New arrows in the quiver for targeting care management: high-risk versus high-opportunity case identification.

PubMed

Bernstein, Richard H

2007-01-01

"Care management" purposefully obscures the distinctions between disease and case management and stresses their common features: action in the present to prevent adverse future outcomes and costs. It includes identifying a high-need population by referrals, screening, or data analysis, assessing those likely to benefit from interventions, intervening, evaluating the intervention, and adjusting interventions when needed. High-risk individuals can be identified using at least 9 techniques, from referrals and questionnaires to retrospective claims analysis and predictive models. Other than referrals, software based on the risk-adjustment methodology that we have adapted can incorporate all these methodologies. Because the risk adjustment employs extensive case mix and severity adjustment, it provides care managers with 3 innovative ways to identify not only high-risk individuals but also high-opportunity cases.

Interval-Timing Deficits in Individuals at High Risk for Schizophrenia

ERIC Educational Resources Information Center

Penney, T.B.; Meck, W.H.; Roberts, S.A.; Gibbon, J.; Erlenmeyer-Kimling, L.

2005-01-01

A duration-bisection procedure was used to study the effects of signal modality and divided attention on duration classification in participants at high genetic risk for schizophrenia (HrSz), major affective disorder (HrAff), and normal controls (NC). Participants learned short and long target durations during training and classified probe…

Quality control for normal liquid-based cytology: Rescreening, high-risk HPV targeted reviewing and/or high-risk HPV detection?

PubMed Central

Depuydt, Christophe E; Arbyn, Marc; Benoy, Ina H; Vandepitte, Johan; Vereecken, Annie J; Bogers, Johannes J

2009-01-01

The objective of this prospective study was to compare the number of CIN2+cases detected in negative cytology by different quality control (QC) methods. Full rescreening, high-risk (HR) human papillomavirus (HPV)-targeted reviewing and HR HPV detection were compared. Randomly selected negative cytology detected by BD FocalPoint™ (NFR), by guided screening of the prescreened which needed further review (GS) and by manual screening (MS) was used. A 3-year follow-up period was available. Full rescreening of cytology only detected 23.5% of CIN2+ cases, whereas the cytological rescreening of oncogenic positive slides (high-risk HPV-targeted reviewing) detected 7 of 17 CIN2+ cases (41.2%). Quantitative real-time PCR for 15 oncogenic HPV types detected all CIN2+ cases. Relative sensitivity to detect histological CIN2+ was 0.24 for full rescreening, 0.41 for HR-targeted reviewing and 1.00 for HR HPV detection. In more than half of the reviewed negative cytological preparations associated with histological CIN2+cases no morphologically abnormal cells were detected despite a positive HPV test. The visual cut-off for the detection of abnormal cytology was established at 6.5 HR HPV copies/cell. High-risk HPV detection has a higher yield for detection of CIN2+ cases as compared to manual screening followed by 5% full review, or compared to targeted reviewing of smears positive for oncogenic HPV types, and show diagnostic properties that support its use as a QC procedure in cytologic laboratories. PMID:18544049

Inter-individual variability in high-throughput risk prioritization of environmental chemicals (IVIVE)

EPA Science Inventory

We incorporate inter-individual variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which hav...

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis.

PubMed

Kraus, Michael; Rapisarda, Attilio; Lam, Max; Thong, Jamie Y J; Lee, Jimmy; Subramaniam, Mythily; Collinson, Simon L; Chong, Siow Ann; Keefe, Richard S E

2016-12-01

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review.

PubMed

Glenthøj, Louise Birkedal; Hjorthøj, Carsten; Kristensen, Tina Dam; Davidson, Charlie Andrew; Nordentoft, Merete

2017-01-01

Cognitive deficits are prominent features of the ultra-high risk state for psychosis that are known to impact functioning and course of illness. Cognitive remediation appears to be the most promising treatment approach to alleviate the cognitive deficits, which may translate into functional improvements. This study systematically reviewed the evidence on the effectiveness of cognitive remediation in the ultra-high risk population. The electronic databases MEDLINE, PsycINFO, and Embase were searched using keywords related to cognitive remediation and the UHR state. Studies were included if they were peer-reviewed, written in English, and included a population meeting standardized ultra-high risk criteria. Six original research articles were identified. All the studies provided computerized, bottom-up-based cognitive remediation, predominantly targeting neurocognitive function. Four out of five studies that reported a cognitive outcome found cognitive remediation to improve cognition in the domains of verbal memory, attention, and processing speed. Two out of four studies that reported on functional outcome found cognitive remediation to improve the functional outcome in the domains of social functioning and social adjustment. Zero out of the five studies that reported such an outcome found cognitive remediation to affect the magnitude of clinical symptoms. Research on the effect of cognitive remediation in the ultra-high risk state is still scarce. The current state of evidence indicates an effect of cognitive remediation on cognition and functioning in ultra-high risk individuals. More research on cognitive remediation in ultra-high risk is needed, notably in large-scale trials assessing the effect of neurocognitive and/or social cognitive remediation on multiple outcomes.

Establishing a Program for Individuals at High Risk for Breast Cancer

PubMed Central

Cadiz, Fernando; Kuerer, Henry M.; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu

2013-01-01

Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining “high risk”; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk. PMID:23833688

Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis

PubMed Central

Lin, Ashleigh; Yung, Alison R.; Koutsouleris, Nikolaos; Nelson, Barnaby; Cropley, Vanessa L.; Velakoulis, Dennis; McGorry, Patrick D.; Pantelis, Christos; Wood, Stephen J.

2017-01-01

Abstract Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions. PMID:27369472

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals.

PubMed

Okwundu, Charles I; Uthman, Olalekan A; Okoromah, Christy An

2012-07-11

More than 30 years into the global HIV/AIDS epidemic, infection rates remain alarmingly high, with over 2.7 million people becoming infected every year. There is a need for HIV prevention strategies that are more effective. Oral antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a reliable tool in preventing the transmission of HIV. To evaluate the effects of oral antiretroviral chemoprophylaxis in preventing HIV infection in HIV-uninfected high-risk individuals. We revised the search strategy from the previous version of the review and conducted an updated search of MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in April 2012. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing trials. Randomised controlled trials that evaluated the effects of any antiretroviral agent or combination of antiretroviral agents in preventing HIV infection in high-risk individuals Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. Relative risk with a 95% confidence interval (CI) was used as the measure of effect. We identified 12 randomised controlled trials that meet the criteria for the review. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high risk men and women.Overall results from the four trials that compared TDF-FTC versus placebo showed a

Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma.

PubMed

Hassannia, Behrouz; Wiernicki, Bartosz; Ingold, Irina; Qu, Feng; Van Herck, Simon; Tyurina, Yulia Y; Bayır, Hülya; Abhari, Behnaz A; Angeli, Jose Pedro Friedmann; Choi, Sze Men; Meul, Eline; Heyninck, Karen; Declerck, Ken; Chirumamilla, Chandra Sekhar; Lahtela-Kakkonen, Maija; Van Camp, Guy; Krysko, Dmitri V; Ekert, Paul G; Fulda, Simone; De Geest, Bruno G; Conrad, Marcus; Kagan, Valerian E; Berghe, Wim Vanden; Vandenabeele, Peter; Berghe, Tom Vanden

2018-06-25

High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical ferroptosis induction). Noncanonical ferroptosis induction is characterized by an increase in intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which is sufficient to induce ferroptosis. This double-edged mechanism might explain the superior efficacy of WA as compared with etoposide or cisplatin in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing the growth and relapse rate of neuroblastoma xenografts. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced accumulation at the tumor site. Collectively, our data propose a novel therapeutic strategy to efficiently kill cancer cells by ferroptosis.

Effects of policies designed to keep firearms from high-risk individuals.

PubMed

Webster, Daniel W; Wintemute, Garen J

2015-03-18

This article summarizes and critiques available evidence from studies published between 1999 and August 2014 on the effects of policies designed to keep firearms from high-risk individuals in the United States. Some prohibitions for high-risk individuals (e.g., those under domestic violence restraining orders, violent misdemeanants) and procedures for checking for more types of prohibiting conditions are associated with lower rates of violence. Certain laws intended to prevent prohibited persons from accessing firearms-rigorous permit-to-purchase, comprehensive background checks, strong regulation and oversight of gun dealers, and requiring gun owners to promptly report lost or stolen firearms-are negatively associated with the diversion of guns to criminals. Future research is needed to examine whether these laws curtail nonlethal gun violence and whether the effects of expanding prohibiting conditions for firearm possession are modified by the presence of policies to prevent diversion.

The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers.

PubMed

Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik; Rossing, Peter; Lambers Heerspink, Hiddo Jan

2015-10-01

Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes. Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI). SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2. In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings. © 2015 The British Pharmacological Society.

Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma.

PubMed

Ackermann, Sandra; Goeser, Felix; Schulte, Johannes H; Schramm, Alexander; Ehemann, Volker; Hero, Barbara; Eggert, Angelika; Berthold, Frank; Fischer, Matthias

2011-02-15

High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. The Polo-like kinase 1 (PLK1) is highly expressed in many human cancers and is a target of the novel small-molecule inhibitor BI 2536, which has shown promising anticancer activity in adult malignancies. Here, we investigated the effect of BI 2536 on neuroblastoma cells in vitro and in vivo to explore PLK1 as a potential target in high-risk neuroblastoma therapy. PLK1 transcript levels were analyzed by microarrays in 476 primary neuroblastoma specimens, and correlation with prognostic markers and patient outcome was examined. To explore the effect of PLK1 inhibition on neuroblastoma cells, 7 cell lines were treated with BI 2536 and changes in growth properties were determined. Furthermore, nude mice with IMR-32 and SK-N-AS xenografts were treated with BI 2536. PLK1 is highly expressed in unfavorable neuroblastoma and in neuroblastoma cell lines. Expression of PLK1 is associated with unfavorable prognostic markers such as stage 4, age >18 months, MYCN amplification, unfavorable gene expression-based classification, and adverse patient outcome (P < 0.001 each). On treatment with nanomolar doses of BI 2536, all neuroblastoma cell lines analyzed showed significantly reduced proliferation, cell cycle arrest, and cell death. Moreover, BI 2536 abrogated growth of neuroblastoma xenografts in nude mice. Elevated PLK1 expression is significantly associated with high-risk neuroblastoma and unfavorable patient outcome. Inhibition of PLK1 using BI 2536 exhibits strong antitumor activity on human neuroblastoma cells in vitro and in vivo, opening encouraging new perspectives for the treatment of high-risk neuroblastoma. ©2010 AACR.

Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis.

PubMed

Reniers, Renate L E P; Lin, Ashleigh; Yung, Alison R; Koutsouleris, Nikolaos; Nelson, Barnaby; Cropley, Vanessa L; Velakoulis, Dennis; McGorry, Patrick D; Pantelis, Christos; Wood, Stephen J

2017-03-01

Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparability on knowledge, attitudes, and behaviors between STD clinic clients and high-risk individuals in community.

PubMed

Du, Ping; Thomas, Rosalind; McNutt, Louise-Anne; Bruce Coles, F

2008-01-01

To assess the feasibility and generalizability of STD clinic samples for studying STD-related knowledge, attitudes, and behaviors (KAB), and healthcare preferences among individuals at high risk for STDs in the same community. An STD clinic and a community sample were selected from each of two urban areas in New York State. At each STD clinic, 100 individuals were interviewed. In each community, about 400 individuals were selected by random-digit-dialing telephone survey during the same period. Community sample participants were defined as having high-risk profiles on the basis of five items related to their sexual behaviors. The STD clinic samples were younger and had a larger proportion of men and nonwhite people compared with the high-risk community samples. Although the majority of STD clinic clients would seek healthcare at the STD clinics, high-risk community participants were more likely to prefer private doctors for STDs care (P < .0001 for both areas). Overall STD-related KAB were similar between STD clinic and high-risk community samples; however, STD clinic clients may be more knowledgeable about specific STDs and more likely to feel embarrassment about getting an STD. The findings comparing KAB between high-risk community subjects and STD clinic attendees also varied by geographic location. STD clinic samples may not be sufficiently representative of community STD-related KAB collected by telephone surveys, even for that subset of community respondents with high-risk behaviors associated with STDs.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

NASA Astrophysics Data System (ADS)

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, Daegab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-03-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

PubMed Central

Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2016-01-01

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

Novel target for high-risk neuroblastoma identified in pre-clinical research | Center for Cancer Research

Cancer.gov

Pre-clinical research by investigators at the Center for Cancer Research and their colleagues have identified a number of novel epigenetic targets for high-risk neuroblastoma and validated a promising new targeted inhibitor in pre-clinical models.  Read more...

Individual survival curves comparing subjective and observed mortality risks.

PubMed

Bissonnette, Luc; Hurd, Michael D; Michaud, Pierre-Carl

2017-12-01

We compare individual survival curves constructed from objective (actual mortality) and elicited subjective information (probability of survival to a given target age). We develop a methodology to estimate jointly subjective and objective individual survival curves accounting for rounding on subjective reports of perceived survival. We make use of the long follow-up period in the Health and Retirement Study and the high quality of mortality data to estimate individual survival curves that feature both observed and unobserved heterogeneity. This allows us to compare objective and subjective estimates of remaining life expectancy for various groups and compare welfare effects of objective and subjective mortality risk using the life cycle model of consumption. We find that subjective and objective hazards are not the same. The median welfare loss from misperceptions of mortality risk when annuities are not available is 7% of current wealth at age 65 whereas more than 25% of respondents have losses larger than 60% of wealth. When annuities are available and exogenously given, the welfare loss is substantially lower. Copyright © 2017 John Wiley & Sons, Ltd.

Individual risk of cutaneous melanoma in New Zealand: developing a clinical prediction aid.

PubMed

Sneyd, Mary Jane; Cameron, Claire; Cox, Brian

2014-05-22

New Zealand and Australia have the highest melanoma incidence rates worldwide. In New Zealand, both the incidence and thickness have been increasing. Clinical decisions require accurate risk prediction but a simple list of genetic, phenotypic and behavioural risk factors is inadequate to estimate individual risk as the risk factors for melanoma have complex interactions. In order to offer tailored clinical management strategies, we developed a New Zealand prediction model to estimate individual 5-year absolute risk of melanoma. A population-based case-control study (368 cases and 270 controls) of melanoma risk factors provided estimates of relative risks for fair-skinned New Zealanders aged 20-79 years. Model selection techniques and multivariate logistic regression were used to determine the important predictors. The relative risks for predictors were combined with baseline melanoma incidence rates and non-melanoma mortality rates to calculate individual probabilities of developing melanoma within 5 years. For women, the best model included skin colour, number of moles > =5 mm on the right arm, having a 1st degree relative with large moles, and a personal history of non-melanoma skin cancer (NMSC). The model correctly classified 68% of participants; the C-statistic was 0.74. For men, the best model included age, place of occupation up to age 18 years, number of moles > =5 mm on the right arm, birthplace, and a history of NMSC. The model correctly classified 67% of cases; the C-statistic was 0.71. We have developed the first New Zealand risk prediction model that calculates individual absolute 5-year risk of melanoma. This model will aid physicians to identify individuals at high risk, allowing them to individually target surveillance and other management strategies, and thereby reduce the high melanoma burden in New Zealand.

Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

PubMed

Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

2014-05-01

We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

Effect of Precede-Proceed Model on Preventive Behaviors for Type 2 Diabetes Mellitus in High-Risk Individuals.

PubMed

Moshki, Mahdi; Dehnoalian, Atefeh; Alami, Ali

2017-04-01

This study sought to assess the effect of precede-proceed model on preventive behaviors for type 2 diabetes mellitus (DM) in high-risk individuals. In this semi-experimental study, 164 high-risk individuals for type 2 DM were selected and were randomly divided into two groups of intervention and control ( n = 85). Educational intervention was performed as a single session face-to-face instruction for 1.5 hr for the intervention group participants. Data were collected before (baseline) and immediately and 1 month after the intervention in the two groups. The mean score of predisposing (knowledge) factors ( p = .001), reinforcing factors ( p = .001), and enabling factors ( p = .02) were significantly different at baseline and 1 month after the intervention in the intervention group compared with the control group ( p < .05). A significant improvement occurred in the nutritional habits of high-risk participants in the intervention group at 1 month after the intervention compared with controls ( p = .001). The precede-proceed model can be effective for promoting the preventive behaviors for type 2 DM in high-risk individuals.

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

Therapeutic lipid target achievements among high and highest risk patients: results from the CEPHEUS study in the Arabian Gulf.

PubMed

Al-Rasadi, Khalid; Al-Zakwani, Ibrahim; Al Mahmeed, Wael; Arafah, Mohamed; Al-Hinai, Ali T; Shehab, Abdullah; Al Tamimi, Omer; Alawadhi, Mahmoud

2014-12-01

To determine lipid target achievements of low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apo B) in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS) in Arabian Gulf States patients with high and highest risk according to the joint Consensus Statement of the American Diabetes Association (ADA) and American College of Cardiology Foundation (ACC). CEPHEUS was conducted in patients (≥ 18 years of age) in six Middle Eastern countries between November 2009 and July 2010 on lipid lowering drugs (LLDs). Serum samples collected included total cholesterol (TC), LDL-C, HDL-C, triglycerides (TGs), apo B, and apolipoprotein A1 (apo A1). The overall mean age of the cohort (n = 5275) was 56 ± 13 years, 58% (n = 3060) were male and 69% (n = 3635) were highest risk. LDL-C target was achieved in 25%, non-HDL-C in 36% and apo B in 38% of patients in the highest risk cohort compared with LDL-C 46%, non-HDL-C 58% and apo B 51% in the high risk group. In patients with TGs ≥ 2.2 mmol/L, LDL-C target was achieved in 16% and apo B in 15% of patients in the highest risk group compared with LDL-C 32% and apo B 22% in the high risk cohort. Despite being on LLDs, a large proportion of high and highest risk patients in the Arabian Gulf are not at recommended lipid targets and remain at a substantial residual risk for cardiovascular diseases. Apo B may be used as an additional target in patients with triglycerides ≥ 2.2 mmol/L. The findings should be interpreted in light of the study's limitations.

Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma.

PubMed

Lochmann, Timothy L; Powell, Krista M; Ham, Jungoh; Floros, Konstantinos V; Heisey, Daniel A R; Kurupi, Richard I J; Calbert, Marissa L; Ghotra, Maninderjit S; Greninger, Patricia; Dozmorov, Mikhail; Gowda, Madhu; Souers, Andrew J; Reynolds, C Patrick; Benes, Cyril H; Faber, Anthony C

2018-05-16

High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death. Retinoic acid (RA)-resistant neuroblastoma cells were sensitive to GSK-J4. In addition, GSK-J4 was effective at blocking the growth of chemorefractory and patient-derived xenograft models of high-risk neuroblastoma in vivo. Furthermore, GSK-J4 and RA combination increased differentiation and ER stress over GSK-J4 effects and limited the growth of neuroblastomas resistant to either drug alone. In MYCN -amplified neuroblastoma, PUMA induction by GSK-J4 sensitized tumors to the B cell lymphoma 2 (BCL-2) inhibitor venetoclax, demonstrating that epigenetic-targeted therapies and BCL-2 homology domain 3 mimetics can be rationally combined to treat this high-risk subset of neuroblastoma. Therefore, H3K27 demethylation inhibition is a promising therapeutic target to treat high-risk neuroblastoma, and H3K27 demethylation can be part of rational combination therapies to induce robust antineuroblastoma activity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A systematic review of basic life support training targeted to family members of high-risk cardiac patients.

PubMed

Cartledge, Susie; Bray, Janet E; Leary, Marion; Stub, Dion; Finn, Judith

2016-08-01

Targeting basic life support (BLS) training to bystanders who are most likely to witness an out of hospital cardiac arrest (OHCA) is an important public health intervention. We performed a systematic review examining the evidence of the effectiveness of providing BLS training to family members of high-risk cardiac patients. A search of Ovid MEDLINE, CINAL, EMBASE, Informit, Cochrane Library, Web of Science, Scopus, ERIC and ProQuest Dissertations and Theses Global was conducted. We included all studies training adult family members of high-risk cardiac patients regardless of methods used for cardiopulmonary resuscitation (CPR) or BLS training. Two reviewers independently extracted data and evaluated the quality of evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We included 26 of the 1172 studies identified. The majority of studies were non-randomised controlled trials (n=18), of very low to moderate quality. Currently, there is insufficient evidence to indicate a benefit of this intervention for patients; largely because of low numbers of OHCA events and high loss to follow-up. However, the majority of trained individuals were able to competently perform BLS skills, reported a willingness to use these skills and experienced lower anxiety. Whilst there is no current evidence for improvement in patient outcomes from targeted BLS training for family members, this group are willing and capable to learn these skills. Future research may need to examine longer periods of follow-up using alternate methods (e.g. cardiac arrest registries), and examine the effectiveness of training in the modern era. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Self-efficacy and health behaviors toward the prevention of diabetes among high risk individuals living in Appalachia.

PubMed

Serrano, Elena; Leiferman, Jennifer; Dauber, Sarah

2007-04-01

Recent clinical trials indicate that type 2 diabetes can largely be prevented through lifestyle factors. In order to identify important modalities for the prevention of diabetes in medically underserved counties of Virginia (Appalachia), a questionnaire was administered to 135 at-risk individuals, having reported at least one risk factor for diabetes. The questionnaire assessed attitudes, self-efficacy, diet, and physical activity toward the prevention of type 2 diabetes. Overall, none of the respondents reported being told by a physician that they were at risk for diabetes. Overweight was the most frequently reported risk factor (87.0%), followed by physical inactivity (67.3%). More than one-third (38.9%) reported at least three diabetes symptoms. When stratified by low and high risk level, there were no significant differences in self-efficacy, control, and healthy dietary behaviors (p < .05). High risk individuals did report having lower rates of full health insurance coverage, being less active and running out of food more frequently than low risk individuals, however. The findings suggest that cost-effective prevention efforts should incorporate physician education, include screenings, and address self-efficacy enhancing strategies toward preventing type 2 diabetes.

Health risks of space exploration: targeted and nontargeted oxidative injury by high-charge and high-energy particles.

PubMed

Li, Min; Gonon, Géraldine; Buonanno, Manuela; Autsavapromporn, Narongchai; de Toledo, Sonia M; Pain, Debkumar; Azzam, Edouard I

2014-03-20

During deep space travel, astronauts are often exposed to high atomic number (Z) and high-energy (E) (high charge and high energy [HZE]) particles. On interaction with cells, these particles cause severe oxidative injury and result in unique biological responses. When cell populations are exposed to low fluences of HZE particles, a significant fraction of the cells are not traversed by a primary radiation track, and yet, oxidative stress induced in the targeted cells may spread to nearby bystander cells. The long-term effects are more complex because the oxidative effects persist in progeny of the targeted and affected bystander cells, which promote genomic instability and may increase the risk of age-related cancer and degenerative diseases. Greater understanding of the spatial and temporal features of reactive oxygen species bursts along the tracks of HZE particles, and the availability of facilities that can simulate exposure to space radiations have supported the characterization of oxidative stress from targeted and nontargeted effects. The significance of secondary radiations generated from the interaction of the primary HZE particles with biological material and the mitigating effects of antioxidants on various cellular injuries are central to understanding nontargeted effects and alleviating tissue injury. Elucidation of the mechanisms underlying the cellular responses to HZE particles, particularly under reduced gravity and situations of exposure to additional radiations, such as protons, should be useful in reducing the uncertainty associated with current models for predicting long-term health risks of space radiation. These studies are also relevant to hadron therapy of cancer.

Individual and Parental Risk Factors for Sexual Exploitation Among High-Risk Youth in Uganda.

PubMed

Self-Brown, Shannon; Culbreth, Rachel; Wilson, Rebecca; Armistead, Lisa; Kasirye, Rogers; Swahn, Monica H

2018-04-01

This study examined risk factors to determine associations with commercial sexual exploitation of children and youth (CSEC) in a convenience sample of adolescents living in the slums in Kampala, Uganda. Individual-level factors included demographic, adverse experiences (ever living on the streets; victim of dating violence, parental abuse, or rape), and behavioral risk (social media, alcohol use, age at first intercourse). Parental-risk factors included parent alcohol use and approval attitudes toward youth sex. Analyses included those who self-reported sexually active adolescents ( n = 593) of whom 39% reported CSEC history. CSEC was significantly associated with being female (odds ratio [ OR] = 6.85, 95% confidence interval (CI) = [4.22, 11.12]), living on the streets ( OR = 2.68; 95% CI = [1.65, 4.36]), using social media ( OR = 1.48; 95% CI = [0.94, 2.35]), being a victim of physical dating violence ( OR = 1.74; 95% CI = [1.08, 2.80]), and ever being raped ( OR = 4.03; 95% CI = [2.51, 6.47]). Further analyses suggested differential risk associates among females and males. This study contributes to our knowledge of risk factors for CSEC among adolescents living in high-risk circumstances in low-resource countries and suggests that preventive efforts should prioritize adolescents with a history of living on the streets who engage in social media, use alcohol, and have a history of trauma.

Prediction of diabetes based on baseline metabolic characteristics in individuals at high risk.

PubMed

Defronzo, Ralph A; Tripathy, Devjit; Schwenke, Dawn C; Banerji, Maryann; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; Gastaldelli, Amalia

2013-11-01

Individuals with impaired glucose tolerance (IGT) are at high risk for developing type 2 diabetes mellitus (T2DM). We examined which characteristics at baseline predicted the development of T2DM versus maintenance of IGT or conversion to normal glucose tolerance. We studied 228 subjects at high risk with IGT who received treatment with placebo in ACT NOW and who underwent baseline anthropometric measures and oral glucose tolerance test (OGTT) at baseline and after a mean follow-up of 2.4 years. In a univariate analysis, 45 of 228 (19.7%) IGT individuals developed diabetes. After adjusting for age, sex, and center, increased fasting plasma glucose, 2-h plasma glucose, G0-120 during OGTT, HbA1c, adipocyte insulin resistance index, ln fasting plasma insulin, and ln I0-120, as well as family history of diabetes and presence of metabolic syndrome, were associated with increased risk of diabetes. At baseline, higher insulin secretion (ln [I0-120/G0-120]) during the OGTT was associated with decreased risk of diabetes. Higher β-cell function (insulin secretion/insulin resistance or disposition index; ln [I0-120/G0-120 × Matsuda index of insulin sensitivity]; odds ratio 0.11; P < 0.0001) was the variable most closely associated with reduced risk of diabetes. In a stepwise multiple-variable analysis, only HbA1c and β-cell function (ln insulin secretion/insulin resistance index) predicted the development of diabetes (r = 0.49; P < 0.0001).

