 at CETP (each P-interaction <0.05). The per-minor-allele increase in HDL-C for rs1800588 at LIPC and rs1532624 at CETP was greater in active than inactive women, whereas the reverse was observed for rs10096633 at LPL. Minor-allele carrier status at the LPL SNP was associated with a reduced risk of MI in active (Hazard Ratio [HR] 0.42, 95% Confidence Interval [CI] 0.23–0.76) but not amongst inactive women (HR 1.10, 95% CI 0.83–1.44; P-interaction=0.007). By contrast, carrier status at the CETP SNP was associated with a reduced risk of MI regardless of activity level (HR 0.72, 95% CI 0.57–0.92; P-interaction=0.71). No association between LIPC SNP carrier status and MI risk was noted Conclusions The effects of common variants in the LPL, LIPC and CETP genes on HDL-C levels are modified by PA. For a common variant in LPL, the impact on MI varied by activity level, while the effects of a common variant in CETP on MI risk did not. PMID:21252145

Identifying individuals for primary cardiovascular disease prevention in UK general practice: priorities and resource implications

PubMed Central

Holt, Tim A; Thorogood, Margaret; Griffiths, Frances; Munday, Stephen; Stables, David

2008-01-01

Targeted cardiovascular disease prevention relies on risk-factor information held in primary care records. A risk algorithm, the ‘e-Nudge’, was applied to data from a population of ≥50-year-olds in 19 West Midlands practices, to identify those individuals at risk of cardiovascular disease. Altogether, 5.9% were identified aged 50–74 years at ≥20% 10-year risk based on existing data, and a further 26.4% were potentially at risk but had missing risk-factor information; 9.2% of patients aged over 50 years with established cardiovascular disease had at least one modifiable risk factor outside the audit target of the Quality and Outcomes Framework. Implications for resource allocation are discussed. PMID:18611316

[Application of negative binomial regression and modified Poisson regression in the research of risk factors for injury frequency].

PubMed

Cao, Qingqing; Wu, Zhenqiang; Sun, Ying; Wang, Tiezhu; Han, Tengwei; Gu, Chaomei; Sun, Yehuan

2011-11-01

To Eexplore the application of negative binomial regression and modified Poisson regression analysis in analyzing the influential factors for injury frequency and the risk factors leading to the increase of injury frequency. 2917 primary and secondary school students were selected from Hefei by cluster random sampling method and surveyed by questionnaire. The data on the count event-based injuries used to fitted modified Poisson regression and negative binomial regression model. The risk factors incurring the increase of unintentional injury frequency for juvenile students was explored, so as to probe the efficiency of these two models in studying the influential factors for injury frequency. The Poisson model existed over-dispersion (P < 0.0001) based on testing by the Lagrangemultiplier. Therefore, the over-dispersion dispersed data using a modified Poisson regression and negative binomial regression model, was fitted better. respectively. Both showed that male gender, younger age, father working outside of the hometown, the level of the guardian being above junior high school and smoking might be the results of higher injury frequencies. On a tendency of clustered frequency data on injury event, both the modified Poisson regression analysis and negative binomial regression analysis can be used. However, based on our data, the modified Poisson regression fitted better and this model could give a more accurate interpretation of relevant factors affecting the frequency of injury.

Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-08-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

Dietary screening tool identifies nutritional risk in older adults123

PubMed Central

Miller, Paige E; Mitchell, Diane C; Hartman, Terryl J; Lawrence, Frank R; Sempos, Christopher T; Smiciklas-Wright, Helen

2009-01-01

Background: No rapid methods exist for screening overall dietary intakes in older adults. Objective: The purpose of this study was to develop and evaluate a scoring system for a diet screening tool to identify nutritional risk in community-dwelling older adults. Design: This cross-sectional study in older adults (n = 204) who reside in rural areas examined nutrition status by using an in-person interview, biochemical measures, and four 24-h recalls that included the use of dietary supplements. Results: The dietary screening tool was able to characterize 3 levels of nutritional risk: at risk, possible risk, and not at risk. Individuals classified as at nutritional risk had significantly lower indicators of diet quality (Healthy Eating Index and Mean Adequacy Ratio) and intakes of protein, most micronutrients, dietary fiber, fruit, and vegetables. The at-risk group had higher intakes of fats and oils and refined grains. The at-risk group also had the lowest serum vitamin B-12, folate, β-cryptoxanthin, lutein, and zeaxanthin concentrations. The not-at-nutritional-risk group had significantly higher lycopene and β-carotene and lower homocysteine and methylmalonic acid concentrations. Conclusion: The dietary screening tool is a simple and practical tool that can help to detect nutritional risk in older adults. PMID:19458013

Grades and Graduation: A Longitudinal Risk Perspective to Identify Student Dropouts

ERIC Educational Resources Information Center

Bowers, Alex J.

2010-01-01

Studies of student risk of school dropout have shown that present predictors of at-risk status do not accurately identify a large percentage of students who eventually drop out. Through the analysis of the entire Grade 1-12 longitudinal cohort-based grading histories of the class of 2006 for two school districts in the United States, the author…

Methodology to identify risk-significant components for inservice inspection and testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, M.T.; Hartley, R.S.; Jones, J.L. Jr.

1992-08-01

Periodic inspection and testing of vital system components should be performed to ensure the safe and reliable operation of Department of Energy (DOE) nuclear processing facilities. Probabilistic techniques may be used to help identify and rank components by their relative risk. A risk-based ranking would allow varied DOE sites to implement inspection and testing programs in an effective and cost-efficient manner. This report describes a methodology that can be used to rank components, while addressing multiple risk issues.

The importance of identifying and modifying unemployment predictor variables in the evolution of a novel model of care for low back pain in the general population.

PubMed

Harris, Simon A; Rampersaud, Y Raja

2016-01-01

Care for low back pain (LBP) is costly, fragmented and, in non-compensation populations, rarely specifically addresses factors associated with maintaining employment status or return to work (RTW). This study aimed to identify modifiable independent risk factors for (1) a negative work status at presentation and (2) a change in work status during treatment in a cohort of LBP patients. The results are intended to inform improvement in best-evidence care pathways to maximize societal outcomes and overall value of a new model of care. A prospective observational study was carried out. Work-eligible, non-workers compensation patients with recurrent or persistent LBP ≥6 weeks and ≤12 months. The Inter-professional Spine Assessment and Education Clinics (ISAEC)-a novel Government-funded shared-care model of management for LBP. This study used the following methods: (1) Cross-sectional analysis of baseline data from the initial ISAEC consultation (t0) from December 2012 to April 2014. Work status at t0 was dichotomized as employed (E) or underemployed (UE; unemployed, modified work duty, or disability). Multivariate logistic regression modeling was used to determine independent predictors of UE status at t0. (2) Bivariate analysis of longitudinal data from t0 to 6 months (t1) to identify risk factors for work status change. Employment journey categorized into four groups: Et0/Et1-employed at t0 and employed at t1; Et0/UEt1-employed at t0 and underemployed at t1; UEt0/Et1-underemployed at t0 and employed at t1; UEt0/UEt1-underemployed at t0 and underemployed at t1. This study yielded the following results: (1) Initial consultation data on 462 consecutive patients (Et0=344, UEt0=118). Multivariate logistic regression identified legal claim, depression, smoking, and higher STarT Back (or Oswestry Disability Index [ODI]) score as independent risk factors for UEt0. (2) Overall UE rate did not significantly change during longitudinal analysis (n=178, UEt0=25.5%, UEt1

Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-06-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

Identifying Adolescents at Highly Elevated Risk for Suicidal Behavior in the Emergency Department

PubMed Central

Berona, Johnny; Czyz, Ewa; Horwitz, Adam G.; Gipson, Polly Y.

2015-01-01

Abstract Objective: The feasibility and concurrent validity of adolescent suicide risk screening in medical emergency departments (EDs) has been documented. The objectives of this short-term prospective study of adolescents who screened positive for suicide risk in the ED were: 1) to examine adolescents' rate of suicidal behavior during the 2 months following their ED visits and compare it with reported rates for psychiatric samples; and 2) to identify possible predictors of acute risk for suicidal behavior in this at-risk sample. Method: Participants were 81 adolescents, ages 14–19 years, seeking services for psychiatric and nonpsychiatric chief complaints, who screened positive for suicide risk because of recent suicidal ideation, a suicide attempt, and/or depression plus alcohol or substance misuse. A comprehensive assessment of suicidal behavior, using the Columbia-Suicide Severity Rating Scale, was conducted at baseline and 2 month follow-up. Results: Six adolescents (7.4%) reported a suicide attempt and 15 (18.5%) engaged in some type of suicidal behavior (actual, aborted, or interrupted suicide attempt; preparatory behavior) during the 2 months following their ED visit. These rates suggest that this screen identified a high-risk sample. Furthermore, adolescents who screened positive for suicidal ideation and/or attempt plus depression and alcohol/substance misuse were most likely to engage in future suicidal behavior (38.9%). Conclusions: In this study, use of a higher screen threshold (multiple suicide risk factors) showed promise for identifying highly elevated acute risk for suicidal behavior. PMID:25746114

Identifying neonates at a very high risk for mortality among children with congenital diaphragmatic hernia managed with extracorporeal membrane oxygenation.

PubMed

Haricharan, Ramanath N; Barnhart, Douglas C; Cheng, Hong; Delzell, Elizabeth

2009-01-01

The purpose of this study was to identify mortality risk factors in children with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO) and generate a prediction score for those at a very high risk for mortality. Data on first ECMO runs of all neonates with CDH, between January 1997 and June 2007, were obtained from the Extracorporeal Life Support Organization registry (N = 2678). The data were split into "training data (TD)" (n = 2006) and "validation data" (n = 672). The primary outcome analyzed was in-hospital mortality. Modified Poisson regression was used for analyses. Overall in-hospital mortality among 2678 neonates (males, 57%; median age at ECMO, 1 day) was 52%. The univariate and multivariable analyses were performed using TD. An empirically weighted mortality prediction score was generated with possible scores ranging from 0 to 35 points. Of 69 who scored 14 or higher in the TD, 62 died (positive predictive value [PPV], 90%), of 37 with 15 or higher, 35 died (PPV, 95%), of 23 with 16 or higher, 22 died (PPV, 96%). A cut-off point of 15 was chosen and was tested using the separate validation dataset. In validation data, the cut-off point 15 had a PPV of 96% (23 died of 24). Scoring 15 or higher on the prediction score identifies neonates with CDH at a very high risk for mortality among those managed with ECMO and could be used in surgical decision making and counseling.

Effects of newspaper coverage on public knowledge about modifiable cancer risks.

PubMed

Stryker, Jo Ellen; Moriarty, Cortney M; Jensen, Jakob D

2008-07-01

This study explores the relationship between cancer newspaper coverage and public knowledge about cancer prevention, confirming self-reported associations between news exposure and cancer prevention knowledge with descriptions of newspaper coverage of modifiable cancer risks. Content analyses (N = 954) revealed that newspapers pay relatively little attention to cancer prevention. However, there is greater newspaper attention to tobacco and diet than to exercise, sun, and alcohol. Survey analysis (the National Cancer Institute's Health Information National Trends Survey) revealed that after controlling for differences based on gender, race, age, income, and education, attention to health news was significantly associated with knowledge about cancer risks associated with food and smoking but not for knowledge about exercise, sun, or alcohol. These findings conform to the findings of the content analysis data and provide a validation of a self-reported measure of media exposure, as well as evidence suggesting a threshold below which news coverage may not generate public knowledge about cancer prevention.

Effects of E-Cigarette Health Warnings and Modified Risk Ad Claims on Adolescent E-Cigarette Craving and Susceptibility.

PubMed

Andrews, J Craig; Mays, Darren; Netemeyer, Richard G; Burton, Scot; Kees, Jeremy

2018-04-16

A between-subjects experiment examines the effects of different warning types and modified risk e-cigarette ad claims on adolescent e-cigarette craving and future e-cigarette susceptibility for two different themes. One theme focuses on nicotine and addiction, and the other on the effects of potentially harmful constituents (e.g., flavored chemicals and lung disease). The effects of warning type (control, text-only, graphic health warning (GHW) and text) and modified risk e-cigarette ad claims (control, exposure reduction, risk reduction) are tested experimentally with two different arms (themes) for a sample of 1,011 adolescents who had tried either e-cigarettes or cigarettes. For addiction, the text-only warning led to significantly less e-cigarette susceptibility than the no warning control condition. As expected, there were no differences between the GHW + text condition and text-only or control conditions for e-cigarette craving. An interaction between warning type and modified risk claims revealed significantly fewer e-cigarette cravings and less susceptibility for the text-only warning and no claim (control) condition than for any other condition. For fatal lung disease, the GHW + text condition led to fewer e-cigarette cravings and less susceptibility than the text-only warning and no warning (control) conditions. Warning type effects can be very different under different themes (e.g., addiction, fatal lung disease). In general, our results point to the effectiveness of the text-only warning for addiction and GHW + text for fatal lung disease. Relative exposure and risk modification claims (e.g., less nicotine; less addicting) tend to undercut addiction warnings. More than one type of e-cigarette warning may be necessary as e-cigarette research evolves. Our results show different warning type effects (e.g., text-only; GHW + text) on e-cigarette craving and future susceptibility for adolescent experimenters depending on the risk theme (e.g., addiction; lung

The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese.

PubMed

Abe, Makiko; Ito, Hidemi; Oze, Isao; Nomura, Masatoshi; Ogawa, Yoshihiro; Matsuo, Keitaro

2017-12-01

Little is known about the difference of genetic predisposition for CRC between ethnicities; however, many genetic traits common to colorectal cancer have been identified. This study investigated whether more SNPs identified in GWAS in East Asian population could improve the risk prediction of Japanese and explored possible application of genetic risk groups as an instrument of the risk communication. 558 Patients histologically verified colorectal cancer and 1116 first-visit outpatients were included for derivation study, and 547 cases and 547 controls were for replication study. Among each population, we evaluated prediction models for the risk of CRC that combined the genetic risk group based on SNPs from GWASs in European-population and a similarly developed model adding SNPs from GWASs in East Asian-population. We examined whether adding East Asian-specific SNPs would improve the discrimination. Six SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) from 23 SNPs by European-based GWAS and five SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) among ten SNPs by Asian-based GWAS were selected in CRC risk prediction model. Compared with a 6-SNP-based model, an 11-SNP model including Asian GWAS-SNPs showed improved discrimination capacity in Receiver operator characteristic analysis. A model with 11 SNPs resulted in statistically significant improvement in both derivation (P = 0.0039) and replication studies (P = 0.0018) compared with six SNP model. We estimated cumulative risk of CRC by using genetic risk group based on 11 SNPs and found that the cumulative risk at age 80 is approximately 13% in the high-risk group while 6% in the low-risk group. We constructed a more efficient CRC risk prediction model with 11 SNPs including newly identified East Asian-based GWAS SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279). Risk grouping based on 11 SNPs depicted lifetime difference of CRC risk. This might be useful for

Identifying Balance Measures Most Likely to Identify Recent Falls.

PubMed

Criter, Robin E; Honaker, Julie A

2016-01-01

Falls sustained by older adults are an increasing health care issue. Early identification of those at risk for falling can lead to successful prevention of falls. Balance complaints are common among individuals who fall or are at risk for falling. The purpose of this study was to evaluate the clinical utility of a multifaceted balance protocol used for fall risk screening, with the hypothesis that this protocol would successfully identify individuals who had a recent fall (within the previous 12 months). This is a retrospective review of 30 individuals who self-referred for a free fall risk screening. Measures included case history, Activities-Specific Balance Confidence Scale, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, and Dynamic Visual Acuity. Statistical analyses were focused on the ability of the test protocol to identify a fall within the past 12 months and included descriptive statistics, clinical utility indices, logistic regression, receiver operating characteristic curve, area under the curve analysis, effect size (Cohen d), and Spearman correlation coefficients. All individuals who self-referred for this free screening had current imbalance complaints, and were typically women (70%), had a mean age of 77.2 years, and had a fear of falling (70%). Almost half (46.7%) reported at least 1 lifetime fall and 40.0% within the past 12 months. Regression analysis suggested that the Timed Up and Go test was the most important indicator of a recent fall. A cutoff score of 12 or more seconds was optimal (sensitivity: 83.3%; specificity: 61.1%). Older adults with current complaints of imbalance have a higher rate of falls, fall-related injury, and fear of falling than the general community-dwelling public. The Timed Up and Go test is useful for determining recent fall history in individuals with imbalance.

Using Hospitalization and Mortality Data to Identify Areas at Risk for Adolescent Suicide.

PubMed

Chen, Kun; Aseltine, Robert H

2017-08-01

The purpose of this study is to use statewide data on inpatient hospitalizations for suicide attempts and suicide mortality to identify communities and school districts at risk for adolescent suicide. Five years of data (2010-2014) from the Office of the Connecticut Medical Examiner and the Connecticut Hospital Inpatient Discharge Database were analyzed. A mixed-effects Poisson regression model was used to assess whether suicide attempt/mortality rates in the state's 119 school districts were significantly better or worse than expected after adjusting for 10 community-level characteristics. Ten districts were at significantly higher risk for suicidal behavior, with suicide mortality/hospitalization rates ranging from 154% to 241% of their expected rates, after accounting for their community characteristics. Four districts were identified as having significantly lower risk for suicide attempts than expected after accounting for community-level advantages and disadvantages. Data capturing hospitalization for suicide attempts and suicide deaths can inform prevention activities by identifying high-risk areas to which resources should be allocated, as well as low-risk areas that may provide insight into the best practices in suicide prevention. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting

PubMed Central

Litwin, Alain H.; Smith, Bryce D.; Koppelman, Elisa A.; McKee, M. Diane; Christiansen, Cindy L.; Gifford, Allen L.; Weinbaum, Cindy M.; Southern, William N.

2012-01-01

Objectives. We evaluated an intervention designed to identify patients at risk for hepatitis C virus (HCV) through a risk screener used by primary care providers. Methods. A clinical reminder sticker prompted physicians at 3 urban clinics to screen patients for 12 risk factors and order HCV testing if any risks were present. Risk factor data were collected from the sticker; demographic and testing data were extracted from electronic medical records. We used the t test, χ2 test, and rank-sum test to compare patients who had and had not been screened and developed an analytic model to identify the incremental value of each element of the screener. Results. Among screened patients, 27.8% (n = 902) were identified as having at least 1 risk factor. Of screened patients with risk factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements (injection drug use, intranasal drug use, elevated alanine aminotransferase, transfusions before 1992, ≥ 20 lifetime sex partners, maternal HCV, existing liver disease) accounted for all HCV infections identified. Conclusions. A brief risk screener with a paper-based clinical reminder was effective in increasing HCV testing in a primary care setting. PMID:22994166

The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia.

PubMed

Hussain, Mohammad Akhtar; Al Mamun, Abdullah; Peters, Sanne Ae; Woodward, Mark; Huxley, Rachel R

2016-10-05

In Indonesia, coronary heart disease (CHD) and stroke are estimated to cause more than 470 000 deaths annually. In order to inform primary prevention policies, we estimated the sex- and age-specific burden of CHD and stroke attributable to five major and modifiable vascular risk factors: cigarette smoking, hypertension, diabetes, elevated total cholesterol, and excess body weight. Population attributable risks for CHD and stroke attributable to these risk factors individually were calculated using summary statistics obtained for prevalence of each risk factor specific to sex and to two age categories (<55 and ≥55 years) from a national survey in Indonesia. Age- and sex-specific relative risks for CHD and stroke associated with each of the five risk factors were derived from prospective data from the Asia-Pacific region. Hypertension was the leading vascular risk factor, explaining 20%-25% of all CHD and 36%-42% of all strokes in both sexes and approximately one-third of all CHD and half of all strokes across younger and older age groups alike. Smoking in men explained a substantial proportion of vascular events (25% of CHD and 17% of strokes). However, given that these risk factors are likely to be strongly correlated, these population attributable risk proportions are likely to be overestimates and require verification from future studies that are able to take into account correlation between risk factors. Implementation of effective population-based prevention strategies aimed at reducing levels of major cardiovascular risk factors, especially blood pressure, total cholesterol, and smoking prevalence among men, could reduce the growing burden of CVD in the Indonesian population.

Developing a tool for nurses to assess risk of infection in pediatric oncology patients in China: a modified Delphi study.

PubMed

Zhou, Yufeng; Cui, Yan; Wang, Hong; Wang, Fang; Lu, Chao; Shen, Yan

2016-09-01

Infections are identified as the most common preventable cause of death in pediatric oncology patients. Assessing and stratifying risk of infections are essential to prevent infection in these patients. To date, no tool can fulfill this demand in China. This study aimed to develop a nursing work-based and Chinese-specific tool for pediatric nurses to assess risk of infection in oncology patients. This research was a modified Delphi study. Based on a literature review, a 37-item questionnaire rating on a 0-5 scale was developed. Twenty-four experts from 8 hospitals in 6 provinces of China were consulted for three rounds. Consensus for each item in the first round was defined as: the rating mean was>3 and the coefficient of variation (CV) was<0.5. Consensus for each item in the second round was defined as CV<0.3. Consensus among experts was defined as: P value of Kendall's coefficient of concordance ( W )<0.05. After three rounds of consultation, a two-part tool was developed: the Immune Status Scale (ISS) and the Checklist of Risk Factors of Infection (CRFI). There were 5 items in the ISS and 14 in the CRFI. Based on the ISS score, nurses could stratify children into the low-risk and high-risk groups. For high-risk children, nurses should screen risk factors of infection every day by the CRFI, and twice weekly for low-risk children. Further study is needed to verify this tool's efficacy. © 2016 the Journal of Biomedical Research. All rights reserved.

The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload.

PubMed

Trinh, Emilie; Weber, Catherine

2017-01-01

Fluid overload in patients on conventional hemodialysis is a frequent complication, associated with increased cardiovascular morbidity and mortality. The dialysate sodium prescription is a potential modifiable risk factor. Our primary objective was to describe associations between dialysate-to-serum sodium gradient and parameters of fluid status. A secondary objective was to evaluate the 6-month risk of hospitalization and mortality in relation to sodium gradient. We performed a cross-sectional study of 110 prevalent conventional hemodialysis patients at a single center. The associations of sodium gradient with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and blood pressure (BP) were analyzed. The mean serum sodium gradient was 4.6 ± 3.6 mEq/L. There was a direct correlation between sodium gradient and IDWG% ( r = 0.48, p < 0.01) as well as UF rate ( r = 0.44, p < 0.01). In a logistic regression model, a 1 mEq/L higher sodium gradient was associated with increased risk of IDWG% >3% (OR 1.33, p < 0.01) and increased risk of UF rate >10 mL/kg/h (OR 1.16, p = 0.03), but there were no associations with intradialytic hypotension, intradialytic hypertension or BP. No significant differences were found with 6-month hospitalization or mortality risk in relation to sodium gradient. A higher sodium gradient was associated with significant increases in IDWG and UF rates, known to be associated with poor outcomes, but was not associated with intradialytic hypotension. Individualizing the dialysate sodium prescription to minimize sodium gap may lead to less fluid overload in conventional hemodialysis patients.

[Diagnostic evaluation of the developmental level in children identified at risk of delay through the Child Development Evaluation Test].

PubMed

Rizzoli-Córdoba, Antonio; Campos-Maldonado, Martha Carmen; Vélez-Andrade, Víctor Hugo; Delgado-Ginebra, Ismael; Baqueiro-Hernández, César Iván; Villasís-Keever, Miguel Ángel; Reyes-Morales, Hortensia; Ojeda-Lara, Lucía; Davis-Martínez, Erika Berenice; O'Shea-Cuevas, Gabriel; Aceves-Villagrán, Daniel; Carrasco-Mendoza, Joaquín; Villagrán-Muñoz, Víctor Manuel; Halley-Castillo, Elizabeth; Sidonio-Aguayo, Beatriz; Palma-Tavera, Josuha Alexander; Muñoz-Hernández, Onofre

The Child Development Evaluation (or CDE Test) was developed in Mexico as a screening tool for child developmental problems. It yields three possible results: normal, slow development or risk of delay. The modified version was elaborated using the information obtained during the validation study but its properties according to the base population are not known. The objective of this work was to establish diagnostic confirmation of developmental delay in children 16- to 59-months of age previously identified as having risk of delay through the CDE Test in primary care facilities. A population-based cross-sectional study was conducted in one Mexican state. CDE test was administered to 11,455 children 16- to 59-months of age from December/2013 to March/2014. The eligible population represented the 6.2% of the children (n=714) who were identified at risk of delay through the CDE Test. For inclusion in the study, a block randomization stratified by sex and age group was performed. Each participant included in the study had a diagnostic evaluation using the Battelle Development Inventory, 2 nd edition. From the 355 participants included with risk of delay, 65.9% were male and 80.2% were from rural areas; 6.5% were false positives (Total Development Quotient ˃90) and 6.8% did not have any domain with delay (Domain Developmental Quotient <80). The proportion of delay for each domain was as follows: communication 82.5%; cognitive 80.8%; social-personal 33.8%; motor 55.5%; and adaptive 41.7%. There were significant differences in the percentages of delay both by age and by domain/subdomain evaluated. In 93.2% of the participants, developmental delay was corroborated in at least one domain evaluated. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Immediately modifiable risk factors attributable to colorectal cancer in Malaysia.

PubMed

Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

2017-08-04

This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal

Root Source Analysis/ValuStream[Trade Mark] - A Methodology for Identifying and Managing Risks

NASA Technical Reports Server (NTRS)

Brown, Richard Lee

2008-01-01

Root Source Analysis (RoSA) is a systems engineering methodology that has been developed at NASA over the past five years. It is designed to reduce costs, schedule, and technical risks by systematically examining critical assumptions and the state of the knowledge needed to bring to fruition the products that satisfy mission-driven requirements, as defined for each element of the Work (or Product) Breakdown Structure (WBS or PBS). This methodology is sometimes referred to as the ValuStream method, as inherent in the process is the linking and prioritizing of uncertainties arising from knowledge shortfalls directly to the customer's mission driven requirements. RoSA and ValuStream are synonymous terms. RoSA is not simply an alternate or improved method for identifying risks. It represents a paradigm shift. The emphasis is placed on identifying very specific knowledge shortfalls and assumptions that are the root sources of the risk (the why), rather than on assessing the WBS product(s) themselves (the what). In so doing RoSA looks forward to anticipate, identify, and prioritize knowledge shortfalls and assumptions that are likely to create significant uncertainties/ risks (as compared to Root Cause Analysis, which is most often used to look back to discover what was not known, or was assumed, that caused the failure). Experience indicates that RoSA, with its primary focus on assumptions and the state of the underlying knowledge needed to define, design, build, verify, and operate the products, can identify critical risks that historically have been missed by the usual approaches (i.e., design review process and classical risk identification methods). Further, the methodology answers four critical questions for decision makers and risk managers: 1. What s been included? 2. What's been left out? 3. How has it been validated? 4. Has the real source of the uncertainty/ risk been identified, i.e., is the perceived problem the real problem? Users of the RoSA methodology

Association analysis identifies 65 new breast cancer risk loci.

PubMed

Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; Ghoussaini, Maya; Carroll, Jason S; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Aronson, Kristan J; Arun, Banu; Auer, Paul L; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D; Castelao, Jose E; Chan, Tsun L; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L; Collée, Margriet; Conroy, Don M; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Doheny, Kimberly F; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M; García-Sáenz, José A; Gaudet, Mia M; Georgoulias, Vassilios; Giles, Graham G; Glendon, Gord; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Grenaker Alnæs, Grethe I; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela N; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P; Ma, Edmond S K; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Noh, Dong-Young; Nordestgaard, Børge G; Norman, Aaron; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V Shane; Park, Sue K; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F

2017-11-02

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

PubMed Central

Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

2015-01-01

Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

Model of areas for identifying risks influencing the compliance of technological processes and products

NASA Astrophysics Data System (ADS)

Misztal, A.; Belu, N.

2016-08-01

Operation of every company is associated with the risk of interfering with proper performance of its fundamental processes. This risk is associated with various internal areas of the company, as well as the environment in which it operates. From the point of view of ensuring compliance of the course of specific technological processes and, consequently, product conformity with requirements, it is important to identify these threats and eliminate or reduce the risk of their occurrence. The purpose of this article is to present a model of areas of identifying risk affecting the compliance of processes and products, which is based on multiregional targeted monitoring of typical places of interference and risk management methods. The model is based on the verification of risk analyses carried out in small and medium-sized manufacturing companies in various industries..

Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients

PubMed Central

Tran, John; Jeanmonod, Donald; Agresti, Darin; Hamden, Khalief; Jeanmonod, Rebecca K.

2016-01-01

Introduction The National Emergency X-radiography Utilization Study (NEXUS) criteria are used extensively in emergency departments to rule out C-spine injuries (CSI) in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. Methods This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. Results We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65–101). The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4%) cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9–100]) with a negative predictive value of 100 (98.7–100). Conclusion Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls. PMID:27330655

Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients.

PubMed

Tran, John; Jeanmonod, Donald; Agresti, Darin; Hamden, Khalief; Jeanmonod, Rebecca K

2016-05-01

The National Emergency X-radiography Utilization Study (NEXUS) criteria are used extensively in emergency departments to rule out C-spine injuries (CSI) in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65-101). The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4%) cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9-100]) with a negative predictive value of 100 (98.7-100). Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls.

Role of contextual factors in the rehabilitation of adolescent survivors of traumatic brain injury: emerging concepts identified through modified narrative review.

PubMed

Ciccia, Angela Hein; Threats, Travis

2015-07-01

Recently research in traumatic brain injury (TBI) intervention has identified the benefits of contextualized, embedded, functionally based approaches to maximize treatment outcomes. An essential component of contextualized intervention is the direct and purposeful consideration of the broader context, in which the person with TBI functions. However, systematic consideration of contextual factors remains limited both in research and clinical practice. The purposes of this modified narrative review were (1) to provide a succinct review of the available literature regarding the contextual factors that are specific to adolescent survivors of TBI, one of highest incidence groups for brain injury; (2) to connect these contextual factors to the direct long-term management of TBI and to identify their potential impact on outcome; and (3) to highlight areas that are open to research and clinical advances that could enhance positive outcomes for adolescent survivors of TBI. The framework of the World Health Organization's (WHO) International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY; 2007) was used as a foundation for this review. A systematic literature search was conducted using databases and hand searches. A total of 102 articles were originally identified. Twenty-five original research articles, eight review papers and four expert opinion papers met inclusion and exclusion criteria and were included in the final review. The body of research specifically focused on contextual factors is an emerging area. Early findings indicate that a focus on the direct modification of contextual factors is promising for the facilitation of positive outcomes long into the chronic phase of management for adolescences who have survived a TBI. The contextual factors included in this review were the overall ability of the school to support a student post-TBI, family psychosocial risk (sibling/sibling relationships/stress/burden/support), coping

Trends in major modifiable risk factors for severe perineal trauma, 1996–2006

PubMed Central

Kudish, Bela; Sokol, Robert J.; Kruger, Michael

2009-01-01

Objective To examine what effect the major modifiable risk factors for severe perineal trauma have had on the rates of this trauma over time. Methods A retrospective observational cohort study of singleton vaginal deliveries taken from a perinatal database for the period 1996 through 2006. Results A total of 46 239 singleton vertex vaginal deliveries met the inclusion criteria. Major risk factors for severe perineal trauma were increased maternal age (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.1–1.5), non–African American ethnicity (OR 1.5, 95% CI 1.3–1.7), nulliparity (OR 4.8, 95% CI 4.11–5.6), fetal birth weight (OR 2.2, 95% CI 1.9–2.4), forceps (OR 8.3, 95% CI 5.4–10.8), vacuum (OR 2.9, 95% CI 1.9–4.4), and midline episiotomy (OR 5.7, 95% CI 5.0–6.4). Evaluation of the changes in rates of these factors over the study period revealed that decline in the rates of episiotomy and use of forceps accounted for a reduction in severe lacerations of more than 50%. Conclusion Reduction of severe perineal trauma by restricted use of the 2 modifiable clinical variables, episiotomy and forceps, is evident over time. PMID:18420204

Exploring demands from the perspective of employees identified as being at risk of burnout

PubMed Central

Gauche, Cecile; de Beer, Leon T.; Brink, Lizelle

2017-01-01

ABSTRACT Purpose: Burnout has become an occupational health concern. However, little is known about the experiences of individuals identified as being at risk of burnout. This study aimed to address this gap by exploring employees’ experiences of well-being who were identified as burnout risks. Method: Interviews were conducted with 26 employees who agreed to participate in the study. A phenomenological approach was taken, with a case study design as the research strategy. Results: Three major themes were identified: job demands, life demands, and health concerns. It was evident that participants were experiencing demanding conditions in both their work and personal lives, indicating burnout to be a multi-domain phenomenon. Conclusions: Professionals and managers should take note of these results to assist and support employees who are identified as being at risk of burnout. PMID:28784048

Modified social ecological model: a tool to guide the assessment of the risks and risk contexts of HIV epidemics.

PubMed

Baral, Stefan; Logie, Carmen H; Grosso, Ashley; Wirtz, Andrea L; Beyrer, Chris

2013-05-17

Social and structural factors are now well accepted as determinants of HIV vulnerabilities. These factors are representative of social, economic, organizational and political inequities. Associated with an improved understanding of multiple levels of HIV risk has been the recognition of the need to implement multi-level HIV prevention strategies. Prevention sciences research and programming aiming to decrease HIV incidence requires epidemiologic studies to collect data on multiple levels of risk to inform combination HIV prevention packages. Proximal individual-level risks, such as sharing injection devices and unprotected penile-vaginal or penile-anal sex, are necessary in mediating HIV acquisition and transmission. However, higher order social and structural-level risks can facilitate or reduce HIV transmission on population levels. Data characterizing these risks is often far more actionable than characterizing individual-level risks. We propose a modified social ecological model (MSEM) to help visualize multi-level domains of HIV infection risks and guide the development of epidemiologic HIV studies. Such a model may inform research in epidemiology and prevention sciences, particularly for key populations including men who have sex with men (MSM), people who inject drugs (PID), and sex workers. The MSEM builds on existing frameworks by examining multi-level risk contexts for HIV infection and situating individual HIV infection risks within wider network, community, and public policy contexts as well as epidemic stage. The utility of the MSEM is demonstrated with case studies of HIV risk among PID and MSM. The MSEM is a flexible model for guiding epidemiologic studies among key populations at risk for HIV in diverse sociocultural contexts. Successful HIV prevention strategies for key populations require effective integration of evidence-based biomedical, behavioral, and structural interventions. While the focus of epidemiologic studies has traditionally been on

Combining Knowledge and Data Driven Insights for Identifying Risk Factors using Electronic Health Records

PubMed Central

Sun, Jimeng; Hu, Jianying; Luo, Dijun; Markatou, Marianthi; Wang, Fei; Edabollahi, Shahram; Steinhubl, Steven E.; Daar, Zahra; Stewart, Walter F.

2012-01-01

Background: The ability to identify the risk factors related to an adverse condition, e.g., heart failures (HF) diagnosis, is very important for improving care quality and reducing cost. Existing approaches for risk factor identification are either knowledge driven (from guidelines or literatures) or data driven (from observational data). No existing method provides a model to effectively combine expert knowledge with data driven insight for risk factor identification. Methods: We present a systematic approach to enhance known knowledge-based risk factors with additional potential risk factors derived from data. The core of our approach is a sparse regression model with regularization terms that correspond to both knowledge and data driven risk factors. Results: The approach is validated using a large dataset containing 4,644 heart failure cases and 45,981 controls. The outpatient electronic health records (EHRs) for these patients include diagnosis, medication, lab results from 2003–2010. We demonstrate that the proposed method can identify complementary risk factors that are not in the existing known factors and can better predict the onset of HF. We quantitatively compare different sets of risk factors in the context of predicting onset of HF using the performance metric, the Area Under the ROC Curve (AUC). The combined risk factors between knowledge and data significantly outperform knowledge-based risk factors alone. Furthermore, those additional risk factors are confirmed to be clinically meaningful by a cardiologist. Conclusion: We present a systematic framework for combining knowledge and data driven insights for risk factor identification. We demonstrate the power of this framework in the context of predicting onset of HF, where our approach can successfully identify intuitive and predictive risk factors beyond a set of known HF risk factors. PMID:23304365

Association analysis identifies 65 new breast cancer risk loci

PubMed Central

Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Chen, Xiao Qing; Fachal, Laura; McCue, Karen; McCart Reed, Amy E.; Ghoussaini, Maya; Carroll, Jason; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; Cheng, Ting-Yuan David; Chia, Kee Seng; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung-Won; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Marchand, Loic Le; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Lee, Chuen Neng; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S.K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Mohd Taib, Nur Aishah; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong-Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I.A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofieva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J. Th.; Saloustros, Emmanouil; Sandler, Dale P.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J.; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A.; Tengström, Maria; Teo, Soo H.; Terry, Mary Beth; Tessier, Daniel C.; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J.; Van Den Berg, David; van den Ouweland, Ans M.W.; van der Kolk, Lizet; van der Luijt, Rob B.; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H.; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R.; Yip, Cheng Har; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R.; Antoniou, Antonis C.; Droit, Arnaud; Andrulis, Irene L.; Amos, Christopher I.; Couch, Fergus J.; Pharoah, Paul D.P.; Chang-Claude, Jenny; Hall, Per; Hunter, David J.; Milne, Roger L.; García-Closas, Montserrat; Schmidt, Marjanka K.; Chanock, Stephen J.; Dunning, Alison M.; Edwards, Stacey L.; Bader, Gary D.; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F.

2017-01-01

Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci associated with overall breast cancer at p<5x10-8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention. PMID:29059683

Standardised survey method for identifying catchment risks to water quality.

PubMed

Baker, D L; Ferguson, C M; Chier, P; Warnecke, M; Watkinson, A

2016-06-01

This paper describes the development and application of a systematic methodology to identify and quantify risks in drinking water and recreational catchments. The methodology assesses microbial and chemical contaminants from both diffuse and point sources within a catchment using Escherichia coli, protozoan pathogens and chemicals (including fuel and pesticides) as index contaminants. Hazard source information is gathered by a defined sanitary survey process involving use of a software tool which groups hazards into six types: sewage infrastructure, on-site sewage systems, industrial, stormwater, agriculture and recreational sites. The survey estimates the likelihood of the site affecting catchment water quality, and the potential consequences, enabling the calculation of risk for individual sites. These risks are integrated to calculate a cumulative risk for each sub-catchment and the whole catchment. The cumulative risks process accounts for the proportion of potential input sources surveyed and for transfer of contaminants from upstream to downstream sub-catchments. The output risk matrices show the relative risk sources for each of the index contaminants, highlighting those with the greatest impact on water quality at a sub-catchment and catchment level. Verification of the sanitary survey assessments and prioritisation is achieved by comparison with water quality data and microbial source tracking.

Identifying the necessary and sufficient number of risk factors for predicting academic failure.

PubMed

Lucio, Robert; Hunt, Elizabeth; Bornovalova, Marina

2012-03-01

Identifying the point at which individuals become at risk for academic failure (grade point average [GPA] < 2.0) involves an understanding of which and how many factors contribute to poor outcomes. School-related factors appear to be among the many factors that significantly impact academic success or failure. This study focused on 12 school-related factors. Using a thorough 5-step process, we identified which unique risk factors place one at risk for academic failure. Academic engagement, academic expectations, academic self-efficacy, homework completion, school relevance, school safety, teacher relationships (positive relationship), grade retention, school mobility, and school misbehaviors (negative relationship) were uniquely related to GPA even after controlling for all relevant covariates. Next, a receiver operating characteristic curve was used to determine a cutoff point for determining how many risk factors predict academic failure (GPA < 2.0). Results yielded a cutoff point of 2 risk factors for predicting academic failure, which provides a way for early identification of individuals who are at risk. Further implications of these findings are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Identifying novel genetic determinants of hemostatic balance.