Assessing and Managing Risk with Suicidal Individuals

ERIC Educational Resources Information Center

Linehan, Marsh M.; Comtois, Katherine A.; Ward-Ciesielski, Erin F.

2012-01-01

The University of Washington Risk Assessment Protocol (UWRAP) and Risk Assessment and Management Protocol (UWRAMP) have been used in numerous clinical trials treating high-risk suicidal individuals over several years. These protocols structure assessors and treatment providers to provide a thorough suicide risk assessment, review standards of care…

Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

PubMed Central

Li, Min; Gonon, Géraldine; Buonanno, Manuela; Autsavapromporn, Narongchai; de Toledo, Sonia M.; Pain, Debkumar

2014-01-01

Abstract Significance: During deep space travel, astronauts are often exposed to high atomic number (Z) and high-energy (E) (high charge and high energy [HZE]) particles. On interaction with cells, these particles cause severe oxidative injury and result in unique biological responses. When cell populations are exposed to low fluences of HZE particles, a significant fraction of the cells are not traversed by a primary radiation track, and yet, oxidative stress induced in the targeted cells may spread to nearby bystander cells. The long-term effects are more complex because the oxidative effects persist in progeny of the targeted and affected bystander cells, which promote genomic instability and may increase the risk of age-related cancer and degenerative diseases. Recent Advances: Greater understanding of the spatial and temporal features of reactive oxygen species bursts along the tracks of HZE particles, and the availability of facilities that can simulate exposure to space radiations have supported the characterization of oxidative stress from targeted and nontargeted effects. Critical Issues: The significance of secondary radiations generated from the interaction of the primary HZE particles with biological material and the mitigating effects of antioxidants on various cellular injuries are central to understanding nontargeted effects and alleviating tissue injury. Future Directions: Elucidation of the mechanisms underlying the cellular responses to HZE particles, particularly under reduced gravity and situations of exposure to additional radiations, such as protons, should be useful in reducing the uncertainty associated with current models for predicting long-term health risks of space radiation. These studies are also relevant to hadron therapy of cancer. Antioxid. Redox Signal. 20, 1501–1523. PMID:24111926

Clinically significant personality traits in individuals at high risk of developing psychosis.

PubMed

Sevilla-Llewellyn-Jones, Julia; Camino, Gustavo; Russo, Debra A; Painter, Michelle; Montejo, Angel L; Ochoa, Susana; Jones, Peter B; Perez, Jesus

2018-03-01

It is still unclear to what extent personality may influence the development of psychosis. We aimed to explore significant personality traits in individuals at high-risk (HR) for psychosis. Personalities of forty HR individuals and a matched sample of 40 healthy volunteers (HVs) were evaluated with the Millon Multiaxial Inventory (MCMI-III). They were also assessed with the Positive and Negative Symptoms Scale (PANSS), Beck Depression and Anxiety Inventories (BDI-II and BAI), Global Assessment of Functioning (GAF) and Mini-International Neuropsychiatric Interview (MINI 6.0.0). Fisher's exact test was employed to compare frequency of traits. Mann-Whitney U test and logistic regression were used to establish relationships between traits and symptoms, and the effect of age, sex and symptoms on such traits. Most HR individuals (97.5%) had at least one significant trait; 75% had personality disorders, mainly depressive, borderline or schizotypal. Only histrionic and narcissistic traits were more prevalent in HVs. Negative symptoms were related to schizoid and paranoid traits. Depression was more severe with borderline traits. Most HR individuals (67.6%) had more than one DSM-IV Axis I diagnosis, mainly depressive/anxiety disorders. Transition rate was low (5%). Certain personality profiles may not be markers for conversions to psychosis but contribute to high morbidity in HR individuals. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk, individual differences, and environment: an Agent-Based Modeling approach to sexual risk-taking.

PubMed

Nagoski, Emily; Janssen, Erick; Lohrmann, David; Nichols, Eric

2012-08-01

Risky sexual behaviors, including the decision to have unprotected sex, result from interactions between individuals and their environment. The current study explored the use of Agent-Based Modeling (ABM)-a methodological approach in which computer-generated artificial societies simulate human sexual networks-to assess the influence of heterogeneity of sexual motivation on the risk of contracting HIV. The models successfully simulated some characteristics of human sexual systems, such as the relationship between individual differences in sexual motivation (sexual excitation and inhibition) and sexual risk, but failed to reproduce the scale-free distribution of number of partners observed in the real world. ABM has the potential to inform intervention strategies that target the interaction between an individual and his or her social environment.

Targeting a high-risk group for fall prevention: strategies for health plans.

PubMed

Jennings, Lee A; Reuben, David B; Kim, Sung-Bou; Keeler, Emmett; Roth, Carol P; Zingmond, David S; Wenger, Neil S; Ganz, David A

2015-09-01

Although Medicare has implemented incentives for health plans to reduce fall risk, the best way to identify older people at high risk of falling and to use screening results to target fall prevention services remains unknown. We evaluated 4 different strategies using a combination of administrative data and patient-reported information that health plans could easily obtain. Observational study. We used data from 1776 patients 75 years or older in 4 community-based primary care practices who screened positive for a fear of falling and/or a history of falls. For these patients, we predicted fall-related injuries in the 24 months after the date of screening using claims/encounter data. After controlling for age and gender, we predicted the number of fall-related injuries by adding Elixhauser comorbidity count, any claim for a fall-related injury during the 12 months prior to screening, and falls screening question responses in a sequential fashion using negative binomial regression models. Basic patient characteristics, including age and Elixhauser comorbidity count, were strong predictors of fall-related injury. Among falls screening questions, a positive response to, "Have you fallen 2 or more times in the past year?" was the most predictive of a fall-related injury (incidence rate ratio [IRR], 1.56; 95% CI, 1.25-1.94). Prior claim for a fall-related injury also independently predicted this type of injury (IRR, 1.41; 95% CI, 1.05-1.89). The best model for predicting fall-related injuries combined all of these approaches. The combination of administrative data and a simple screening item can be used by health plans to target patients at high risk for future fall-related injuries.

Impact of high-risk conjunctions on Active Debris Removal target selection

NASA Astrophysics Data System (ADS)

Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

2015-10-01

Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target selection is the collision probability accumulated by every object. This paper shows the impact of high-probability conjunctions on the collision probability accumulated by individual objects as well as the probability of any collision occurring in orbit. Such conjunctions cannot be predicted far in advance and, consequently, not all the objects that will be involved in such dangerous conjunctions can be removed through ADR. Therefore, a debris remediation method that would address such events at short notice, and thus help prevent likely collisions, is suggested.

Developmental dyslexia: predicting individual risk

PubMed Central

Thompson, Paul A; Hulme, Charles; Nash, Hannah M; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J

2015-01-01

Background Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. Methods The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6 months (T1) at approximately annual intervals on tasks tapping cognitive, language, and executive-motor skills. The children were recruited to three groups: children at family risk of dyslexia, children with concerns regarding speech, and language development at 3;06 years and controls considered to be typically developing. At 8 years, children were classified as ‘dyslexic’ or not. Logistic regression models were used to predict the individual risk of dyslexia and to investigate how risk factors accumulate to predict poor literacy outcomes. Results Family-risk status was a stronger predictor of dyslexia at 8 years than low language in preschool. Additional predictors in the preschool years include letter knowledge, phonological awareness, rapid automatized naming, and executive skills. At the time of school entry, language skills become significant predictors, and motor skills add a small but significant increase to the prediction probability. We present classification accuracy using different probability cutoffs for logistic regression models and ROC curves to highlight the accumulation of risk factors at the individual level. Conclusions Dyslexia is the outcome of multiple risk factors and children with language difficulties at school entry are at high risk. Family history of dyslexia is a predictor of literacy outcome from the preschool years. However, screening does not reach an acceptable clinical level until close to school entry when letter knowledge, phonological awareness, and RAN, rather than family risk, together provide good sensitivity and specificity as a screening battery. PMID:25832320

Stigma related to labels and symptoms in individuals at clinical high-risk for psychosis.

PubMed

Yang, Lawrence H; Link, Bruce G; Ben-David, Shelly; Gill, Kelly E; Girgis, Ragy R; Brucato, Gary; Wonpat-Borja, Ahtoy J; Corcoran, Cheryl M

2015-10-01

Despite advances that the psychosis "clinical high-risk" (CHR) identification offers, risk of stigma exists. Awareness of and agreement with stereotypes has not yet been evaluated in CHR individuals. Furthermore, the relative stigma associated with symptoms, as opposed to the label of risk, is not known, which is critical because CHR identification may reduce symptom-related stigma. Thirty-eight CHR subjects were ascertained using standard measures from the Center of Prevention and Evaluation/New York State Psychiatric Institute/ Columbia University. Labeling-related measures adapted to the CHR group included "stereotype awareness and self-stigma" ("Stereotype awareness", "Stereotype Agreement", "Negative emotions [shame]"), and a parallel measure of "Negative emotions (shame)" for symptoms. These measures were examined in relation to symptoms of anxiety and depression, adjusting for core CHR symptoms (e.g. attenuated psychotic symptoms). CHR participants endorsed awareness of mental illness stereotypes, but largely did not themselves agree with these stereotypes. Furthermore, CHR participants described more stigma associated with symptoms than they did with the risk-label itself. Shame related to symptoms was associated with depression, while shame related to the risk-label was associated with anxiety. Both stigma of the risk-label and of symptoms contribute to the experience of CHR individuals. Stereotype awareness was relatively high and labeling-related shame was associated with increased anxiety. Yet limited agreement with stereotypes indicated that labeling-related stigma had not fully permeated self-conceptions. Furthermore, symptom-related stigma appeared more salient overall and was linked with increased depression, suggesting that alleviating symptom-related shame via treating symptoms might provide major benefit. Copyright © 2015. Published by Elsevier B.V.

Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

PubMed Central

Minetti, Andrea; Hurtado, Northan; Grais, Rebecca F.; Ferrari, Matthew

2014-01-01

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals. PMID:24131555

A Systematic Review of Interventions to Improve Adherence to Melanoma Preventive Behaviors for Individuals at Elevated Risk

PubMed Central

Wu, Yelena P.; Aspinwall, Lisa G.; Conn, Bridgid M.; Stump, Tammy; Grahmann, Bridget; Leachman, Sancy A.

2016-01-01

Background and Objectives To examine the effectiveness of behavioral interventions for melanoma prevention targeted to individuals at elevated risk due to personal and/or family history. Methods Through literature searches in 5 search databases (through July 2014), 20 articles describing 14 unique interventions focused on melanoma prevention among individuals at elevated risk for the disease were identified. Interventions targeting only patients undergoing active treatment for melanoma were excluded. Results The average study quality was moderate. The majority of interventions (6 out of 9, 66% of studies) led to improvements in one or more photoprotective behaviors, particularly for improvements in use of protective clothing (3 out of 5, 60% of studies), and frequency and/or thoroughness of skin self-examinations (9 out of 12, 75%). Fewer interventions (5 out of 14, 36%) targeted uptake of total body skin examinations (60% led to improvements). Also, fewer interventions targeted all three preventive behaviors (5 out of 14, 36%). Conclusions Findings suggest future interventions should aim to improve adherence across multiple preventive behaviors, over a longer time period (past 8 months post-intervention), and target high-risk children. Studies should include adequate sample sizes to investigate moderators and mediators of intervention effectiveness. Interventions may be strengthened by new techniques, such as incorporating family members (e.g., to improve thoroughness of skin self-examinations) and eHealth technology. PMID:27090434

Individual and combined effects of multiple high-risk triggers on postcessation smoking urge and lapse.

PubMed

Lam, Cho Y; Businelle, Michael S; Aigner, Carrie J; McClure, Jennifer B; Cofta-Woerpel, Ludmila; Cinciripini, Paul M; Wetter, David W

2014-05-01

Negative affect, alcohol consumption, and presence of others smoking have consistently been implicated as risk factors for smoking lapse and relapse. What is not known, however, is how these factors work together to affect smoking outcomes. This paper uses ecological momentary assessment (EMA) collected during the first 7 days of a smoking cessation attempt to test the individual and combined effects of high-risk triggers on smoking urge and lapse. Participants were 300 female smokers who enrolled in a study that tested an individually tailored smoking cessation treatment. Participants completed EMA, which recorded negative affect, alcohol consumption, presence of others smoking, smoking urge, and smoking lapse, for 7 days starting on their quit date. Alcohol consumption, presence of others smoking, and negative affect were, independently and in combination, associated with increase in smoking urge and lapse. The results also found that the relationship between presence of others smoking and lapse and the relationship between negative affect and lapse were moderated by smoking urge. The current study found significant individual effects of alcohol consumption, presence of other smoking, and negative affect on smoking urge and lapse. Combing the triggers increased smoking urge and the risk for lapse to varying degrees, and the presence of all 3 triggers resulted in the highest urge and lapse risk.

World Health Organization cardiovascular risk stratification and target organ damage.

PubMed

Piskorz, D; Bongarzoni, L; Citta, L; Citta, N; Citta, P; Keller, L; Mata, L; Tommasi, A

2016-01-01

Prediction charts allow treatment to be targeted according to simple markers of cardiovascular risk; many algorithms do not recommend screening asymptomatic target organ damage which could change dramatically the assessment. To demonstrate that target organ damage is present in low cardiovascular risk hypertensive patients and it is more frequent and severe as global cardiovascular risk increases. Consecutive hypertensive patients treated at a single Latin American center. Cardiovascular risk stratified according to 2013 WHO/ISH risk prediction chart America B. Left ventricular mass assessed by Devereux method, left ventricular hypertrophy considered >95g/m(2) in women and >115g/m(2) in men. Transmitral diastolic peak early flow velocity to average septal/lateral peak early diastolic relaxation velocity (E/e' ratio) measured cut off value >13. Systolic function assessed by tissue Doppler average interventricular septum/lateral wall mitral annulus rate systolic excursion (s wave). A total of 292 patients were included of whom 159 patients (54.5%) had cardiovascular risk of <10%, 90 (30.8%) had cardiovascular risk of 10-20% and 43 (14.7%) had cardiovascular risk of >20%. Left ventricular hypertrophy was detected in 17.6% low risk patients, 27.8% in medium risk and 23.3% in high risk (p<0.05), abnormal E/e' ratio was found in 13.8%, 31.1% and 27.9%, respectively (p<0.05). Mean s wave was 8.03+8, 8.1+9 and 8.7+1cm/s for low, intermediate and high risk patients, respectively (p<0.025). Target organ damage is more frequent and severe in high risk; one over four subjects was misclassified due to the presence of asymptomatic target organ damage. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

Individualized glycaemic targets and pharmacotherapy in type 2 diabetes.

PubMed

Bailey, Clifford J; Aschner, Pablo; Del Prato, Stefano; LaSalle, James; Ji, Linong; Matthaei, Stephan

2013-09-01

The Global Partnership for Effective Diabetes Management, established to provide practical guidance to improve patient outcomes in diabetes, has developed and modified recommendations to improve glycaemic control in type 2 diabetes. The Global Partnership advocates an individualized therapeutic approach and, as part of the process to customize therapy, has previously identified specific type 2 diabetes patient subgroups that require special consideration. This article builds on earlier publications, expanding the scope of practical guidance to include newly diagnosed individuals with complications and women with diabetes in pregnancy. Good glycaemic control remains the cornerstone of managing type 2 diabetes, and plays a vital role in preventing or delaying the onset and progression of diabetic complications. Individualizing therapeutic goals and treatments to meet glycaemic targets safely and without delay remains paramount, in addition to a wider programme of care to reduce cardiovascular risk factors and improve patient outcomes.

Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study.

PubMed

Morales, Clotilde; Plana, Núria; Arnau, Anna; Matas, Laia; Mauri, Marta; Vila, Àlex; Vila, Lluís; Soler, Cristina; Montesinos, Jesús; Masana, Lluís; Pedro-Botet, Juan

Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

PubMed Central

Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles

2016-01-01

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

PubMed

Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles

2016-06-03

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.

Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention.

PubMed

Fiore-Gartland, Andrew; Carpp, Lindsay N; Naidoo, Kogieleum; Thompson, Ethan; Zak, Daniel E; Self, Steve; Churchyard, Gavin; Walzl, Gerhard; Penn-Nicholson, Adam; Scriba, Thomas J; Hatherill, Mark

2018-03-01

Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. Such risk-targeted strategies may offer a rapid, ethical and cost-effective path towards decreasing the burden of TB disease and interrupting transmission and would also be critical to achieving TB elimination in countries nearing elimination. We also discuss design considerations for a Correlate of Risk Targeted Intervention Study (CORTIS), which could provide proof-of-concept for the strategy. One such study in South Africa is currently enrolling 1500 high-risk and 1700 low-risk individuals, as defined by biomarker status, and is randomizing high-risk participants to TB preventive therapy or standard of care treatment. All participants are monitored for progression to active TB with primary objectives to assess efficacy of the treatment and performance of the biomarker. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective.

PubMed

Corcoran, C M; Keilp, J G; Kayser, J; Klim, C; Butler, P D; Bruder, G E; Gur, R C; Javitt, D C

2015-10-01

Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7-26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

PubMed

Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I; Jackson, Anne U; Schmidt, Ellen M; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J; Shungin, Dmitry; Hughes, Maria F; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M; Magnusson, Patrik K; Salfati, Elias L; Rallidis, Loukianos S; Theusch, Elizabeth; Smith, Andrew J P; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H; Joehanes, Roby; Kim, Stuart K; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O; Bochud, Murielle; Absher, Devin; Adair, Linda S; Amin, Najaf; Arking, Dan E; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R; Barroso, Inês; Bevan, Stephen; Bis, Joshua C; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Bornstein, Stefan R; Brown, Morris J; Burnier, Michel; Cabrera, Claudia P; Chambers, John C; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S; Chung, Ren-Hua; Collins, Francis S; Connell, John M; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F; Doney, Alex S F; Drenos, Fotios; Edkins, Sarah; Eicher, John D; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H Franco; Franco-Cereceda, Anders; Fraser, Ross M; Ganesh, Santhi K; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H; Goodarzi, Mark O; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A; Hingorani, Aroon D; Hirschhorn, Joel N; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A; Hunt, Steven C; Ikram, M Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S; Kosova, Gulum; Krauss, Ronald M; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S; Marouli, Eirini; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E; Morris, Andrew D; Morrison, Alanna C; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J; O'Reilly, Paul F; Ong, Ken K; Paccaud, Fred; Palmer, Cameron D; Parsa, Afshin; Pedersen, Nancy L; Penninx, Brenda W; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P; Psaty, Bruce M; Quertermous, Thomas; Rao, Dabeeru C; Rasheed, Asif; Rayner, N William N W R; Renström, Frida; Rettig, Rainer; Rice, Kenneth M; Roberts, Robert; Rose, Lynda M; Rossouw, Jacques; Samani, Nilesh J; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H; Smith, Albert V; Sosa, Maria X; Spector, Tim D; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E; Stringham, Heather M; Sundstrom, Johan; Swift, Amy J; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D; Tremoli, Elena; Uitterlinden, Andre G; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M; van Iperen, Erik P A; Vasan, Ramachandran S; Verwoert, Germaine C; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F; Vollenweider, Peter; Wagner, Aline; Wain, Louise V; Wareham, Nicholas J; Watkins, Hugh; Weder, Alan B; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F; Wong, Tien Y; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S; Mohlke, Karen L; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J; Willer, Cristen J; Franke, Lude; Hovingh, G Kees; Taylor, Kent D; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L; Njølstad, Inger; Schwarz, Peter Eh; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I; Rotter, Jerome I; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G; Kuulasmaa, Kari; Franks, Paul W; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N A; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J F; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P; Newton-Cheh, Christopher; Munroe, Patricia B

2016-10-01

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

PubMed Central

Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A.; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H. Franco; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N William N.W.R.; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.-H.; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter EH.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H.-Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

2016-01-01

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation. PMID:27618452

Developmental dyslexia: predicting individual risk.

PubMed

Thompson, Paul A; Hulme, Charles; Nash, Hannah M; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J

2015-09-01

Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6 months (T1) at approximately annual intervals on tasks tapping cognitive, language, and executive-motor skills. The children were recruited to three groups: children at family risk of dyslexia, children with concerns regarding speech, and language development at 3;06 years and controls considered to be typically developing. At 8 years, children were classified as 'dyslexic' or not. Logistic regression models were used to predict the individual risk of dyslexia and to investigate how risk factors accumulate to predict poor literacy outcomes. Family-risk status was a stronger predictor of dyslexia at 8 years than low language in preschool. Additional predictors in the preschool years include letter knowledge, phonological awareness, rapid automatized naming, and executive skills. At the time of school entry, language skills become significant predictors, and motor skills add a small but significant increase to the prediction probability. We present classification accuracy using different probability cutoffs for logistic regression models and ROC curves to highlight the accumulation of risk factors at the individual level. Dyslexia is the outcome of multiple risk factors and children with language difficulties at school entry are at high risk. Family history of dyslexia is a predictor of literacy outcome from the preschool years. However, screening does not reach an acceptable clinical level until close to school entry when letter knowledge, phonological awareness, and RAN, rather than family risk, together provide good sensitivity and specificity as a screening battery. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by

The influence of groups and alcohol consumption on individual risk-taking.

PubMed

Erskine-Shaw, Marianne; Monk, Rebecca L; Qureshi, Adam W; Heim, Derek

2017-10-01

Research addressing the influence of alcohol and groups on risky behaviour has yielded contradictory findings regarding the extent to which intoxicated groups exaggerate or minimise risk-taking. Previous work has examined the effect of intoxication on risk-taking focusing on collective group decision-making, and to date the influence of alcohol consumption and groups on individual risk-taking has yet to be explored experimentally. The current study therefore examined the impact of intoxication and groups on individual risk-taking. In a mixed design, 99 social drinkers (62 female) attended an experimental session individually (N=48) or in groups of three (N=51). Individuals completed the study in isolation while groups were tested in the same room. Participants completed two behavioural measures of risk-taking: Balloon Analogue Risk Task (BART) and Stoplight Task (SLT), both before and following consumption of an alcoholic (0.6g/kg males, 0.5g/kg females) or a placebo beverage. Those who participated in groups took significantly more risks in both tasks than those in isolation. Alcohol did not increase risk-taking on either risk-taking tasks. However, those who consumed placebo were significantly less risky on the SLT, compared to baseline. No interactions were found between context and beverage on risk-taking. The findings do not support a combined effect of alcohol and groups on individual risk-taking. Rather, results indicate that risk-taking behaviour is influenced by peer presence regardless of alcohol consumption. Targeting the influence of groups (above those of alcohol) may hold promise for reducing risk-taking behaviours in drinking environments. Copyright © 2017 Elsevier B.V. All rights reserved.

Individualized pharmacokinetic risk assessment for development of diabetes in high risk population.

PubMed

Gupta, N; Al-Huniti, N H; Veng-Pedersen, P

2007-10-01

The objective of this study is to propose a non-parametric pharmacokinetic prediction model that addresses the individualized risk of developing type-2 diabetes in subjects with family history of type-2 diabetes. All selected 191 healthy subjects had both parents as type-2 diabetic. Glucose was administered intravenously (0.5 g/kg body weight) and 13 blood samples taken at specified times were analyzed for plasma insulin and glucose concentrations. All subjects were followed for an average of 13-14 years for diabetic or normal (non-diabetic) outcome. The new logistic regression model predicts the development of diabetes based on body mass index and only one blood sample at 90 min analyzed for insulin concentration. Our model correctly identified 4.5 times more subjects (54% versus 11.6%) predicted to develop diabetes and more than twice the subjects (99% versus 46.4%) predicted not to develop diabetes compared to current non-pharmacokinetic probability estimates for development of type-2 diabetes. Our model can be useful for individualized prediction of development of type-2 diabetes in subjects with family history of type-2 diabetes. This improved prediction may be an important mediating factor for better perception of risk and may result in an improved intervention.

Individual influences on lifestyle change to reduce vascular risk: a qualitative literature review

PubMed Central

Murray, Jenni; Honey, Stephanie; Hill, Kate; Craigs, Cheryl; House, Allan

2012-01-01

Background Management of cardiovascular risk includes adoption of healthy lifestyles. Uptake and completion rates for lifestyle programmes are low and many barriers and facilitators to lifestyle behaviour change have been reported in the literature. Clarity on which barriers and facilitators to target during consultations in primary care may support a more systematic approach to lifestyle behaviour change in those at high risk of cardiovascular events. Aim To identify the main barriers and facilitators to lifestyle behaviour change in individuals at high risk of cardiovascular events. Design A content synthesis of the qualitative literature reporting patient-level influences on lifestyle change. Method Qualitative studies involving patients at high risk of cardiovascular events were identified through electronic searching and screening against predefined selection criteria. Factors (reported influences) were extracted and, using a clustering technique, organised into categories that were then linked to key themes through relationship mapping. Results A total of 348 factors were extracted from 33 studies. Factors were organised into 20 categories and from these categories five key themes were identified: emotions, beliefs, information and communication, friends and family support, and cost/transport. Conclusion It is possible to organise the large number of self-reported individual influences on lifestyle behaviours into a small number of themes. Further research is needed to clarify which of these patient-level barriers and facilitators are the best predictors of uptake and participation in programmes aimed at helping people to change lifestyle. PMID:22687232

Personalized prevention in high risk individuals: Managing hormones and beyond.