PubMed

Ginsburg, D

2005-08-01

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

Quantitative Microbial Risk Assessment Tutorial – SDMProjectBuilder: Import Local Data Files to Identify and Modify Contamination Sources and Input Parameters

EPA Science Inventory

Twelve example local data support files are automatically downloaded when the SDMProjectBuilder is installed on a computer. They allow the user to modify values to parameters that impact the release, migration, fate, and transport of microbes within a watershed, and control delin...

A simple risk score identifies individuals at high risk of developing Type 2 diabetes: a prospective cohort study.

PubMed

Rahman, Mushtaqur; Simmons, Rebecca K; Harding, Anne-Helen; Wareham, Nicholas J; Griffin, Simon J

2008-06-01

Randomized trials have demonstrated that Type 2 diabetes is preventable among high-risk individuals. To date, such individuals have been identified through population screening using the oral glucose tolerance test. To assess whether a risk score comprising only routinely collected non-biochemical parameters was effective in identifying those at risk of developing Type 2 diabetes. Population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40-79 recruited from UK general practices attended a health check between 1993 and 1998 (n = 25 639) and were followed for a mean of 5 years for diabetes incidence. The Cambridge Diabetes Risk Score was computed for 24 495 individuals with baseline data on age, sex, prescription of steroids and anti-hypertensive medication, family history of diabetes, body mass index and smoking status. We examined the incidence of diabetes across quintiles of the risk score and plotted a receiver operating characteristic (ROC) curve to assess discrimination. There were 323 new cases of diabetes, a cumulative incidence of 2.76/1000 person-years. Those in the top quintile of risk were 22 times more likely to develop diabetes than those in the bottom quintile (odds ratio 22.3; 95% CI: 11.0-45.4). In all, 54% of all clinically incident cases occurred in individuals in the top quintile of risk (risk score > 0.37). The area under the ROC was 74.5%. The risk score is a simple, effective tool for the identification of those at risk of developing Type 2 diabetes. Such methods may be more feasible than mass population screening with biochemical tests in defining target populations for prevention programmes.

Genetically modified organisms: do the benefits outweigh the risks?

PubMed

Hug, Kristina

2008-01-01

The objective of this literature review is to analyze the implications of using genetically modified organisms (GMOs) as well as international and European position regarding such organisms. Review of international and European legal requirements and ethical guidelines and relevant publications, found and accessed with the help of PubMed and Lund University Library databases. The article discusses the main application areas of GMOs, the expansion of using GMOs in the world as well as the advantages and disadvantages of the implications of their usage. It further provides an overview of the suggested ways to tackle or avoid the GMO-related risks. The international and European positions regarding the application of GMOs are discussed and European Directives, Regulations, and ethical guidelines are overviewed. The article further presents the public attitudes towards GMOs in Europe as well as overviews surveys conducted at the national level. Suggested steps to tackle the challenge of developing and managing biotechnology for the benefit of public health and the environment are presented.

In-depth Investigation of Genetic Region Identifies Mechanism that Contributes to Cancer Risk

Cancer.gov

Investigators in the Laboratory of Translational Genomics have identified a genetic variant in a multi-cancer risk locus at chromosome 5p15.33 that explains, at least in part, the molecular mechanism through which this variant influences cancer risk.

Improvement of Physical Therapist Assessment of Risk of Falls in the Hospital and Discharge Handover Through an Intervention to Modify Clinical Behavior.

PubMed

Thomas, Susie; Mackintosh, Shylie

2016-06-01

Discharge from the hospital is a high risk transition period for older adults at risk of falls. Guidelines relevant to physical therapists for managing this risk are well documented, but commonly not implemented. This project implemented an intervention to improve physical therapists' adherence to key guideline recommendations for managing risk of falls on discharge from one hospital. A pretest-posttest study design was undertaken and was underpinned by the Theoretical Domains Framework (TDF) to aid in the design of interventions to increase physical therapists' adherence to guideline recommendations and to identify barriers to these interventions. A multifaceted intervention was implemented, including the establishment of a governance committee, education sessions, development of a "pathway" to guide practice, modification of an existing standardized assessment proforma, development of standardized processes and indicators for handover, increasing availability of educational handouts, audit and feedback processes, and allocation of dedicated staffing to oversee falls prevention within the physical therapy department. There were significant improvements in physical therapist behavior leading to key guideline recommendations being met, including: the proportion of patients who were identified to be at risk of falls (6.3% preintervention versus 94.8% postintervention) prior to discharge, an increase in documentation of clinical handover at discharge (68.6% preintervention versus 90.9% postintervention), and improvement in the quality of this documented clinical handover (34.9% of case notes met 5 criteria preintervention versus 92.9% postintervention). The approach was resource intensive and consequently may be difficult to replicate at other sites. A multifaceted intervention underpinned by the TDF, designed to modify physical therapists' behavior to improve adherence to guideline recommendations for managing risk of falls on discharge from one hospital, was

Using decision tree analysis to identify risk factors for relapse to smoking

PubMed Central

Piper, Megan E.; Loh, Wei-Yin; Smith, Stevens S.; Japuntich, Sandra J.; Baker, Timothy B.

2010-01-01

This research used classification tree analysis and logistic regression models to identify risk factors related to short- and long-term abstinence. Baseline and cessation outcome data from two smoking cessation trials, conducted from 2001 to 2002, in two Midwestern urban areas, were analyzed. There were 928 participants (53.1% women, 81.8% white) with complete data. Both analyses suggest that relapse risk is produced by interactions of risk factors and that early and late cessation outcomes reflect different vulnerability factors. The results illustrate the dynamic nature of relapse risk and suggest the importance of efficient modeling of interactions in relapse prediction. PMID:20397871

Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus.

PubMed

Urowitz, Murray B; Ibañez, Dominique; Su, Jiandong; Gladman, Dafna D

2016-05-01

The traditional Framingham Risk Factor Score (FRS) underestimates the risk for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We aimed to determine whether an adjustment to the FRS would more accurately reflect the higher prevalence of CAD among patients with SLE. Patients with SLE without a previous history of CAD or diabetes followed regularly at the University of Toronto Lupus Clinic were included. A modified FRS (mFRS) was calculated by multiplying the items by 1.5, 2, 3, or 4. In the first part of the study, using one-third of all eligible patients, we evaluated the sensitivity and specificity of the FRS and the different multipliers for the mFRS. In the second part of the study, using the remaining 2/3 of the eligible patients, we compared the predictive ability of the FRS to the mFRS. In the third part of the study, we assessed the prediction for CAD in a time-dependent analysis of the FRS and mFRS. There were 905 women (89.3%) with a total of 95 CAD events included. In part 1, we determined that a multiplier of 2 provided the best combination of sensitivity and specificity. In part 2, 2.4% of the patients were classified as moderate/high risk based on the classic FRS and 17.3% using the 2FRS (the FRS with a multiplier of 2). In part 3, a time-dependent covariate analysis for the prediction of the first CAD event revealed an HR of 3.22 (p = 0.07) for the classic FRS and 4.37 (p < 0.0001) for the 2FRS. An mFRS in which each item is multiplied by 2 more accurately predicts CAD in patients with SLE.

Identifying Children at High Risk for a Child Maltreatment Report

ERIC Educational Resources Information Center

Dubowitz, Howard; Kim, Jeongeun; Black, Maureen M.; Weisbart, Cindy; Semiatin, Joshua; Magder, Laurence S.

2011-01-01

Objective: To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method: The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for…

The effectiveness of using the workplace to identify and address modifiable health risk factors in deprived populations.

PubMed

Abbas, Syed Zakir; Pollard, Tessa M; Wynn, Philip; Learmonth, Alyson; Joyce, Kerry; Bambra, Clare

2015-09-01

To establish whether a programme of targeted health screening, with referral to appropriate interventions, offered to an employed but socioeconomically deprived group was effective in overcoming barriers to uptake of such services and improving a range of surrogate health markers for participants. Low-paid local government employees from socially and economically deprived areas in North-East England were invited to attend a free health check. Health checks were conducted within working hours and close to their worksite, and included assessment of a range of lifestyle and health-related risk factors, including those associated with cardiovascular disease (CVD). A range of additional interventions were offered where indicated. Participants were invited to repeat screening approximately 9 months later. 635 (20% response rate) employees in the target age group (≥40 years) attended the first check. Most health risk markers improved in those (N=427) attending both health checks, as did the mean CVD risk score (t=2.86, p=0.004). 269 referrals were made to the intervention programmes. This workplace programme had a positive impact on cardiovascular health, but attendance rates were low. These findings suggest that workplace health screening activities may have the potential to improve health in a group often considered hard to reach by other routes, but do not offer a straightforward solution in overcoming barriers to access for such subgroups within the working population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry.

PubMed

Sapkota, Yadav; Vivo, Immaculata De; Steinthorsdottir, Valgerdur; Fassbender, Amelie; Bowdler, Lisa; Buring, Julie E; Edwards, Todd L; Jones, Sarah; O, Dorien; Peterse, Daniëlle; Rexrode, Kathryn M; Ridker, Paul M; Schork, Andrew J; Thorleifsson, Gudmar; Wallace, Leanne M; Kraft, Peter; Morris, Andrew P; Nyholt, Dale R; Edwards, Digna R Velez; Nyegaard, Mette; D'Hooghe, Thomas; Chasman, Daniel I; Stefansson, Kari; Missmer, Stacey A; Montgomery, Grant W

2017-09-12

Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10 -9 ) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.

Mapping eQTLs in the Norfolk Island Genetic Isolate Identifies Candidate Genes for CVD Risk Traits

PubMed Central

Benton, Miles C.; Lea, Rod A.; Macartney-Coxson, Donia; Carless, Melanie A.; Göring, Harald H.; Bellis, Claire; Hanna, Michelle; Eccles, David; Chambers, Geoffrey K.; Curran, Joanne E.; Harper, Jacquie L.; Blangero, John; Griffiths, Lyn R.

2013-01-01

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10−7) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations. PMID:24314549

CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis.

PubMed

Ham, Annelies C; Ziere, Gijsbertus; Broer, Linda; Swart, Karin M A; Enneman, Anke W; van Dijk, Suzanne C; van Wijngaarden, Janneke P; van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; Dhonukshe-Rutten, Rosalie A M; van Schoor, Natasja M; Zillikens, M Carola; van Gelder, Teun; de Vries, Oscar J; Lips, Paul; Deeg, Dorly J H; de Groot, Lisette C P G M; Hofman, Albert; Witkamp, Renger F; Uitterlinden, André G; Stricker, Bruno H; van der Velde, Nathalie

2017-01-01

To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. Three prospective studies; the Rotterdam Study, B-PROOF, and LASA. Community-dwelling individuals living in or near five Dutch cities. There were 11,485 participants aged ≥55 years. Fall incidents were recorded prospectively. Benzodiazepine use was determined using pharmacy dispensing records or interviews. Cox proportional hazard models adjusted for age and sex were applied to determine the association between benzodiazepine use and fall risk stratified for CYP2C9 genotype and comparing benzodiazepine users to nonusers. The results of the three studies were combined applying meta-analysis. Within benzodiazepine users, the association between genotypes and fall risk was also assessed. Three thousand seven hundred five participants (32%) encountered a fall during 91,996 follow-up years, and 4% to 15% (depending on the study population) used benzodiazepines. CYP2C9 variants had frequencies of 13% for the *2 allele and 6% for the *3 allele. Compared to nonusers, current benzodiazepine use was associated with an 18% to 36% increased fall risk across studies with a combined hazard ratio (HR) = 1.26 (95% confidence interval [CI], 1.13; 1.40). CYP2C9*2 or *3 allele variants modified benzodiazepine-related fall risk. Compared to nonusers, those carrying a CYP2C9*2 or *3 allele and using benzodiazepines had a 45% increased fall risk (HR, 1.45 95% CI, 1.21; 1.73), whereas CYP2C9*1 homozygotes using benzodiazepines had no increased fall risk (HR, 1.14; 95% CI, 0.90; 1.45). Within benzodiazepine users, having a CYP2C9*2 or *3 allele was associated with an increased fall risk (HR, 1.35; 95% CI, 1.06; 1.72). Additionally, we observed an allele dose effect; heterozygous allele carriers had a fall risk of (HR = 1.30; 95% CI, 1.05; 1.61), and homozygous allele carriers of (HR = 1.91 95% CI, 1.23; 2.96). CYP2C9*2 and *3 allele variants modify benzodiazepine-related fall risk. Those

Identifying and reducing risk factors related to trainee-client sexual misconduct.

PubMed

Hamilton, J C; Spruill, J

1999-06-01

Sexual misconduct involving therapists-in-training and their clients is addressed. Personal and situational factors that may constitute risk factors for the development of inappropriate sexual activity between trainees and their clients are identified. Although there may be certain characteristics that put particular students at risk for such involvement, the authors believe this risk is more strongly related to systemic, programmatic, and pedagogic characteristics of the environments in which students train. Examples include, respectively, the decline of concern over transference and countertransference, failure to include education about client-therapist sexual attraction and the consequences of sexual misconduct in graduate psychology curricula, and the reluctance of supervisors to deal straightforwardly with trainees' sexual feelings. Suggestions for reducing risks for client-therapist sexual misconduct are directed toward these situational factors.

Hospital Readmission and Social Risk Factors Identified from Physician Notes.

PubMed

Navathe, Amol S; Zhong, Feiran; Lei, Victor J; Chang, Frank Y; Sordo, Margarita; Topaz, Maxim; Navathe, Shamkant B; Rocha, Roberto A; Zhou, Li

2018-04-01

To evaluate the prevalence of seven social factors using physician notes as compared to claims and structured electronic health records (EHRs) data and the resulting association with 30-day readmissions. A multihospital academic health system in southeastern Massachusetts. An observational study of 49,319 patients with cardiovascular disease admitted from January 1, 2011, to December 31, 2013, using multivariable logistic regression to adjust for patient characteristics. All-payer claims, EHR data, and physician notes extracted from a centralized clinical registry. All seven social characteristics were identified at the highest rates in physician notes. For example, we identified 14,872 patient admissions with poor social support in physician notes, increasing the prevalence from 0.4 percent using ICD-9 codes and structured EHR data to 16.0 percent. Compared to an 18.6 percent baseline readmission rate, risk-adjusted analysis showed higher readmission risk for patients with housing instability (readmission rate 24.5 percent; p < .001), depression (20.6 percent; p < .001), drug abuse (20.2 percent; p = .01), and poor social support (20.0 percent; p = .01). The seven social risk factors studied are substantially more prevalent than represented in administrative data. Automated methods for analyzing physician notes may enable better identification of patients with social needs. © Health Research and Educational Trust.

Meat consumption as a risk factor for type 2 diabetes.

PubMed

Barnard, Neal; Levin, Susan; Trapp, Caroline

2014-02-21

Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern.

Meat Consumption as a Risk Factor for Type 2 Diabetes

PubMed Central

Barnard, Neal; Levin, Susan; Trapp, Caroline

2014-01-01

Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern. PMID:24566443

Under the radar: a cross-sectional study of the challenge of identifying at-risk alcohol consumption in the general practice setting.

PubMed

Paul, Christine; Yoong, Sze Lin; Sanson-Fisher, Rob; Carey, Mariko; Russell, Grant; Makeham, Meredith

2014-04-28

Primary care providers are an important source of information regarding appropriate alcohol consumption. As early presentation to a provider for alcohol-related concerns is unlikely, it is important that providers are able to identify at-risk patients in order to provide appropriate advice. This study aimed to report the sensitivity, specificity, positive predictive value and negative predictive value of General Practitioner (GP) assessment of alcohol consumption compared to patient self-report, and explore characteristics associated with GP non-detection of at-risk status. GP practices were selected from metropolitan and regional locations in Australia. Eligible patients were adults presenting for general practice care who were able to understand English and provide informed consent. Patients completed a modified AUDIT-C by touchscreen computer as part of an omnibus health survey while waiting for their appointment. GPs completed a checklist for each patient, including whether the patient met current Australian guidelines for at-risk alcohol consumption. Patient self-report and GP assessments were compared for each patient. GPs completed the checklist for 1720 patients, yielding 1565 comparisons regarding alcohol consumption. The sensitivity of GPs' detection of at-risk alcohol consumption was 26.5%, with specificity of 96.1%. Higher patient education was associated with GP non-detection of at-risk status. GP awareness of which patients might benefit from advice regarding at-risk alcohol consumption appears low. Given the complexities associated with establishing whether alcohol consumption is 'at-risk', computer-based approaches to routine screening of patients are worthy of exploration as a method for prompting the provision of advice in primary care.

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

PubMed

Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

2010-12-01

A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat

PubMed Central

Brevik, Asgeir; Joshi, Amit D.; Corral, Román; Onland-Moret, N. Charlotte; Siegmund, Kimberly D.; Le Marchand, Loïc; Baron, John A.; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

2010-01-01

Background A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents, and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Methods Using a family-based study we investigated the role of polymorphisms in four BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between high-red meat or poultry diets and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Results Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared to carriers of the Gln/Gln genotype (OR 0.15, 95% CI 0.03-0.69, p = 0.015). The association between higher red meat intake (>3 servings/week) and CRC was modified by the PARP Val762Ala SNP (case-only interaction p = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction p = 0.0009). Conclusions We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Impact Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a high-red meat diet. PMID:21037106

State infant mortality: an ecologic study to determine modifiable risks and adjusted infant mortality rates.

PubMed

Paul, David A; Mackley, Amy; Locke, Robert G; Stefano, John L; Kroelinger, Charlan

2009-05-01

To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization procedures. Final risk adjusted IMR's were standardized and states were compared with the United States adjusted rates. Models for IMR in individual states in 2001 (r2 = 0.66, P < 0.01) and 2002 (r2 = 0.81, P < 0.01) were tested. African-American race, teen birth rate, and smoking during pregnancy remained independently associated with state infant mortality rates for 2001 and 2002. Ninety five percent confidence intervals (CI) were calculated around the regression lines to model the expected IMR. After adjustment, some states maintained a consistent IMR; for instance, Vermont and New Hampshire remained low, while Delaware and Louisiana remained high. However, other states such as Mississippi, which have traditionally high infant mortality rates, remained within the expected 95% CI for IMR after adjustment indicating confounding affected the initial unadjusted rates. Non-modifiable demographic variables, including the percentage of non-Hispanic African-American and Hispanic populations of the state are major factors contributing to individual variation in state IMR. Race and ethnicity may confound or modify the IMR in states that shifted inside or outside the 95% CI following adjustment. Other factors including smoking during pregnancy and teen birth rate, which are

Hazardous drinking and military community functioning: identifying mediating risk factors.

PubMed

Foran, Heather M; Heyman, Richard E; Slep, Amy M Smith

2011-08-01

Hazardous drinking is a serious societal concern in military populations. Efforts to reduce hazardous drinking among military personnel have been limited in effectiveness. There is a need for a deeper understanding of how community-based prevention models apply to hazardous drinking in the military. Community-wide prevention efforts may be most effective in targeting community functioning (e.g., support from formal agencies, community cohesion) that impacts hazardous drinking via other proximal risk factors. The goal of the current study is to inform community-wide prevention efforts by testing a model of community functioning and mediating risk factors of hazardous drinking among active duty U.S. Air Force personnel. A large, representative survey sample of U.S. Air Force active duty members (N = 52,780) was collected at 82 bases worldwide. Hazardous drinking was assessed with the widely used Alcohol Use Disorders Identification Test (Saunders, Aasland, Babor, de la Fuente, & Grant, 1993). A variety of individual, family, and community measures were also assessed. Structural equation modeling was used to test a hypothesized model of community functioning, mediating risk factors and hazardous drinking. Depressive symptoms, perceived financial stress, and satisfaction with the U.S. Air Force were identified as significant mediators of the link between community functioning and hazardous drinking for men and women. Relationship satisfaction was also identified as a mediator for men. These results provide a framework for further community prevention research and suggest that prevention efforts geared at increasing aspects of community functioning (e.g., the U.S. Air Force Community Capacity model) may indirectly lead to reductions in hazardous drinking through other proximal risk factors.

Modifying Electroglottograph-Identified Intervals of Phonation: The Effect on Stuttering.

ERIC Educational Resources Information Center

Gow, Merrilyn L.; Ingham, Roger J.

1992-01-01

This study, involving an adolescent and adult male with stuttering problems, evaluated modification of the frequency of electroglottograph-measured phonation intervals on stuttering and speech naturalness. Both subjects demonstrated that stuttering could be controlled by modifying the frequency of phonation intervals within short duration ranges,…

A scoping review of epidemiologic risk factors for pediatric obesity: Implications for future childhood obesity and dental caries prevention research.

PubMed

Chi, Donald L; Luu, Monique; Chu, Frances

2017-06-01

What are the non-modifiable (socioeconomic, genetic) and modifiable factors (physical activity, dietary behaviors) related to childhood (under age 12) obesity? How can this knowledge be applied to oral health professionals' efforts to prevent or manage dental caries in children? Studies have identified risk factors for childhood obesity. The purpose of this scoping review was to develop a conceptual model to identify non-modifiable and modifiable risk factors for childhood obesity and to illustrate how these findings are relevant in developing interventions aimed at preventing obesity and dental caries in children. The authors searched PubMed and Embase and limited the study to English-language publications. A total of 2,572 studies were identified. After de-duplication, 2,479 studies remained and were downloaded into a citation-management tool. Two authors screened the titles and abstracts for relevance. Two hundred and sixty studies remained and were retrieved for a full-text review, and 80 studies were excluded, resulting in 180 studies included in the scoping review. An inductive content analytic methods was used to organize all statistically significant obesity risk factors into seven domains, which were classified as non-modifiable or modifiable; then a conceptual model of common risk factors associated with childhood obesity and dental caries was developed. Non-modifiable obesity risk factors include biological and developmental (e.g., genes, developmental conditions, puberty), sociodemographic and household (e.g., race/ethnicity, socioeconomic status, parent education, unemployment), cultural (e.g., degree of acculturation), and community (e.g., neighborhood composition). Modifiable risk factors included behavioral (e.g., diet, physical activity, weight), psychosocial (e.g., maternal stress, family functioning, parenting practices, child temperament), and medical (e.g., parent smoking, maternal health, child health). Identifying common risk factors has

Identifying Falls Risk Screenings Not Documented with Administrative Codes Using Natural Language Processing

PubMed Central

Zhu, Vivienne J; Walker, Tina D; Warren, Robert W; Jenny, Peggy B; Meystre, Stephane; Lenert, Leslie A

2017-01-01

Quality reporting that relies on coded administrative data alone may not completely and accurately depict providers’ performance. To assess this concern with a test case, we developed and evaluated a natural language processing (NLP) approach to identify falls risk screenings documented in clinical notes of patients without coded falls risk screening data. Extracting information from 1,558 clinical notes (mainly progress notes) from 144 eligible patients, we generated a lexicon of 38 keywords relevant to falls risk screening, 26 terms for pre-negation, and 35 terms for post-negation. The NLP algorithm identified 62 (out of the 144) patients who falls risk screening documented only in clinical notes and not coded. Manual review confirmed 59 patients as true positives and 77 patients as true negatives. Our NLP approach scored 0.92 for precision, 0.95 for recall, and 0.93 for F-measure. These results support the concept of utilizing NLP to enhance healthcare quality reporting. PMID:29854264

Identifying high-risk roadways for infrastructure investment using naturalistic driving data.

DOT National Transportation Integrated Search

2015-08-01

The state-of-the-practice for most municipal traffic agencies seeking to identify high-risk road segments : has been to use prior crash history. While historic traffic crash data is recognized to be valuable in : improving roadway safety, it relies o...

Problem formulation in the environmental risk assessment for genetically modified plants

PubMed Central

Wolt, Jeffrey D.; Keese, Paul; Raybould, Alan; Burachik, Moisés; Gray, Alan; Olin, Stephen S.; Schiemann, Joachim; Sears, Mark; Wu, Felicia

2009-01-01

Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation. PMID:19757133

Genome-wide association study identifies multiple loci associated with bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

2014-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

Identifying areas of deforestation risk for REDD+ using a species modeling tool

PubMed Central

Riveros, Juan Carlos; Forrest, Jessica L

2014-01-01

Background To implement the REDD+ mechanism (Reducing Emissions for Deforestation and Forest Degradation, countries need to prioritize areas to combat future deforestation CO2 emissions, identify the drivers of deforestation around which to develop mitigation actions, and quantify and value carbon for financial mechanisms. Each comes with its own methodological challenges, and existing approaches and tools to do so can be costly to implement or require considerable technical knowledge and skill. Here, we present an approach utilizing a machine learning technique known as Maximum Entropy Modeling (Maxent) to identify areas at high deforestation risk in the study area in Madre de Dios, Peru under a business-as-usual scenario in which historic deforestation rates continue. We link deforestation risk area to carbon density values to estimate future carbon emissions. We quantified area deforested and carbon emissions between 2000 and 2009 as the basis of the scenario. Results We observed over 80,000 ha of forest cover lost from 2000-2009 (0.21% annual loss), representing over 39 million Mg CO2. The rate increased rapidly following the enhancement of the Inter Oceanic Highway in 2005. Accessibility and distance to previous deforestation were strong predictors of deforestation risk, while land use designation was less important. The model performed consistently well (AUC > 0.9), significantly better than random when we compared predicted deforestation risk to observed. If past deforestation rates continue, we estimate that 132,865 ha of forest could be lost by the year 2020, representing over 55 million Mg CO2. Conclusions Maxent provided a reliable method for identifying areas at high risk of deforestation and the major explanatory variables that could draw attention for mitigation action planning under REDD+. The tool is accessible, replicable and easy to use; all necessary for producing good risk estimates and adapt models after potential landscape change. We

Identifying areas of deforestation risk for REDD+ using a species modeling tool.

PubMed

Aguilar-Amuchastegui, Naikoa; Riveros, Juan Carlos; Forrest, Jessica L

2014-01-01

To implement the REDD+ mechanism (Reducing Emissions for Deforestation and Forest Degradation, countries need to prioritize areas to combat future deforestation CO2 emissions, identify the drivers of deforestation around which to develop mitigation actions, and quantify and value carbon for financial mechanisms. Each comes with its own methodological challenges, and existing approaches and tools to do so can be costly to implement or require considerable technical knowledge and skill. Here, we present an approach utilizing a machine learning technique known as Maximum Entropy Modeling (Maxent) to identify areas at high deforestation risk in the study area in Madre de Dios, Peru under a business-as-usual scenario in which historic deforestation rates continue. We link deforestation risk area to carbon density values to estimate future carbon emissions. We quantified area deforested and carbon emissions between 2000 and 2009 as the basis of the scenario. We observed over 80,000 ha of forest cover lost from 2000-2009 (0.21% annual loss), representing over 39 million Mg CO2. The rate increased rapidly following the enhancement of the Inter Oceanic Highway in 2005. Accessibility and distance to previous deforestation were strong predictors of deforestation risk, while land use designation was less important. The model performed consistently well (AUC > 0.9), significantly better than random when we compared predicted deforestation risk to observed. If past deforestation rates continue, we estimate that 132,865 ha of forest could be lost by the year 2020, representing over 55 million Mg CO2. Maxent provided a reliable method for identifying areas at high risk of deforestation and the major explanatory variables that could draw attention for mitigation action planning under REDD+. The tool is accessible, replicable and easy to use; all necessary for producing good risk estimates and adapt models after potential landscape change. We propose this approach for developing

Identifying Students at Risk: An Examination of Computer-Adaptive Measures and Latent Class Growth Analysis

ERIC Educational Resources Information Center

Keller-Margulis, Milena; McQuillin, Samuel D.; Castañeda, Juan Javier; Ochs, Sarah; Jones, John H.

2018-01-01

Multitiered systems of support depend on screening technology to identify students at risk. The purpose of this study was to examine the use of a computer-adaptive test and latent class growth analysis (LCGA) to identify students at risk in reading with focus on the use of this methodology to characterize student performance in screening.…

Feasibility of a Modified E-PASS and POSSUM System for Postoperative Risk Assessment in Patients with Spinal Disease.

PubMed

Chun, Dong Hyun; Kim, Do Young; Choi, Sun Kyu; Shin, Dong Ah; Ha, Yoon; Kim, Keung Nyun; Yoon, Do Heum; Yi, Seong

2018-04-01

This retrospective case control study aimed to evaluate the feasibility of using Estimation of Physiological Ability and Surgical Stress (E-PASS) and Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) systems in patients undergoing spinal surgical procedures. Degenerative spine disease has increased in incidence in aging societies, as has the number of older adult patients undergoing spinal surgery. Many older adults are at a high surgical risk because of comorbidity and poor general health. We retrospectively reviewed 217 patients who had undergone spinal surgery at a single tertiary care. We investigated complications within 1 month after surgery. Criteria for both skin incision in E-PASS and operation magnitude in the POSSUM system were modified to fit spine surgery. We calculated the E-PASS and POSSUM scores for enrolled patients, and investigated the relationship between postoperative complications and both surgical risk scoring systems. To reinforce the predictive ability of the E-PASS system, we adjusted equations and developed modified E-PASS systems. The overall complication rate for spinal surgery was 22.6%. Forty-nine patients experienced 58 postoperative complications. Nineteen major complications, including hematoma, deep infection, pleural effusion, progression of weakness, pulmonary edema, esophageal injury, myocardial infarction, pneumonia, reoperation, renal failure, sepsis, and death, occurred in 17 patients. The area under the receiver operating characteristic curve (AUC) for predicted postoperative complications after spine surgery was 0.588 for E-PASS and 0.721 for POSSUM. For predicted major postoperative complications, the AUC increased to 0.619 for E-PASS and 0.842 for POSSUM. The AUC of the E-PASS system increased from 0.588 to 0.694 with the Modified E-PASS equation. The POSSUM system may be more useful than the E-PASS system for estimating postoperative surgical risk in patients undergoing

A modified fetal heart rate tracing interpretation system for prediction of cesarean section

PubMed Central

Schnettler, William T.; Rogers, Jennifer; Barber, Rachel E.; Hacker, Michele R.

2013-01-01

Objective To investigate whether a modified version of the 2008 National Institute of Child Health and Human Development (NICHD) interpretation system upon admission decreases cesarean delivery risk. Methods This retrospective cohort study ascribed a modified category to the first 30 min of fetal heart rate (FHR) tracings in labor. Category I was divided into two subsets (Ia and Ib) by the presence of accelerations. Category II was divided into four subsets (IIa–IId) based on baseline FHR, variability, response to stimulation and decelerations. Log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). Results A category was ascribed to 910 women. Most FHR tracings were Category Ia (65.8%), Ib (7.7%), IIb (11.8%) and IId (14.0%). Category Ib tracings (fewer than two accelerations) were 2.26 (95% CI: 1.13–4.52) times more likely to result in cesarean delivery for abnormal FHR tracing than Category Ia tracings. A similar increase in risk was seen when comparing Category IIb and Category IId with Category Ia. Conclusion Application of a modified version of the 2008 NICHD FHR interpretation system to the initial 30 min of labor can identify women at increased risk of cesarean delivery for abnormal FHR tracing. PMID:21942513

Genetic Modifiers of Neurofibromatosis Type 1-Associated Café-au-Lait Macule Count Identified Using Multi-platform Analysis

PubMed Central

Pemov, Alexander; Sung, Heejong; Hyland, Paula L.; Sloan, Jennifer L.; Ruppert, Sarah L.; Baldwin, Andrea M.; Boland, Joseph F.; Bass, Sara E.; Lee, Hyo Jung; Jones, Kristine M.; Zhang, Xijun; Mullikin, James C.; Widemann, Brigitte C.; Wilson, Alexander F.; Stewart, Douglas R.

2014-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant, monogenic disorder of dysregulated neurocutaneous tissue growth. Pleiotropy, variable expressivity and few NF1 genotype-phenotype correlates limit clinical prognostication in NF1. Phenotype complexity in NF1 is hypothesized to derive in part from genetic modifiers unlinked to the NF1 locus. In this study, we hypothesized that normal variation in germline gene expression confers risk for certain phenotypes in NF1. In a set of 79 individuals with NF1, we examined the association between gene expression in lymphoblastoid cell lines with NF1-associated phenotypes and sequenced select genes with significant phenotype/expression correlations. In a discovery cohort of 89 self-reported European-Americans with NF1 we examined the association between germline sequence variants of these genes with café-au-lait macule (CALM) count, a tractable, tumor-like phenotype in NF1. Two correlated, common SNPs (rs4660761 and rs7161) between DPH2 and ATP6V0B were significantly associated with the CALM count. Analysis with tiled regression also identified SNP rs4660761 as significantly associated with CALM count. SNP rs1800934 and 12 rare variants in the mismatch repair gene MSH6 were also associated with CALM count. Both SNPs rs7161 and rs4660761 (DPH2 and ATP6V0B) were highly significant in a mega-analysis in a combined cohort of 180 self-reported European-Americans; SNP rs1800934 (MSH6) was near-significant in a meta-analysis assuming dominant effect of the minor allele. SNP rs4660761 is predicted to regulate ATP6V0B, a gene associated with melanosome biology. Individuals with homozygous mutations in MSH6 can develop an NF1-like phenotype, including multiple CALMs. Through a multi-platform approach, we identified variants that influence NF1 CALM count. PMID:25329635

Hypertension Risk Subsequent to Gestational Dysglycemia Is Modified by Race/Ethnicity.

PubMed

Bentley-Lewis, Rhonda; Huynh, Jennifer; Li, Sylvia; Wenger, Julia; Thadhani, Ravi

2016-01-01

Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a mean±standard deviation of 4.1±2.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P=0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P=0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted. © 2015 American Heart Association, Inc.

Quantifying prognosis with risk predictions.

PubMed

Pace, Nathan L; Eberhart, Leopold H J; Kranke, Peter R

2012-01-01

Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes.

Incident Risk Factors and Major Bleeding in Patients with Atrial Fibrillation Treated with Oral Anticoagulants: A Comparison of Baseline, Follow-up and Delta HAS-BLED Scores with an Approach Focused on Modifiable Bleeding Risk Factors.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-04-01

 When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the 'delta HAS-BLED score' (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score.  A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean 'delta HAS-BLED score' of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a 'delta HAS-BLED' score ≥1, compared with only 59.0% in patients without major bleeding ( p  < 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49).  In this 'real-world' nationwide AF cohort, follow-up HAS-BLED or 'delta HAS-BLED score' was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of 'modifiable bleeding risk factors'. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to 'flag up' patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits. Schattauer GmbH Stuttgart.

Risk factors for first time incidence sciatica: a systematic review.

PubMed

Cook, Chad E; Taylor, Jeffrey; Wright, Alexis; Milosavljevic, Steven; Goode, Adam; Whitford, Maureen

2014-06-01

Characteristically, sciatica involves radiating leg pain that follows a dermatomal pattern along the distribution of the sciatic nerve. To our knowledge, there are no studies that have investigated risk factors associated with first time incidence sciatica. The purpose of the systematic review was to identify the longitudinal risk factors associated with first time incidence sciatica and to report incidence rates for the condition. For the purposes of this review, first time incidence sciatica was defined as either of the following: 1) no prior history of sciatica or 2) transition from a pain-free state to sciatica. Studies included subjects of any age from longitudinal, observational, cohort designs. The study was a systematic review. Eight of the 239 articles identified by electronic search strategies met the inclusion criteria. Risk factors and their respective effect estimates were reported using descriptive analysis and the preferred reporting items for systematic reviews and meta-analyses guidelines. Modifiable risk factors included smoking, obesity, occupational factors and health status. Non-modifiable factors included age, gender and social class. Incidence rates varied among the included studies, in part reflecting the variability in the operationalized definition of sciatica but ranged from <1% to 37%. A majority of the identified risk factors associated with first time sciatica are modifiable, suggesting the potential benefits of primary prevention. In addition, those risk factors are also associated with unhealthy lifestyles, which may function concomitantly toward the development of sciatica. Sciatica as a diagnosis is inconsistently defined among studies. © 2013 John Wiley & Sons, Ltd.

Role of Cigarette Sensory Cues in Modifying Puffing Topography

PubMed Central

Rees, Vaughan W.; Kreslake, Jennifer M.; Wayne, Geoffrey Ferris; O Connor, Richard J.; Cummings, K. Michael; Connolly, Gregory N.

2012-01-01

Background Human puffing topography promotes tobacco dependence by ensuring nicotine delivery, but the factors that determine puffing behavior are not well explained by existing models. Chemosensory cues generated by variations in cigarette product design features may serve as conditioned cues to allow the smoker to optimize nicotine delivery by adjusting puffing topography. Internal tobacco industry research documents were reviewed to understand the influence of sensory cues on puffing topography, and to examine how the tobacco industry has designed cigarettes, including modified risk tobacco products (MRTPs), to enhance puffing behavior to optimize nicotine delivery and product acceptability. Methods Relevant internal tobacco industry documents were identified using systematic searching with key search terms and phrases, and then snowball sampling method was applied to establish further search terms. Results Modern cigarettes are designed by cigarette manufacturers to provide sensory characteristics that not only maintain appeal, but provide cues which inform puffing intensity. Alterations in the chemosensory cues provided in tobacco smoke play an important role in modifying smoking behavior independently of the central effects of nicotine. Conclusions An associative learning model is proposed to explain the influence of chemosensory cues on variation in puffing topography. These cues are delivered via tobacco smoke and are moderated by design features and additives used in cigarettes. The implications for regulation of design features of modified risk tobacco products, which may act to promote intensive puffing while lowering risk perceptions, are discussed. PMID:22365895

Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers

PubMed Central

Walker, Logan C; Marquart, Louise; Pearson, John F; Wiggins, George A R; O'Mara, Tracy A; Parsons, Michael T; Barrowdale, Daniel; McGuffog, Lesley; Dennis, Joe; Benitez, Javier; Slavin, Thomas P; Radice, Paolo; Frost, Debra; Godwin, Andrew K; Meindl, Alfons; Schmutzler, Rita Katharina; Isaacs, Claudine; Peshkin, Beth N; Caldes, Trinidad; Hogervorst, Frans BL; Lazaro, Conxi; Jakubowska, Anna; Montagna, Marco; Chen, Xiaoqing; Offit, Kenneth; Hulick, Peter J; Andrulis, Irene L; Lindblom, Annika; Nussbaum, Robert L; Nathanson, Katherine L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Couch, Fergus J; Spurdle, Amanda B

2017-01-01

Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk. To conduct the first genome-wide association analysis of copy-number variants (CNVs) with breast or ovarian cancer risk in a cohort of 2500 BRCA1 pathogenic variant carriers, CNV discovery was performed using multiple calling algorithms and Illumina 610k SNP array data from a previously published genome-wide association study. Our analysis, which focused on functionally disruptive genomic deletions overlapping gene regions, identified a number of loci associated with risk of breast or ovarian cancer for BRCA1 pathogenic variant carriers. Despite only including putative deletions called by at least two or more algorithms, detection of selected CNVs by ancillary molecular technologies only confirmed 40% of predicted common (>1% allele frequency) variants. These include four loci that were associated (unadjusted P<0.05) with breast cancer (GTF2H2, ZNF385B, NAALADL2 and PSG5), and two loci associated with ovarian cancer (CYP2A7 and OR2A1). An interesting finding from this study was an association of a validated CNV deletion at the CYP2A7 locus (19q13.2) with decreased ovarian cancer risk (relative risk=0.50, P=0.007). Genomic analysis found this deletion coincides with a region displaying strong regulatory potential in ovarian tissue, but not in breast epithelial cells. This study highlighted the need to verify CNVs in vitro, but also provides evidence that experimentally validated CNVs (with plausible biological consequences) can modify risk of breast or ovarian cancer in BRCA1 pathogenic variant carriers. PMID:28145423

Classification of drugs with different risk profiles.