PubMed

Evans, D Gareth; Howell, Sacha J; Howell, Anthony

2018-06-01

Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold. The options for risk reduction in such women include endocrine chemoprevention with the selective estrogen receptor modulators tamoxifen and raloxifene or the aromatase inhibitors anastrozole or exemestane. NICE recommends offering anastrozole to postmenopausal women at high-risk of breast cancer as cost effectiveness analysis showed this to be cost saving to the National Health Service. Overall uptake to chemoprevention has been disappointingly low but this may improve with the improved efficacy of aromatase inhibitors, particularly the lack of toxicity to the endometrium and thrombogenic risks. Novel approaches to chemoprevention under investigation include lower dose and topical tamoxifen, denosumab, anti-progestins and metformin. Although oophorectomy is usually only recommended to women at increased risk of ovarian cancer it has been shown in numerous studies to reduce breast cancer risks in the general population and in those with mutations in BRCA1/2. However, recent evidence from studies that have confined analysis to true prospective follow up have cast doubt on the efficacy of oophorectomy to reduce breast cancer risk in BRCA1 mutation carriers, at least in the short-term. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Spatial Working Memory Ability in Individuals at Ultra High Risk for Psychosis

PubMed Central

Goghari, Vina M.; Brett, Caroline; Tabraham, Paul; Johns, Louise; Valmaggia, Lucia; Broome, Matthew; Woolley, James; Bramon, Elvira; Howes, Oliver

2014-01-01

The goal of this investigation was to clarify the nature of spatial working memory difficulties in individuals at ultra high risk (UHR) for psychosis. We evaluated spatial working memory and intelligence in 96 individuals at UHR for psychosis, 28 patients with first episode psychosis (FEP), and 23 healthy controls. Fourteen UHR individuals developed a psychotic disorder during follow-up. Compared to controls, the UHR group was impaired in both the short-term maintenance of material and in the effective use of strategy, but not more immediate memory. These impairments were not as severe as those in the FEP group, as the UHR group performed better than the FEP group. A similar pattern of results was found for the intelligence measures. Discriminant function analyses demonstrated short-term maintenance of material significantly differentiated the UHR and healthy control groups even when accounting for full scale intelligence quotient (IQ); whereas full scale IQ significantly differentiated the UHR and FEP groups and FEP and control groups. Notably, within the UHR group, impaired spatial working memory performance was associated with lower global functioning, but not full scale IQ. The subgroup of UHR individuals who later developed psychosis was not significantly more impaired on any aspect of working memory performance than the group of UHR individuals who did not develop psychosis. Given, the relationship between spatial working memory deficits and functional outcome, these results indicate that cognitive remediation could be useful in individuals at UHR for psychosis to potentially improve functioning. PMID:24398256

An Individualized Risk Calculator for Research in Prodromal Psychosis.

PubMed

Cannon, Tyrone D; Yu, Changhong; Addington, Jean; Bearden, Carrie E; Cadenhead, Kristin S; Cornblatt, Barbara A; Heinssen, Robert; Jeffries, Clark D; Mathalon, Daniel H; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Kattan, Michael W

2016-10-01

Approximately 20%-35% of individuals 12-35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients. The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples. The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors. The multivariate model achieved a concordance index of 0.71 and, as reported in an article by Carrión et al., published concurrently with this one, was validated in an independent external data set. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome. A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases. Given that the risk calculator can be validly applied only for patients who screen positive on the Structured Clinical

Risk of inpatient stay for mental illness among individuals with substance use disorders.

PubMed

Prince, Jonathan D

2012-09-01

Whereas most studies of inpatient stay for mental illness examine whether substance use is present, this study identified types or combinations of abused substances that most increased hospitalization risk. Logistic regression of data from the 2007 National Survey of Drug Use and Health (N=37,654) was used to predict past-year hospitalization of individuals with DSM-IV substance use disorders. Even after the inclusion of control variables, adults with four types of substance abuse or dependence were more likely to be hospitalized than adults without substance abuse or dependence. High-risk disorders included abuse of or dependence on opioid analgesics (odds ratio [OR]=6.85, p<.001), cocaine (OR=2.65, p<.05), alcohol and cocaine (OR=2.58, p<.05), and alcohol and marijuana (OR=3.10, p<.01). Researchers examining inpatient stays may find it beneficial to look at abuse of specific substances or combinations of substances, and efforts to prevent inpatient stays could target people with high-risk substance use disorders.

Individual and social determinants of multiple chronic disease behavioral risk factors among youth.

PubMed

Alamian, Arsham; Paradis, Gilles

2012-03-22

Behavioral risk factors are known to co-occur among youth, and to increase risks of chronic diseases morbidity and mortality later in life. However, little is known about determinants of multiple chronic disease behavioral risk factors, particularly among youth. Previous studies have been cross-sectional and carried out without a sound theoretical framework. Using longitudinal data (n = 1135) from Cycle 4 (2000-2001), Cycle 5 (2002-2003) and Cycle 6 (2004-2005) of the National Longitudinal Survey of Children and Youth, a nationally representative sample of Canadian children who are followed biennially, the present study examines the influence of a set of conceptually-related individual/social distal variables (variables situated at an intermediate distance from behaviors), and individual/social ultimate variables (variables situated at an utmost distance from behaviors) on the rate of occurrence of multiple behavioral risk factors (physical inactivity, sedentary behavior, tobacco smoking, alcohol drinking, and high body mass index) in a sample of children aged 10-11 years at baseline. Multiple behavioral risk factors were assessed using a multiple risk factor score. All statistical analyses were performed using SAS, version 9.1, and SUDAAN, version 9.01. Multivariate longitudinal Poisson models showed that social distal variables including parental/peer smoking and peer drinking (Log-likelihood ratio (LLR) = 187.86, degrees of freedom (DF) = 8, p < .001), as well as individual distal variables including low self-esteem (LLR = 76.94, DF = 4, p < .001) increased the rate of occurrence of multiple behavioral risk factors. Individual ultimate variables including age, sex, and anxiety (LLR = 9.34, DF = 3, p < .05), as well as social ultimate variables including family socioeconomic status, and family structure (LLR = 10.93, DF = 5, p = .05) contributed minimally to the rate of co-occurrence of behavioral risk factors. The results suggest targeting individual

Maternal embryonic leucine zipper kinase is a novel target for proliferation-associated high-risk myeloma

PubMed Central

Bolomsky, Arnold; Heusschen, Roy; Schlangen, Karin; Stangelberger, Kathrin; Muller, Joséphine; Schreiner, Wolfgang; Zojer, Niklas; Caers, Jo; Ludwig, Heinz

2018-01-01

Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene expression profiling-defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified in order to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analyzed the activity of the MELK inhibitor OTSSP167 both in vitro and in vivo. MELK was found to be significantly overexpressed in the proliferative subgroup of myeloma. This finding translated into poor overall survival in patients with high vs. low MELK expression. Enrichment analysis of upregulated genes in myeloma cells of MELKhigh patients confirmed the strong implications in myeloma cell proliferation. Targeting MELK with OTSSP167 impaired the growth and survival of myeloma cells, thereby affecting central survival factors such as MCL-1 and IRF4. This activity was also observed in the 5TGM.1 murine model of myeloma. OTSSP167 reduced bone marrow infiltration and serum paraprotein levels in a dose-dependent manner. In addition, we revealed a strong link between MELK and other proliferation-associated high-risk genes (PLK-1, EZH2, FOXM1, DEPDC1) and MELK inhibition also impaired the expression of those genes. We therefore conclude that MELK is an essential component of a proliferative gene signature and that pharmacological inhibition of MELK represents an attractive novel approach to overcome the poor prognosis of high-risk patients with a proliferative expression pattern. PMID:29122991

Effect of intensive structured care on individual blood pressure targets in primary care: multicentre randomised controlled trial.

PubMed

Stewart, Simon; Carrington, Melinda J; Swemmer, Carla H; Anderson, Craig; Kurstjens, Nicol P; Amerena, John; Brown, Alex; Burrell, Louise M; de Looze, Ferdinandus J; Harris, Mark; Hung, Joseph; Krum, Henry; Nelson, Mark; Schlaich, Markus; Stocks, Nigel P; Jennings, Garry L

2012-11-20

To determine the effectiveness of intensive structured care to optimise blood pressure control based on individual absolute risk targets in primary care. Pragmatic multicentre randomised controlled trial. General practices throughout Australia, except Northern Territory, 2009-11. Of 2185 patients from 119 general practices who were eligible for drug treatment for hypertension according to national guidelines 416 (19.0%) achieved their individual blood pressure target during a 28 day run-in period of monotherapy. After exclusions, 1562 participants not at target blood pressure (systolic 150 (SD 17) mm Hg, diastolic 88 (SD 11) mm Hg) were randomised (1:2 ratio) to usual care (n=524) or the intervention (n=1038). Computer assisted clinical profiling and risk target setting (all participants) with intensified follow-up and stepwise drug titration (initial angiotensin receptor blocker monotherapy or two forms of combination therapy using angiotensin receptor blockers) for those randomised to the intervention. The control group received usual care. The primary outcome was individual blood pressure target achieved at 26 weeks. Secondary outcomes were change in mean sitting systolic and diastolic blood pressure, absolute risk for cardiovascular disease within five years based on the Framingham risk score, and proportion and rate of adverse events. On an intention to treat basis, there was an 8.8% absolute difference in individual blood pressure target achieved at 26 weeks in favour of the intervention group compared with usual care group (358/988 (36.2%) v 138/504 (27.4%)): adjusted relative risk 1.28 (95% confidence interval 1.10 to 1.49, P=0.0013). There was also a 9.5% absolute difference in favour of the intervention group for achieving the classic blood pressure target of ≤ 140/90 mm Hg (627/988 (63.5%) v 272/504 (54.0%)): adjusted relative risk 1.18 (1.07 to 1.29, P<0.001). The intervention group achieved a mean adjusted reduction in systolic blood pressure of 13

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

PubMed Central

Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

2012-01-01

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing.

PubMed

Morey, Rajendra A; Inan, Seniha; Mitchell, Teresa V; Perkins, Diana O; Lieberman, Jeffrey A; Belger, Aysenil

2005-03-01

Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Cross-sectional case-control design. Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d' (a measure based on the hit rate and the false-alarm rate). The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals.

Underreporting of high-risk water and sanitation practices undermines progress on global targets.

PubMed

Vedachalam, Sridhar; MacDonald, Luke H; Shiferaw, Solomon; Seme, Assefa; Schwab, Kellogg J

2017-01-01

Water and sanitation indicators under the Millennium Development Goals failed to capture high-risk practices undertaken on a regular basis. In conjunction with local partners, fourteen rounds of household surveys using mobile phones with a customized open-source application were conducted across nine study geographies in Asia and Africa. In addition to the main water and sanitation facilities, interviewees (n = 245,054) identified all water and sanitation options regularly used for at least one season of the year. Unimproved water consumption and open defecation were targeted as high-risk practices. We defined underreporting as the difference between the regular and main use of high-risk practices. Our estimates of high-risk practices as the main option matched the widely accepted Demographic and Health Surveys (DHS) estimates within the 95% confidence interval. However, estimates of these practices as a regular option was far higher than the DHS estimates. Across the nine geographies, median underreporting of unimproved water use was 5.5%, with a range of 0.5% to 13.9%. Median underreporting of open defecation was much higher at 9.9%, with a range of 2.7% to 11.5%. This resulted in an underreported population of 25 million regularly consuming unimproved water and 50 million regularly practicing open defecation. Further examination of data from Ethiopia suggested that location and socio-economic factors were significant drivers of underreporting. Current global monitoring relies on a framework that considers the availability and use of a single option to meet drinking water and sanitation needs. Our analysis demonstrates the use of multiple options and widespread underreporting of high-risk practices. Policies based on current monitoring data, therefore, fail to consider the range of challenges and solutions to meeting water and sanitation needs, and result in an inflated sense of progress. Mobile surveys offer a cost-effective and innovative platform to rapidly

Underreporting of high-risk water and sanitation practices undermines progress on global targets

PubMed Central

Vedachalam, Sridhar; MacDonald, Luke H.; Shiferaw, Solomon; Seme, Assefa; Schwab, Kellogg J.

2017-01-01

Water and sanitation indicators under the Millennium Development Goals failed to capture high-risk practices undertaken on a regular basis. In conjunction with local partners, fourteen rounds of household surveys using mobile phones with a customized open-source application were conducted across nine study geographies in Asia and Africa. In addition to the main water and sanitation facilities, interviewees (n = 245,054) identified all water and sanitation options regularly used for at least one season of the year. Unimproved water consumption and open defecation were targeted as high-risk practices. We defined underreporting as the difference between the regular and main use of high-risk practices. Our estimates of high-risk practices as the main option matched the widely accepted Demographic and Health Surveys (DHS) estimates within the 95% confidence interval. However, estimates of these practices as a regular option was far higher than the DHS estimates. Across the nine geographies, median underreporting of unimproved water use was 5.5%, with a range of 0.5% to 13.9%. Median underreporting of open defecation was much higher at 9.9%, with a range of 2.7% to 11.5%. This resulted in an underreported population of 25 million regularly consuming unimproved water and 50 million regularly practicing open defecation. Further examination of data from Ethiopia suggested that location and socio-economic factors were significant drivers of underreporting. Current global monitoring relies on a framework that considers the availability and use of a single option to meet drinking water and sanitation needs. Our analysis demonstrates the use of multiple options and widespread underreporting of high-risk practices. Policies based on current monitoring data, therefore, fail to consider the range of challenges and solutions to meeting water and sanitation needs, and result in an inflated sense of progress. Mobile surveys offer a cost-effective and innovative platform to rapidly

Neuroanatomical and Symptomatic Sex Differences in Individuals at Clinical High Risk for Psychosis.

PubMed

Guma, Elisa; Devenyi, Gabriel A; Malla, Ashok; Shah, Jai; Chakravarty, M Mallar; Pruessner, Marita

2017-01-01

Sex differences have been widely observed in clinical presentation, functional outcome and neuroanatomy in individuals with a first-episode of psychosis, and chronic patients suffering from schizophrenia. However, little is known about sex differences in the high-risk stages for psychosis. The present study investigated sex differences in cortical and subcortical neuroanatomy in individuals at clinical high risk (CHR) for psychosis and healthy controls (CTL), and the relationship between anatomy and clinical symptoms in males at CHR. Magnetic resonance images were collected in 26 individuals at CHR (13 men) and 29 CTLs (15 men) to determine total and regional brain volumes and morphology, cortical thickness, and surface area (SA). Clinical symptoms were assessed with the brief psychiatric rating scale. Significant sex-by-diagnosis interactions were observed with opposite directions of effect in male and female CHR subjects relative to their same-sex controls in multiple cortical and subcortical areas. The right postcentral, left superior parietal, inferior parietal supramarginal, and angular gyri [<5% false discovery rate (FDR)] were thicker in male and thinner in female CHR subjects compared with their same-sex CTLs. The same pattern was observed in the right superior parietal gyrus SA at the regional and vertex level. Using a recently developed surface-based morphology pipeline, we observed sex-specific shape differences in the left hippocampus (<5% FDR) and amygdala (<10% FDR). Negative symptom burden was significantly higher in male compared with female CHR subjects ( p  = 0.04) and was positively associated with areal expansion of the left amygdala in males (<5% FDR). Some limitations of the study include the sample size, and data acquisition at 1.5 T. This study demonstrates neuroanatomical sex differences in CHR subjects, which may be associated with variations in symptomatology in men and women with psychotic symptoms.

Targeting adolescent risk-taking behaviors: the contributions of egocentrism and sensation-seeking.

PubMed

Greene, K; Krcmar, M; Walters, L H; Rubin, D L; Jerold; Hale, L

2000-08-01

Tremendous resources are spent each year developing programs and messages targeting adolescent risk behavior. Adolescents are often reasonably well educated about methods for health promotion such as preventing HIV infection, yet they fail to act accordingly. One widely used individual difference variable, sensation-seeking, has been incorporated in health message design to some extent, but it fails to take development into account. Research on adolescent egocentrism suggests adolescents experience personal fable which can lead to an exaggerated sense of invulnerability. The present study sampled adolescents and college students to examine relative contributions of egocentrism and sensation-seeking to risk-taking behavior. Results indicate a latent factor labeled risk-seeking (primarily indicated by disinhibition and risk-taking personality, and to a lesser degree by invulnerability, experience-seeking, boredom susceptibility, and thrill and adventure-seeking) indeed predicted a latent factor labeled delinquent behavior (primarily indicated by alcohol consumption and delinquency, and to a lesser degree by drug use, drinking and driving, and risky driving). Other results indicate consistently high personal fable combined with high sensation-seeking explained most risk-taking behavior. Implications and directions for future research are discussed. Copyright 2000 The Association for Professionals in Services for Adolescents.

Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention

PubMed Central

Martinson, Holly A.; Lyons, Traci R.; Giles, Erin D.; Borges, Virginia F.; Schedin, Pepper

2014-01-01

The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. PMID:23664839

Effects of baseline risk information on social and individual choices.

PubMed

Gyrd-Hansen, Dorte; Kristiansen, Ivar Sønbø; Nexøe, Jørgen; Nielsen, Jesper Bo

2002-01-01

This article analyzes preferences for risk reductions in the context of individual and societal decision making. The effect of information on baseline risk is analyzed in both contexts. The results indicate that if individuals are to imagine that they suffer from 1 low-risk and 1 high-risk ailment, and are offered a specified identical absolute risk reduction, a majority will ceteris paribus opt for treatment of the low-risk ailment. A different preference structure is elicited when priority questions are framed as social choices. Here, a majority will prefer to treat the high-risk group of patients. The preference reversal demonstrates the extent to which baseline risk information can influence preferences in different choice settings. It is argued that presentation of baseline risk information may induce framing effects that lead to nonoptimal resource allocations. A solution to this problem may be to not present group-specific baseline risk information when eliciting preferences.

Different type 2 diabetes risk assessments predict dissimilar numbers at 'high risk': a retrospective analysis of diabetes risk-assessment tools.

PubMed

Gray, Benjamin J; Bracken, Richard M; Turner, Daniel; Morgan, Kerry; Thomas, Michael; Williams, Sally P; Williams, Meurig; Rice, Sam; Stephens, Jeffrey W

2015-12-01

Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under-reported, however, whether a different risk tool alters the predicted risk of an individual. This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. Cross-sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes(®), Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at 'high risk' followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes. © British Journal of General Practice 2015.

Biological phenotypes associated with individuals at high risk for developing alcohol-related disorders: Part 1.

PubMed

Hill, S Y

2000-01-01

This article reviews the results of studies concerning particular classes of biological phenotypes that may have relevance for alcohol dependence. Broadly defined, these classes include brain neurotransmitter systems and neuroelectric potentials. Evidence is presented concerning genotypic variation in alcoholics and high-risk relatives suggesting that the etiology of alcoholism and other addictive diseases is mediated in part through suboptimal neurotransmitter functioning. Research opportunities are offered with respect to specific candidate genes that have been cloned from these neurotransmitter systems that could be most fully utilized in family-based genetic analyses. Additional evidence is offered, suggesting that characteristics of particular neuroelectric potentials (e.g. the amplitude of the P300 component of the event-related potential) may provide another dimension of potential markers that could be used to identify children at risk. Finally, methodological considerations specific to high risk studies are discussed. Among these are the need to include a plan for studying more severe cases of alcohol dependence that are relatively uncomplicated by other major psychiatric disorders. Plans for long-term follow-up of children at highest risk for developing the disorder should also be included. Multiple domains of inquiry should not be viewed as "unfocused" but rather as an economical means for utilizing highly characterized samples of individuals meeting rigorous research criteria.

Targeted Killings: A Legally Viable, High Risk Course of Action

DTIC Science & Technology

2009-05-04

Section 413b of Title 50, United States Code ), 19 will target the individual. As Seymour Hersh reports, ―under federal law, a Presidential Finding... Kantian ethics ).‖ 23 This desire to mitigate impact on the civilian population is integral to the mission of the United Nations, where member...and War A Study in Comparative Ethics (Louisville, KY: Westminster / John Knox Press, 1993), 59. 14 capture is unfeasible. Barak explicitly states

A randomized controlled trial targeting alcohol use and sexual assault risk among college women at high risk for victimization.

PubMed

Gilmore, Amanda K; Lewis, Melissa A; George, William H

2015-11-01

Sexual assault risk reduction programs do not target alcohol use despite the widespread knowledge that alcohol use is a risk factor for being victimized. The current study assessed the effectiveness of a web-based combined sexual assault risk and alcohol use reduction program using a randomized control trial. A total of 207 college women between the ages of 18 and 20 who engaged in heavy episodic drinking were randomized to one of five conditions: full assessment only control condition, sexual assault risk reduction condition, alcohol use reduction condition, combined sexual assault risk and alcohol use reduction condition, and a minimal assessment only condition. Participants completed a 3-month follow-up survey on alcohol-related sexual assault outcomes, sexual assault outcomes, and alcohol use outcomes. Significant interactions revealed that women with higher severity of sexual assault at baseline experienced less incapacitated attempted or completed rapes, less severity of sexual assaults, and engaged in less heavy episodic drinking compared to the control condition at the 3-month follow-up. Web-based risk reduction programs targeting both sexual assault and alcohol use may be the most effective way to target the highest risk sample of college students for sexual assault: those with a sexual assault history and those who engage in heavy episodic drinking. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Randomized Controlled Trial Targeting Alcohol Use and Sexual Assault Risk among College Women at High Risk for Victimization

PubMed Central

Gilmore, Amanda K.; Lewis, Melissa A.; George, William H.

2015-01-01

Current sexual assault risk reduction programs do not target alcohol use despite the widespread knowledge that alcohol use is a risk factor for being victimized. The current study assessed the effectiveness of a web-based combined sexual assault risk and alcohol use reduction program using a randomized control trial. A total of 207 college women between the ages of 18 and 20 who engaged in heavy episodic drinking were randomized to one of five conditions: full assessment only control condition, sexual assault risk reduction condition, alcohol use reduction condition, combined sexual assault risk and alcohol use reduction condition, and a minimal assessment only condition. Participants completed a 3-month follow-up survey on alcohol-related sexual assault outcomes, sexual assault outcomes, and alcohol use outcomes. Significant interactions revealed that women with higher incidence and severity of sexual assault at baseline experienced less incapacitated attempted or completed rapes, less incidence/severity of sexual assaults, and engaged in less heavy episodic drinking compared to the control condition at the 3-month follow-up. Web-based risk reduction programs targeting both sexual assault and alcohol use may be the most effective way to target the highest risk sample of college students for sexual assault: those with a sexual assault history and those who engage in heavy episodic drinking. PMID:26408290

A prospective study of carpal tunnel syndrome: workplace and individual risk factors.

PubMed

Burt, Susan; Deddens, James A; Crombie, Ken; Jin, Yan; Wurzelbacher, Steve; Ramsey, Jessica

2013-08-01

To quantify the risk for carpal tunnel syndrome (CTS) from workplace physical factors, particularly hand activity level and forceful exertion, while taking into account individual factors including age, gender, body mass index (BMI), and pre-existing medical conditions. Three healthcare and manufacturing workplaces were selected for inclusion on the basis of range of exposure to hand activity level and forceful exertion represented by their jobs. Each study participant's job tasks were observed and evaluated onsite and videotaped for further analysis, including frequency and duration of exertion and postural deviation. Individual health assessment entailed electrodiagnostic testing of median and ulnar nerves, physical examination and questionnaires at baseline with annual follow-up for 2 years. The incidence of dominant hand CTS during the study was 5.11 per 100 person-years (29 cases). Adjusted HRs for dominant hand CTS were as follows: working with forceful exertion ≥ 20% but <60% of the time: 2.83 (1.18, 6.79) and ≥ 60% of the time vs <20%: 19.57 (5.96, 64.24), BMI ≥ 30 kg/m(2) (obesity): 3.19 (1.28, 7.98). The American Conference for Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for hand activity level also predicted CTS, HR=1.40 (1.11, 1.78) for each unit increase in the TLV ratio, controlling for obesity and job strain. Workplace and individual risk factors both contribute to the risk for CTS. Time spent in forceful exertion can be a greater risk for CTS than obesity if the job exposure is high. Preventive workplace efforts should target forceful exertions.

Targeted Embolization of Aneurysms Associated With Brain Arteriovenous Malformations at High Risk for Surgical Resection: A Case-Control Study.