PubMed

Saedder, Eva Aggerholm; Brock, Birgitte; Nielsen, Lars Peter; Bonnerup, Dorthe Krogsgaard; Lisby, Marianne

2015-08-01

A risk stratification approach is needed to identify patients at high risk of medication errors and a resulting high need of medication review. The aim of this study was to perform risk stratification (distinguishing between low-risk, medium-risk and high-risk drugs) for drugs found to cause serious adverse reactions due to medication errors. The study employed a modified Delphi technique. Drugs from a systematic literature search were included into two rounds of a Delphi process. A panel of experts was asked to evaluate each identified drug's potential for harm and for clinically relevant drug-drug interactions on a scale from 1 (low risk) to 9 (high risk). A total of 36 experts were appointed to serve on the panel. Consensus was reached for 29/57 (51%) drugs or drug classes that cause harm, and for 32/57 (56%) of the drugs or drug classes that cause interactions. For the remaining drugs, a decision was made based on the median score. Two lists, one stating the drugs' potential for causing harm and the other stating clinically relevant drug-drug interactions, were stratified into low-risk, medium-risk and high-risk drugs. Based on a modified Delphi technique, we created two lists of drugs stratified into a low-risk, a medium-risk and a high-risk group of clinically relevant interactions or risk of harm to patients. The lists could be incorporated into a risk-scoring tool that stratifies the performance of medication reviews according to patients' risk of experiencing adverse reactions. none. not relevant.

The Readmission Risk Flag: Using the Electronic Health Record to Automatically Identify Patients at Risk for 30-day Readmission

PubMed Central

Baillie, Charles A.; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C. William; Behta, Maryam; Umscheid, Craig A.

2015-01-01

Background Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. Objective To develop and implement an automated prediction model integrated into our health system’s EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Design Retrospective and prospective cohort. Setting Healthcare system consisting of three hospitals. Patients All adult patients admitted from August 2009 to September 2012. Interventions An automated readmission risk flag integrated into the EHR. Measures Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Results Using retrospective data, a single risk factor, ≥2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a c-statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%) and c-statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. Conclusions An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. PMID:24227707

The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission.

PubMed

Baillie, Charles A; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C William; Behta, Maryam; Umscheid, Craig A

2013-12-01

Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Retrospective and prospective cohort. Healthcare system consisting of 3 hospitals. All adult patients admitted from August 2009 to September 2012. An automated readmission risk flag integrated into the EHR. Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Using retrospective data, a single risk factor, ≥ 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. © 2013 Society of Hospital Medicine.

Sexual Risk Behavior Among Youth With Bipolar Disorder: Identifying Demographic and Clinical Risk Factors.

PubMed

Krantz, Megan; Goldstein, Tina; Rooks, Brian; Merranko, John; Liao, Fangzi; Gill, Mary Kay; Diler, Rasim; Hafeman, Danella; Ryan, Neal; Goldstein, Benjamin; Yen, Shirley; Hower, Heather; Hunt, Jeffrey; Keller, Martin; Strober, Michael; Axelson, David; Birmaher, Boris

2018-02-01

This study aims to document rates of sexual activity among youth with bipolar spectrum disorder (BD) and to examine demographic and clinical factors associated with first sexual activity and sexual risk behavior during follow-up. The sample was drawn from the Course and Outcome of Bipolar Youth (COBY) study of 413 youth 7 to 17 years at baseline who met criteria for bipolar spectrum disorder according to the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Psychiatric symptoms during follow-up were assessed using the Adolescent Longitudinal Interview Follow-Up Evaluation (ALIFE). Sexual behavior and level of sexual risk (e.g., unprotected sex, multiple partners, and/or partners with known sexually transmitted infections) were assessed by trained evaluators using the ALIFE Psychosocial Functioning Scale. Analyses were conducted in relation to first sexual behavior during follow-up and then to subsequent sexual behaviors (mean 9.7 years, standard deviation 3.2). Sexually active COBY youth (n = 292 of 413; 71%) were more likely females, using substances, and not living with both parents. Consistent with findings among healthy youth, earlier first sexual activity in the sample was significantly associated with low socioeconomic status, female sex, comorbid disruptive behavior disorder, and substance use. As with healthy youth, sexual risk behavior during follow-up was significantly associated with non-Caucasian race, low socioeconomic status, substance use, and history of sexual abuse. Of those COBY youth who were sexually active, 11% reported sexual assault or abuse, 36% reported becoming pregnant (or the significant other becoming pregnant), and 15% reported having at least 1 abortion (or the significant other having an abortion) during follow-up. Hypomanic symptoms during follow-up were temporally associated with the greatest risk for sexual risk behavior. Demographic and clinical factors could help identify youth with bipolar spectrum

Quantitative Microbial Risk Assessment Tutorial - SDMProjectBuilder: Import Local Data Files to Identify and Modify Contamination Sources and Input ParametersUpdated 2017

EPA Science Inventory

Twelve example local data support files are automatically downloaded when the SDMProjectBuilder is installed on a computer. They allow the user to modify values to parameters that impact the release, migration, fate, and transport of microbes within a watershed, and control delin...

A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

PubMed

Clark, Renee M; Besterfield-Sacre, Mary E

2009-03-01

We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers.

PubMed

Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuan-Lin; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Kim, Sungeun; Saykin, Andrew J; De Jager, Philip L; Albert, Marilyn; Moghekar, Abhay; O'Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M; Lee, Virginia Man-Yee; Shaw, Leslie M; Trojanowski, John Q; Schellenberg, Gerard; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Peskind, Elaine R; Li, Ge; Di Narzo, Antonio F; Kauwe, John S K; Goate, Alison M; Cruchaga, Carlos

2017-05-01

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ 42 ), tau, and phosphorylated tau (ptau 181 ) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau 181 , including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ 42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10 -8 ) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10 -8 ) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10 -2 ), disease progression (GLIS1: β = 0.277, P = 1.92 × 10 -2 ), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10 -3 ). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ 42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau 181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings

Identifying high-risk small business industries for occupational safety and health interventions.

PubMed

Okun, A; Lentz, T J; Schulte, P; Stayner, L

2001-03-01

Approximately one-third (32%) of U.S. workers are employed in small business industries (those with 80% of workers in establishments with fewer than 100 employees), and approximately 53 million persons in private industry work in small business establishments. This study was performed to identify small business industries at high risk for occupational injuries, illnesses, and fatalities. Small business industries were identified from among all three- and four-digit Standard Industrial Classification (SIC) codes and ranked using Bureau of Labor Statistics (BLS) data by rates and numbers of occupational injuries, illnesses, and fatalities. Both incidence rates and number of injury, illness, and fatality cases were evaluated. The 253 small business industries identified accounted for 1,568 work-related fatalities (34% of all private industry). Transportation incidents and violent acts were the leading causes of these fatalities. Detailed injury and illness data were available for 105 small business industries, that accounted for 1,476,400 work-related injuries, and 55,850 occupational illnesses. Many of the small business industries had morbidity and mortality rates exceeding the average rates for all private industry. The highest risk small business industries, based on a combined morbidity and mortality index, included logging, cut stone and stone products, truck terminals, and roofing, siding, and sheet metal work. Identification of high-risk small business industries indicates priorities for those interested in developing targeted prevention programs.

Using a single binge drinking question to identify Russian women at risk for an alcohol-exposed pregnancy.

PubMed

Balachova, Tatiana; Sobell, Linda Carter; Agrawal, Sangeeta; Isurina, Galina; Tsvetkova, Larissa; Volkova, Elena; Bohora, Som

2015-07-01

Low rates of contraception and at-risk drinking place many Russian women at risk of an alcohol-exposed pregnancy (AEP). The only realistic way to determine when women are at risk of AEP is by self-reports. A U.S. study found that a single binge-drinking question (SBD) effectively identified nearly all women whose drinking placed them at risk of AEP. The present study replicated the U.S. Participants were 689 non-pregnant Russian women of childbearing age who were at AEP risk. Their answers to SBD, "During the previous three months, how often did you have four or more drinks on one occasion", were compared with their reports of binge drinking on a 90-day Timeline Followback (TLFB) calendar. The SBD identified 99% of at-risk Russian women as binge drinkers, replicating U.S. Only 8% of the women were identified at-risk using a second AEP criterion of ≥8 drinks on average per week. Although Russian women did not report heavy weekly drinking and two-thirds did not meet AUDIT criteria for problem drinking, when they did drink, 40% of the time it was binge drinking. Almost all Russian women who were at risk of an AEP were identified by a single binge-drinking question. Results from this study suggest that Russian health care practitioners can use SBD to successfully screen women for AEP risk. SBD identified 99% of Russian women who were at AEP risk. Consequently, it is recommended that SBD be incorporated into routine health care screenings at OB/GYN clinic visits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychosocial and cultural factors affecting the perceived risk of genetically modified food: an overview of the literature.

PubMed

Finucane, Melissa L; Holup, Joan L

2005-04-01

The rapid globalization of the world economy has increased the need for an astute understanding of cultural differences in perceptions, values, and ways of thinking about new food technologies. In this paper, we describe how socio-psychological and cultural factors may affect public perceptions of the risk of genetically modified (GM) food. We present psychological, sociological, and anthropological research on risk perception as a framework for understanding cross-national differences in reactions to GM food. Differences in the cultural values and circumstances of people in the US, European countries, and the developing world are examined. The implications of cultural theory for risk communication and decision making about GM food are discussed and directions for future research highlighted.

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders.

PubMed

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-06-04

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as "relatively low", contrasting with 21.4% rated as "relatively high". Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders.

Typical patterns of modifiable health risk factors (MHRFs) in elderly women in Germany: results from the cross-sectional German Health Update (GEDA) study, 2009 and 2010.

PubMed

Jentsch, Franziska; Allen, Jennifer; Fuchs, Judith; von der Lippe, Elena

2017-04-04

Modifiable health risk factors (MHRFs) significantly affect morbidity and mortality rates and frequently occur in specific combinations or risk clusters. Using five MHRFs (smoking, high-risk alcohol consumption, physical inactivity, low intake of fruits and vegetables, and obesity) this study investigates the extent to which risk clusters are observed in a representative sample of women aged 65 and older in Germany. Additionally, the structural composition of the clusters is systematically compared with data and findings from other countries. A pooled data set of Germany's representative cross-sectional surveys GEDA09 and GEDA10 was used. The cohort comprised 4,617 women aged 65 and older. Specific risk clusters based on five MHRFs are identified, using hierarchical cluster analysis. The MHRFs were defined as current smoking (daily or occasionally), risk alcohol consumption (according to the Alcohol Use Disorders Identification Test, a sum score of 4 or more points), physical inactivity (less active than 5 days per week for at least 30 min and lack of sports-related activity in the last three months), low intake of fruits and vegetables (less than one serving of fruits and one of vegetables per day), and obesity (a body mass index equal to or greater than 30). A total of 4,292 cases with full information on these factors are included in the cluster analysis. Extended analyses were also performed to include the number of chronic diseases by age and socioeconomic status of group members. A total of seven risk clusters were identified. In a comparison with data from international studies, the seven risk clusters were found to be stable with a high degree of structural equivalency. Evidence of the stability of risk clusters across various study populations provides a useful starting point for long-term targeted health interventions. The structural clusters provide information through which various MHRFs can be evaluated simultaneously.

The association between creatinine versus cystatin C-based eGFR and cardiovascular risk in children with chronic kidney disease using a modified PDAY risk score.

PubMed

Sharma, Sheena; Denburg, Michelle R; Furth, Susan L

2017-08-01

Children with chronic kidney disease (CKD) have a high prevalence of cardiovascular disease (CVD) risk factors which may contribute to the development of cardiovascular events in adulthood. Among adults with CKD, cystatin C-based estimates of glomerular filtration rate (eGFR) demonstrate a stronger predictive value for cardiovascular events than creatinine-based eGFR. The PDAY (Pathobiological Determinants of Atherosclerosis in Youth) risk score is a validated tool used to estimate the probability of advanced coronary atherosclerotic lesions in young adults. To assess the association between cystatin C-based versus creatinine-based eGFR (eGFR cystatin C and eGFR creatinine, respectively) and cardiovascular risk using a modified PDAY risk score as a proxy for CVD in children and young adults. We performed a cross-sectional study of 71 participants with CKD [median age 15.5 years; inter-quartile range (IQR) 13, 17], and 33 healthy controls (median age 15.1 years; IQR 13, 17). eGFR was calculated using age-appropriate creatinine- and cystatin C-based formulas. Median eGFR creatinine and eGFR cystatin C for CKD participants were 50 (IQR 30, 75) and 53 (32, 74) mL/min/1.73 m 2 , respectively. For the healthy controls, median eGFR creatinine and eGFR cystatin were 112 (IQR 85, 128) and 106 mL/min/1.73m 2 (95, 123) mL/min/1.73 m 2 , respectively. A modified PDAY risk score was calculated based on sex, age, serum lipoprotein concentrations, obesity, smoking status, hypertension, and hyperglycemia. Modified PDAY scores ranged from -2 to 20. The Spearman's correlations of eGFR creatinine and eGFR cystatin C with coronary artery PDAY scores were -0.23 (p = 0.02) and -0.28 (p = 0.004), respectively. Ordinal logistic regression also showed a similar association of higher eGFR creatinine and higher eGFR cystatin C with lower PDAY scores. When stratified by age <18 or ≥18 years, the correlations of eGFR creatinine and eGFR cystatin C with PDAY score were modest and similar in

Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study.

PubMed

Jenum, Anne K; Mørkrid, Kjersti; Sletner, Line; Vangen, Siri; Vange, Siri; Torper, Johan L; Nakstad, Britt; Voldner, Nanna; Rognerud-Jensen, Odd H; Berntsen, Sveinung; Mosdøl, Annhild; Skrivarhaug, Torild; Vårdal, Mari H; Holme, Ingar; Yajnik, Chittaranjan S; Birkeland, Kåre I

2012-02-01

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria. This was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l. OGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%, P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic minorities 37%, P< 0.001). Using the WHO criteria, ethnic minority origin was an independent predictor (South Asians, odds ratio (OR) 2.24 (95% confidence interval (CI) 1.26-3.97); Middle Easterners, OR 2.13 (1.12-4.08)) after adjustments for age, parity, and prepregnant body mass index (BMI). This increased OR was unapparent after further adjustments for body height (proxy for early life socioeconomic status), education and family history of diabetes. Using the modified IADPSG criteria, prepregnant BMI (1.09 (1.05-1.13)) and ethnic minority origin (South Asians, 2.54 (1.56-4.13)) were independent predictors, while education, body height and family history had little impact. GDM prevalence was overall 2.4-times higher with the modified IADPSG criteria compared with the WHO criteria. The new criteria identified many subjects with a relatively mild increase in FPG, strongly associated with South Asian origin and prepregnant overweight.

Risk Prioritization Tool to Identify the Public Health Risks of Wildlife Trade: The Case of Rodents from Latin America.

PubMed

Bueno, I; Smith, K M; Sampedro, F; Machalaba, C C; Karesh, W B; Travis, D A

2016-06-01

Wildlife trade (both formal and informal) is a potential driver of disease introduction and emergence. Legislative proposals aim to prevent these risks by banning wildlife imports, and creating 'white lists' of species that are cleared for importation. These approaches pose economic harm to the pet industry, and place substantial burden on importers and/or federal agencies to provide proof of low risk for importation of individual species. As a feasibility study, a risk prioritization tool was developed to rank the pathogens found in rodent species imported from Latin America into the United States with the highest risk of zoonotic consequence in the United States. Four formally traded species and 16 zoonotic pathogens were identified. Risk scores were based on the likelihood of pathogen release and human exposure, and the severity of the disease (consequences). Based on the methodology applied, three pathogens (Mycobacterium microti, Giardia spp. and Francisella tularensis) in one species (Cavia porcellus) were ranked as highest concern. The goal of this study was to present a methodological approach by which preliminary management resources can be allocated to the identified high-concern pathogen-species combinations when warranted. This tool can be expanded to other taxa and geographic locations to inform policy surrounding the wildlife trade. © 2015 Blackwell Verlag GmbH.

A Modified MuDPIT Separation Identified 4,488 Proteins in a System Wide Analysis of Quiescence in Yeast

PubMed Central

Webb, Kristofor J.; Xu, Tao; Park, Sung Kyu; Yates, John R.

2013-01-01

A modified multidimensional protein identification technology (MudPIT) separation was coupled to an LTQ Orbitrap Velos mass spectrometer and used to rapidly identify the near complete yeast proteome from a whole cell tryptic digest. This modified on-line two dimensional liquid chromatography separation consists of 39 strong cation exchange steps followed by a short 18.5 min reversed-phase (RP) gradient. A total of 4,269 protein identifications were made from 4,189 distinguishable protein families from yeast during log phase growth. The “Micro” MudPIT separation performed as well as a standard MudPIT separation in 40% less gradient time. The majority of the yeast proteome can now be routinely covered in less than a days’ time with high reproducibility and sensitivity. The newly devised separation method was used to detect changes in protein expression during cellular quiescence in yeast. An enrichment in the GO annotations ‘oxidation reduction’, ‘catabolic processing’ and ‘cellular response to oxidative stress’ was seen in the quiescent cellular fraction, consistent with their long lived stress resistant phenotypes. Heterogeneity was observed in the stationary phase fraction with a less dense cell population showing reductions in KEGG pathway categories of ‘Ribosome’ and ‘Proteasome’, further defining the complex nature of yeast populations present during stationary phase growth. In total 4,488 distinguishable protein families were identified in all cellular conditions tested. PMID:23540446

Identifying Occupations at Risk for Laryngeal Disorders Requiring Specialty Voice Care.

PubMed

Mori, Matthew C; Francis, David O; Song, Phillip C

2017-10-01

Objective To identify occupational groups' use of specialty voice clinic evaluation. Study Design Retrospective cohort study. Setting Tertiary subspecialty clinic. Subjects and Methods We analyzed data collected on patients presenting to the Massachusetts Eye and Ear Infirmary Voice and Speech Laboratory over a 20-year period (1993-2013). The relative risk (RR) and 99% confidence interval (CI) of presentation were calculated for each occupational category in the greater Boston population using year-matched data from the Bureau of Labor Statistics (BLS). Results The records of 12,120 new patients were reviewed. Using year- and occupation-matched BLS data from 2005 to 2013, 2726 patients were included in the cohort analysis. Several occupations had significantly higher risk of presentation. These included arts and entertainment (RR 4.98, CI 4.18-5.95), law (RR 3.24, CI 2.48-4.23), education (RR 3.08, CI 2.70-3.52), and social services (RR 2.07, CI 1.57-2.73). In contrast, many occupations had significantly reduced risk of presentation for laryngological disorders, for example, maintenance (RR 0.25, CI 0.15-0.42), food preparation (RR 0.35, CI 0.26-0.48), and administrative support (RR 0.49, CI 0.41-0.57). Conclusion Certain occupations are associated with higher use of laryngological services presumably because of their vocational voice needs. In addition to confirming findings from other studies, we identified several new occupation groups with increased or decreased risk for laryngologic disorders. Understanding what factors predispose to requiring specialty voice evaluation may help in targeting preventative efforts.

What’s the risk? Identifying potential human pathogens within grey-headed flying foxes faeces

PubMed Central

Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

2018-01-01

Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

Work Ability Index as tool to identify workers at risk of premature work exit.

PubMed

Roelen, Corné A M; Heymans, Martijn W; Twisk, Jos W R; van der Klink, Jac J L; Groothoff, Johan W; van Rhenen, Willem

2014-12-01

To investigate the Work Ability Index (WAI) as tool for identifying workers at risk of premature work exit in terms of disability pension, unemployment, or early retirement. Prospective cohort study of 11,537 male construction workers (mean age 45.5 years), who completed the WAI at baseline and reported their work status (employed, unemployed, disability pension, or retired) after mean 2.3 years of follow-up. Associations between WAI scores and work status were investigated by multinomial logistic regression analysis. The ability of the WAI to discriminate between workers at high and low risk of premature work exit was analyzed by the area (AUC) under the receiver operating characteristic curve. 9,530 (83 %) construction workers had complete data for analysis. At follow-up, 336 (4 %) workers reported disability pension, 125 (1 %) unemployment, and 255 (3 %) retirement. WAI scores were prospectively associated with the risk of disability pension at follow-up, but not with the risk of unemployment and early retirement. The WAI showed fair discrimination to identify workers at risk of disability pension [AUC = 0.74; 95 % confidence interval (CI) 0.70-0.77]. The discriminative ability decreased with age from AUC = 0.78 in workers aged 30-39 years to AUC = 0.69 in workers ≥50 years of age. Discrimination failed for unemployment (AUC = 0.51; 95 % CI 0.47-0.55) and early retirement (AUC = 0.58; 95 % CI 0.53-0.61). The WAI can be used to identify construction workers <50 years of age at increased risk of disability pension and invite them for preventive interventions.

Lipids and lipid changes with synthetic and biologic disease-modifying antirheumatic drug therapy in rheumatoid arthritis: implications for cardiovascular risk.

PubMed

Myasoedova, Elena

2017-05-01

To highlight recently published studies addressing lipid changes with disease-modifying antirheumatic drug use and outline implications on cardiovascular outcomes in rheumatoid arthritis (RA). Growing evidence suggests lower lipid levels are present in patients with active RA vs. general population, and significant modifications of lipid profile with inflammation suppression. Increase in lipid levels in patients with RA on synthetic and biological disease-modifying antirheumatic drugs may be accompanied by antiatherogenic changes in lipid composition and function. The impact of lipid changes on cardiovascular outcomes in RA is a subject of active research. The role of lipids in cardiovascular risk in RA may be overpowered by the benefits of inflammation suppression with antirheumatic medication use. Recommendations on lipid management in RA are evolving but uncertainty exists regarding frequency of lipid testing and goals of treatment. Knowledge about quantitative and qualitative lipid changes in RA is expanding. The relative role of lipids in cardiovascular risk in the context of systemic inflammation and antirheumatic therapy remains uncertain, delaying development of effective strategies for cardiovascular risk management in RA. Studies are underway to address these knowledge gaps and may be expected to inform cardiovascular risk management in RA and the general population.

Identifying risk factors for victimization among male prisoners in Taiwan.

PubMed

Kuo, Shih-Ya; Cuvelier, Steven J; Huang, Yung-Shun

2014-02-01

This study identified risk factors for prison victimization in Taiwan with an application of Western literature and assessed the extent of its applicability in an Eastern context. The sample was drawn from four male prisons located in Northern, Central, Southern, and Eastern Taiwan; a total of 1,181 valid surveys were collected. The results generally support the major findings of the extant Western studies. Crowding, however, was not significantly associated with the risk of victimization in any of the statistical models, which might be related to the different experiences and living conditions in the free community between Taiwanese and American inmates. This study generated clear policy implications, which may reduce prison victimization and engender a greater sense of well-being in the prison environment.

Depression as a modifiable factor to decrease the risk of dementia

PubMed Central

Almeida, O P; Hankey, G J; Yeap, B B; Golledge, J; Flicker, L

2017-01-01

Depression is an accepted risk factor for dementia, but it is unclear if this relationship is causal. This study investigated whether dementia associated with depression decreases with antidepressant use and is independent of the time between exposure to depression and the onset of dementia. We completed a 14-year longitudinal study of 4922 cognitively healthy men aged 71–89 years, and collected information about history of past depression, current depression and severity of depressive symptoms. Other measures included use of antidepressants, age, education, smoking and history of diabetes, hypertension, coronary heart disease, and stroke. The onset of dementia and death during follow-up was ascertained via the Western Australian Data Linkage System. A total of 682 men had past (n=388) or current (n=294) depression. During 8.9 years follow-up, 903 (18.3%) developed dementia and 1884 (38.3%) died free of dementia. The sub-hazard ratios (SHRs) of dementia for men with past and current depression were 1.3 (95% confidence interval (CI)=1.0, 1.6) and 1.5 (95% CI=1.2, 2.0). The use of antidepressants did not decrease this risk. Compared to men with no symptoms, the SHRs of dementia associated with questionable, mild-to-moderate and severe depressive symptoms were 1.2 (95% CI=1.0, 1.4), 1.7 (95% CI=1.4, 2.2) and 2.1 (95% CI=1.4, 3.2), respectively. The association between depression and dementia was only apparent during the initial 5 years of follow-up. Older men with history of depression are at increased risk of developing dementia, but depression is more likely to be a marker of incipient dementia than a truly modifiable risk factor. PMID:28463236

Developing a Model for Identifying Students at Risk of Failure in a First Year Accounting Unit

ERIC Educational Resources Information Center

Smith, Malcolm; Therry, Len; Whale, Jacqui

2012-01-01

This paper reports on the process involved in attempting to build a predictive model capable of identifying students at risk of failure in a first year accounting unit in an Australian university. Identifying attributes that contribute to students being at risk can lead to the development of appropriate intervention strategies and support…

Use of a modified Delphi panel to identify and weight criteria for prioritization of zoonotic diseases in Switzerland.

PubMed

Stebler, N; Schuepbach-Regula, G; Braam, P; Falzon, L C

2015-09-01

Zoonotic diseases have a significant impact on public health globally. To prevent or reduce future zoonotic outbreaks, there is a constant need to invest in research and surveillance programs while updating risk management strategies. However, given the limited resources available, disease prioritization based on the need for their control and surveillance is important. This study was performed to identify and weight disease criteria for the prioritization of zoonotic diseases in Switzerland using a semi-quantitative research method based on expert opinion. Twenty-eight criteria relevant for disease control and surveillance, classified under five domains, were selected following a thorough literature review, and these were evaluated and weighted by seven experts from the Swiss Federal Veterinary Office using a modified Delphi panel. The median scores assigned to each criterion were then used to rank 16 notifiable and/or emerging zoonoses in Switzerland. The experts weighted the majority of the criteria similarly, and the top three criteria were Severity of disease in humans, incidence and prevalence of the disease in humans and treatment in humans. Based on these weightings, the three highest ranked diseases were Avian Influenza, Bovine Spongiform Encephalitis, and Bovine Tuberculosis. Overall, this study provided a preliminary list of criteria relevant for disease prioritization in Switzerland. These were further evaluated in a companion study which involved a quantitative prioritization method and multiple stakeholders. Copyright © 2015 Elsevier B.V. All rights reserved.

A risk-based classification scheme for genetically modified foods. II: Graded testing.

PubMed

Chao, Eunice; Krewski, Daniel

2008-12-01

This paper presents a graded approach to the testing of crop-derived genetically modified (GM) foods based on concern levels in a proposed risk-based classification scheme (RBCS) and currently available testing methods. A graded approach offers the potential for more efficient use of testing resources by focusing less on lower concern GM foods, and more on higher concern foods. In this proposed approach to graded testing, products that are classified as Level I would have met baseline testing requirements that are comparable to what is widely applied to premarket assessment of GM foods at present. In most cases, Level I products would require no further testing, or very limited confirmatory analyses. For products classified as Level II or higher, additional testing would be required, depending on the type of the substance, prior dietary history, estimated exposure level, prior knowledge of toxicity of the substance, and the nature of the concern related to unintended changes in the modified food. Level III testing applies only to the assessment of toxic and antinutritional effects from intended changes and is tailored to the nature of the substance in question. Since appropriate test methods are not currently available for all effects of concern, future research to strengthen the testing of GM foods is discussed.

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

PubMed

Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

2016-01-01

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

Modifiable predictors of depression following childhood maltreatment: a systematic review and meta-analysis

PubMed Central

Braithwaite, E C; O'Connor, R M; Degli-Esposti, M; Luke, N; Bowes, L

2017-01-01

Although maltreatment experiences in childhood increase the risk for depression, not all maltreated children become depressed. This review aims to systematically examine the existing literature to identify modifiable factors that increase vulnerability to, or act as a buffer against, depression, and could therefore inform the development of targeted interventions. Thirteen databases (including Medline, PsychINFO, SCOPUS) were searched (between 1984 and 2014) for prospective, longitudinal studies published in English that included at least 300 participants and assessed associations between childhood maltreatment and later depression. The study quality was assessed using an adapted Newcastle–Ottawa Scale checklist. Meta-analyses (random effects models) were performed on combined data to estimate the effect size of the association between maltreatment and depression. Meta-regressions were used to explore effects of study size and quality. We identified 22 eligible articles (N=12 210 participants), of which 6 examined potential modifiable predictors of depression following maltreatment. No more than two studies examined the same modifiable predictor; therefore, it was not possible to examine combined effects of modifiable predictors with meta-regression. It is thus difficult to draw firm conclusions from this study, but initial findings indicate that interpersonal relationships, cognitive vulnerabilities and behavioral difficulties may be modifiable predictors of depression following maltreatment. There is a lack of well-designed, prospective studies on modifiable predictors of depression following maltreatment. A small amount of initial research suggests that modifiable predictors of depression may be specific to maltreatment subtypes and gender. Corroboration and further investigation of causal mechanisms is required to identify novel targets for intervention, and to inform guidelines for the effective treatment of maltreated children. PMID:28675390

Hispanic ethnicity and fatal fall risk: do age, gender, and community modify the relationship?

PubMed

Landy, David C; Mintzer, Michael J; Silva, Amanda K; Dearwater, Stephen R; Schulman, Carl I

2012-06-01

Hispanic ethnicity is associated with a reduced risk of fatal falls in the elderly despite lower socioeconomic standing. The factors responsible for this "Hispanic paradox" are unknown. We hypothesized that age and gender would modify this relationship and that the association would be accentuated in a community with prominent Hispanic culture. The number of fatal falls in a 3-year period in the United States (US) and in Miami-Dade County, Florida (MDC) were obtained through the CDC's WISQARS database and the Florida Office of Vital Statistics. US Census Bureau data were used to define the total at-risk populations by age group and gender. Age group- and gender-specific ratios of the risk of fatal fall in Hispanic to white non-Hispanic individuals were calculated. In the US and MDC, Hispanic ethnicity was associated with a reduced risk of fatal fall across all age and gender subgroups. In the US, the risk reduction associated with Hispanic ethnicity grew from 11% and 23% in 65- to 74-year-old men and women, respectively, to 43% for both men and women over 84-years-old. This relationship was stronger in MDC than nationally in five of the six age and gender subgroups examined. Older individuals, women, and residents of communities with prominent Hispanic culture have the greatest reduction in fatal fall risk associated with Hispanic ethnicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders

PubMed Central

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-01-01

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as “relatively low”, contrasting with 21.4% rated as “relatively high”. Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders. PMID:28587226

Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure.

PubMed

Lee, Pei-Chen; Rhodes, Shannon L; Sinsheimer, Janet S; Bronstein, Jeff; Ritz, Beate

2013-06-01

We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Under the radar: a cross-sectional study of the challenge of identifying at-risk alcohol consumption in the general practice setting

PubMed Central

2014-01-01

Background Primary care providers are an important source of information regarding appropriate alcohol consumption. As early presentation to a provider for alcohol-related concerns is unlikely, it is important that providers are able to identify at-risk patients in order to provide appropriate advice. This study aimed to report the sensitivity, specificity, positive predictive value and negative predictive value of General Practitioner (GP) assessment of alcohol consumption compared to patient self-report, and explore characteristics associated with GP non-detection of at-risk status. Method GP practices were selected from metropolitan and regional locations in Australia. Eligible patients were adults presenting for general practice care who were able to understand English and provide informed consent. Patients completed a modified AUDIT-C by touchscreen computer as part of an omnibus health survey while waiting for their appointment. GPs completed a checklist for each patient, including whether the patient met current Australian guidelines for at-risk alcohol consumption. Patient self-report and GP assessments were compared for each patient. Results GPs completed the checklist for 1720 patients, yielding 1565 comparisons regarding alcohol consumption. The sensitivity of GPs’ detection of at-risk alcohol consumption was 26.5%, with specificity of 96.1%. Higher patient education was associated with GP non-detection of at-risk status. Conclusions GP awareness of which patients might benefit from advice regarding at-risk alcohol consumption appears low. Given the complexities associated with establishing whether alcohol consumption is ‘at-risk’, computer-based approaches to routine screening of patients are worthy of exploration as a method for prompting the provision of advice in primary care. PMID:24766913

PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease.

PubMed

Noyce, Alastair J; R'Bibo, Lea; Peress, Luisa; Bestwick, Jonathan P; Adams-Carr, Kerala L; Mencacci, Niccolo E; Hawkes, Christopher H; Masters, Joseph M; Wood, Nicholas; Hardy, John; Giovannoni, Gavin; Lees, Andrew J; Schrag, Anette

2017-02-01

A number of early features can precede the diagnosis of Parkinson's disease (PD). To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population. Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD ("intermediate markers"), including smell loss, rapid eye movement-sleep behavior disorder, and finger-tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed. A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow-up (all P values < 0.001). Incident PD diagnoses during follow-up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores. The online PREDICT-PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder

The Nursing Home Pneumonia Risk Index: A Simple, Valid MDS-Based Method of Identifying 6-Month Risk for Pneumonia and Mortality.

PubMed

Sloane, Philip D; Zimmerman, Sheryl; Ward, Kimberly; Reed, David; Preisser, John S; Weber, David J

2017-09-01

Pneumonia is the leading infectious cause of hospitalization and death for nursing home (NH) residents; however, diagnosis is often delayed because classic signs of infection are not present. We sought to identify NH residents at high risk for pneumonia, to identify persons to target for more intensive surveillance and preventive measures. Based on a literature review, we identified key risk factors for pneumonia and compiled them for use as prediction tool, limiting risk factors to those available on the Minimum Data Set (MDS). Next, we tested the tool's ability to predict 6-month pneumonia incidence and mortality rates in a sample of 674 residents from 7 NHs, evaluating it both as a continuous and a dichotomous variable, and applying both logistic regression and survival analysis to calculate estimates. NH Pneumonia Risk Index scores ranged from -1 to 6, with a mean of 2.1, a median of 2, and a mode of 2. For the outcome of pneumonia, a 1-point increase in the index was associated with a risk odds ratio of 1.26 (P = .038) or a hazard ratio of 1.24 (P = .037); using it as a dichotomous variable (≤2 vs ≥3), the corresponding figures were a risk odds ratio of 1.78 (P = .045) and a hazard ratio of 1.82 (P = .025). For the outcome of mortality, a 1-point increase in the NH Pneumonia Risk Index was associated with a risk odds ratio of 1.58 (P = .002) and a hazard ratio of 1.45 (P = .013); using the index as a dichotomous variable, the corresponding figures were a risk odds ratio of 3.71 (P < .001) and a hazard ratio of 3.29 (P = .001). The NH Pneumonia Risk Index can be used by NH staff to identify residents for whom to apply especially intensive preventive measures and surveillance. Because of its strong association with mortality, the index may also be valuable in care planning and discussion of advance directives. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression.

PubMed

Tin, Adrienne; Nadkarni, Girish; Evans, Anne M; Winkler, Cheryl A; Bottinger, Erwin; Rebholz, Casey M; Sarnak, Mark J; Inker, Lesley A; Levey, Andrew S; Lipkowitz, Michael S; Appel, Lawrence J; Arking, Dan E; Coresh, Josef; Grams, Morgan E

2018-05-18

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles-genetic variants associated with CKD risk commonly present in persons of African descent-may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) ( n =588; Bonferroni significance threshold P <6.5×10 -5 ) and replicated findings in 678 black participants with CKD in Bio Me , an electronic medical record-linked biobank. We tested the metabolite association with CKD progression in AASK, Bio Me , and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK ( P =4.7×10 -5 ) and replicated in Bio Me ( P =5.7×10 -3 ) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and Bio Me participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; Bio Me , 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression. Copyright © 2018 by the American Society of Nephrology.

Risk of cancer in patients receiving non-biologic disease-modifying therapy for rheumatoid arthritis compared with the UK general population

PubMed Central

Mercer, Louise K.; Davies, Rebecca; Galloway, James B.; Low, Audrey; Lunt, Mark; Dixon, William G.; Watson, Kath D.; Symmons, Deborah P. M.

2013-01-01

Objectives. To quantify the risk of cancer and compare it with that for the general population in a modern cohort of UK patients with RA and to identify risk factors for cancer among this cohort. Methods. The study population comprised biologic-naïve RA subjects receiving non-biologic disease-modifying therapy recruited to the British Society for Rheumatology Biologics Register from 2002 to 2009. Standardized incidence ratios (SIRs) for cancers were calculated using age- and gender-specific cancer rates in the English population. Poisson regression models adjusted for age and gender using England general population data were used to determine the association of other predictors with incident malignancy. Results. The cohort comprised 3771 individuals with RA contributing 13 315 person-years of follow-up. One hundred and eighty-two cancers were reported: 156 solid and 26 myelo- or lymphoproliferative cancers. The overall SIR was 1.28 (95% CI 1.10, 1.48). Risks of lung cancer (SIR 2.39, 95% CI 1.75, 3.19), Hodgkin lymphoma (SIR 12.82, 95% CI 4.16, 29.92) and non-Hodgkin lymphoma (SIR 3.12, 95% CI 1.79, 5.07) were higher compared with the general population and risks of prostate cancer (SIR 0.35, 95% CI 0.11, 0.82) and cancers of the female genital organs (SIR 0.35, 95% CI 0.10, 0.90) were reduced. Within the cohort, cancer risk was more than 2-fold higher in current or ex-smokers than in non-smokers. Conclusion. The overall incidence of cancer was increased in this national cohort of subjects with RA. The association of RA with certain cancers needs to be considered when studying the effects of biologic therapy, such as anti-TNF, on cancer risk. PMID:23238979

Modifiable risk factors associated with prediabetes in men and women: a cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes (PREDAPS-Study).

PubMed

Díaz-Redondo, Alicia; Giráldez-García, Carolina; Carrillo, Lourdes; Serrano, Rosario; García-Soidán, Francisco Javier; Artola, Sara; Franch, Josep; Díez, Javier; Ezkurra, Patxi; Millaruelo, José Manuel; Seguí, Mateu; Sangrós, Javier; Martínez-Candela, Juan; Muñoz, Pedro; Goday, Albert; Regidor, Enrique

2015-01-22

Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when

Profiling illness perceptions to identify patients at-risk for decline in health status after heart valve replacement.

PubMed

Kohlmann, Sebastian; Rimington, Helen; Weinman, John

2012-06-01

Identification of risk factors for decline in health status by profiling illness perceptions before and one year after heart valve replacement surgery. Prospective data from N=225 consecutively admitted first time valve replacement patients was assessed before and one year after surgery. Patients were asked about their illness perceptions (Illness Perception Questionnaire-Revised) and mood state (Hospital Anxiety and Depression Scale). Health status was defined by quality of life (Short-Form 36) and New York Heart Association (NYHA) class. Cluster analyses were conducted to identify illness perception profiles over time. Predictors of health status after surgery were analyzed with multivariate methods. Patients were grouped according to the stability and nature (positive, negative) of their illness perception profile over one year. One year after surgery patients holding a negative illness perception profile showed a lower physical quality of life and were diagnosed in a higher New York Heart Association class than patients changing to positive and patients with stable positive illness perceptions (P<.001). Over and above biological determinants, post-surgery physical quality of life and NYHA class were both predicted by pre-surgery illness perception profiles (P<.05). Patients going for heart valve replacement surgery can be easily categorized into illness perception profiles that predict health status one year after surgery. These patients could benefit from early screening as negative illness perceptions are modifiable risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Applying Concept Mapping Methodology to Identify the Perceptions of Risk and Protective Factors for Childhood Obesity among Southeast Asian Refugees.