PubMed

Alexander, Matthew D; Hippe, Daniel S; Cooke, Daniel L; Hallam, Danial K; Hetts, Steven W; Kim, Helen; Lawton, Michael T; Sekhar, Laligam N; Kim, Louis J; Ghodke, Basavaraj V

2018-03-01

High-risk components of brain arteriovenous malformations (BAVMs) can be targeted to reduce the risk of lesion rupture. To evaluate targeted embolization of aneurysms against other means of treatment with a case-control analysis; we previously investigated this approach associated with BAVMs. Retrospective analysis of patients with BAVMs was performed, identifying patients treated with intention to occlude only an aneurysm associated with a BAVM. For each targeted aneurysm embolization (TAE) patient identified, 4 control patients were randomly selected, controlling for rupture status, age, and Spetzler-Martin plus Lawton-Young supplemental score. Analysis was performed to compare rates of adverse events (hemorrhage, new seizure, and death) between the 2 groups. Thirty-two patients met inclusion criteria, and 128 control patients were identified, out of 1103 patients treated during the study period. Thirty-four adverse events occurred (15 ruptures, 15 new seizures, and 11 deaths) during the follow-up period (mean 1157 d for the TAE cohort and 1036 d for the non-TAE cohort). Statistically lower associations were noted for the TAE group for any adverse event (hazard ratio 0.28, P = .037) and the composite outcome of hemorrhage or new seizure (hazard ratio 0.20, P = .029). For BAVMs at high risk for surgical resection, TAE can be performed safely and effectively. Patients treated with TAE had better outcomes than matched patients undergoing other combinations of treatment. TAE can be considered for BAVMs with high operative risk prior to radiosurgery or when no other treatment options are available. Copyright © 2017 by the Congress of Neurological Surgeons

Diagnostic and Prognostic Significance of Brief Limited Intermittent Psychotic Symptoms (BLIPS) in Individuals at Ultra High Risk

PubMed Central

Fusar-Poli, Paolo; Cappucciati, Marco; De Micheli, Andrea; Rutigliano, Grazia; Bonoldi, Ilaria; Tognin, Stefania; Ramella-Cravaro, Valentina; Castagnini, Augusto; McGuire, Philip

2017-01-01

Background: Brief Limited Intermittent Psychotic Symptoms (BLIPS) are key inclusion criteria to define individuals at ultra high risk for psychosis (UHR). Their diagnostic and prognostic significance is unclear. Objectives: To address the baseline diagnostic relationship between BLIPS and the ICD-10 categories and examine the longitudinal prognostic impact of clinical and sociodemographic factors. Methods: Prospective long-term study in UHR individuals meeting BLIPS criteria. Sociodemographic and clinical data, including ICD-10 diagnoses, were automatically drawn from electronic health records and analyzed using Kaplan–Meier failure function (1-survival), Cox regression models, bootstrapping methods, and Receiver Operating Characteristics (ROC) curve. Results: Eighty BLIPS were included. At baseline, two-thirds (68%) of BLIPS met the diagnostic criteria for ICD-10 Acute and Transient Psychotic Disorder (ATPD), most featuring schizophrenic symptoms. The remaining individuals met ICD-10 diagnostic criteria for unspecified nonorganic psychosis (15%), mental and behavioral disorders due to use of cannabinoids (11%), and mania with psychotic symptoms (6%). The overall 5-year risk of psychosis was 0.54. Recurrent episodes of BLIPS were relatively rare (11%) but associated with a higher risk of psychosis (hazard ratio [HR] 3.98) than mono-episodic BLIPS at the univariate analysis. Multivariate analysis revealed that seriously disorganizing or dangerous features increased greatly (HR = 4.39) the risk of psychosis (0.89 at 5-year). Bootstrapping confirmed the robustness of this predictor (area under the ROC = 0.74). Conclusions: BLIPS are most likely to fulfill the ATPD criteria, mainly acute schizophrenic subtypes. About half of BLIPS cases develops a psychotic disorder during follow-up. Recurrent BLIPS are relatively rare but tend to develop into psychosis. BLIPS with seriously disorganizing or dangerous features have an extreme high risk of psychosis. PMID:28053130

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

Risk Adjustment, Reinsurance Improved Financial Outcomes For Individual Market Insurers With The Highest Claims.

PubMed

Jacobs, Paul D; Cohen, Michael L; Keenan, Patricia

2017-04-01

The Affordable Care Act (ACA) reformed the individual health insurance market. Because insurers can no longer vary their offers of coverage based on applicants' health status, the ACA established a risk adjustment program to equalize health-related cost differences across plans. The ACA also established a temporary reinsurance program to subsidize high-cost claims. To assess the impact of these programs, we compared revenues to claims costs for insurers in the individual market during the first two years of ACA implementation (2014 and 2015), before and after the inclusion of risk adjustment and reinsurance payments. Before these payments were included, for the 30 percent of insurers with the highest claims costs, claims (not including administrative expenses) exceeded premium revenues by $90-$397 per enrollee per month. The effect was reversed after these payments were included, with revenues exceeding claims costs by $0-$49 per month. The risk adjustment and reinsurance programs were relatively well targeted in the first two years. While there is ongoing discussion regarding the future of the ACA, our findings can shed light on how risk-sharing programs can address risk selection among insurers-a pervasive issue in all health insurance markets. Project HOPE—The People-to-People Health Foundation, Inc.

An Individualized Risk Calculator for Research in Prodromal Psychosis

PubMed Central

Cannon, Tyrone D.; Yu, Changhong; Addington, Jean; Bearden, Carrie E.; Cadenhead, Kristin S.; Cornblatt, Barbara A.; Heinssen, Robert; Jeffries, Clark D.; Mathalon, Daniel H.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Kattan, Michael

2016-01-01

Objective About 20–35% of individuals aged 12–30 years who meet criteria for a prodromal risk syndrome convert to psychosis within two years. However, this estimate ignores the fact that clinical high-risk (CHR) cases vary considerably in risk. Here we sought to create a risk calculator that can ascertain the probability of conversion to psychosis in individual patients based on profiles of risk indicators. The high risk category predicted by this calculator can inform research criteria going forward. Method Subjects were 596 CHR participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS 2) who were followed up to the time of conversion to psychosis or last contact (up to 2 years). Our scope was limited to predictors supported by prior studies and readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1000 bootstrap resamples. Results The 2-year probability of conversion to psychosis in this sample was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis, while stressful life events, traumas, and family history of schizophrenia were not significant predictors. The multivariate model achieved a Concordance index of 0.71, and was validated in an independent external dataset. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome. Conclusions A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained CHR cases. Given that the risk calculator can only be validly applied for patients who screen positive on the Structured

An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

2014-01-01

Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk.

PubMed

Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

2017-06-01

There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c) target concentrations. To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD) ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013). For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70]) and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%), LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target) is more appropriate at the individual level. Há controvérsias sobre se o controle do colesterol plasmático deve ou não se basear em metas de concentração de colesterol LDL (LDL-c). Comparar o impacto estimado de diferentes estratégias hipolipemiantes, baseadas ou não em metas de LDL-c, sobre o

The genetic landscape of high-risk neuroblastoma | Office of Cancer Genomics

Cancer.gov

Abstract: Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative.

Neuroanatomy Predicts Individual Risk Attitudes

PubMed Central

Gilaie-Dotan, Sharon; Tymula, Agnieszka; Cooper, Nicole; Kable, Joseph W.; Glimcher, Paul W.

2014-01-01

Over the course of the last decade a multitude of studies have investigated the relationship between neural activations and individual human decision-making. Here we asked whether the anatomical features of individual human brains could be used to predict the fundamental preferences of human choosers. To that end, we quantified the risk attitudes of human decision-makers using standard economic tools and quantified the gray matter cortical volume in all brain areas using standard neurobiological tools. Our whole-brain analysis revealed that the gray matter volume of a region in the right posterior parietal cortex was significantly predictive of individual risk attitudes. Participants with higher gray matter volume in this region exhibited less risk aversion. To test the robustness of this finding we examined a second group of participants and used econometric tools to test the ex ante hypothesis that gray matter volume in this area predicts individual risk attitudes. Our finding was confirmed in this second group. Our results, while being silent about causal relationships, identify what might be considered the first stable biomarker for financial risk-attitude. If these results, gathered in a population of midlife northeast American adults, hold in the general population, they will provide constraints on the possible neural mechanisms underlying risk attitudes. The results will also provide a simple measurement of risk attitudes that could be easily extracted from abundance of existing medical brain scans, and could potentially provide a characteristic distribution of these attitudes for policy makers. PMID:25209279

Neurological soft signs precede the onset of schizophrenia: a study of individuals with schizotypy, ultra-high-risk individuals, and first-onset schizophrenia.

PubMed

Chan, Raymond C K; Cui, Hui-Ru; Chu, Min-Yi; Zhang, Tian-Hong; Wang, Ya; Wang, Yi; Li, Zhi; Lui, Simon S Y; Wang, Ji-Jun; Cheung, Eric F C

2018-02-01

Neurological soft signs (NSS) are one of the biomarkers for schizophrenia spectrum disorders. However, a few studies have examined the prevalence of NSS across the schizophrenia spectrum. The present study adopted a quasi-longitudinal study design and examined the prevalence of NSS and their associations with clinical and behavioural manifestations in participants in different stages of the illness. The abridged version of the Cambridge Neurological Inventory was administered to 39 patients with the first-episode schizophrenia, 39 individuals with ultra-high risk (UHR) for psychosis, 39 individuals with schizotypy, and 39 healthy controls. Patients with the first-episode schizophrenia had a higher prevalence of NSS in motor coordination than healthy controls as well as individuals with UHR and schizotypy. Individuals with UHR exhibited a higher prevalence of sensory integration items than individuals with schizotypy and healthy controls. Discriminant analysis classified the membership of the individuals correctly across the spectrum with an accuracy of up to 60.9%. In particular, NSS could discriminate individuals with UHR from healthy controls at up to 85.9% accuracy. These findings suggest that NSS are robust biomarkers to detect and discriminate individuals in different stages of the schizophrenia spectrum from healthy controls.

219. Changes in Functional Networks Underlying Social Cognition Following Cognitive Training in Individuals at Risk for Psychosis

PubMed Central

Haut, Kristen; Saxena, Abhishek; Yin, Hong; Carol, Emily; Dodell-Feder, David; Lincoln, Sarah Hope; Tully, Laura; Keshavan, Matcheri; Seidman, Larry J.; Nahum, Mor; Hooker, Christine

2017-01-01

Abstract Background: Deficits in social cognition are prominent features of schizophrenia that play a large role in functional impairments and disability. Performance deficits in these domains are associated with altered activity in functional networks, including those that support social cognitive abilities such as emotion recognition. These social cognitive deficits and alterations in neural networks are present prior to the onset of frank psychotic symptoms and thus present a potential target for intervention in early phases of the illness, including in individuals at clinical high risk (CHR) for psychosis. This study assessed changes in social cognitive functional networks following targeted cognitive training (TCT) in CHR individuals. Methods: 14 CHR subjects (7 male, mean age = 21.9) showing attenuated psychotic symptoms as assessed by the SIPS were included in the study. Subjects underwent a clinical evaluation and a functional MRI session prior to and subsequent to completing 40 hours (8 weeks) of targeted cognitive and social cognitive training using Lumosity and SocialVille. 14 matched healthy control (HC) subjects also underwent a single fMRI session as a comparison group for functional activity. Resting state fMRI was acquired as well as fMRI during performance of an emotion recognition task. Group level differences in BOLD activity between HC and CHR group before TCT, and CHR group before and after TCT were computed. Changes in social cognitive network functional connectivity at rest and during task performance was evaluated using seed-based connectivity analyses and psychophysiological interaction (PPI). Results: Prior to training, CHR individuals demonstrated hyperactivity in the amygdala, posterior cingulate, and superior temporal sulcus (STS) during emotion recognition, suggesting inefficient processing. This hyperactivity normalized somewhat after training, with CHR individuals showing less hyperactivity in the amygdala in response to emotional

Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus.

PubMed

Dunkler, Daniela; Dehghan, Mahshid; Teo, Koon K; Heinze, Georg; Gao, Peggy; Kohl, Maria; Clase, Catherine M; Mann, Johannes F E; Yusuf, Salim; Oberbauer, Rainer

2013-10-14

Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD

[High Risk Federal Program Areas]: An Overview. High-Risk Series.

ERIC Educational Resources Information Center

Comptroller General of the U.S., Washington, DC.

This report reviews the status of government agencies and operations that have been identified as at "high risk" for waste, fraud, abuse, and mismanagement; describes successful progress in some agencies; and looks at recent reform legislation. Six categories being targeted include accountability of defense programs, ensuring that all…

Self-Reported Adherence among Individuals at High Risk of Metabolic Syndrome: Effect of Knowledge and Attitude.

PubMed

Alefishat, Eman A; Abu Farha, Rana K; Al-Debei, Mutaz M

2017-01-01

This study aimed to evaluate factors that affect adherence in individuals at high risk of metabolic syndrome, with a focus on knowledge and attitude effect. A sample of 900 high-risk individuals with metabolic syndrome was recruited in this cross-sectional study. During the study period, all participants filled in validated structured questionnaires to evaluate the adherence to different management options of metabolic syndrome, knowledge about the syndrome, and health-related attitude. Simple linear regression followed by multiple linear regression analysis were used to evaluate the effect of knowledge, attitude, and other factors on participants' adherence to both medications and lifestyle changes. Of the 900 participants, 436 (48.4%) were nonadherent to medications and 813 (90.3%) were nonadherent to lifestyle changes. Increasing age (r = 0.140, p = 0.000), the presence of hypertension (r = 0.075, p = 0.036), and a more positive attitude toward health (r = 0.230, p = 0.000) were significantly associated with increasing adherence to medications. Higher educational level (r = 0.085, p = 0.023), higher knowledge score (r = 0.135, p = 0.001), and more positive attitude toward health (r = 0.183, p = 0.000) were found to significantly increase the adherence to lifestyle changes, while central obesity (r = -0.106, p = 0.003) was found to significantly decrease the adherence to lifestyle changes. Patients' knowledge about metabolic syndrome and attitude to health affected adherence rates in patients at high risk of metabolic syndrome. Hence, we suggest the need to incorporate patients' educational programs into current management of metabolic syndrome. © 2016 S. Karger AG, Basel.

Inter-Individual Variability in High-Throughput Risk ...

EPA Pesticide Factsheets

We incorporate realistic human variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which have little or no existing TK data. Chemicals are prioritized based on model estimates of hazard and exposure, to decide which chemicals should be first in line for further study. Hazard may be estimated with in vitro HT screening assays, e.g., U.S. EPA’s ToxCast program. Bioactive ToxCast concentrations can be extrapolated to doses that produce equivalent concentrations in body tissues using a reverse TK approach in which generic TK models are parameterized with 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with physiological parameters for a virtual population. Here we draw physiological parameters from realistic estimates of distributions of demographic and anthropometric quantities in the modern U.S. population, based on the most recent CDC NHANES data. A Monte Carlo approach, accounting for the correlation structure in physiological parameters, is used to estimate ToxCast equivalent doses for the most sensitive portion of the population. To quantify risk, ToxCast equivalent doses are compared to estimates of exposure rates based on Bayesian inferences drawn from NHANES urinary analyte biomonitoring data. The inclusion

A prospective study of carpal tunnel syndrome: workplace and individual risk factors

PubMed Central

Burt, Susan; Deddens, James A; Crombie, Ken; Jin, Yan; Wurzelbacher, Steve; Ramsey, Jessica

2015-01-01

Objectives To quantify the risk for carpal tunnel syndrome (CTS) from workplace physical factors, particularly hand activity level and forceful exertion, while taking into account individual factors including age, gender, body mass index (BMI), and pre-existing medical conditions. Methods Three healthcare and manufacturing workplaces were selected for inclusion on the basis of range of exposure to hand activity level and forceful exertion represented by their jobs. Each study participants job tasks were observed and evaluated ’ onsite and videotaped for further analysis, including frequency and duration of exertion and postural deviation. Individual health assessment entailed electrodiagnostic testing of median and ulnar nerves, physical examination and questionnaires at baseline with annual follow-up for 2 years. Results The incidence of dominant hand CTS during the study was 5.11 per 100 person-years (29 cases). Adjusted HRs for dominant hand CTS were as follows: working with forceful exertion ≥20% but <60% of the time: 2.83 (1.18, 6.79) and ≥60% of the time vs <20%: 19.57 (5.96, 64.24), BMI ≥30 kg/m2 (obesity): 3.19 (1.28, 7.98). The American Conference for Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for hand activity level also predicted CTS, HR=1.40 (1.11, 1.78) for each unit increase in the TLV ratio, controlling for obesity and job strain. Conclusions Workplace and individual risk factors both contribute to the risk for CTS. Time spent in forceful exertion can be a greater risk for CTS than obesity if the job exposure is high. Preventive workplace efforts should target forceful exertions. PMID:23788614

Early somatosensory processing in individuals at risk for developing psychoses.

PubMed

Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

2014-01-01

Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia.

Early somatosensory processing in individuals at risk for developing psychoses

PubMed Central

Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

2014-01-01

Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia. PMID:25309363

Pupillometer-based Neurofeedback Cognitive Training to Improve Processing Speed and Social Functioning in Individuals at Clinical High Risk for Psychosis

PubMed Central

Choi, Jimmy; Stevens, Michael; Deasy, Melissa; Haber, Lawrence C.; Dewberry, Michael J.; Pearlson, Godfrey D.; Corcoran, Cheryl M.; Javitt, Daniel C.; Fiszdon, Joanna M.

2016-01-01

Objective Among individuals at clinical high risk (CHR) for psychosis, processing speed (PS) has been related to social and role functioning regardless of conversion to schizophrenia. This information processing dysfunction is a gateway to broader behavioral deficits such as difficulty executing social behaviors. We examined the feasibility of improving information processing relevant to social situations in CHR, including its sustainability at 2-month follow-up, and its association with concurrent social function. Methods This was a double-blind RCT in which 62 CHR participants were randomized to Processing Speed Training (PST) or an active control matched for training format and the same dose and duration of treatment. PST is a tablet-based program that uses pupillometry-based neurofeedback to continually adjust training parameters for an optimal neurocognitive load and to improve visual scanning efficiency by inhibiting selection of non-essential targets and discriminating figure-ground details. Results The PST group showed faster motoric and non-motoric PS at post training and 2-month follow-up. At 2 month follow-up, the PST group reported better overall social adjustment. Changes in PS from baseline to 2 months were correlated with overall social adjustment and social avoidance in the entire sample. Conclusions and Implications for Practice This is the first study to test focal neurofeedback-based cognitive training for PS deficits in the putatively prodromal phase of schizophrenia to address associated social morbidity. Targeting PS appears to be a promising pathway to decreasing co-morbidity and mitigating a risk factor for psychosis. PMID:27560455

Cannabis use in children with individualized risk profiles: Predicting the effect of universal prevention intervention.

PubMed

Miovský, Michal; Vonkova, Hana; Čablová, Lenka; Gabrhelík, Roman

2015-11-01

To study the effect of a universal prevention intervention targeting cannabis use in individual children with different risk profiles. A school-based randomized controlled prevention trial was conducted over a period of 33 months (n=1874 sixth-graders, baseline mean age 11.82). We used a two-level random intercept logistic model for panel data to predict the probabilities of cannabis use for each child. Specifically, we used eight risk/protective factors to characterize each child and then predicted two probabilities of cannabis use for each child if the child had the intervention or not. Using the two probabilities, we calculated the absolute and relative effect of the intervention for each child. According to the two probabilities, we also divided the sample into a low-risk group (the quarter of the children with the lowest probabilities), a moderate-risk group, and a high-risk group (the quarter of the children with the highest probabilities) and showed the average effect of the intervention on these groups. The differences between the intervention group and the control group were statistically significant in each risk group. The average predicted probabilities of cannabis use for a child from the low-risk group were 4.3% if the child had the intervention and 6.53% if no intervention was provided. The corresponding probabilities for a child from the moderate-risk group were 10.91% and 15.34% and for a child from the high-risk group 25.51% and 32.61%. School grades, thoughts of hurting oneself, and breaking the rules were the three most important factors distinguishing high-risk and low-risk children. We predicted the effect of the intervention on individual children, characterized by their risk/protective factors. The predicted absolute effect and relative effect of any intervention for any selected risk/protective profile of a given child may be utilized in both prevention practice and research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Community-Based Culturally Preferred Physical Activity Intervention Targeting Populations at High Risk for Type 2 Diabetes: Results and Implications.

PubMed

Rowan, Chip P; Riddell, Michael C; Gledhill, Norman; Jamnik, Veronica K

2016-12-01

In Canada, an ageing population, obesity rates and high risk among certain ethnocultural populations are driving diabetes prevalence. Given the burden associated with type 2 diabetes and its link to modifiable risk factors, this study aimed to implement culturally preferred physical activities at the community level, targeting individuals at high risk for type 2 diabetes. Glycated hemoglobin (A1C) levels were used to detect potential improvements in glycemic control. Participants were screened for diabetes risk using a questionnaire and capillary point-of-care A1C blood testing. Participants were offered community-based physical activity classes 2 to 3 times per week for 6 months. A subset of participants (n=84) provided additional measurements. In total, 718 subjects were reached during recruitment. Substantial participant dropout took place, and 487 participants were exposed to the intervention. Among those who participated in the physical activity and provided follow up, mean A1C levels were reduced by 0.17 (p=0.002) after 3 months (n=84) and by 0.06 (p=0.35; n=49) after 6 months. The homeostatic model assessment (HOMA-beta) showed a significant improvement of 23.6% after 3 months (n=20; p=0.03) and 45.2% after 6 months (n=12; p=0.02). Resting systolic blood pressure and diastolic blood pressure plus combined hand-grip strength improved after 6 months (n=12). Implementation of this community-based, culturally preferred physical activity program presented several challenges and was associated with significant participant dropout. After considering participant dropout, the relatively small group who participated and provided follow-up measures showed improvements various physiologic measures. Despite efforts to enhance accessibility, it appears that several barriers to physical activity participation remain and need to be explored to enhance the success of future programs. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights

Maladaptive decision making and substance use outcomes in high-risk individuals: preliminary evidence for the role of 5-HTTLPR variation.

PubMed

O'Brien, Jessica W; Lichenstein, Sarah D; Hill, Shirley Y

2014-07-01

Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes. Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86). HR offspring showed poorer performance overall on the IGT and especially poor performance on the final trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no significant COMT by Risk interaction. Significantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was significantly associated with an earlier age at SUD onset. This is the first study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefits during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood.

Understanding Suicide Risk: Identification of High Risk Groups during High Risk Times

PubMed Central

Overholser, James C.; Braden, Abby; Dieter, Lesa

2012-01-01

Background The assessment of suicide risk is a complex task for mental health professionals. Certain demographic groups are associated with completed suicide including males, divorced adults, and Caucasians. However, demographic variables alone provide a crude assessment of suicide risk. Psychiatric diagnosis and recent life events may improve the identification of high risk individuals. Method The current study evaluated 148 individuals who died by suicide compared to 257 adults who died suddenly from accidents or medical problems. Psychological autopsy was used to assess Axis I psychiatric diagnosis and recent stressful life events. Results Suicide completers were significantly more likely than comparison subjects to have a depressive disorder, a substance abuse disorder, and to have experienced interpersonal conflict in the months leading up to their death. A discriminant function analysis revealed that the combination of demographic variables, recent stressful life events, and psychiatric diagnoses best discriminated between suicide completers and comparison subjects. Conclusions Proper assessment of suicide risk should include a comprehensive evaluation of demographic characteristics, recent life stressors, and psychiatric diagnosis. PMID:22140004

Reflections on the Implementation of Low-Dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain.

PubMed

Garrido, Pilar; Sánchez, Marcelo; Belda Sanchis, José; Moreno Mata, Nicolás; Artal, Ángel; Gayete, Ángel; Matilla González, José María; Galbis Caravajal, José Marcelo; Isla, Dolores; Paz-Ares, Luis; Seijo, Luis M

2017-10-01

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM). Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

The Experience of Extended Bowel Resection in Individuals With a High Metachronous Colorectal Cancer Risk: A Qualitative Study.

PubMed

Steel, Emma J; Trainer, Alison H; Heriot, Alexander G; Lynch, Craig; Parry, Susan; Win, Aung K; Keogh, Louise A

2016-07-01

To ascertain individual experiences of extended bowel resection as treatment for colorectal cancer (CRC) in those with a high metachronous CRC risk, including the self-reported adequacy of information received at different time points of treatment and recovery.
. Qualitative.
. Participants were recruited through the Australasian Colorectal Cancer Family Registry and two hospitals in Melbourne, Australia.
. 18 individuals with a high metachronous CRC risk who had an extended bowel resection from 6-12 months ago.
. Semistructured interviews. Data were analyzed thematically.
. In most cases, the treating surgeon decided on the best option regarding surgical treatment. Participants felt well informed about the surgical procedure. Information related to surgical outcomes, recovery, and lifestyle adjustment from surgery was not always adequate. Many participants described ongoing worry about developing another cancer. 
. Patients undergoing an extended resection to reduce metachronous CRC risk require detailed information delivered at more than one time point and relating to several different aspects of the surgical procedure and its outcomes.
. An increased emphasis should be given to the provision of patient information on surgical outcomes, recovery, and lifestyle adjustment. Colorectal nurses could provide support for some of the reported unmet needs.

Risk-targeted maps for Romania

NASA Astrophysics Data System (ADS)

Vacareanu, Radu; Pavel, Florin; Craciun, Ionut; Coliba, Veronica; Arion, Cristian; Aldea, Alexandru; Neagu, Cristian

2018-03-01

Romania has one of the highest seismic hazard levels in Europe. The seismic hazard is due to a combination of local crustal seismic sources, situated mainly in the western part of the country and the Vrancea intermediate-depth seismic source, which can be found at the bend of the Carpathian Mountains. Recent seismic hazard studies have shown that there are consistent differences between the slopes of the seismic hazard curves for sites situated in the fore-arc and back-arc of the Carpathian Mountains. Consequently, in this study we extend this finding to the evaluation of the probability of collapse of buildings and finally to the development of uniform risk-targeted maps. The main advantage of uniform risk approach is that the target probability of collapse will be uniform throughout the country. Finally, the results obtained are discussed in the light of a recent study with the same focus performed at European level using the hazard data from SHARE project. The analyses performed in this study have pointed out to a dominant influence of the quantile of peak ground acceleration used for anchoring the fragility function. This parameter basically alters the shape of the risk-targeted maps shifting the areas which have higher collapse probabilities from eastern Romania to western Romania, as its exceedance probability increases. Consequently, a uniform procedure for deriving risk-targeted maps appears as more than necessary.

Individual deprivation, regional deprivation, and risk for oral clefts in Argentina.

PubMed

Pawluk, Mariela Soledad; Campaña, Hebe; Rittler, Monica; Poletta, Fernando Adrián; Cosentino, Viviana R; Gili, Juan Antonio; Gimenez, Lucas Gabriel; López Camelo, Jorge Santiago

2018-02-19

The aim of this study was to analyze the effects of individual low socioeconomic status (SES) and deprived geographical area (GA) on the occurrence of isolated cleft lip with or without cleft palate (CL±P) in Argentina. This case-control study included 577 newborns with isolated CL±P and 13 344 healthy controls, born between 1992 and 2001, from a total population of 546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic needs were used to establish the degree of geographical area deprivation. An SES index for each individual was established, using maternal age, gravidity, low paternal and maternal education, and low-level paternal occupation. Logistic regression was used to assess the effects of low SES and of deprived GA on CL±P. A slightly increased risk of CL±P was observed in mothers with a low SES, while a deprived GA showed no effect. Native ancestry, acute maternal illnesses, and poor prenatal care were significant risk factors for CL±P for the mothers with low SES, after using propensity scores to adjust for the demographic characteristics in cases and controls. Low individual SES slightly increased the risk for CL±P, but a deprived GA did not have that effect. There was no interaction between individual SES and deprived GA. Factors related to low individual SES-including poor prenatal care, low parental education, lack of information, and lifestyle factors-should be primarily targeted as risk factors for CL±P rather than factors related to a deprived place of residence.

Pilot study on use of home telephoning to identify and recruit high-risk individuals for lung cancer screening.

PubMed

Veronesi, Giulia; Colombo, Paolo; Novellis, Pierluigi; Crepaldi, Alessandro; Lutman, Romano Fabio; Dieci, Elisa; Profili, Manuel; Siracusano, Licia; Alloisio, Marco

2017-03-01

Widespread lung cancer screening with low-dose computed tomography is urgently needed in Europe to identify lung cancers early and reduce lung cancer deaths. The most effective method of identifying high-risk individuals and recruiting them for screening has not been determined. In the present pilot study we investigated direct telephoning to families as a way of identifying high risk individuals and recruiting them to a screening/smoking cessation program, that avoided the selection bias of voluntary screening. Families in the province of Milan, Italy, were contacted by telephone at their homes and asked about family members over 50 years who were heavy smokers (30 or more pack-years). Persons meeting these criteria were contacted and asked to participate in the program. Those who agreed were given an appointment to undergo screening and receive smoking cessation counseling. Among the 1000 contacted families, involving 2300 persons, 44 (1.9%) were eligible for LDCT screening, and 12 (27%) of these participated in the program. The cost of this recruitment strategy pilot study was around 150 euro per screened subject. We obtained useful information on the proportion of the general population eligible for lung cancer screening and the proportion of those who responded. However the cost of home telephone calling is probably too high to be practicable as a method of recruiting high risk persons for screening. Alternative recruitment methods, possibly involving family physicians practitioners, need to be investigated. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Social Cognition in Individuals at Ultra-High Risk for Psychosis: A Meta-Analysis

PubMed Central

van Donkersgoed, R. J. M.; Wunderink, L.; Nieboer, R.; Aleman, A.; Pijnenborg, G. H. M.

2015-01-01

Objective Treatment in the ultra-high risk stage for a psychotic episode is critical to the course of symptoms. Markers for the development of psychosis have been studied, to optimize the detection of people at risk of psychosis. One possible marker for the transition to psychosis is social cognition. To estimate effect sizes for social cognition based on a quantitative integration of the published evidence, we conducted a meta-analysis of social cognitive performance in people at ultra high risk (UHR). Methods A literature search (1970-July 2015) was performed in PubMed, PsychINFO, Medline, Embase, and ISI Web of Science, using the search terms ‘social cognition’, ‘theory of mind’, ‘emotion recognition’, ‘attributional style’, ‘social knowledge’, ‘social perception’, ‘empathy’, ‘at risk mental state’, ‘clinical high risk’, ‘psychosis prodrome’, and ‘ultra high risk’. The pooled effect size (Cohen’s D) and the effect sizes for each domain of social cognition were calculated. A random effects model with 95% confidence intervals was used. Results Seventeen studies were included in the analysis. The overall significant effect was of medium magnitude (d = 0.52, 95% Cl = 0.38–0.65). No moderator effects were found for age, gender and sample size. Sub-analyses demonstrated that individuals in the UHR phase show significant moderate deficits in affect recognition and affect discrimination in faces as well as in voices and in verbal Theory of Mind (TOM). Due to an insufficient amount of studies, we did not calculate an effect size for attributional bias and social perception/ knowledge. A majority of studies did not find a correlation between social cognition deficits and transition to psychosis, which may suggest that social cognition in general is not a useful marker for the development of psychosis. However some studies suggest the possible predictive value of verbal TOM and the recognition of specific emotions in faces

Finding the High-Risk Patient in Primary Prevention Is Not as Easy as a Conventional Risk Score!

PubMed

Ambrose, John A; Acharya, Tushar; Roberts, Micah J

2016-12-01

Patients with coronary artery disease or its equivalent are an appropriate target for guideline-directed therapy. However, finding and treating the individuals at risk for myocardial infarction or sudden death in primary prevention has been problematic. Most initial cardiovascular events are acute syndromes, and only a minority of these occurs in those deemed high risk by contemporary algorithms. Even newer noninvasive modalities cannot detect a majority of those at risk. Furthermore, accurate and early detection of high risk/vulnerability does not guarantee event prevention. Until new tools can be identified, one should consider a few simplistic solutions. In addition to a greater emphasis on lifestyle, earlier use of statins than currently recommended and a direct assault on tobacco could go a long way in reducing acute syndromes and cardiovascular mortality. To achieve the tobacco goal, the medical community would have to be directly and communally engaged. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting condom distribution at high risk places increases condom utilization-evidence from an intervention study in Livingstone, Zambia

PubMed Central

2012-01-01

Background The PLACE-method presumes that targeting HIV preventive activities at high risk places is effective in settings with major epidemics. Livingstone, Zambia, has a major HIV epidemic despite many preventive efforts in the city. A baseline survey conducted in 2005 in places where people meet new sexual partners found high partner turnover and unprotected sex to be common among guests. In addition, there were major gaps in on-site condom availability. This study aimed to assess the impact of a condom distribution and peer education intervention targeting places where people meet new sexual partners on condom use and sexual risk taking among people socializing there. Methods The 2005 baseline survey assessed the presence of HIV preventive activities and sexual risk taking in places where people meet new sexual partners in Livingstone. One township was selected for a non-randomised intervention study on condom distribution and peer education in high risk venues in 2009. The presence of HIV preventive activities in the venues during the intervention was monitored by an external person. The intervention was evaluated after one year with a follow-up survey in the intervention township and a comparison township. In addition, qualitative interviews and focus group discussions were conducted. Results Young people between 17-32 years of age were recruited as peer educators, and 40% were females. Out of 72 persons trained before the intervention, 38 quit, and another 11 had to be recruited. The percentage of venues where condoms were reported to always be available at least doubled in both townships, but was significantly higher in the intervention vs. the control venues in both surveys (84% vs. 33% in the follow-up). There was a reduction in reported sexual risk taking among guests socializing in the venues in both areas, but reporting of recent condom use increased more among people interviewed in the intervention (57% to 84%) than in the control community (55% to 68

Targeting condom distribution at high risk places increases condom utilization-evidence from an intervention study in Livingstone, Zambia.

PubMed

Sandøy, Ingvild Fossgard; Zyaambo, Cosmas; Michelo, Charles; Fylkesnes, Knut

2012-01-05

The PLACE-method presumes that targeting HIV preventive activities at high risk places is effective in settings with major epidemics. Livingstone, Zambia, has a major HIV epidemic despite many preventive efforts in the city. A baseline survey conducted in 2005 in places where people meet new sexual partners found high partner turnover and unprotected sex to be common among guests. In addition, there were major gaps in on-site condom availability. This study aimed to assess the impact of a condom distribution and peer education intervention targeting places where people meet new sexual partners on condom use and sexual risk taking among people socializing there. The 2005 baseline survey assessed the presence of HIV preventive activities and sexual risk taking in places where people meet new sexual partners in Livingstone. One township was selected for a non-randomised intervention study on condom distribution and peer education in high risk venues in 2009. The presence of HIV preventive activities in the venues during the intervention was monitored by an external person. The intervention was evaluated after one year with a follow-up survey in the intervention township and a comparison township. In addition, qualitative interviews and focus group discussions were conducted. Young people between 17-32 years of age were recruited as peer educators, and 40% were females. Out of 72 persons trained before the intervention, 38 quit, and another 11 had to be recruited. The percentage of venues where condoms were reported to always be available at least doubled in both townships, but was significantly higher in the intervention vs. the control venues in both surveys (84% vs. 33% in the follow-up). There was a reduction in reported sexual risk taking among guests socializing in the venues in both areas, but reporting of recent condom use increased more among people interviewed in the intervention (57% to 84%) than in the control community (55% to 68%). It is likely that the

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

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

Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de; Eckert, Franziska; Paulsen, Frank

2016-02-01

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less

The Experience of Extended Bowel Resection in Individuals With a High Metachronous Colorectal Cancer Risk: A Qualitative Study

PubMed Central

Steel, Emma J.; Trainer, Alison H.; Heriot, Alexander G.; Lynch, Craig; Parry, Susan; Win, Aung K.; Keogh, Louise A.

2016-01-01

Purpose/Objectives To ascertain individual experiences of extended bowel resection as treatment for colorectal cancer (CRC) in those with a high metachronous CRC risk, including the self-reported adequacy of information received at different time points of treatment and recovery. Research Approach Qualitative. Setting Participants were recruited through the Australasian Colorectal Cancer Family Registry and two hospitals in Melbourne, Australia. Participants 18 individuals with a high metachronous CRC risk who had an extended bowel resection from 6–12 months ago. Methodologic Approach Semistructured interviews. Data were analyzed thematically. Findings In most cases, the treating surgeon decided on the best option regarding surgical treatment. Participants felt well informed about the surgical procedure. Information related to surgical outcomes, recovery, and lifestyle adjustment from surgery was not always adequate. Many participants described ongoing worry about developing another cancer. Conclusions Patients undergoing an extended resection to reduce metachronous CRC risk require detailed information delivered at more than one time point and relating to several different aspects of the surgical procedure and its outcomes. Interpretation An increased emphasis should be given to the provision of patient information on surgical outcomes, recovery, and lifestyle adjustment. Colorectal nurses could provide support for some of the reported unmet needs. PMID:27314187

Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

PubMed

Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

2016-01-01

A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.

High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis.

PubMed

Yeo-Teh, Nicole S L; Ito, Yoshiaki; Jha, Sudhakar

2018-06-08

Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and E7 achieve persistent expression. The most well-studied cellular targets of the viral oncogenes E6 and E7 are p53 and pRb, respectively. However, recent research has demonstrated the ability of these two viral factors to target many more cellular factors, including proteins which regulate epigenetic marks and splicing changes in the cell. These have the ability to exert a global change, which eventually culminates to uncontrolled proliferation and carcinogenesis.

A Model To Identify Individuals at High Risk for Esophageal Squamous Cell Carcinoma and Precancerous Lesions in Regions of High Prevalence in China.

PubMed

Liu, Mengfei; Liu, Zhen; Cai, Hong; Guo, Chuanhai; Li, Xiang; Zhang, Chaoting; Wang, Hui; Hang, Dong; Liu, Fangfang; Deng, Qiuju; Yang, Xin; Yuan, Wenqing; Pan, Yaqi; Li, Jingjing; Zhang, Chanyuan; Shen, Na; He, Zhonghu; Ke, Yang

2017-10-01

We aimed to develop a population-based model to identify individuals at high risk for esophageal squamous cell carcinoma (ESCC) in regions of China with a high prevalence of this cancer. We collected findings from 15,073 permanent residents (45-69 years old) of 334 randomly selected villages in Hua County, Henan Province, China who underwent endoscopic screening (with iodine staining) for ESCC from January 2012 through September 2015. The entire esophagus and stomach were examined; biopsies were collected from all focal lesions (or from standard sites in the esophagus if no abnormalities were found) and analyzed histologically. Squamous dysplasia, carcinoma in situ, and ESCC were independently confirmed by 2 pathologists. Before endoscopy, subjects completed a questionnaire on ESCC risk factors. Variables were evaluated with unconditional univariate logistic regression analysis; variables found to be significantly associated with ESCC were then analyzed by multivariate logistic regression modeling. We used the Akaike information criterion to develop our final model structure and the coding form of variables with multiple measures. We developed 2 groups of models, separately defining severe dysplasia and above (SDA) (lesions including severe dysplasia and higher-grade lesions) and moderate dysplasia and above (lesions including moderate dysplasia and higher-grade lesions) as outcome events. Age-stratified and whole-age models were developed; their discriminative ability in the full multivariate model and the simple age model was compared. We performed area under the receiver operating characteristic curve (AUC) and the DeLong test to evaluate model performance. Our age-stratified prediction models identified individuals 60 years of age or younger with SDA with an AUC value of 0.795 (95% confidence interval, 0.736-0.854) and individuals older than 60 years with SDA with an AUC value of 0.681 (95% confidence interval, 0.618-0.743). Factors associated with SDA in

Malaria risk factors and care-seeking behaviour within the private sector among high-risk populations in Vietnam: a qualitative study.

PubMed

Chen, Ingrid; Thanh, Huong Ngo Thi; Lover, Andrew; Thao, Phung Thi; Luu, Tang Viet; Thang, Hoang Nghia; Thang, Ngo Duc; Neukom, Josselyn; Bennett, Adam

2017-10-16

Vietnam has successfully reduced malaria incidence by more than 90% over the past 10 years, and is now preparing for malaria elimination. However, the remaining malaria burden resides in individuals that are hardest to reach, in highly remote areas, where many malaria cases are treated through the informal private sector and are not reported to public health systems. This qualitative study aimed to contextualize and characterize the role of private providers, care-seeking behaviour of individuals at high risk of malaria, as well as risk factors that should be addressed through malaria elimination programmes in Vietnam. Semi-structured qualitative interviews were conducted with 11 key informants in Hanoi, 30 providers, 9 potential patients, and 11 individuals at risk of malaria in Binh Phuoc and Kon Tum provinces. Audio recorded interviews were transcribed and uploaded to Atlas TI™, themes were identified, from which programmatic implications and recommendations were synthesized. Qualitative interviews revealed that efforts for malaria elimination in Vietnam should concentrate on reaching highest-risk populations in remote areas as well their care providers, in particular private pharmacies, private clinics, and grocery stores. Among these private providers, diagnosis is currently based on symptoms, leaving unconfirmed cases that are not reported to public health surveillance systems. Among at-risk individuals, knowledge of malaria was limited, and individuals reported not taking full courses of treatment, a practice that threatens selection for drug resistance. Access to insecticide-treated hammock nets, a potentially important preventive measure for settings with outdoor biting Anopheles vectors, was also limited. Malaria elimination efforts in Vietnam can be accelerated by targeting improved treatment, diagnosis, and reporting practices to private pharmacies, private clinics, and grocery stores. Programmes should also seek to increase awareness and

The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis.

PubMed

Corcoran, C M; Kimhy, D; Parrilla-Escobar, M A; Cressman, V L; Stanford, A D; Thompson, J; David, S Ben; Crumbley, A; Schobel, S; Moore, H; Malaspina, D

2011-02-01

Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset of psychosis. It is unclear if social symptoms in clinical high-risk patients reflect depressive symptoms or are a manifestation of negative symptoms. We compared social function scores on the Social Adjustment Scale-Self Report between 56 young people (aged 13-27 years) at clinical high risk for psychosis and 22 healthy controls. The cases were also assessed for depressive and 'prodromal' symptoms (subthreshold positive, negative, disorganized and general symptoms). Poor social function was related to both depressive and negative symptoms, as well as to disorganized and general symptoms. The symptoms were highly intercorrelated but linear regression analysis demonstrated that poor social function was primarily explained by negative symptoms within this cohort, particularly in ethnic minority patients. Although this study demonstrated a relationship between social dysfunction and depressive symptoms in clinical high-risk cases, this association was primarily explained by the relationship of each of these to negative symptoms. In individuals at heightened risk for psychosis, affective changes may be related to a progressive decrease in social interaction and loss of reinforcement of social behaviors. These findings have relevance for potential treatment strategies for social dysfunction in schizophrenia and its risk states and predict that antidepressant drugs, cognitive behavioral therapy and/or social skills training may be effective.

Using 'WeChat' online social networking in a real-world needs analysis of family members of youths at clinical high risk of psychosis.

PubMed

Zhang, TianHong; Xu, LiHua; Tang, YingYing; Cui, HuiRu; Li, HuiJun; Wei, YanYan; Xu, YangYang; Jiang, LiJuan; Zhu, YiKang; Li, ChunBo; Jiang, KaiDa; Xiao, ZePing; Wang, JiJun

2018-04-01

The argument surrounding the safety and effectiveness of interventions for the population of individuals at a clinical high risk of developing psychosis has been ongoing for the past 30 years. However, few studies have assessed the needs of this special young population, who are struggling with the recent onset of psychotic symptoms. The sample consisted of 171 family members of 108 clinical high-risk individuals included from the ShangHai at Risk for Psychosis research programme. A 'WeChat' group was established to provide mutual support. There were 22,007 valid messages sent within the group between 1 April 2015 and 27 June 2016. Chat records were subsequently analysed to determine the needs of families during intervention at the early stages of psychosis. Families of clinical high-risk individuals were highly involved in the entire medical process, and the major concerns of the families of clinical high-risk individuals focused on both functional recovery and medication. The themes of 'take medication', 'go to school' and 'study in school' were often discussed within the group. A family-focused intervention targeting functional recovery and real-time professional explanations of medication would meet the major needs of families of Chinese clinical high-risk individuals.

Association of metabolic syndrome and its individual components with outcomes among patients with high-risk non-ST-segment elevation acute coronary syndromes.

PubMed

Mehta, Rajendra H; Westerhout, Cynthia M; Zheng, Yinggan; Giugliano, Robert P; Huber, Kurt; Prabhakaran, Dorairaj; Harrington, Robert A; Newby, Kristin L; Armstrong, Paul W

2014-08-01

The relationship of metabolic syndrome and its individual components (obesity, hypertension, glucose intolerance, high triglycerides, and low high-density lipoprotein cholesterol) with 1-year mortality in non-ST-segment elevation acute coronary syndromes (NSTE ACS) patients is not known. The association of metabolic syndrome (and its individual components) with all-cause mortality within 1 year was assessed in NSTE ACS patients enrolled in the EARLY ACS trial. Adjusted hazard ratio (HR) and 95% CIs are reported. Of 9,406 patients, 2,596 (27.6%) had metabolic syndrome. Compared with those without metabolic syndrome, patients with this syndrome were younger, were more often female, and had a higher prevalence of comorbid conditions and higher-risk presenting features. Metabolic syndrome was not associated with increased 1-year mortality (HR 1.20, 95% CI 0.97-1.47; P = .09). The risk of 1-year mortality varied across the individual components: high-density lipoprotein <40 mg/dL (men)/<50 mg/dL (women; or dyslipidemia) was associated with higher risk (HR 1.52, 95% CI 1.15-2.02), and triglycerides >150 mg/dL (or dyslipidemia) was associated with lower risk (HR 0.66, 95% CI 0.54-0.81), whereas the other components (ie, body mass index >30 kg/m(2), fasting plasma glucose >100 mg/dL or diabetes, systolic blood pressure >130 mm Hg or diastolic >85 mm Hg [or hypertension]) were associated with neutral risk of this event. The individual components of metabolic syndrome had varying associations with 1-year mortality, and as an integrated diagnosis, metabolic syndrome was not significantly associated with 1-year mortality. Thus, patient case-mix of the studied NSTE ACS population may influence the observed relationship of metabolic syndrome with subsequent cardiovascular events. Copyright © 2014 Mosby, Inc. All rights reserved.

[The Discursive Analysis of Mental Health Promotion Efforts Targeting Community-Dwelling Young Adults at High Risk of Mental Illness].

PubMed

Hsiung, Der-Yun; Yang, Tzu-Ching; Ma, Wei-Fen

2015-08-01

The mental health of adolescents and young adults is an issue of concern worldwide due to the increase in violent incidents that have been perpetrated by members of this age group. Young people at high-risk of mental disability are easily ignored. Therefore, social tensions in society have increased due to safety issues arising from the problems that are associated with mental disabilities in this population. This paper discusses the importance of early identification and early prevention of mental disabilities in high-risk young people, defines high-risk mental illness, and identifies the various subcategories of mental diseases. Based on our review of the literature, the present paper suggests targeting young people in high-risk categories with health promotion that addresses the following six health-promotion lifestyle habits: engaging in regular exercise, eating a balanced diet, managing stress, engaging in social relationships, taking responsibility for personal health, and fulfilling self-actualization. This discursive analysis discusses these strategies as safe and sustained interventions for adolescents and young adults that may improve self-awareness and thus maintain health and enhance opportunities to promote an ideal health status.

Dependence of flood risk perceptions on socioeconomic and objective risk factors

NASA Astrophysics Data System (ADS)

Botzen, W. J. W.; Aerts, J. C. J. H.; van den Bergh, J. C. J. M.

2009-10-01

This study examines flood risk perceptions of individuals in the Netherlands using a survey of approximately 1000 homeowners. Perceptions of a range of aspects of flood risk are elicited. Various statistical models are used to estimate the influence of socioeconomic and geographical characteristics, personal experience with flooding, knowledge of flood threats, and individual risk attitudes on shaping risk belief. The study shows that in general, perceptions of flood risk are low. An analysis of the factors determining risk perceptions provides four main insights relevant for policy makers and insurers. First, differences in expected risk are consistently related to actual risk levels, since individuals in the vicinity of a main river and low-lying areas generally have elevated risk perceptions. Second, individuals in areas unprotected by dikes tend to underestimate their risk of flooding. Third, individuals with little knowledge of the causes of flood events have lower perceptions of flood risk. Fourth, there is some evidence that older and more highly educated individuals have a lower flood risk perception. The findings indicate that increasing knowledge of citizens about the causes of flooding may increase flood risk awareness. It is especially important to target individuals who live in areas unprotected by dike infrastructure, since they tend to be unaware of or ignore the high risk exposure faced.

Running for your life: A review of physical activity and cardiovascular disease risk reduction in individuals with schizophrenia.

PubMed

Chalfoun, Claire; Karelis, Antony D; Stip, Emmanuel; Abdel-Baki, Amal

2016-08-01

Individuals with schizophrenia have a greater risk for cardiometabolic risk factors (e.g. central obesity, insulin resistance, hypertension and dyslipidaemia), cardiovascular diseases and mortality. This risky profile may be explained by the adverse effects of antipsychotic medications and an unhealthy lifestyle (e.g. smoking, poor nutrition and low physical activity). In the general population, physical activity has been shown to be the optimal strategy to improve both cardiometabolic parameters and cardiorespiratory fitness levels. Accordingly, an emerging literature of non-pharmacological interventions (e.g. cognitive behavioural therapy, diet and physical activity) has been studied in individuals with schizophrenia. Therefore, the purpose of this review was 1) to conduct a critical literature review of non-pharmacological interventions that included some kind of physical activity (including supervised and unsupervised exercise training) and target cardiometabolic risk factors in individuals with schizophrenia. 2) To describe the contribution of physical activity alone by reviewing trials of supervised exercise training programmes only. A literature review via systematic keyword search for publications in Medline, PubMed, Embase and PsycINFO was performed. Many non-pharmacological interventions are efficient in reducing cardiovascular disease risk factors when combined with physical activity. Supervised physical activity has been successful in decreasing cardiovascular disease risk, and aerobic interval training appears to provide more benefits by specifically targeting cardiorespiratory fitness levels. In conclusion, physical activity is an effective strategy for addressing cardiovascular disease risk in individuals with schizophrenia. Long-term studies are needed to evaluate the feasibility and impact of exercise training programmes in individuals with schizophrenia.

Suboptimal primary and secondary cardiovascular disease prevention in HIV-positive individuals on antiretroviral therapy.

PubMed

van Zoest, Rosan A; van der Valk, Marc; Wit, Ferdinand W; Vaartjes, Ilonca; Kooij, Katherine W; Hovius, Joppe W; Prins, Maria; Reiss, Peter

2017-08-01

Background We aimed to identify the prevalence of cardiovascular risk factors, and investigate preventive cardiovascular medication use and achievement of targets as per Dutch cardiovascular risk management guidelines among human immunodeficiency virus (HIV)-positive and HIV-negative individuals. Design The design was a cross-sectional analysis within an ongoing cohort study. Methods Data on medication use and cardiovascular disease prevalence were available for 528 HIV-positive and 521 HIV-negative participants. We identified cardiovascular risk factors and applied cardiovascular risk management guidelines, mainly focusing on individuals eligible for (a) primary prevention because of high a priori cardiovascular risk, or for (b) secondary prevention. Results One hundred and three (20%) HIV-positive and 77 (15%) HIV-negative participants were classified as having high cardiovascular risk; 53 (10%) HIV-positive and 27 (5%) HIV-negative participants were eligible for secondary prevention. Of HIV-positive individuals 57% at high cardiovascular risk and 42% of HIV-positive individuals eligible for secondary prevention had systolic blood pressures above guideline-recommended thresholds. Cholesterol levels were above guideline-recommended thresholds in 81% of HIV-positive individuals at high cardiovascular risk and 57% of HIV-positive individuals eligible for secondary prevention. No statistically significant differences were observed between HIV-positive and HIV-negative participants regarding achievement of targets, except for glycaemic control (glycated haemoglobin ≤ 53 mmol/mol) among individuals using diabetes medication (90% vs 50%, p = 0.017) and antiplatelet/anticoagulant use for secondary prevention (85% vs 63%, p = 0.045), which were both superior among HIV-positive participants. Conclusions Cardiovascular risk management is suboptimal in both HIV-positive and HIV-negative individuals and should be improved.