PubMed

Keita, Akilah Dulin; Whittaker, Shannon; Wynter, Jamila; Kidanu, Tamnnet Woldemichael; Chhay, Channavy; Cardel, Michelle; Gans, Kim M

2016-01-01

This study identifies Southeast Asian refugee parents' and grandparents' perceptions of the risk and protective factors for childhood obesity. We used a mixed methods approach (concept mapping) for data collection and analyses. Fifty-nine participants engaged in modified nominal group meetings where they generated statements about children's weight status and structuring meetings where they sorted statements into piles based on similarity and rated statements on relative importance. Concept Systems® software generated clusters of ideas, cluster ratings, and pattern matches. Eleven clusters emerged. Participants rated "Healthy Food Changes Made within the School" and "Parent-related Physical Activity Factors" as most important, whereas "Neighborhood Built Features" was rated as the least important. Cambodian and Hmong participants agreed the most on cluster ratings of relative importance (r = 0.62). The study findings may be used to inform the development of culturally appropriate obesity prevention interventions for Southeast Asian refugee communities.

Identifying and Prioritizing Greater Sage-Grouse Nesting and Brood-Rearing Habitat for Conservation in Human-Modified Landscapes

PubMed Central

Dzialak, Matthew R.; Olson, Chad V.; Harju, Seth M.; Webb, Stephen L.; Mudd, James P.; Winstead, Jeffrey B.; Hayden-Wing, L.D.

2011-01-01

Background Balancing animal conservation and human use of the landscape is an ongoing scientific and practical challenge throughout the world. We investigated reproductive success in female greater sage-grouse (Centrocercus urophasianus) relative to seasonal patterns of resource selection, with the larger goal of developing a spatially-explicit framework for managing human activity and sage-grouse conservation at the landscape level. Methodology/Principal Findings We integrated field-observation, Global Positioning Systems telemetry, and statistical modeling to quantify the spatial pattern of occurrence and risk during nesting and brood-rearing. We linked occurrence and risk models to provide spatially-explicit indices of habitat-performance relationships. As part of the analysis, we offer novel biological information on resource selection during egg-laying, incubation, and night. The spatial pattern of occurrence during all reproductive phases was driven largely by selection or avoidance of terrain features and vegetation, with little variation explained by anthropogenic features. Specifically, sage-grouse consistently avoided rough terrain, selected for moderate shrub cover at the patch level (within 90 m2), and selected for mesic habitat in mid and late brood-rearing phases. In contrast, risk of nest and brood failure was structured by proximity to anthropogenic features including natural gas wells and human-created mesic areas, as well as vegetation features such as shrub cover. Conclusions/Significance Risk in this and perhaps other human-modified landscapes is a top-down (i.e., human-mediated) process that would most effectively be minimized by developing a better understanding of specific mechanisms (e.g., predator subsidization) driving observed patterns, and using habitat-performance indices such as those developed herein for spatially-explicit guidance of conservation intervention. Working under the hypothesis that industrial activity structures risk by

Knowledge regarding risk factors of hypertension among entry year students of a medical university

PubMed Central

Shaikh, Rizwana B.; Mathew, Elsheba; Sreedharan, Jayadevan; Muttappallymyalil, Jayakumary; Sharbatti, Shatha Al; Basha, Shaikh A.

2011-01-01

Context: Hypertension in youth is increasing, but there is a dearth of data about the knowledge of risk factors in this age group. Aims: To assess the knowledge of risk factors of hypertension among university students and associate it with the blood pressure, physical activity, family history of cardiovascular disease (CVD), and sociodemographic variables. Materials and Methods: A cross-sectional survey among students enrolled in the first year, in the four academic programs, with the use of a validated, self-administered questionnaire on physical activity in the past 30 days and knowledge of risk factors of hypertension. A score of 6 on 11 was considered as good knowledge for modifiable risk factors. Blood pressure was also measured. The data was analyzed using PASW-17, Chi square test, and binary logistic regression analysis was done. Results: Of the 110 participants, 69.2% were < 20 years of age, 76.4% were females, and 40% were Arabs. Stress, high cholesterol, obesity, and smoking were identified as risk factors by 75.5, 73.6, 77.6, and 71.8%, respectively; 69.1% considered high salt intake and 62.7% considered high calorie diet as risk factors. Energy drink was considered as a risk factor by 64.5%, coffee consumption 35.5%, physical inactivity 47%, and oral contraceptives 13.6%. Half the group did not consider a family history of CVD as a risk factor, 60% did not consider older age as a risk factor, and 88% did not think male gender was a risk factor. Knowledge of modifiable risk factors was better than that of non-modifiable risk factors. Although nationality, course of study, raised blood pressure, and history of diabetes showed significant association with good knowledge, their net effect was not significant by the Adjusted Odd's Ratio. Conclusions: The study identified some gaps in knowledge regarding both modifiable and non-modifiable risk factors of hypertension among students. A larger study would enable health promotion activities tailored to the

Can we identify patients at risk of life-threatening allergic reactions to food?

PubMed

Turner, P J; Baumert, J L; Beyer, K; Boyle, R J; Chan, C-H; Clark, A T; Crevel, R W R; DunnGalvin, A; Fernández-Rivas, M; Gowland, M H; Grabenhenrich, L; Hardy, S; Houben, G F; O'B Hourihane, J; Muraro, A; Poulsen, L K; Pyrz, K; Remington, B C; Schnadt, S; van Ree, R; Venter, C; Worm, M; Mills, E N C; Roberts, G; Ballmer-Weber, B K

2016-09-01

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection

PubMed Central

Becker, Andrew E; Hernandez, Yasmin G; Frucht, Harold; Lucas, Aimee L

2014-01-01

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several large-volume centers have initiated such screening protocols, and consensus-based guidelines for screening high-risk groups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields. PMID:25170203

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

PubMed

Tobias, J H; Hutchinson, A P; Hunt, L P; McCloskey, E V; Stone, M D; Martin, J C; Thompson, P W; Palferman, T G; Bhalla, A K

2007-01-01

Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the

Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

PubMed Central

van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry TC; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Bo, Roberto Del; Comi, Giacomo P; D’Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc’h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

2017-01-01

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk. PMID:27455348

Geographically Modified PageRank Algorithms: Identifying the Spatial Concentration of Human Movement in a Geospatial Network.

PubMed

Chin, Wei-Chien-Benny; Wen, Tzai-Hung

2015-01-01

A network approach, which simplifies geographic settings as a form of nodes and links, emphasizes the connectivity and relationships of spatial features. Topological networks of spatial features are used to explore geographical connectivity and structures. The PageRank algorithm, a network metric, is often used to help identify important locations where people or automobiles concentrate in the geographical literature. However, geographic considerations, including proximity and location attractiveness, are ignored in most network metrics. The objective of the present study is to propose two geographically modified PageRank algorithms-Distance-Decay PageRank (DDPR) and Geographical PageRank (GPR)-that incorporate geographic considerations into PageRank algorithms to identify the spatial concentration of human movement in a geospatial network. Our findings indicate that in both intercity and within-city settings the proposed algorithms more effectively capture the spatial locations where people reside than traditional commonly-used network metrics. In comparing location attractiveness and distance decay, we conclude that the concentration of human movement is largely determined by the distance decay. This implies that geographic proximity remains a key factor in human mobility.

Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria.

PubMed

Goh, Brian K P; Chow, Pierce K H; Yap, Wai-Ming; Kesavan, Sittampalam M; Song, In-Chin; Paul, Pradeep G; Ooi, Boon-Swee; Chung, Yaw-Fui A; Wong, Wai-Keong

2008-08-01

This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.

Creating a Chinese suicide dictionary for identifying suicide risk on social media.

PubMed

Lv, Meizhen; Li, Ang; Liu, Tianli; Zhu, Tingshao

2015-01-01

Introduction. Suicide has become a serious worldwide epidemic. Early detection of individual suicide risk in population is important for reducing suicide rates. Traditional methods are ineffective in identifying suicide risk in time, suggesting a need for novel techniques. This paper proposes to detect suicide risk on social media using a Chinese suicide dictionary. Methods. To build the Chinese suicide dictionary, eight researchers were recruited to select initial words from 4,653 posts published on Sina Weibo (the largest social media service provider in China) and two Chinese sentiment dictionaries (HowNet and NTUSD). Then, another three researchers were recruited to filter out irrelevant words. Finally, remaining words were further expanded using a corpus-based method. After building the Chinese suicide dictionary, we tested its performance in identifying suicide risk on Weibo. First, we made a comparison of the performance in both detecting suicidal expression in Weibo posts and evaluating individual levels of suicide risk between the dictionary-based identifications and the expert ratings. Second, to differentiate between individuals with high and non-high scores on self-rating measure of suicide risk (Suicidal Possibility Scale, SPS), we built Support Vector Machines (SVM) models on the Chinese suicide dictionary and the Simplified Chinese Linguistic Inquiry and Word Count (SCLIWC) program, respectively. After that, we made a comparison of the classification performance between two types of SVM models. Results and Discussion. Dictionary-based identifications were significantly correlated with expert ratings in terms of both detecting suicidal expression (r = 0.507) and evaluating individual suicide risk (r = 0.455). For the differentiation between individuals with high and non-high scores on SPS, the Chinese suicide dictionary (t1: F 1 = 0.48; t2: F 1 = 0.56) produced a more accurate identification than SCLIWC (t1: F 1 = 0.41; t2: F 1 = 0.48) on different

Creating a Chinese suicide dictionary for identifying suicide risk on social media

PubMed Central

Liu, Tianli

2015-01-01

Introduction. Suicide has become a serious worldwide epidemic. Early detection of individual suicide risk in population is important for reducing suicide rates. Traditional methods are ineffective in identifying suicide risk in time, suggesting a need for novel techniques. This paper proposes to detect suicide risk on social media using a Chinese suicide dictionary. Methods. To build the Chinese suicide dictionary, eight researchers were recruited to select initial words from 4,653 posts published on Sina Weibo (the largest social media service provider in China) and two Chinese sentiment dictionaries (HowNet and NTUSD). Then, another three researchers were recruited to filter out irrelevant words. Finally, remaining words were further expanded using a corpus-based method. After building the Chinese suicide dictionary, we tested its performance in identifying suicide risk on Weibo. First, we made a comparison of the performance in both detecting suicidal expression in Weibo posts and evaluating individual levels of suicide risk between the dictionary-based identifications and the expert ratings. Second, to differentiate between individuals with high and non-high scores on self-rating measure of suicide risk (Suicidal Possibility Scale, SPS), we built Support Vector Machines (SVM) models on the Chinese suicide dictionary and the Simplified Chinese Linguistic Inquiry and Word Count (SCLIWC) program, respectively. After that, we made a comparison of the classification performance between two types of SVM models. Results and Discussion. Dictionary-based identifications were significantly correlated with expert ratings in terms of both detecting suicidal expression (r = 0.507) and evaluating individual suicide risk (r = 0.455). For the differentiation between individuals with high and non-high scores on SPS, the Chinese suicide dictionary (t1: F1 = 0.48; t2: F1 = 0.56) produced a more accurate identification than SCLIWC (t1: F1 = 0.41; t2: F1 = 0.48) on different

Identifying barriers to the provision of bystander cardiopulmonary resuscitation (CPR) in high-risk regions: a qualitative review of emergency calls.

PubMed

Case, Rosalind; Cartledge, Susie; Siedenburg, Josine; Smith, Karen; Straney, Lahn; Barger, Bill; Finn, Judith; Bray, Janet E

2018-06-01

Understanding regional variation in bystander cardiopulmonary resuscitation (CPR) is important to improving out-of-hospital cardiac arrest (OHCA) survival. In this study we aimed to identify barriers to providing bystander CPR in regions with low rates of bystander CPR and where OHCA was recognised in the emergency call. We retrospectively reviewed emergency calls for adults in regions of low bystander CPR in the Australian state of Victoria. Included calls were those where OHCA was identified during the call but no bystander CPR was given. A thematic content analysis was independently conducted by two investigators. Saturation of themes was reached after listening to 139 calls. Calls progressed to the point of compression instructions before EMS arrival in only 26 (18.7%) of cases. Three types of barriers were identified: procedural barriers (time lost due to language barriers and communication issues; telephone problems), CPR knowledge (skill deficits; perceived benefit) and personal factors (physical frailty or disability; patient position; emotional factors). A range of factors are associated with barriers to delivering bystander CPR even in the presence of dispatcher instructions -some of which are modifiable. To overcome these barriers in high-risk regions, targeted public education needs to provide information about what occurs in an emergency call, how to recognise an OHCA and to improve CPR knowledge and skills. Copyright © 2018. Published by Elsevier B.V.

A partner-related risk behavior index to identify people at elevated risk for sexually transmitted infections.

PubMed

Crosby, Richard; Shrier, Lydia A

2013-04-01

The purpose of this study was to develop and test a sexual-partner-related risk behavior index to identify high-risk individuals most likely to have a sexually transmitted infection (STI). Patients from five STI and adolescent medical clinics in three US cities were recruited (N = 928; M age = 29.2 years). Data were collected using audio-computer-assisted self-interviewing. Of seven sexual-partner-related variables, those that were significantly associated with the outcomes were combined into a partner-related risk behavior index. The dependent variables were laboratory-confirmed infection with Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. Nearly one-fifth of the sample (169/928; 18.4%) tested positive for an STI. Three of the seven items were significantly associated with having one or more STIs: sex with a newly released prisoner, sex with a person known or suspected of having an STI, and sexual concurrency. In combined form, this three-item index was significantly associated with STI prevalence (p < .001). In the presence of three covariates (gender, race, and age), those classified as being at-risk by the index were 1.8 times more likely than those not classified as such to test positive for an STI (p < .001). Among individuals at risk for STIs, a three-item index predicted testing positive for one or more of three STIs. This index could be used to prioritize and guide intensified clinic-based counseling for high-risk patients of STI and other clinics.

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

PubMed Central

Houghton, P. W.; Leach, S.; Owen, R. W.; McC Mortensen, N. J.; Hill, M. J.; Williamson, R. C.

1989-01-01

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds. PMID:2765371

Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment

EPA Science Inventory

For presentation at the 45th Annual Symposium of the Society of Toxicology of Canada. The meeting will be held on 4-5 December 2013 at the Ottawa Convention Centre. Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment. Rory Conolly, Offi...

Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.

PubMed

Roussy, J-P; Bessette, L; Bernatsky, S; Rahme, E; Lachaine, J

2013-09-01

Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA. Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years. A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation. Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk. Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non

Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify increased cardio-metabolic risk in young, healthy South Asians.

PubMed

Flowers, Elena; Molina, César; Mathur, Ashish; Reaven, Gerald M

2015-01-01

Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of "high risk" individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. More concentrations of all cardio-metabolic risk factors were significantly higher in "high risk" groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in "high risk" groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.

No evidence that GATA3 rs570613 SNP modifies breast cancer risk

PubMed Central

Johnatty, Sharon E.; Couch, Fergus J.; Fredericksen, Zachary; Tarrell, Robert; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Gschwantler-Kaulich, Daphne; Singer, Christian F.; Fuerhauser, Christine; Fink-Retter, Anneliese; Domchek, Susan M.; Nathanson, Katherine L.; Pankratz, Vernon S.; Lindor, Noralane M.; Godwin, Andrew K.; Caligo, Maria A.; Hopper, John; Southey, Melissa C.; Giles, Graham G.; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Heikkinen, Tuomas; Aaltonen, Kirsimari; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli; Hall, Per; Czene, Kamila; Liu, Jianjun; Peock, Susan; Cook, Margaret; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Pichert, Gabriella; Eccles, Diana; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Douglas, Fiona; Chu, Carol; Hodgson, Shirley; Paterson, Joan; Hogervorst, Frans B.L.; Rookus, Matti A.; Seynaeve, Caroline; Wijnen, Juul; Vreeswijk, Maaike; Ligtenberg, Marjolijn; Luijt, Rob B. van der; van Os, Theo A.M.; Gille, Hans J.P.; Blok, Marinus J.; Issacs, Claudine; Humphreys, Manjeet K.; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga; Antoniou, Antonis C.; Easton, Douglas F.; Chenevix-Trench, Georgia

2009-01-01

GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (Ptrend =0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [1]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper-allele = 1.00, 95% CI 0.94 − 1.05), in ER negative BCAC cases (ORper-allele = 1.02, 95% CI 0.91−1.13), in BRCA1 mutation carriers RRper-allele = 0.99, 95% CI 0.90−1.09) or BRCA2 mutation carriers (RRper-allele = 0.93, 95% CI 0.80−1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women. PMID:19082709

Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers

PubMed Central

Deming, Yuetiva; Li, Zeran; Kapoor, Manav; Harari, Oscar; Del-Aguila, Jorge L.; Black, Kathleen; Carrell, David; Cai, Yefei; Fernandez, Maria Victoria; Budde, John; Ma, Shengmei; Saef, Benjamin; Howells, Bill; Huang, Kuanlin; Bertelsen, Sarah; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Kim, Sungeun; Saykin, Andrew J.; De Jager, Philip L.; Albert, Marilyn; Moghekar, Abhay; O’Brien, Richard; Riemenschneider, Matthias; Petersen, Ronald C.; Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Van Deerlin, Vivianna M.; Lee, Virginia Man-Yee; Shaw, Leslie M.; Trojanowski, John Q.; Schellenberg, Gerard; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Peskind, Elaine R.; Li, Ge; Di Narzo, Antonio F.; Kauwe, John S. K.; Goate, Alison M.; Cruchaga, Carlos

2017-01-01

More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SER-PINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform

Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause.

PubMed

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-08-01

We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193) and a retrospective validation (n = 567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high (≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95% CI 93.9-100.0%) in the validation cohort and 100.0% (95% CI 97.8-100.0%) in bacterial meningitis patients. The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

RISK SCORE FOR IDENTIFYING ADULTS WITH CSF PLEOCYTOSIS AND NEGATIVE CSF GRAM STAIN AT LOW RISK FOR AN URGENT TREATABLE CAUSE

PubMed Central

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H.; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-01-01

Background We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Methods Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n=193) and a retrospective validation (n=567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high ( ≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. Findings A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95%CI 93.9-100.0%) in the validation cohort and 100.0% (95%CI 97.8-100.0%) in bacterial meningitis patients. Interpretation The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. PMID:23619080

Genetic Basis and Genetic Modifiers of β-Thalassemia and Sickle Cell Disease.

PubMed

Thein, Swee Lay

2017-01-01

β-thalassemia and sickle cell disease (SCD) are prototypical Mendelian single gene disorders, both caused by mutations affecting the adult β-globin gene. Despite the apparent genetic simplicity, both disorders display a remarkable spectrum of phenotypic severity and share two major genetic modifiers-α-globin genotype and innate ability to produce fetal hemoglobin (HbF, α 2 γ 2 ).This article provides an overview of the genetic basis for SCD and β-thalassemia, and genetic modifiers identified through phenotype correlation studies. Identification of the genetic variants modifying HbF production in combination with α-globin genotype provide some prediction of disease severity for β-thalassemia and SCD but generation of a personalized genetic risk score to inform prognosis and guide management requires a larger panel of genetic modifiers yet to be discovered.Nonetheless, genetic studies have been successful in characterizing some of the key variants and pathways involved in HbF regulation, providing new therapeutic targets for HbF reactivation.

Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer.

PubMed

Tice, Jeffrey A; Miglioretti, Diana L; Li, Chin-Shang; Vachon, Celine M; Gard, Charlotte C; Kerlikowske, Karla

2015-10-01

Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. © 2015 by American Society of Clinical Oncology.

Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer

PubMed Central

Tice, Jeffrey A.; Miglioretti, Diana L.; Li, Chin-Shang; Vachon, Celine M.; Gard, Charlotte C.; Kerlikowske, Karla

2015-01-01

Purpose Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. Methods We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. Results We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P < .001). Conclusion The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. PMID:26282663

Factors Modifying Burnout in Osteopathic Medical Students.

PubMed

Lapinski, Jessica; Yost, Morgan; Sexton, Patricia; LaBaere, Richard J

2016-02-01

The purposes of the current study are to examine factors modifying burnout and identify which of these factors place osteopathic medical students at risk for developing burnout. The current study used a cross-sectional study design and an anonymous, web-based survey to assess burnout and depression in osteopathic medical students. The survey included Maslach Burnout Inventory, the Patient Health Questionnaire, the Stressors and their impact scale, students' sleeping and studying habits, and students' extracurricular involvement. In total, 1294 osteopathic medical students completed the survey. Burnout was present in 516 (39.9%) osteopathic medical students, and 1006 (77.0%) met criteria for depression. Females were 1.5 times more likely to be burned out in comparison to males. For the burnout subscales, males had lower emotional exhaustion, slightly higher depersonalization, and lower personal accomplishment. Lesbian/gay/bisexual/asexual students were 2.62 times more likely to be burned out compared with heterosexual students. Depression and academic, personal, and family stressors were all strongly linked to overall burnout. Finally, for modifiable factors, average hours of sleep, average hours spent studying, and club involvement appeared to be linked to burnout. The current study suggested that a variety of factors, including non-modifiable, situational, and modifiable, impact burnout in osteopathic medical students. Future research is necessary since burnout in physicians affects the quality of care provided to patients.

GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

PubMed

Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2013-04-24

Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aβ₄₂ are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10⁻⁹ for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10⁻⁸ and p = 3.22 × 10⁻⁹ for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10⁻⁸ for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10⁻⁴, 0.039, 4.86 × 10⁻⁵, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. Copyright © 2013 Elsevier Inc. All rights reserved.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers.

PubMed

Ding, Yuan C; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Paluch-Shimon, Shani-; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M; de Lange, Judith L; Meijers-Heijboer, Hanne E J; Oosterwijk, Jan C; van Asperen, Christi J; Gómez García, Encarna B; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B; Easton, Douglas F; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas V O; Ejlertsen, Bent; Johannsson, Oskar T; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y; Gross, Jenny; Ganz, Patricia A; Beattie, Mary S; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E; Weitzel, Jeffrey; Garber, Judy E; Olopade, Olufunmilayo I; Rubinstein, Wendy S; Tung, Nadine; Blum, Joanne L; Narod, Steven A; Brummel, Sean; Gillen, Daniel L; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S; Couch, Fergus J; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H; Loud, Jennifer T; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L

2012-08-01

We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. ©2012 AACR.

In Search of Modifiable Risk and Protective Factors for Teen Dating Violence

PubMed Central

Smith-Darden, Joanne P.; Kernsmith, Poco D.; Reidy, Dennis E.; Cortina, Kai S.

2018-01-01

The present research explores the additive and interactive effects of anger or hostility (A/H), acceptance of violence (AoV), and constructive conflict resolution strategies (CRS) on the perpetration of physical and sexual teen dating violence (TDV). Adolescents completed surveys assessing physical and sexual TDV perpetration, A/H, AoV, and positive CRS. While the findings require replication with longitudinal data, the results suggest that developing interventions to modify AoV and A/H may have the potential to prevent instances of TDV perpetration among both boys and girls. The results for CRS were mixed and necessitate further exploration. These cross-sectional data provide insight into potentially fruitful areas of exploration for the development and tailoring of prevention strategies for teens at risk for physical and sexual TDV perpetration. PMID:28876526

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

PubMed

Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

2016-03-01

The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43

Semantic Interoperability of Health Risk Assessments

PubMed Central

Rajda, Jay; Vreeman, Daniel J.; Wei, Henry G.

2011-01-01

The health insurance and benefits industry has administered Health Risk Assessments (HRAs) at an increasing rate. These are used to collect data on modifiable health risk factors for wellness and disease management programs. However, there is significant variability in the semantics of these assessments, making it difficult to compare data sets from the output of 2 different HRAs. There is also an increasing need to exchange this data with Health Information Exchanges and Electronic Medical Records. To standardize the data and concepts from these tools, we outline a process to determine presence of certain common elements of modifiable health risk extracted from these surveys. This information is coded using concept identifiers, which allows cross-survey comparison and analysis. We propose that using LOINC codes or other universal coding schema may allow semantic interoperability of a variety of HRA tools across the industry, research, and clinical settings. PMID:22195174

Screening and prioritisation of chemical risks from metal mining operations, identifying exposure media of concern.

PubMed

Pan, Jilang; Oates, Christopher J; Ihlenfeld, Christian; Plant, Jane A; Voulvoulis, Nikolaos

2010-04-01

Metals have been central to the development of human civilisation from the Bronze Age to modern times, although in the past, metal mining and smelting have been the cause of serious environmental pollution with the potential to harm human health. Despite problems from artisanal mining in some developing countries, modern mining to Western standards now uses the best available mining technology combined with environmental monitoring, mitigation and remediation measures to limit emissions to the environment. This paper develops risk screening and prioritisation methods previously used for contaminated land on military and civilian sites and engineering systems for the analysis and prioritisation of chemical risks from modern metal mining operations. It uses hierarchical holographic modelling and multi-criteria decision making to analyse and prioritise the risks from potentially hazardous inorganic chemical substances released by mining operations. A case study of an active platinum group metals mine in South Africa is used to demonstrate the potential of the method. This risk-based methodology for identifying, filtering and ranking mining-related environmental and human health risks can be used to identify exposure media of greatest concern to inform risk management. It also provides a practical decision-making tool for mine acquisition and helps to communicate risk to all members of mining operation teams.

Identifying Risk Factors for Elder Falls in Geriatric Rehabilitation in Israel.

PubMed

Ben Natan, Merav; Heyman, Neomi; Ben Israel, Joshua

2016-01-01

To identify risk factors for elder falls in a geriatric rehabilitation center in Israel. Retrospective chart review study. Four hundred and twelve medical records of inpatients in geriatric rehabilitation were retrospectively analyzed to compare between elders who sustained falls and those who did not. Of elders hospitalized during this year, 14% sustained falls. Fallers included a high proportion of males, with little comorbidity, not obese, and cardiovascular patients. Falls occurred frequently during patients' first week at the facility, mostly during the daytime. The falls occurred frequently in patients' rooms, and a common scenario was a fall during transition. The research findings single out patients who are allegedly at a lower risk of falls than more complex patients. Caregivers in geriatric rehabilitation settings should pay attention to patients who are allegedly at a lower risk of falls than more complex patients, and to cardiovascular patients in particular. © 2014 Association of Rehabilitation Nurses.

Reducing sickness absence from work due to low back pain: how well do intervention strategies match modifiable risk factors?

PubMed

Shaw, William S; Linton, Steven J; Pransky, Glenn

2006-12-01

To assess, from the review literature, the extent to which effective strategies for reducing work absence after acute low back pain (LBP) match empirical risk factors. From 17 recent review articles (2000-2005), disability risk factors and interventions were cross-tabulated to assess levels of relative concordance. Potentially modifiable risk factors included 23 variables describing 3 workplace and 3 personal domains. Effective interventions included 25 strategies that were personal (physical or behavioral), engineering, or administrative in nature. There was a strong risk factor concordance for workplace technical and organizational interventions, graded activity exposure, and cognitive restructuring of pain beliefs. There was less risk factor concordance for exercise, back education, and RTW coordination. Few interventions focused on relieving emotional distress or improving job dissatisfaction, two well-supported risk factors. Gaps between the epidemiological and intervention research of back disability prevention could be reduced by testing mediators of intervention effects or by stratifying outcomes according to pre-intervention risk factors.

Relationship between risk factors and activities of daily living using modified Shah Barthel Index in stroke patients

NASA Astrophysics Data System (ADS)

Kusumaningsih, W.; Rachmayanti, S.; Werdhani, R. A.

2017-08-01

Hypertension and diabetes mellitus are the most common risk factors of stroke. The study aimed to determine the relationship between hypertension and diabetes mellitus risk factors and dependence on assistance with activities of daily living in chronic stroke patients. The study used an analytical observational cross-sectional design. The study’s sample included 44 stroke patients selected using the quota sampling method. The relationship between the variables was analyzed using the bivariate chi-squared test and multivariate logistic regression. Based on the chi-squared test, the relationship between the Modified Shah Barthel Index (MSBI) score and hypertension and diabetes mellitus as stroke risk factors, were p = 0.122 and p = 0.002, respectively. The logistic regression results suggest that hypertension and diabetes mellitus are stroke risk factors related to the MSBI score: p = 0.076 (OR 4.076; CI 95% 0.861-19.297) and p = 0.007 (OR 22.690; CI 95% 2.332-220.722), respectively. Diabetes mellitus is the most prominent risk factor of severe dependency on assistance with activities of daily living in chronic stroke patients.

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

2015-06-01

Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this

Identifying High-Risk Patients without Labeled Training Data: Anomaly Detection Methodologies to Predict Adverse Outcomes

PubMed Central

Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan

2010-01-01

For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083

Identifying at-risk children at school entry: the usefulness of multibehavioral problem profiles.

PubMed

Flanagan, Kelly S; Bierman, Karen L; Kam, Chi-Ming

2003-09-01

Found that 1st-grade teacher ratings of aggressive, hyperactive-inattentive, and low levels of prosocial behaviors made unique contributions to the prediction of school outcomes (measured 2 years later) for 755 children. Person-oriented analyses compared the predictive utility of 5 screening strategies based on child problem profiles to identify children at risk for school problems. A broad screening strategy, in which children with elevations in any 1 of the 3 behavior problem dimensions were identified as "at-risk," showed lower specificity but superior sensitivity, odds ratios, and overall accuracy in the prediction of school outcomes than the other screening strategies that were more narrowly focused or were based on a total problem score. Results are discussed in terms of implications for the screening and design of preventive interventions.

Modifiable risk factors predicting major depressive disorder at four year follow-up: a decision tree approach.

PubMed

Batterham, Philip J; Christensen, Helen; Mackinnon, Andrew J

2009-11-22

Relative to physical health conditions such as cardiovascular disease, little is known about risk factors that predict the prevalence of depression. The present study investigates the expected effects of a reduction of these risks over time, using the decision tree method favoured in assessing cardiovascular disease risk. The PATH through Life cohort was used for the study, comprising 2,105 20-24 year olds, 2,323 40-44 year olds and 2,177 60-64 year olds sampled from the community in the Canberra region, Australia. A decision tree methodology was used to predict the presence of major depressive disorder after four years of follow-up. The decision tree was compared with a logistic regression analysis using ROC curves. The decision tree was found to distinguish and delineate a wide range of risk profiles. Previous depressive symptoms were most highly predictive of depression after four years, however, modifiable risk factors such as substance use and employment status played significant roles in assessing the risk of depression. The decision tree was found to have better sensitivity and specificity than a logistic regression using identical predictors. The decision tree method was useful in assessing the risk of major depressive disorder over four years. Application of the model to the development of a predictive tool for tailored interventions is discussed.

Characterizing Stressors and Modifiable Health Risk Factors Among Homeless Smokers: An Exploratory Pilot Study.

PubMed

Kendzor, Darla E; Reitzel, Lorraine R; Businelle, Michael S

2015-10-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were conducted to characterize the sample as well as the relations between relevant stressors (discrimination, chronic stress, and fear and mistrust) and health risk factors. Inadequate daily consumption of fruits, vegetables, and fiber was common. High-fat diet and insufficient physical activity were also prevalent, and the majority of participants were overweight/obese. Participants commonly endorsed discrimination, fear of victimization, mistrust of others, and several other stressors. Greater endorsement of stressors was associated with a high-fat diet. Results suggest that lifestyle interventions and policy changes may be warranted in homeless shelters to attenuate the potential effects of stressors on high-fat dietary consumption among smokers. © 2015 Society for Public Health Education.

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

PubMed

Bruse, Shannon; Moreau, Michael; Bromberg, Yana; Jang, Jun-Ho; Wang, Nan; Ha, Hongseok; Picchi, Maria; Lin, Yong; Langley, Raymond J; Qualls, Clifford; Klensney-Tait, Julia; Zabner, Joseph; Leng, Shuguang; Mao, Jenny; Belinsky, Steven A; Xing, Jinchuan; Nyunoya, Toru

2016-01-07

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes. We performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro. Our integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.

A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

PubMed Central

Bond, David; Foley, Edan

2009-01-01

Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling. PMID:19893628

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Self-Identified Sexual Orientation and Sexual Risk Behavior Among HIV-Infected Latino Males.

PubMed

Champion, Jane Dimmitt; Szlachta, Alaina

2016-01-01

The HIV testing, disclosure, and sexual practices of ethnic minority men suggest that addressing sexual risk behavior and the underlying reasons for not receiving HIV testing or disclosing HIV-infection status-unique to differing populations-would improve public health interventions. Descriptive behaviors and underlying perspectives reported in our study suggest that public health interventions for HIV-infected Latino men who self-identify as heterosexual should explicitly identify substance use, needle sharing, and unprotected sex to current partners as behaviors placing both oneself and one's partners at high risk for contracting HIV. However, diversity of sexual behavior among gay, straight, and bisexual HIV-infected Latino men in our study ultimately suggested that clinicians should not rely on simplistic conceptions of sexuality in assessment of self-care needs. Care in presentation and discussion of self-identified sexual preference and sexual behavior is indicated, as these do not determine actual sexual orientation or behavior and vice versa. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Drake, Christopher L.

2016-01-01

Study Objectives: A primary focus of the National Institute of Mental Health's current strategic plan is “predicting” who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. Methods: A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Results: Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49–1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. Conclusions: The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts

Contribution of modifiable risk factors for hypertension and type-2 diabetes in Peruvian resource-limited settings

PubMed Central

Carrillo-Larco, Rodrigo M; Gilman, Robert H; Checkley, William; Smeeth, Liam

2016-01-01

Background It is important to understand the local burden of non-communicable diseases including within-country heterogeneity. The aim of this study was to characterise hypertension and type-2 diabetes profiles across different Peruvian geographical settings emphasising the assessment of modifiable risk factors. Methods Analysis of the CRONICAS Cohort Study baseline assessment was conducted. Cardiometabolic outcomes were blood pressure categories (hypertension, prehypertension, normal) and glucose metabolism disorder status (diabetes, prediabetes, normal). Exposures were study setting and six modifiable factors (smoking, alcohol drinking, leisure time and transport-related physical activity levels, TV watching, fruit/vegetables intake and obesity). Poisson regression models were used to report prevalence ratios (PR). Population attributable risks (PAR) were also estimated. Results Data from 3238 participants, 48.3% male, mean age 45.3 years, were analysed. Age-standardised (WHO population) prevalence of prehypertension and hypertension was 24% and 16%, whereas for prediabetes and type-2 diabetes it was 18% and 6%, respectively. Outcomes varied according to study setting (p<0.001). In multivariable model, hypertension was higher among daily smokers (PR 1.76), heavy alcohol drinkers (PR 1.61) and the obese (PR 2.06); whereas only obesity (PR 2.26) increased the prevalence of diabetes. PAR showed that obesity was an important determinant for hypertension (15.7%) and type-2 diabetes (23.9%). Conclusions There is an evident heterogeneity in the prevalence of and risk factors for hypertension and diabetes within Peru. Prehypertension and prediabetes are highly prevalent across settings. Our results emphasise the need of understanding the epidemiology of cardiometabolic conditions to appropriately implement interventions to tackle the burden of non-communicable diseases. PMID:26248550

Development of quality indicators for low-risk labor care provided by midwives using a RAND-modified Delphi method.

PubMed

Ueda, Kayo; Ohtera, Shosuke; Kaso, Misato; Nakayama, Takeo

2017-09-22

In childbirth, most deliveries are low-risk, defined as spontaneous labor at full term without special high-risk facts or complications, especially in high-resource countries where maternal and perinatal mortality rates are very low. Indeed, the majority of mothers and infants have no serious conditions during labor. However, the quality of care provided is not assured, and performance may vary by birthing facility and provider. The overuse of technology in childbirth in some parts of the world is almost certainly based on assumptions like, "something can go wrong at any minute." There is a need to assess the quality of care provided for mothers and infants in low-risk labor. We aimed to develop specific quality indicators for low-risk labor care provided primarily by midwives in Japan. We used a RAND-modified Delphi method, which integrates evidence review with expert consensus development. The procedure comprises five steps: (1) literature review, including clinical practice guidelines, to extract and develop quality indicator candidates; (2) formation of a multidisciplinary panel; (3) independent panel ratings (Round 1); (4) panel meeting and independent panel ratings (Round 2); and (5) independent panel ratings (Round 3). The three independent panel ratings (Rounds 1-3) were held between July and December 2012. The assembled multidisciplinary panel comprised eight clinicians (two pediatricians, three obstetricians, and three midwives) and three mothers who were nonclinicians. Evidentiary review extracted 166 key recommendations from 32 clinical practice guidelines, and 31 existing quality indicators were added. After excluding duplicate recommendations and quality indicators, the panel discussed 25 candidate indicators. Of these, 18 were adopted, one was modified, six were not adopted, and four were added during the meeting, respectively. We established 23 quality indicators for low-risk labor care provided by midwives in labor units in Japan.

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

PubMed

Gohel, M C; Patel, M M; Amin, A F

2003-05-01

This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

Poverty, AIDS and child health: identifying highest-risk children in South Africa.

PubMed

Cluver, Lucie; Boyes, Mark; Orkin, Mark; Sherr, Lorraine

2013-10-11

Identifying children at the highest risk of negative health effects is a prerequisite to effective public health policies in Southern Africa. A central ongoing debate is whether poverty, orphanhood or parental AIDS most reliably indicates child health risks. Attempts to address this key question have been constrained by a lack of data allowing distinction of AIDS-specific parental death or morbidity from other causes of orphanhood and chronic illness. To examine whether household poverty, orphanhood and parental illness (by AIDS or other causes) independently or interactively predict child health, developmental and HIV-infection risks. We interviewed 6 002 children aged 10 - 17 years in 2009 - 2011, using stratified random sampling in six urban and rural sites across three South African provinces. Outcomes were child mental health risks, educational risks and HIV-infection risks. Regression models that controlled for socio-demographic co-factors tested potential impacts and interactions of poverty, AIDS-specific and other orphanhood and parental illness status. Household poverty independently predicted child mental health and educational risks, AIDS orphanhood independently predicted mental health risks and parental AIDS illness independently predicted mental health, educational and HIV-infection risks. Interaction effects of poverty with AIDS orphanhood and parental AIDS illness were found across all outcomes. No effects, or interactions with poverty, were shown by AIDS-unrelated orphanhood or parental illness. The identification of children at highest risk requires recognition and measurement of both poverty and parental AIDS. This study shows negative impacts of poverty and AIDS-specific vulnerabilities distinct from orphanhood and adult illness more generally. Additionally, effects of interaction between family AIDS and poverty suggest that, where these co-exist, children are at highest risk of all.

The Effectiveness of Injury Prevention Programs to Modify Risk Factors for Non-Contact Anterior Cruciate Ligament and Hamstring Injuries in Uninjured Team Sports Athletes: A Systematic Review

PubMed Central

Monajati, Alireza; Larumbe-Zabala, Eneko; Goss-Sampson, Mark; Naclerio, Fernando

2016-01-01

Background Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. Objective The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. Data Sources PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Main Results Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Conclusions Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors. PMID:27171282

The Effectiveness of Injury Prevention Programs to Modify Risk Factors for Non-Contact Anterior Cruciate Ligament and Hamstring Injuries in Uninjured Team Sports Athletes: A Systematic Review.

PubMed

Monajati, Alireza; Larumbe-Zabala, Eneko; Goss-Sampson, Mark; Naclerio, Fernando

2016-01-01

Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors.

Identifying the women at risk of antenatal anxiety and depression: A systematic review.