Suboptimal primary and secondary cardiovascular disease prevention in HIV-positive individuals on antiretroviral therapy

PubMed Central

van der Valk, Marc; Wit, Ferdinand W; Vaartjes, Ilonca; Kooij, Katherine W; Hovius, Joppe W; Prins, Maria; Reiss, Peter

2017-01-01

Background We aimed to identify the prevalence of cardiovascular risk factors, and investigate preventive cardiovascular medication use and achievement of targets as per Dutch cardiovascular risk management guidelines among human immunodeficiency virus (HIV)-positive and HIV-negative individuals. Design The design was a cross-sectional analysis within an ongoing cohort study. Methods Data on medication use and cardiovascular disease prevalence were available for 528 HIV-positive and 521 HIV-negative participants. We identified cardiovascular risk factors and applied cardiovascular risk management guidelines, mainly focusing on individuals eligible for (a) primary prevention because of high a priori cardiovascular risk, or for (b) secondary prevention. Results One hundred and three (20%) HIV-positive and 77 (15%) HIV-negative participants were classified as having high cardiovascular risk; 53 (10%) HIV-positive and 27 (5%) HIV-negative participants were eligible for secondary prevention. Of HIV-positive individuals 57% at high cardiovascular risk and 42% of HIV-positive individuals eligible for secondary prevention had systolic blood pressures above guideline-recommended thresholds. Cholesterol levels were above guideline-recommended thresholds in 81% of HIV-positive individuals at high cardiovascular risk and 57% of HIV-positive individuals eligible for secondary prevention. No statistically significant differences were observed between HIV-positive and HIV-negative participants regarding achievement of targets, except for glycaemic control (glycated haemoglobin ≤ 53 mmol/mol) among individuals using diabetes medication (90% vs 50%, p = 0.017) and antiplatelet/anticoagulant use for secondary prevention (85% vs 63%, p = 0.045), which were both superior among HIV-positive participants. Conclusions Cardiovascular risk management is suboptimal in both HIV-positive and HIV-negative individuals and should be improved. PMID:28578613

Episodic memory functions in first episode psychosis and clinical high risk individuals.

PubMed

Greenland-White, Sarah E; Ragland, J Daniel; Niendam, Tara A; Ferrer, Emilio; Carter, Cameron S

2017-10-01

Individuals with schizophrenia have disproportionate memory impairments when encoding relational versus item-specific information, and when using recollection versus familiarity during retrieval. It is unclear whether this pattern is unique to people with chronic schizophrenia, or if it occurs in individuals after a first episode of psychosis (FE), or when at clinical high-risk for psychosis (CHR). We administered the Relational and Item-Specific Memory task (RiSE) to 22 CHR, 101 FE, and 58 typically developing (TD) participants. We examined group differences in item and relational encoding, and familiarity-based and recollection-based retrieval using parametric analysis and structural equation modeling (SEM). Longitudinal data allowed us to examine relations between baseline RiSE performance and change in clinical symptoms at 1-year follow-up in the FE group. Groups did not differ on familiarity. FE and CHR groups were equally impaired on overall recognition accuracy. Although recollection was impaired in both FE and CHR groups following relational encoding, only the FE group had impaired recollection following item encoding. SEM showed atypical relationships between familiarity and recollection, as well as familiarity and item recognition for both the FE and CHR groups. For FE individuals, better baseline recognition accuracy predicted less severe negative symptoms at 1-year follow-up. Impaired relational and recollective memory may reflect neurodevelopmental abnormalities predating conversion to psychosis. These memory deficits appear related to negative symptom changes. In contrast, item specific recollection deficits appear to occur after the development of full psychosis. Familiarity appears to be a relatively preserved memory function across the psychosis spectrum. Copyright © 2017 Elsevier B.V. All rights reserved.

A Population-based Screening of Type 2 Diabetes in High-risk Population of Yasuj, Iran

PubMed Central

Yazdanpanah, Behrouz; Yazdanpanah, Behzad; Mobasheri, Ali

2014-01-01

ABSTRACT Complications associated with diabetes can be prevented by early diagnostics. A high-risk population was screened for diabetes, and the prevalence of undiagnosed diabetes mellitus (DM) and impaired fasting glucose (IFG) were used for examining the impacts of lifestyle, social and anthropometric features, and other risk factors. The target population comprised 30-65 years old residents from the western suburbs of Yasuj. Homes were approached, and a standard questionnaire was used for collecting information on sex, blood pressure, weight, height, and BMI for each participant. The high-risk participants were recognized according to the National Diabetes Prevention and Control Committee criteria and were introduced to an assigned laboratory. Blood samples were collected after 12-hour fasting for the measurement of total cholesterol, triglycerides and fasting glucose levels. The statistical analysis was performed with the SPSS statistical package, using a logistic regression model. Out of 2,569 individuals, 1,336 (52%) were with high-risk diabetes, 71.5% were female, and 28.5% were male. Of 191 (7.4%) individuals with known diabetes, 5 (2.6%) had type 1 diabetes; 881 (66.9%) out of 1,336 high-risk individuals were referred to assigned laboratory. Of 881 high-risk individuals, 157 (17.8%) had fasting blood sugar (FBS) ≥126 mg/dL and 118 (13.4%) had FBS between110 and 125 mg/dL. Percentages of participants with triglyceride ≥150 mg/dL and cholesterol ≥200 mg/dL were 298 (33.8%) and 207 (23.5%) respectively. Diabetes was associated with ageing, dyslipidaemia, family history of diabetes, lower physical activity on occupation, intake of lower dietary fibre, and non-literacy in the sampled population. This study suggests that diabetes is a common health problem in this area. Furthermore, considerable rate of newly-diagnosed diabetes signifies the importance of the screening programme. PMID:25895201

Risk-Taking: Individual and Family Interests.

PubMed

Iltis, Ana S

2015-08-01

Decisions regarding clinical procedures or research participation typically require the informed consent of individuals. When individuals are unable to give consent, the informed permission of a legally authorized representative or surrogate is required. Although many proposed procedures are aimed primarily at benefiting the individual, some are not. I argue that, particularly when individuals are asked to assume risks primarily or exclusively for the benefit of others, family members ought to be engaged in the informed consent process. Examples of procedures in which individuals are asked to assume risks primarily or exclusively for the benefit of others include living organ donation and research participation. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Social and individual risk factors for suicide ideation among Chinese children and adolescents: A multilevel analysis.

PubMed

Tan, Ling; Xia, Tiansheng; Reece, Christy

2018-04-01

The objective of this study was to investigate the prevalence and predictors of suicide ideation among primary, middle and high school students. We used multilevel modelling to investigate suicide ideation among 12,733 Chinese children and adolescents aged 9-18 years from wide range of areas across China. Approximately, 32.09% of children and adolescents reported suicide ideation, with females were more likely to report suicide ideation than males (38.09% vs. 29.95%). Our results showed that the risk factors in primary school students were different from middle and high school student groups, whereas significant risk factors for middle and high school students were similar. The city's standard of living as indicated by the Engel coefficient and the city's divorce rate were positively associated with the prevalence of suicide ideation; in contrast, the school's pupil-to-teacher ratio was negatively correlated with elevated suicide ideation. Significant risk factors for suicide ideation included study anxiety, self-accusation tendency, impulsive tendency, terror tendency and physical symptoms. These results have important implications for the prevention of suicide, suggesting that both contextual (city-level) and compositional (individual-level) factors could be important targets for prevention and intervention for children and adolescents at risk of suicide ideation. © 2016 International Union of Psychological Science.

Perceived ethnic discrimination and persecutory paranoia in individuals at ultra-high risk for psychosis.

PubMed

Shaikh, Madiha; Ellett, Lyn; Dutt, Anirban; Day, Fern; Laing, Jennifer; Kroll, Jasmine; Petrella, Sabrina; McGuire, Philip; Valmaggia, Lucia R

2016-07-30

Despite a consensus that psychosocial adversity plays a role in the onset of psychosis, the nature of this role in relation to persecutory paranoia remains unclear. This study examined the complex relationship between perceived ethnic discrimination and paranoid ideation in individuals at Ultra High Risk (UHR) for psychosis using a virtual reality paradigm to objectively measure paranoia. Data from 64 UHR participants and 43 healthy volunteers were analysed to investigate the relationship between perceived ethnic discrimination and persecutory ideation in a virtual reality environment. Perceived ethnic discrimination was higher in young adults at UHR in comparison to healthy controls. A positive correlation was observed between perceived ethnic discrimination and paranoid persecutory ideation in the whole sample. Perceived ethnic discrimination was not a significant predictor of paranoid persecutory ideation in the VR environment. Elevated levels of perceived ethnic discrimination are present in individuals at UHR and are consistent with current biopsychosocial models in which psychosocial adversity plays a key role in the development of psychosis and attenuated symptomatology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Scalable principles of community-based high-value care for seriously ill individuals: Diamonds in the rough.

PubMed

Parikh, Ravi B; Bowman, Brynn; Dahlin, Constance; Twohig, Jeanne S; Meier, Diane E

2017-03-01

Early, integrated palliative care has been shown to improve quality of life and reduce utilization in both inpatient and outpatient settings. As health systems shift to risk-based payment structures, palliative care will play an increasing role in improving value of care outside of the hospital. Based on successful models of community-based palliative care, we identify six principles - interdisciplinary team-based care; 24/7 access and responsiveness; concurrent palliative care with disease-directed treatment; targeting services to high-risk patients; integrated medical and social supports; and caregiver support - that are widely implemented because of their impact on improving value for seriously ill individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

PubMed

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

Disrupted resting brain graph measures in individuals at high risk for alcoholism.

PubMed

Holla, Bharath; Panda, Rajanikant; Venkatasubramanian, Ganesan; Biswal, Bharat; Bharath, Rose Dawn; Benegal, Vivek

2017-07-30

Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

76 FR 34953 - Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... Corporation Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program... Corporation (FCIC), operating through the Risk Management Agency (RMA), announces its intent to award... same time as funding availability for similar but separate program, the Risk Management Education and...

Different type 2 diabetes risk assessments predict dissimilar numbers at ‘high risk’: a retrospective analysis of diabetes risk-assessment tools

PubMed Central

Gray, Benjamin J; Bracken, Richard M; Turner, Daniel; Morgan, Kerry; Thomas, Michael; Williams, Sally P; Williams, Meurig; Rice, Sam; Stephens, Jeffrey W

2015-01-01

Background Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under-reported, however, whether a different risk tool alters the predicted risk of an individual. Aim This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. Design and setting Cross-sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. Method Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes®, Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. Results Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at ‘high risk’ followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). Conclusion The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes. PMID:26541180

Individual-Level Risk Factors of Incarcerated Youth

ERIC Educational Resources Information Center

Pyle, Nicole; Flower, Andrea; Fall, Anna Mari; Williams, Jacob

2016-01-01

This systematic review sought to understand the individual characteristics of incarcerated youth within the major risk factor domains identified by the U.S. Office of Juvenile Justice and Delinquency Prevention (OJJDP). A comprehensive search of the literature from 1979 to 2013 identified 85 articles of individual-level risk characteristics that…

The occurrence of high-risk factors for hearing loss in very-low-birth-weight neonates: a retrospective exploratory study of targeted hearing screening.

PubMed

Kanji, Amisha; Khoza-Shangase, Katijah

2012-12-01

The current study aimed at determining the type and frequency of high-risk factors for hearing loss in a group of very-low-birth-weight (VLBW) neonates in a tertiary hospital in South Africa with the objective of collating evidence that could be used in arguing for or against revisiting targeted hearing screening in developing countries. Furthermore, the study aimed at investigating the relationship between the identified high-risk factors and hearing screening results. In a retrospective data review design, data were collated from files from the VLBW project; this included hearing screening records, as well as records from participant medical and audiology files. Records of 86 neonates with birth weights ranging between 680 g and 1500 g were reviewed. Findings indicated that neonatal jaundice, exposure to human immunodeficiency virus (HIV), mechanical or assisted ventilation, and neonatal intensive care unit stay greater than 48 hours were the most frequently occurring high-risk factors for hearing loss in the current sample. These factors are consistent with those listed in the high-risk register of the Health Professions Council of South Africa for the South African context. Findings confirm the complexity of risk factors, and the influence that a variety of factors such as poor follow-up or return rate might have on the implementation of early hearing detection and intervention. The importance of establishing context-specific risk factors for effective implementation of targeted screening protocols where niversal newborn hearing screening is not yet a reality was highlighted by the current study.

Cancer risk awareness and screening uptake in individuals at higher risk for colon cancer: a cross-sectional study

PubMed Central

Salimzadeh, Hamideh; Bishehsari, Faraz; Delavari, Alireza; Barzin, Gilda; Amani, Mohammad; Majidi, Azam; Sadjadi, Alireza; Malekzadeh, Reza

2016-01-01

Objective We aimed to measure cancer knowledge and feasibility of a screening colonoscopy among a cohort of individuals at higher risk of colon cancer. Methods This study was conducted as part of an ongoing screening cohort, in which first degree relatives (FDRs) of patients with colon cancer are invited to participate in a free of charge screening colonoscopy. We enrolled 1017 FDRs in the study between 2013 and 2014 measuring their data on demographics, cancer knowledge and colonoscopy uptake. A p value of <0.05 was considered statistically significant. Results The relative's mean age was 48.7 years. Only about 28% of FDRs were aware of their increased risk for cancer, near 35.0% had ever heard about colonoscopy with 22% aware of the correct age to start screening. Comparing cancer knowledge of FDRs at high risk versus those at moderate risk, we recorded non-significant differences (p>0.05). Almost two-thirds of FDRs expressed willingness to undergo a colonoscopy and 49.2% completed the procedure, of which 12.8% had advanced neoplasm. Conclusions Our data indicated that remarkable numbers of FDRs were not still informed of their cancer risk or never received a physician recommendation for screening. The desirable uptake at first invitation, which would be higher over successive invitations, supports the feasibility of a family-based recruitment approach for early screening. This has promising implications to introduce targeted screening colonoscopy into the healthcare system in Iran and other developing nations. PMID:27998901

Public Health Implications of Recommendations to Individualize Glycemic Targets in Adults With Diabetes

PubMed Central

Laiteerapong, Neda; John, Priya M.; Nathan, Aviva G.; Huang, Elbert S.

2013-01-01

OBJECTIVE To estimate how many U.S. adults with diabetes would be eligible for individualized A1C targets based on 1) the 2012 American Diabetes Association (ADA) guideline and 2) a published approach for individualized target ranges. RESEARCH DESIGN AND METHODS We studied adults with diabetes ≥20 years of age from the National Health and Nutrition Examination Survey 2007–2008 (n = 757). We assigned A1C targets based on duration, age, diabetes-related complications, and comorbid conditions according to 1) the ADA guideline and 2) a strategy by Ismail-Beigi focused on setting target ranges. We estimated the number and proportion of adults with each A1C target and compared individualized targets to measured levels. RESULTS Using ADA guideline recommendations, 31% (95% CI 27–34%) of the U.S. adult diabetes population would have recommended A1C targets of <7.0%, and 69% (95% CI 66–73%) would have A1C targets less stringent than <7.0%. Using the Ismail-Beigi strategy, 56% (51–61%) would have an A1C target of ≤7.0%, and 44% (39–49%) would have A1C targets less stringent than <7.0%. If a universal A1C <7.0% target were applied, 47% (41–54%) of adults with diabetes would have inadequate glycemic control; this proportion declined to 30% (26–36%) with the ADA guideline and 31% (27–36%) with the Ismail-Beigi strategy. CONCLUSIONS Using individualized glycemic targets, about half of U.S. adults with diabetes would have recommended A1C targets of ≥7.0% but one-third would still be considered inadequately controlled. Diabetes research and performance measurement goals will need to be revised in order to encourage the individualization of glycemic targets. PMID:22961575

Coping strategies and self-esteem in the high-risk offspring of bipolar parents.

PubMed

Goodday, Sarah M; Bentall, Richard; Jones, Steven; Weir, Arielle; Duffy, Anne

2018-03-01

This study investigated whether there were differences in coping strategies and self-esteem between offspring of parents with bipolar disorder (high-risk) and offspring of unaffected parents (control), and whether these psychological factors predicted the onset and recurrence of mood episodes. High-risk and control offspring were followed longitudinally as part of the Flourish Canadian high-risk bipolar offspring cohort study. Offspring were clinically assessed annually by a psychiatrist using semi-structured interviews and completed a measure of coping strategies and self-esteem. In high-risk offspring, avoidant coping strategies significantly increased the hazard of a new onset Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised mood episode or recurrence (hazard ratio: 1.89, p = 0.04), while higher self-esteem significantly decreased this hazard (hazard ratio: 2.50, p < 0.01). Self-esteem and avoidant coping significantly interacted with one another ( p < 0.05), where the risk of a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised new onset mood episode or recurrence was only significantly increased among high-risk offspring with both high avoidant coping and low self-esteem. A reduction of avoidant coping strategies in response to stress and improvement of self-esteem may be useful intervention targets for preventing the new onset or recurrence of a clinically significant mood disorder among individuals at high familial risk.

Dysphagia in individuals with tetraplegia: incidence and risk factors

PubMed Central

Shem, Kazuko; Castillo, Kathleen; Wong, Sandra; Chang, James

2011-01-01

Background/objective Dysphagia following cervical spinal cord injury (SCI) can increase risk for pulmonary complications that may delay the rehabilitative process. The objective of this study was to identify risk factors for dysphagia after cervical SCI. Design Prospective cohort study. Methods Individuals with cervical SCI within 31 days of injury underwent a bedside swallow evaluation (BSE) followed by a videofluoroscopy swallow study (VFSS) within 72 hours of the BSE. Subjects were diagnosed as having dysphagia if they had positive findings in either BSE or VFSS. Results Twenty-nine patients (7 female and 22 male) were enrolled. Of these, 21 (72%) had high cervical tetraplegia (C4 or higher) and 8 (38%) had lower cervical tetraplegia. A tracheostomy was present in 18 (62%) patients; 15 (52%) subjects were on ventilators. Dysphagia was diagnosed in 12 (41%) subjects. Dysphagia was noted in 62% of the subjects with tracheostomy and 53% of the subjects on the ventilator, but only tracheostomy resulted in a statistically significant association with dysphagia (P = 0.047). All three subjects who had nasogastric tubes were diagnosed with dysphagia (P = 0.029). The relationships between dysphagia and gender, high versus low tetraplegia, presence of halo or collar, head injury, and ventilator use were not statistically significant, but age was a significant risk factor (P = 0.028). Conclusions Dysphagia is present in about 41% of individuals with acute tetraplegia. Only age, tracheostomy, and nasogastric tubes were identified as significant risk factors for dysphagia for individuals with tetraplegia. No relationship between dysphagia and level of SCI, spine surgery, collar, and ventilator use was found to exist. PMID:21528631

Affective functioning among early adolescents at high and low familial risk for depression and their mothers: A focus on individual and transactional processes across contexts

PubMed Central

McMakin, Dana L.; Burkhouse, Katie L.; Olino, Thomas M.; Siegle, Greg J.; Dahl, Ronald E.; Silk, Jennifer S.

2013-01-01

This study aimed to characterize affective functioning in families of youth at high familial risk for depression, with particular attention to features of affective functioning that appear to be critical to adaptive functioning but have been underrepresented in prior research including: positive and negative affect across multiple contexts, individual and transactional processes, and affective flexibility. Interactions among early adolescents (ages 9-14) and their mothers were coded for affective behaviors across both positive and negative contexts. Primary analyses compared never-depressed youth at high (n=44) and low (n=57) familial risk for depression. The high risk group showed a relatively consistent pattern for low positive affect across negative and positive contexts at both the individual and transactional level. In contrast to prior studies focusing on negative affect that did not support disruptions in negative affect, the data from this study suggest variability by context: (i.e. increased negativity in a positive, but not negative, context) and individual vs. transactional processes (e.g., negative escalation). Findings are discussed in concert with attention to affect flexibility, contextual and transactional factors. PMID:21744058

Risk assessment of Pakistani individuals for diabetes (RAPID).

PubMed

Riaz, Musarrat; Basit, Abdul; Hydrie, Muhammad Zafar Iqbal; Shaheen, Fariha; Hussain, Akhtar; Hakeem, Rubina; Shera, Abdus Samad

2012-12-01

To develop and evaluate a risk score to predict people at high risk of developing type 2 diabetes in Pakistan. Cross sectional data regarding primary prevention of diabetes in Pakistan. Diabetes risk score was developed by using simple parameters namely age, waist circumference, and family history of diabetes. Odds ratios of the model were used to assign a score value for each variable and the diabetes risk score was calculated as the sum of those scores. We externally validated the score using two data from 1264 subjects and 856 subjects aged 25 years and above from two separate studies respectively. Validating this score using the first data from the second screening study gave an area under the receive operator characteristics curve [AROC] of 0.758. A cut point of 4 had a sensitivity of 47.0% and specificity of 88% and in the second data AROC is 0.7 with 44% sensitivity and 89% specificity. A simple diabetes risk score, based on a set of variables can be used for the identification of high risk individuals for early intervention to delay or prevent type 2 diabetes in Pakistani population. Copyright © 2012 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Characterizing and reaching high-risk drinkers using audience segmentation.

PubMed

Moss, Howard B; Kirby, Susan D; Donodeo, Fred

2009-08-01

Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment, including where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions, and research efforts. We described the results of a segmentation analysis of those individuals who self-reported to consume 5 or more drinks per drinking episode at least twice in the last 30 days. The study used the proprietary PRIZM (Claritas, Inc., San Diego, CA) audience segmentation database merged with the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top 10 of the 66 PRIZM audience segments for this risky drinking pattern are described. For five of these segments we provided additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers resided. The top 10 audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge-drinking behavior is referred to as the "Cyber Millenials." This cluster is characterized as "the nation's tech

Inter-Individual Variability in High-Throughput Risk Prioritization of Environmental Chemicals (Sot)

EPA Science Inventory

We incorporate realistic human variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which have...

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.

PubMed

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S; Johnson, Kipp W; Ze, Yi; Tomlinson, Max S; Readhead, Ben; Dudley, Joel T; Kullo, Iftikhar J

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease.

How temporary insurance for high-risk individuals may play out under health reform.

PubMed

Chollet, Deborah J

2010-06-01

The Patient Protection and Affordable Care Act guarantees that people with health problems will be able to buy private health insurance as of 2014. In the interim, a new federal high-risk program will accept those who are denied private insurance and have not found coverage from any other source. Such sources include a state high-risk pool or, in a handful of states, a designated carrier of last resort. However, restricted eligibility for the federal program suggests that state high-risk pools, in particular, will continue to be critical yet problematic sources of coverage for the next few years.

Nonverbal dominance behavior among individuals at risk for mania.

PubMed

Bartholomew, Morgan E; Johnson, Sheri L

2014-04-01

Research suggests that people with bipolar disorder may be highly motivated to attain dominance and may over-estimate their social power (Johnson and Carver, 2012). This manic temperament may provide an adaptive advantage in the pursuit of dominance and leadership (Akiskal and Akiskal, 1992). It was hypothesized that people at high risk for bipolar disorder, as defined by the Hypomanic Personality Scale (HPS), would fail to assume a submissive role when it was appropriate to do so. Participants (81 undergraduates) completed an image description task with a confederate. Participants were randomly assigned to interact with a confederate who assumed one of three nonverbal postures: dominant (expanded), neutral, or submissive (constricted). Nonverbal dominance behavior was defined as the rate at which participants expanded their body span during the task. Consistent with hypotheses, an ANOVA indicated an interaction of Mania risk x Dominance condition on body expansion. Whereas participants with low mania risk (HPS scores) adapted complementary behavior in response to the confederate, participants with high mania risk demonstrated a consistently dominant (expanded) nonverbal posture. A major limitation of this study is the use of an analog measure of mania risk in place of clinical diagnoses. In this experiment, participants at high risk for mania maintained a dominant posture even when submissiveness would have been more appropriate. It is argued that persistent dominance behavior may play an important role in the interpersonal interactions of individuals at risk for bipolar disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

The Risk of Hepatocellular Carcinoma Among Individuals With Acquired Immunodeficiency Syndrome in the United States

PubMed Central

Sahasrabuddhe, Vikrant V.; Shiels, Meredith S.; McGlynn, Katherine A.; Engels, Eric A.

2014-01-01

BACKGROUND Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). METHODS The authors analyzed population-based registry linkage data from the US HIV/AIDS Cancer Match Study (1980–2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category. RESULTS Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5–4.3). Although HCC incidence increased steadily across calendar periods (Ptrend < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5–3.9) between the monotherapy/dual therapy era (1990–1995) and the recent highly active antiretroviral therapy era (2001–2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (Ptrend < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8–2.8). CONCLUSIONS HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV-infected population. PMID:22736272

The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States.

PubMed

Sahasrabuddhe, Vikrant V; Shiels, Meredith S; McGlynn, Katherine A; Engels, Eric A

2012-12-15

Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The authors analyzed population-based registry linkage data from the US HIV/AIDS Cancer Match Study (1980-2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category. Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5-4.3). Although HCC incidence increased steadily across calendar periods (P(trend) < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5-3.9) between the monotherapy/dual therapy era (1990-1995) and the recent highly active antiretroviral therapy era (2001-2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (P(trend) < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8-2.8). HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV-infected population. Published 2012 American Cancer Society.

Diagnostic and Prognostic Significance of DSM-5 Attenuated Psychosis Syndrome in Services for Individuals at Ultra High Risk for Psychosis.

PubMed

Fusar-Poli, Paolo; De Micheli, Andrea; Cappucciati, Marco; Rutigliano, Grazia; Davies, Cathy; Ramella-Cravaro, Valentina; Oliver, Dominic; Bonoldi, Ilaria; Rocchetti, Matteo; Gavaghan, Lauren; Patel, Rashmi; McGuire, Philip

2018-02-15

The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown. Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested. In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%-35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value. The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Developmental changes and individual differences in risk and perspective taking in adolescence.

PubMed

Crone, Eveline A; Bullens, L; van der Plas, E A A; Kijkuit, E J; Zelazo, P D

2008-01-01

Despite the assumed prevalence of risk-taking behavior in adolescence, the laboratory evidence of risk taking remains scarce, and the individual variation poorly understood. Drawing from neuroscience studies, we tested whether risk and reward orientation are influenced by the perspective that adolescents take when making risky decisions. Perspective taking was manipulated by cuing participants prior to each choice whether the decision was made for "self," or from the perspective of an "other" (the experimenter in Experiment 1; a hypothetical peer in Experiment 2). In Experiment 1, we show a developmental decrease in risk-taking behavior across different stages of adolescence. In addition, all age groups made fewer risky choices for the experimenter, but the difference between self and other was larger in early adolescence. In Experiment 2, we show that high sensation-seeking (SS) adolescents make more risky choices than low SS adolescents, but both groups make a similar differentiation for other individuals (low risk-taking or high risk-taking peers). Together, the results show that younger adolescents and high SS adolescents make more risky choices for themselves, but can appreciate that others may make fewer risky choices. The developmental change toward more rational decisions versus emotional, impulsive decisions may reflect, in part, more efficient integration of others' perspectives into one's decision making. These developmental results are discussed regarding brain systems important for risk taking and perspective taking.

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

PubMed Central

Fusar-Poli, Paolo; Schultze-Lutter, Frauke; Cappucciati, Marco; Rutigliano, Grazia; Bonoldi, Ilaria; Stahl, Daniel; Borgwardt, Stephan; Riecher-Rössler, Anita; Addington, Jean; Perkins, Diana O.; Woods, Scott W.; McGlashan, Thomas; Lee, Jimmy; Klosterkötter, Joachim; Yung, Alison R.; McGuire, Philip

2016-01-01

Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis.

PubMed

Fusar-Poli, Paolo; Schultze-Lutter, Frauke; Cappucciati, Marco; Rutigliano, Grazia; Bonoldi, Ilaria; Stahl, Daniel; Borgwardt, Stephan; Riecher-Rössler, Anita; Addington, Jean; Perkins, Diana O; Woods, Scott W; McGlashan, Thomas; Lee, Jimmy; Klosterkötter, Joachim; Yung, Alison R; McGuire, Philip

2016-05-01

The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR-). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR-: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%-24%, I (2) = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = -.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = -1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = -.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38 monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38 monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk for psychosis. © The Author 2015. Published by

180. Predictors of Being ‘Most Impacted’ by Psychosis in Self-Identity Among Individuals at Clinical High Risk for Psychosis

PubMed Central

Yang, Lawrence; McFarlane, William; Seidman, Larry J.; Corcoran, Cheryl; Link, Bruce; Bryang, Caitlin; Kline, Emily; Cloutier, Anna; Woodberry, Kristen; Kennedy, Leda

2017-01-01

Abstract Background: While the clinical high risk state for psychosis syndrome (CHR) offers substantial benefits, being identified as CHR may also elicit stigma. Specifically, the comparative impacts upon youths’ self-concept of being “told” by others, versus initial self-identification of being at-risk (i.e., what CHR youth themselves “think”) remains unknown. Methods: Stigma assessments were conducted with 100 CHR individuals in an NIH-funded study at Columbia Medical Center, Harvard Medical Center, and Maine Medical Center from 2011 to present. Individuals were assessed whether they had been “told” by health professionals or school officials outside of the specialized CHR clinic that they were at risk and whether they self-identified or themselves “thought” they were at risk. Logistic regression models were used to assess these 2 variables’ effects upon CHR youth being “most impacted” by a psychotic disorder. Results: When examining each variable singly, being told was associated with a 4.67 increased likelihood of being most impacted by psychosis risk (P < .05). Likewise, thinking one was at risk for psychosis when examined alone was associated with a 3.87 increased likelihood of being most impacted by psychosis-risk (P < .05). When entering both variables as predictors, being told remained associated with a 3.61 greater likelihood of being most impacted by psychosis-risk (P < .05). In this model, thinking one was at risk for psychosis was no longer a significant predictor. These results were consistent even after controlling for sociodemographics, clinical variables, and site differences. Conclusion: When both told and think were considered, only being told that one was CHR remained associated with over a 3-fold greater likelihood of being most impacted by psychosis risk. This highlights the importance of “labeling by others,” including by mental health professionals and school officials who are not part of specialized CHR services

The importance of reaching lipid targets: statins and the prevention of atherosclerosis.

PubMed

Schwandt, P

2003-06-01

To help prevent the development of coronary heart disease (CHD), the European and NCEP guidelines have recommended target cholesterol levels for all individuals. Lifestyle changes are advocated for individuals not achieving these targets. Intervention with lipid-modifying agents may be required for patients at high risk of a cardiovascular event and statins are generally recognised as first-line therapy. Unfortunately, large numbers of patients at risk of cardiovascular events are not being treated to the guideline targets. Primary care physicians are in a good position to improve lipid management by assessing risk factors, implementing lipid management strategies, monitoring whether targets are being reached and amending treatment appropriately. Furthermore, by educating and motivating patients,primary care physicians may improve compliance with lifestyle changes and medication. These approaches may help more patients to achieve recommended lipid levels and prevent the development of cardiovascular disease.

Impaired decision-making under risk in individuals with alcohol dependence

PubMed Central

Brevers, Damien; Bechara, Antoine; Cleeremans, Axel; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

2014-01-01

Background Alcohol dependence is associated with poor decision-making under ambiguity, that is, when decisions are to be made in the absence of known probabilities of reward and loss. However, little is known regarding decisions made by individuals with alcohol dependence in the context of known probabilities (decision under risk). In this study, we investigated the relative contribution of these distinct aspects of decision making to alcohol dependence. Methods Thirty recently detoxified and sober asymptomatic alcohol-dependent individuals, and thirty healthy control participants were tested for decision-making under ambiguity (using the Iowa Gambling Task), and decision-making under-risk (using the Cups Task and Coin Flipping Task). We also tested their capacities for working memory storage (Digit-span Forward), and dual-tasking (Operation-span Task). Results Compared to healthy control participants, alcohol-dependent individuals made disadvantageous decisions on the Iowa Gambling Task, reflecting poor decisions under ambiguity. They also made more risky choices on the Cups and Coin Flipping Tasks reflecting poor decision-making under risk. In addition, alcohol-dependent participants showed some working memory impairments, as measured by the dual tasking, and the degree of this impairment correlated with high-risk decision-making, thus suggesting a relationship between processes sub-serving working memory and risky decisions. Conclusion These results suggest that alcohol dependent individuals are impaired in their ability to decide optimally in multiple facets of uncertainty (i.e., both risk and ambiguity), and that at least some aspects of these deficits are linked to poor working memory processes. PMID:24948198

Gender differences in predicting high-risk drinking among undergraduate students.

PubMed

Wilke, Dina J; Siebert, Darcy Clay; Delva, Jorge; Smith, Michael P; Howell, Richard L

2005-01-01

The purpose of this study was to examine gender differences in college students' high-risk drinking as measured by an estimated blood alcohol concentration (eBAC) based on gender, height, weight, self-reported number of drinks, and hours spent drinking. Using a developmental/contextual framework, high-risk drinking is conceptualized as a function of relevant individual characteristics, interpersonal factors, and contextual factors regularly mentioned in the college drinking literature. Individual characteristics include race, gender, and age; interpersonal characteristics include number of sexual partners and having experienced forced sexual contact. Finally, contextual factors include Greek membership, living off-campus, and perception of peer drinking behavior. This study is a secondary data analysis of 1,422 students at a large university in the Southeast. Data were gathered from a probability sample of students through a mail survey. A three-step hierarchical logistic regression analysis showed gender differences in the pathway for high-risk drinking. For men, high-risk drinking was predicted by a combination of individual characteristics and contextual factors. For women, interpersonal factors, along with individual characteristics and contextual factors, predicted high-risk drinking, highlighting the importance of understanding female sexual relationships and raising questions about women's risk-taking behavior. Implications for prevention and assessment are discussed.

Management of high-risk perioperative systems.

PubMed

Dain, Steven

2006-06-01

The perioperative system is a complex system that requires people, materials, and processes to come together in a highly ordered and timely manner. However, when working in this high-risk system, even well-organized, knowledgeable, vigilant, and well-intentioned individuals will eventually make errors. All systems need to be evaluated on a continual basis to reduce the risk of errors, make errors more easily recognizable, and provide methods for error mitigation. A simple approach to risk management that may be applied in clinical medicine is discussed.

Preferences regarding targeted education and risk assessment in people with a family history of major depressive disorder.

PubMed

Quinn, Veronica; Meiser, Bettina; Wilde, Alex; Cousins, Zoe; Barlow-Stewart, Kristine; Mitchell, Philip B; Schofield, Peter R

2014-10-01

Genetic testing for susceptibility to major depressive disorder (MDD) is not available for clinical use at present. Given this, family history remains the best predictor for development of MDD, and family-history-based risk assessment and information about familial aspects of MDD may be useful to clients at increased risk for MDD attending for genetic counseling. This study uses a mixed-methods design to assess the information needs and preferences of people at increased familial risk for MDD. Telephone interviews were conducted with 23 individuals, who had at least one first-degree relative with MDD and were recruited through advertisements placed on depression education websites. The most preferred way to access depression information was via the internet (87 % of participants), although this preference may have been due to the internet-based recruitment method. The second most preferred dissemination strategy (56 %) was face-to-face delivery through a health professional, including genetic counselors. Individuals reported a need for information about etiology and development of MDD, reproductive decision-making, early detection of symptoms and risk-reducing strategies. Nearly all participants expressed an interest in risk assessment. The present study found evidence of a high level of interest for information targeted to people at increased familial risk for MDD. Genetic counselors are likely to be called upon increasingly to provide supportive counseling to assist clients at increased familial risk in interpreting and contextualizing such information once it becomes available.

How effective are strategies for non-communicable disease prevention and control in a high risk population in a developing country? Isfahan Healthy Heart Programme

PubMed Central

Baghaei, Abdolmehdi; Rabiei, Katayoun; Gharipour, Mojgan; Tavasoli, Ali Akbar; Shirani, Shahin; Bahonar, Ahamad; Davarpanah, Amir Hossein; Ramezani, Mohammad Arash; Kelishadi, Roya

2010-01-01

Introduction The Isfahan Healthy Heart Programme (IHHP) is a community-based programme for non-communicable diseases prevention and control using both a population and high risk approach in Iran. This study demonstrated the efficacy of IHHP interventional strategies to improve lifestyle behaviours in a population at risk for developing cardiovascular diseases. Material and methods Healthy Lifestyle for NCDs High Risk Population is one of ten projects of IHHP. High risk individuals were defined as those who have at least one risk factor for developing coronary artery disease (CAD). Changes of behavioural indicators have been compared between two areas with a survey after 5 years of intervention. Results Among high risk individuals in the intervention and reference areas, 77.8% and 82.5% had at least one major risk factor for CAD. The prevalence of major risk factors for CAD (except cigarette smoking) was decreased in both intervention and reference areas during 5 years of intervention and the pattern of diet and physical activity was improved. Conclusions Interventional activities in IHHP targeting the high risk population seem to be effective in improving lifestyle behaviour, increasing awareness and control of risk factors of the high risk population. PMID:22371716

Contributions of early cortical processing and reading ability to functional status in individuals at clinical high risk for psychosis.

PubMed

Carrión, Ricardo E; Cornblatt, Barbara A; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M; Olsen, Ruth H; Javitt, Daniel C

2015-05-01

There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. The sample consisted of 34 CHR individuals and 33 healthy comparison subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. Copyright © 2015 Elsevier B.V. All rights reserved.

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

PubMed

Quaife, Samantha L; Ruparel, Mamta; Beeken, Rebecca J; McEwen, Andy; Isitt, John; Nolan, Gary; Sennett, Karen; Baldwin, David R; Duffy, Stephen W; Janes, Samuel M; Wardle, Jane

2016-04-20

Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

DOE PAGES

Cucinotta, Francis A.; Cacao, Eliedonna

2017-05-12

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

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

Cucinotta, Francis A.; Cacao, Eliedonna

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

Comparing probabilistic microbial risk assessments for drinking water against daily rather than annualised infection probability targets.

PubMed

Signor, R S; Ashbolt, N J

2009-12-01

Some national drinking water guidelines provide guidance on how to define 'safe' drinking water. Regarding microbial water quality, a common position is that the chance of an individual becoming infected by some reference waterborne pathogen (e.g. Cryptsporidium) present in the drinking water should < 10(-4) in any year. However the instantaneous levels of risk to a water consumer vary over the course of a year, and waterborne disease outbreaks have been associated with shorter-duration periods of heightened risk. Performing probabilistic microbial risk assessments is becoming commonplace to capture the impacts of temporal variability on overall infection risk levels. A case is presented here for adoption of a shorter-duration reference period (i.e. daily) infection probability target over which to assess, report and benchmark such risks. A daily infection probability benchmark may provide added incentive and guidance for exercising control over short-term adverse risk fluctuation events and their causes. Management planning could involve outlining measures so that the daily target is met under a variety of pre-identified event scenarios. Other benefits of a daily target could include providing a platform for managers to design and assess management initiatives, as well as simplifying the technical components of the risk assessment process.

Sources of HIV-Prevention Information for Individuals at High Risk.

ERIC Educational Resources Information Center

Sagrestano, Lynda M.; Heiss-Wendt, Renate M.; Mizan, Ainon N.; Kittleson, Mark J.; Sarvela, Paul D.

2001-01-01

Identified the best methods of reaching people at high risk with HIV-prevention messages. Data from men who had sex with men, injection drug users, sex workers, HIV-positive people, heterosexuals, migrant workers, and perinatal women indicated that over 70 percent were exposed to HIV-prevention messages, though sources of exposure varied by risk…

The management of women at high risk for the development of breast cancer: risk estimation and preventative strategies.

PubMed

Sakorafas, George H

2003-04-01

Despite recent progress in the diagnostic and therapeutic approaches to the management of women with breast cancer, at least one third of these women will ultimately die from their disease. This resulted in a new focus on breast cancer prevention, especially for the woman designed as "high-risk". The continuing challenge is to identify reliable markers to accurately recognize this group of women, who are more likely to develop breast cancer. This will allow a targeted specific counseling and the application of preventative measures. Management options in high-risk women include intensive cancer surveillance, chemoprevention (mainly using tamoxifen), and prophylactic surgery (preferentially total mastectomy). Cancer surveillance is the most preferred management option. Currently, no data exists comparing prophylactic mastectomy vs. surveillance vs. chemoprevention. Thus, despite significant advances in our understanding of the biology of breast cancer, many questions remain unanswered concerning the optimal management of the high-risk woman. Patient counseling has a central role in the decision-making process and should be based on a multidisciplinary approach. The individual woman will make the final decision based on the amount of risk she is willing to accept. It is hoped that other preventative methods, such as gene therapy based on an accurate identification of specific genetic changes, will be developed in the future.

The Neural Correlates of Health Risk Perception in Individuals with Low and High Numeracy

ERIC Educational Resources Information Center

Vogel, Stephan E.; Keller, Carmen; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz; Dohle, Simone; Siegrist, Michael; Grabner, Roland H.

2016-01-01

The ability to use numerical information in different contexts is a major goal of mathematics education. In health risk communication, outcomes of a medical condition are frequently expressed in probabilities. Difficulties to accurately represent probability information can result in unfavourable medical decisions. To support individuals with…

Non-targeted effects of ionizing radiation–implications for low dose risk

PubMed Central

Kadhim, Munira; Salomaa, Sisko; Wright, Eric; Hildebrandt, Guido; Belyakov, Oleg V.; Prise, Kevin M.; Little, Mark P.

2014-01-01

Non-DNA targeted effects of ionizing radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionizing radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the Non-targeted effects of ionizing radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. PMID:23262375

Incorporating additional targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany M

2015-01-01

Recently, researchers have investigated the effectiveness and efficiency of presenting secondary targets during learning trials for individuals with autism spectrum disorder (ASD). This instructional method may be more efficient than typical methods used with learners with ASD, because learners may acquire secondary targets without additional instruction. This review will discuss the recent literature on providing secondary targets during teaching trials for individuals with ASD, identify common aspects and results among these studies, and identify areas for future research. © Society for the Experimental Analysis of Behavior.

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease

PubMed Central

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S.; Johnson, Kipp W.; Ze, Yi; Tomlinson, Max S.; Readhead, Ben; Dudley, Joel T.; Kullo, Iftikhar J.

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease. PMID:29888052

Risk-Based School Inspections: Impact of Targeted Inspection Approaches on Dutch Secondary Schools

ERIC Educational Resources Information Center

Ehren, Melanie C.; Shackleton, Nichola

2016-01-01

In most countries, publicly funded schools are held accountable to one inspectorate and are judged against agreed national standards. Many inspectorates of education have recently moved towards more proportional risk-based inspection models, targeting high-risk schools for visits, while schools with satisfactory student attainment levels are…

Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c Targets in Patients with Type 2 Diabetes Mellitus.

PubMed

Bannister, Margaret; Berlanga, Jenny

2016-09-01

Type 2 diabetes is a progressive condition that may require the combination of three oral treatments to achieve optimal glycemic management to prevent microvascular and macrovascular complications whilst minimizing the risk of acute complications and side effects or adverse reactions to treatments. With the widening availability of treatment options and increasing importance of individualized treatment pathways, including personalized HbA1c targets, this article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions.

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

PubMed

Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen D A; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G

2018-01-01

Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

PubMed

Quach, Caroline

2014-12-01

Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual risks and social determinants.

PubMed

Goldhaber-Fiebert, Jeremy D; Jeon, Christie Y; Cohen, Ted; Murray, Megan B

2011-04-01

A growing body of evidence supports the role of type 2 diabetes as an individual-level risk factor for tuberculosis (TB), though evidence from developing countries with the highest TB burdens is lacking. In developing countries, TB is most common among the poor, in whom diabetes may be less common. We assessed the relationship between individual-level risk, social determinants and population health in these settings. We performed individual-level analyses using the World Health Survey (n = 124,607; 46 countries). We estimated the relationship between TB and diabetes, adjusting for gender, age, body mass index, education, housing quality, crowding and health insurance. We also performed a longitudinal country-level analysis using data on per-capita gross domestic product and TB prevalence and incidence and diabetes prevalence for 1990-95 and 2003-04 (163 countries) to estimate the relationship between increasing diabetes prevalence and TB, identifying countries at risk for disease interactions. In lower income countries, individuals with diabetes are more likely than non-diabetics to have TB [univariable odds ratio (OR): 2.39; 95% confidence interval (CI): 1.84-3.10; multivariable OR: 1.81; 95% CI: 1.37-2.39]. Increases in TB prevalence and incidence over time were more likely to occur when diabetes prevalence also increased (OR: 4.7; 95% CI: 1.0-22.5; OR: 8.6; 95% CI: 1.9-40.4). Large populations, prevalent TB and projected increases in diabetes make countries like India, Peru and the Russia Federation areas of particular concern. Given the association between diabetes and TB and projected increases in diabetes worldwide, multi-disease health policies should be considered.

Suicide risk in a representative sample of people receiving HIV care: Time to target most-at-risk populations (ANRS VESPA2 French national survey)

PubMed Central

Fressard, Lisa; Préau, Marie; Sagaon-Teyssier, Luis; Suzan-Monti, Marie; Guagliardo, Valérie; Mora, Marion; Roux, Perrine; Dray-Spira, Rosemary; Spire, Bruno

2017-01-01

Background Suicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care. Methods The ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors. Results Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk. Conclusions Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV. PMID:28192455

Suicide risk in a representative sample of people receiving HIV care: Time to target most-at-risk populations (ANRS VESPA2 French national survey).

PubMed

Carrieri, Maria Patrizia; Marcellin, Fabienne; Fressard, Lisa; Préau, Marie; Sagaon-Teyssier, Luis; Suzan-Monti, Marie; Guagliardo, Valérie; Mora, Marion; Roux, Perrine; Dray-Spira, Rosemary; Spire, Bruno

2017-01-01

Suicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care. The ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors. Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk. Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV.

Somatotype of the individuals with lower extremity amputation and its association with cardiovascular risk.

PubMed

Mozumdar, Arupendra; Roy, Subrata K

2008-03-01

Anthropometric somatotyping is one of the methods to describe the shape of the human body, which shows some associations with an individual's health and disease condition, especially with cardiovascular diseases (CVD). Individuals with lower extremity amputation (LEA) are known to be more vulnerable to the cardiovascular risk. The objectives of the present study are to report the somatotype of the individuals having lower extremity amputation, to study the possible variation in somatotype between two groups of amputated individuals, and to study the association between cardiovascular disease risk factor and somatotype components among individuals with locomotor disability. 102 adult male individuals with unilateral lower-extremity amputation residing in Calcutta and adjoining areas were investigated. The anthropometric data for somatotyping and data on cardiovascular risk traits (such as body mass index, blood pressure measurements, blood lipids) have been collected. The somatotyping technique of Carter & Heath (1990) has been followed. The result shows high mean values of endomorphy and mesomorphy components and a low mean value of the ectomorphy component among the amputated individuals having cardiovascular risks. The results of both discriminant analysis and logistic regression analysis show a significant relationship between somatotype components and CVD risk among the individuals with LEA. The findings of the present study support the findings of similar studies conducted on the normal population. Diagnosis of CVD risk condition through somatotyping can be utilized in prevention/treatment management for the individuals with LEA.

An individual risk prediction model for lung cancer based on a study in a Chinese population.

PubMed

Wang, Xu; Ma, Kewei; Cui, Jiuwei; Chen, Xiao; Jin, Lina; Li, Wei

2015-01-01

Early detection and diagnosis remains an effective yet challenging approach to improve the clinical outcome of patients with cancer. Low-dose computed tomography screening has been suggested to improve the diagnosis of lung cancer in high-risk individuals. To make screening more efficient, it is necessary to identify individuals who are at high risk. We conducted a case-control study to develop a predictive model for identification of such high-risk individuals. Clinical data from 705 lung cancer patients and 988 population-based controls were used for the development and evaluation of the model. Associations between environmental variants and lung cancer risk were analyzed with a logistic regression model. The predictive accuracy of the model was determined by calculating the area under the receiver operating characteristic curve and the optimal operating point. Our results indicate that lung cancer risk factors included older age, male gender, lower education level, family history of cancer, history of chronic obstructive pulmonary disease, lower body mass index, smoking cigarettes, a diet with less seafood, vegetables, fruits, dairy products, soybean products and nuts, a diet rich in meat, and exposure to pesticides and cooking emissions. The area under the curve was 0.8851 and the optimal operating point was obtained. With a cutoff of 0.35, the false positive rate, true positive rate, and Youden index were 0.21, 0.87, and 0.66, respectively. The risk prediction model for lung cancer developed in this study could discriminate high-risk from low-risk individuals.

Descriptive and numeric estimation of risk for psychotic disorders among affected individuals and relatives: implications for clinical practice.

PubMed

Austin, Jehannine C; Hippman, Catriona; Honer, William G

2012-03-30

Studies show that individuals with psychotic illnesses and their families want information about psychosis risks for other relatives. However, deriving accurate numeric probabilities for psychosis risk is challenging, and people have difficulty interpreting probabilistic information; thus, some have suggested that clinicians should use risk descriptors, such as "moderate" or "quite high", rather than numbers. Little is known about how individuals with psychosis and their family members use quantitative and qualitative descriptors of risk in the specific context of chance for an individual to develop psychosis. We explored numeric and descriptive estimations of psychosis risk among individuals with psychotic disorders and unaffected first-degree relatives. In an online survey, respondents numerically and descriptively estimated risk for an individual to develop psychosis in scenarios where they had: A) no affected family members; and B) an affected sibling. Participants comprised 219 affected individuals and 211 first-degree relatives participated. Affected individuals estimated significantly higher risks than relatives. Participants attributed all descriptors between "very low" and "very high" to probabilities of 1%, 10%, 25% and 50%+. For a given numeric probability, different risk descriptors were attributed in different scenarios. Clinically, brief interventions around risk (using either probabilities or descriptors alone) are vulnerable to miscommunication and potentially negative consequences-interventions around risk are best suited to in-depth discussion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quantifying links between stroke and risk factors: a study on individual health risk appraisal of stroke in a community of Chongqing.

PubMed

Wu, Yazhou; Zhang, Ling; Yuan, Xiaoyan; Wu, Yamin; Yi, Dong

2011-04-01

The objective of this study is to investigate the risk factors of stroke in a community in Chongqing by setting quantitative criteria for determining the risk factors of stroke. Thus, high-risk individuals can be identified and laid a foundation for predicting individual risk of stroke. 1,034 cases with 1:2 matched controls (2,068) were chosen from five communities in Chongqing including Shapingba, Xiaolongkan, Tianxingqiao, Yubei Road and Ciqikou. Participants were interviewed with a uniform questionnaire. The risk factors of stroke and the odds ratios of risk factors were analyzed with a logistic regression model, and risk exposure factors of different levels were converted into risk scores using statistical models. For men, ten risk factors including hypertension (5.728), family history of stroke (4.599), and coronary heart disease (5.404), among others, were entered into the main effect model. For women, 11 risk factors included hypertension (5.270), family history of stroke (4.866), hyperlipidemia (4.346), among others. The related risk scores were added to obtain a combined risk score to predict the individual's risk of stoke in the future. An individual health risk appraisal model of stroke, which was applicable to individuals of different gender, age, health behavior, disease and family history, was established. In conclusion, personal diseases including hypertension, diabetes mellitus, etc., were very important to the prevalence of stoke. The prevalence of stroke can be effectively reduced by changing unhealthy lifestyles and curing the positive individual disease. The study lays a foundation for health education to persuade people to change their unhealthy lifestyles or behaviors, and could be used in community health services.

The Risks of Missing the 2°C Target and the Risks of Framing the Target As 2°C

NASA Astrophysics Data System (ADS)

Nichols, L. H.

2014-12-01

The publication of IPCC AR5 has made it very clear that we are at risk of missing the 2°C target. It has also made it clear that the risks of missing this target would be very dire. But when read through a precautionary lens, it also illustrates potential risks of framing an appropriate climate target as 2°C. We ought to be doing all we can to limit the extent of climate change as much as possible, and framing our target as limiting warming to 2°C may mask the demandingness and urgency of addressing climate change aggressively and holistically. In this session I will summarize my work on what precaution demands in the face of climate change and discuss how it applies to AR5. I argue for a Catastrophic Precautionary Principle that gives us strong moral reasons to take precautionary measures against threats of catastrophe, such as those posed by climate change. I will explain how the IPCC's discussion of the five reasons for concern about climate change support a strong moral argument that we ought to be taking a much more precautionary approach to climate policy than is currently evidenced by UNFCCC agreements and domestic policies around the world. While AR5 supports the conclusion that we should not risk missing the 2°C target, it also supports reevaluating what our target - and more generally what our comprehensive approach to climate policy - should be. In this way, I will discuss the complex science-ethics-policy nexus and the role of climate science in guiding precautionary global climate policies.

Factors associated with experiences of genetic discrimination among individuals at risk for Huntington disease

PubMed Central

Bombard, Yvonne; Palin, JoAnne; Friedman, Jan M.; Veenstra, Gerry; Creighton, Susan; Paulsen, Jane S.; Bottorff, Joan L.; Hayden, Michael R.

2013-01-01

The purpose of this study was to identify factors that are associated with experiencing genetic discrimination (GD) among individuals at risk for Huntington disease (HD). Multivariable logistic regression analysis was used to examine factors associated with experiencing GD in data from a cross-sectional, self-report survey of 293 individuals at risk for HD. The study sample comprised 167 genetically tested respondents, and 66 who were not tested (80% response rate). Overall, individuals who learn they are at risk for HD at a younger age (OR = 3.1; 95% CI: 1.5–6.2; P = 0.002), are mutation-positive (OR = 2.8; 95% CI: 1.4–6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4–5.1; P = 0.002) are more likely to experience GD, particularly in insurance, family, and social settings. Further, younger age was associated with discrimination in insurance (OR = 0.97; 95% CI: 0.94–1.00; P = 0.038). This study provides evidence that some people who are at risk for HD were more likely to experience GD than others. Individuals who learned they are at risk for HD at a younger age and those who are mutation-positive were more likely to experience GD, particularly in insurance, family, and social settings. Younger individuals were more likely to experience discrimination in the insurance setting. Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD. PMID:21184581

Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation

PubMed Central

Moss, Howard B.; Kirby, Susan D.; Donodeo, Fred

2010-01-01

Background Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically-defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment; where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions and research efforts. Methods We describe the results of a segmentation analysis of those individuals who self-report consuming five or more drinks per drinking episode at least twice in the last 30-days. The study used the proprietary PRIZM™ audience segmentation database merged with Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top ten of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provide additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers reside. Results The top ten audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation's tech-savvy singles

Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals

PubMed Central

Dunlop, Malcolm G.; Tenesa, Albert; Farrington, Susan M.; Ballereau, Stephane; Brewster, David H.; Pharoah, Paul DP.; Schafmayer, Clemens; Hampe, Jochen; Völzke, Henry; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; von Holst, Susanna; Picelli, Simone; Lindblom, Annika; Jenkins, Mark A.; Hopper, John L.; Casey, Graham; Duggan, David; Newcomb, Polly; Abulí, Anna; Bessa, Xavier; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Niittymäki, Iina; Tuupanen, Sari; Karhu, Auli; Aaltonen, Lauri; Zanke, Brent W.; Hudson, Thomas J.; Gallinger, Steven; Barclay, Ella; Martin, Lynn; Gorman, Maggie; Carvajal-Carmona, Luis; Walther, Axel; Kerr, David; Lubbe, Steven; Broderick, Peter; Chandler, Ian; Pittman, Alan; Penegar, Steven; Campbell, Harry; Tomlinson, Ian; Houlston, Richard S.

2016-01-01

Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. In a large, multi-population study, we set out to assess the feasibility of CRC risk prediction using common genetic variant data, combined with other risk factors. We built a risk prediction model and applied it to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate colorectal cancer risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence colorectal cancer risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266), and in combination with gender, age and family history (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4,187 independent samples. 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. Results Median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10−16), confirmed in external validation sets (Sweden p=1.2×10−6, Finland p=2×10−5). Mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05–1.13). Discriminative performance was poor across the risk spectrum (area under curve (AUC) for genotypes alone - 0.57; AUC for genotype/age/gender/FH - 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion We show that genotype data provides additional information that complements age, gender and FH as risk factors. However, individualized genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential, since it

Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity.

PubMed

Zhong, Fanyi; Xu, Mengyang; Bruno, Richard S; Ballard, Kevin D; Zhu, Jiangjiang

2017-04-01

Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m 2 ) and women ( n = 40; 34.9 ± 6.7 kg/m 2 ), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to

Perceptions of Community HIV/STI Risk Among U.S Women Living in Areas with High Poverty and HIV Prevalence Rates.

PubMed

Blackstock, Oni J; Frew, Paula; Bota, Dorothy; Vo-Green, Linda; Parker, Kim; Franks, Julie; Hodder, Sally L; Justman, Jessica; Golin, Carol E; Haley, Danielle F; Kuo, Irene; Adimora, Adaora A; Rompalo, Anne; Soto-Torres, Lydia; Wang, Jing; Mannheimer, Sharon B

2015-08-01

Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community's HIV/STI risk. We explored perceptions of community HIV/STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women's HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/STI risk driven by structural factors.

Perceptions of Community HIV/ STI Risk Among U.S Women Living in Areas with High Poverty and HIV Prevalence Rates

PubMed Central

Blackstock, Oni J.; Frew, Paula; Bota, Dorothy; Vo-Green, Linda; Parker, Kim; Franks, Julie; Hodder, Sally L.; Justman, Jessica; Golin, Carol E.; Haley, Danielle F.; Kuo, Irene; Adimora, Adaora A.; Rompalo, Anne; Soto-Torres, Lydia; Wang, Jing; Mannheimer, Sharon B.

2015-01-01

Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community’s HIV/STI risk. We explored perceptions of community HIV/ STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women’s HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/ STI risk driven by structural factors. PMID:26320916

Nurse-coordinated multidisciplinary, family-based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: a paired, cluster-randomised controlled trial.

PubMed

Wood, D A; Kotseva, K; Connolly, S; Jennings, C; Mead, A; Jones, J; Holden, A; De Bacquer, D; Collier, T; De Backer, G; Faergeman, O

2008-06-14

Our aim was to investigate whether a nurse-coordinated multidisciplinary, family-based preventive cardiology programme could improve standards of preventive care in routine clinical practice. In a matched, cluster-randomised, controlled trial in eight European countries, six pairs of hospitals and six pairs of general practices were assigned to an intervention programme (INT) or usual care (UC) for patients with coronary heart disease or those at high risk of developing cardiovascular disease. The primary endpoints-measured at 1 year-were family-based lifestyle change; management of blood pressure, lipids, and blood glucose to target concentrations; and prescription of cardioprotective drugs. Analysis was by intention to treat. The trial is registered as ISRCTN 71715857. 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC, respectively. In patients with coronary heart disease who smoked in the month before the event, 136 (58%) in the INT and 154 (47%) in the UC groups did not smoke 1 year afterwards (difference in change 10.4%, 95% CI -0.3 to 21.2, p=0.06). Reduced consumption of saturated fat (196 [55%] vs 168 [40%]; 17.3%, 6.4 to 28.2, p=0.009), and increased consumption of fruit and vegetables (680 [72%] vs 349 [35%]; 37.3%, 18.1 to 56.5, p=0.004), and oily fish (156 [17%] vs 81 [8%]; 8.9%, 0.3 to 17.5, p=0.04) at 1 year were greatest in the INT group. High-risk individuals and partners showed changes only for fruit and vegetables (p=0.005). Blood-pressure target of less than 140/90 mm Hg was attained by both coronary (615 [65%] vs 547 [55%]; 10.4%, 0.6 to 20.2, p=0.04) and high-risk (586 [58%] vs 407 [41%]; 16.9%, 2.0 to 31.8, p=0.03) patients in the INT groups. Achievement of total cholesterol of less than 5 mmol/L did not differ between groups, but in high-risk patients the difference in change from baseline to 1 year was 12.7% (2.4 to 23.0, p=0.02) in favour of INT. In the hospital group

The Dual Participants: A High Risk Drinking Driver Target Group.

ERIC Educational Resources Information Center

Kline, Michael V.; And Others

1988-01-01

Studied dual participants (N=2,525), multiple offender drinking driver program participants who also attend non-drinking driver alcohol treatment programs. Findings support need for drinking driver programs to be aware of high risk dual participants and for alcohol-related treatment programs to provide drinking and driving education to all dual…

Objective Understanding of Front-of-Package Nutrition Labels among Nutritionally At-Risk Individuals

PubMed Central

Ducrot, Pauline; Méjean, Caroline; Julia, Chantal; Kesse-Guyot, Emmanuelle; Touvier, Mathilde; Fezeu, Léopold K.; Hercberg, Serge; Péneau, Sandrine

2015-01-01

In the ongoing debate about front-of-package (FOP) nutrition labels, little data exist regarding nutritionally at-risk populations, although they are critical targets of prevention programs. This study aimed to compare the impact of FOP labels on the ability to rank products according to their nutritional quality among French adults potentially at risk of poor dietary quality (N = 14,230). Four labels were evaluated: Guideline Daily Amounts (GDA), Multiple Traffic Lights (MTL), 5-Color Nutrition Label (5-CNL), Green Tick (Tick), along with a reference without label. Mixed models were used to assess how individual characteristics and FOP labels were associated with the ability to rank products. Older participants and those with a lower educational level, income, nutritional knowledge, and likelihood of reading nutrition facts were less skilled at ranking food products according to nutritional quality. Compared with individual characteristics, nutrition labels had an increased impact on food product ranking ability. Overall, 5-CNL corresponded to the highest rate of correct responses, followed by MTL, GDA, and Tick (p < 0.0001). The strongest impact of 5-CNL was observed among individuals with no nutritional knowledge (odds ratio (OR): 20.24; 95% confidence interval (CI): 13.19–31.06). Therefore, 5-CNL appeared to be effective at informing consumers, including those who are nutritionally at-risk, about the nutritional quality of food products. PMID:26305255

Objective Understanding of Front-of-Package Nutrition Labels among Nutritionally At-Risk Individuals.

PubMed

Ducrot, Pauline; Méjean, Caroline; Julia, Chantal; Kesse-Guyot, Emmanuelle; Touvier, Mathilde; Fezeu, Léopold K; Hercberg, Serge; Péneau, Sandrine

2015-08-24

In the ongoing debate about front-of-package (FOP) nutrition labels, little data exist regarding nutritionally at-risk populations, although they are critical targets of prevention programs. This study aimed to compare the impact of FOP labels on the ability to rank products according to their nutritional quality among French adults potentially at risk of poor dietary quality (N = 14,230). Four labels were evaluated: Guideline Daily Amounts (GDA), Multiple Traffic Lights (MTL), 5-Color Nutrition Label (5-CNL), Green Tick (Tick), along with a reference without label. Mixed models were used to assess how individual characteristics and FOP labels were associated with the ability to rank products. Older participants and those with a lower educational level, income, nutritional knowledge, and likelihood of reading nutrition facts were less skilled at ranking food products according to nutritional quality. Compared with individual characteristics, nutrition labels had an increased impact on food product ranking ability. Overall, 5-CNL corresponded to the highest rate of correct responses, followed by MTL, GDA, and Tick (p < 0.0001). The strongest impact of 5-CNL was observed among individuals with no nutritional knowledge (odds ratio (OR): 20.24; 95% confidence interval (CI): 13.19-31.06). Therefore, 5-CNL appeared to be effective at informing consumers, including those who are nutritionally at-risk, about the nutritional quality of food products.

Sun-protective behaviors in populations at high risk for skin cancer

PubMed Central

Diao, Diana Y; Lee, Tim K

2014-01-01

Over 3 million new cases of skin cancer are diagnosed in the US annually. Melanoma, a subtype of skin cancer that can be fatal if the disease is not detected and treated at an early stage, is the most common cancer for those aged 25–29 years and the second most common cancer in adolescents and young adults aged 15–29 years. The primary carcinogen for the genesis of skin cancers is ultraviolet light from solar radiation and tanning beds. In spite of massive health campaigns to raise public awareness on ultraviolet radiation, sun-protective practices still fall behind. A plausible explanation is the lack of behavioral change in the populations at risk; in this review article, we examine sun-protective behavior in the four high-risk skin cancer groups: skin cancer survivors, individuals with a family history of melanoma, individuals with physical characteristics associated with skin cancer risk, and organ transplantation patients. Findings in the literature demonstrate that increased knowledge and awareness does not consequently translate into behavioral changes in practice. Behavior can differ as a result of different attitudes and beliefs, depending on the population at risk. Thus, intervention should be tailored to the population targeted. A multidisciplinary health team providing consultation and education is required to influence these much needed changes. PMID:24379732

Cancer risk awareness and screening uptake in individuals at higher risk for colon cancer: a cross-sectional study.

PubMed

Salimzadeh, Hamideh; Bishehsari, Faraz; Delavari, Alireza; Barzin, Gilda; Amani, Mohammad; Majidi, Azam; Sadjadi, Alireza; Malekzadeh, Reza

2016-12-20

We aimed to measure cancer knowledge and feasibility of a screening colonoscopy among a cohort of individuals at higher risk of colon cancer. This study was conducted as part of an ongoing screening cohort, in which first degree relatives (FDRs) of patients with colon cancer are invited to participate in a free of charge screening colonoscopy. We enrolled 1017 FDRs in the study between 2013 and 2014 measuring their data on demographics, cancer knowledge and colonoscopy uptake. A p value of <0.05 was considered statistically significant. The relative's mean age was 48.7 years. Only about 28% of FDRs were aware of their increased risk for cancer, near 35.0% had ever heard about colonoscopy with 22% aware of the correct age to start screening. Comparing cancer knowledge of FDRs at high risk versus those at moderate risk, we recorded non-significant differences (p>0.05). Almost two-thirds of FDRs expressed willingness to undergo a colonoscopy and 49.2% completed the procedure, of which 12.8% had advanced neoplasm. Our data indicated that remarkable numbers of FDRs were not still informed of their cancer risk or never received a physician recommendation for screening. The desirable uptake at first invitation, which would be higher over successive invitations, supports the feasibility of a family-based recruitment approach for early screening. This has promising implications to introduce targeted screening colonoscopy into the healthcare system in Iran and other developing nations. 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/.

New Insight Into the Biology, Risk Stratification, and Targeted Treatment of Myelodysplastic Syndromes.

PubMed

Haider, Mintallah; Duncavage, Eric J; Afaneh, Khalid F; Bejar, Rafael; List, Alan F

2017-01-01

In myelodysplastic syndromes (MDS), somatic mutations occur in five major categories: RNA splicing, DNA methylation, activated cell signaling, myeloid transcription factors, and chromatin modifiers. Although many MDS cases harbor more than one somatic mutation, in general, there is mutual exclusivity of mutated genes within a class. In addition to the prognostic significance of individual somatic mutations, more somatic mutations in MDS have been associated with poor prognosis. Prognostic assessment remains a critical component of the personalization of care for patient with MDS because treatment is highly risk adapted. Multiple methods for risk stratification are available with the revised International Prognostic Scoring System (IPSS-R), currently considered the gold standard. Increasing access to myeloid gene panels and greater evidence for the diagnostic and predictive value of somatic mutations will soon make sequencing part of the standard evaluation of patients with MDS. In the absence of formal guidelines for their prognostic use, well-validated mutations can still refine estimates of risk made with the IPSS-R. Not only are somatic gene mutations advantageous in understanding the biology of MDS and prognosis, they also offer potential as biomarkers and targets for the treatment of patients with MDS. Examples include deletion 5q, spliceosome complex gene mutations, and TP53 mutations.

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

PubMed

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets.

PubMed

Bieszk, Nella; Grabner, Michael; Wei, Wenhui; Bonine, Nicole G; Stephenson, Judith J

2016-01-01

To evaluate awareness of the 2012 American Diabetes Association (ADA) Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C) goals in the management of type 2 diabetes (T2D). The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS) study used the HealthCore claims database to identify T2D patients, stratified by risk, and their treating physicians to assess primary care physician and endocrinologist awareness of the 2012 ADA Position Statement. Physicians completed online surveys on A1C targets before and after receiving an educational intervention to review the position statement. Of 125 responding physicians (mean age 50.3 years, 12.8% endocrinologists) who were linked to 125 patient profiles (mean age 56.9 years, 42% female, mean A1C 7.2%), 92% were at least somewhat aware of the position statement prior to the intervention and 59% believed that the statement would impact how they set A1C targets. The educational intervention resulted in mostly less stringent goal setting for both lower and higher risk patients, but changes were not significant. The proportion of physician-assigned A1C targets within ADA-recommended ranges increased from 56% to 66% post-intervention ( P <0.0001). Physicians treating T2D are aware of the 2012 ADA Position Statement and believe that it may influence treatment goals. While patient-specific A1C targets were not significantly impacted, physicians indicated that they would make targets more or less stringent for lower and higher risk patients, respectively, across their practice. Further research into optimizing physician education regarding individualized A1C targets is warranted.

The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets

PubMed Central

Bieszk, Nella; Grabner, Michael; Wei, Wenhui; Bonine, Nicole G; Stephenson, Judith J

2016-01-01

Objective To evaluate awareness of the 2012 American Diabetes Association (ADA) Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C) goals in the management of type 2 diabetes (T2D). Research design and methods The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS) study used the HealthCore claims database to identify T2D patients, stratified by risk, and their treating physicians to assess primary care physician and endocrinologist awareness of the 2012 ADA Position Statement. Physicians completed online surveys on A1C targets before and after receiving an educational intervention to review the position statement. Results Of 125 responding physicians (mean age 50.3 years, 12.8% endocrinologists) who were linked to 125 patient profiles (mean age 56.9 years, 42% female, mean A1C 7.2%), 92% were at least somewhat aware of the position statement prior to the intervention and 59% believed that the statement would impact how they set A1C targets. The educational intervention resulted in mostly less stringent goal setting for both lower and higher risk patients, but changes were not significant. The proportion of physician-assigned A1C targets within ADA-recommended ranges increased from 56% to 66% post-intervention (P<0.0001). Conclusion Physicians treating T2D are aware of the 2012 ADA Position Statement and believe that it may influence treatment goals. While patient-specific A1C targets were not significantly impacted, physicians indicated that they would make targets more or less stringent for lower and higher risk patients, respectively, across their practice. Further research into optimizing physician education regarding individualized A1C targets is warranted. PMID:27877071

The Evidence Base for Interventions Targeting Individuals With Work-Related PTSD: A Systematic Review and Recommendations.

PubMed

Torchalla, Iris; Strehlau, Verena

2018-03-01

The purpose of this study was to summarize the evidence base for interventions targeting individuals with work-related posttraumatic stress disorder (PTSD), to make recommendations for clinicians and administrative decision makers involved in their rehabilitation, and to guide future research in this area. Particular attention was given to studies that were conducted in naturalistic clinical settings or in a workers' compensation claim context. Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycINFO, CINAHL, PILOTS, and EMBASE identified 11 articles. Study populations included railroad personnel, police officers, disaster workers, and individuals with industrial injuries. Interventions included trauma-focused cognitive-behavioral therapy and eye movement desensitization and reprocessing. Several studies specifically targeted workers who had failed to return to work (RTW) after standard PTSD treatment. The results suggest that psychotherapy interventions are beneficial for helping clients recover from PTSD symptoms and RTW. In studies that reported on work status, RTW rates increased over time and generally lay between 58% and 80% across follow-up time points. Narrative impressions were supplemented by calculation of Risk Differences for individuals working at pretreatment versus posttreatment. Clinical consideration, methodological issues limiting the current body of work, and recommendations for future research are discussed.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0

Dietary Fiber, Carbohydrate Quality and Quantity, and Mortality Risk of Individuals with Diabetes Mellitus

PubMed Central

Burger, Koert N. J.; Beulens, Joline W. J.; van der Schouw, Yvonne T.; Sluijs, Ivonne; Spijkerman, Annemieke M. W.; Sluik, Diewertje; Boeing, Heiner; Kaaks, Rudolf; Teucher, Birgit; Dethlefsen, Claus; Overvad, Kim; Tjønneland, Anne; Kyrø, Cecilie; Barricarte, Aurelio; Bendinelli, Benedetta; Krogh, Vittorio; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Nilsson, Peter M.; Orho-Melander, Marju; Rolandsson, Olov; Huerta, José María; Crowe, Francesca; Allen, Naomi; Nöthlings, Ute

2012-01-01

Background Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown. Objective To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. Methods This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992–2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. Results During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75–0.91]) and CVD mortality risk (0.76[0.64–0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07–1.88]), carbohydrate (1.67[1.18–2.37]) and sugar intake (1.53[1.12–2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI≤25 kg/m2; 22% of study population) but not among overweight individuals (P interaction≤0.04). These associations became stronger after exclusion of energy misreporters. Conclusions High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes. PMID:22927948

Suicide risk factors among trans feminine individuals in Lebanon

PubMed Central

Kaplan, Rachel L.; Nehme, Simon; Aunon, Frances; de Vries, David; Wagner, Glenn

2016-01-01

Transgender women are disproportionately affected by high rates of depression and suicide attempts. It is therefore important to identify factors that influence suicidal risk, particularly in the Middle East where little research has examined the mental health of transgender women. We examined risk factors associated with suicide attempts among 54 trans feminine individuals in Beirut, Lebanon. Data were collected using interviewer-administered questionnaires and analyzed using bivariate statistics. Twenty-five (46%) participants reported having ever attempted suicide. Among them, only one participant received some kind of counseling in response to the attempted suicide. Low general social support, low social integration, and low support from peers were significantly associated with a history of attempted suicide, as were being more open about transgender identity in public and any hormone use (past or current). These findings suggest that progression in gender transition can have unintended consequences related to mental health and suicide risk, while social support systems can mitigate the impact of mental health problems. Some of these findings mirror other contexts around the globe and can inform mental health services for trans feminine individuals in Lebanon, the greater Middle East region, and other international settings. PMID:27616943

Environmental risk assessment of triclosan and ibuprofen in marine sediments using individual and sub-individual endpoints.

PubMed

Pusceddu, F H; Choueri, R B; Pereira, C D S; Cortez, F S; Santos, D R A; Moreno, B B; Santos, A R; Rogero, J R; Cesar, A

2018-01-01

The guidelines for the Environmental Risk Assessment (ERA) of pharmaceuticals and personal care products (PPCP) recommend the use of standard ecotoxicity assays and the assessment of endpoints at the individual level to evaluate potential effects of PPCP on biota. However, effects at the sub-individual level can also affect the ecological fitness of marine organisms chronically exposed to PPCP. The aim of the current study was to evaluate the environmental risk of two PPCP in marine sediments: triclosan (TCS) and ibuprofen (IBU), using sub-individual and developmental endpoints. The environmental levels of TCS and IBU were quantified in marine sediments from the vicinities of the Santos submarine sewage outfall (Santos Bay, São Paulo, Brazil) at 15.14 and 49.0 ng g -1 , respectively. A battery (n = 3) of chronic bioassays (embryo-larval development) with a sea urchin (Lytechinus variegatus) and a bivalve (Perna perna) were performed using two exposure conditions: sediment-water interface and elutriates. Moreover, physiological stress through the Neutral Red Retention Time Assay (NRRT) was assessed in the estuarine bivalve Mytella charruana exposed to TCS and IBU spiked sediments. These compounds affected the development of L. variegatus and P. perna (75 ng g -1 for TCS and 15 ng g -1 for IBU), and caused a significant decrease in M. charruana lysosomal membrane stability at environmentally relevant concentrations (0.08 ng g -1 for TCS and 0.15 ng g -1 for IBU). Chemical and ecotoxicological data were integrated and the risk quotient estimated for TCS and IBU were higher than 1.0, indicating a high environmental risk of these compounds in sediments. These are the first data of sediment risk assessment of pharmaceuticals and personal care products of Latin America. In addition, the results suggest that the ERA based only on individual-level and standard toxicity tests may overlook other biological effects that can affect the health of marine organisms

Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis.

PubMed

Loewy, Rachel; Fisher, Melissa; Schlosser, Danielle A; Biagianti, Bruno; Stuart, Barbara; Mathalon, Daniel H; Vinogradov, Sophia

2016-07-01

Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2016.

Effects of a Televised Two-City Safer Sex Mass Media Campaign Targeting High-Sensation-Seeking and Impulsive-Decision-Making Young Adults

PubMed Central

Zimmerman, Rick S.; Palmgreen, Philip M.; Noar, Seth M.; Lustria, Mia Liza A.; Lu, Hung-Yi; Horosewski, Mary Lee

2015-01-01

This study evaluates the ability of a safer sex televised public service announcement (PSA) campaign to increase safer sexual behavior among at-risk young adults. Independent, monthly random samples of 100 individuals were surveyed in each city for 21 months as part of an interrupted-time-series design with a control community. The 3-month high-audience-saturation campaign took place in Lexington, KY, with Knoxville, TN, as a comparison city. Messages were especially designed and selected for the target audience (those above the median on a composite sensation-seeking/impulsive-decision-making scale). Data indicate high campaign exposure among the target audience, with 85%–96% reporting viewing one or more PSAs. Analyses indicate significant 5-month increases in condom use, condom-use self-efficacy, and behavioral intentions among the target group in the campaign city with no changes in the comparison city. The results suggest that a carefully targeted, intensive mass media campaign using televised PSAs can change safer sexual behaviors. PMID:17602097

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials

PubMed Central

Whiteley, William N; Adams, Harold P; Bath, Philip MW; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter AG

2013-01-01

Summary Background Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. Methods We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Findings Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. Interpretation There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.

PubMed

Whiteley, William N; Adams, Harold P; Bath, Philip M W; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter A G

2013-06-01

Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who

Context-Dependent Pathways of the Transmission of Risk from Communities to Individuals

PubMed Central

Lamont, Andrea E.; Van Horn, M. Lee; Hawkins, J. David

2016-01-01

Research has consistently documented the role of environmental risk factors in the onset of delinquent behavior among youth. Less is known about the processes through which these contextual risks are translated to individual youth behavior. The aim of the current study is to examine the role of family risk factors in the transmission of community risk. Data was obtained from a nationally representative sample of over 30,000 middle school youth and community key informants (CKI). A multilevel, moderated mediation model was estimated with family risk as the moderator of the effect of CKI ratings of community risk on youth perceptions of risk. Results showed that when youth came from low risk families (measured by parental use of positive family management strategies), youth perceptions of risk mediated the effects of community risk on youth delinquency; however, there was no evidence of a significant mediated effect under conditions of high risk (measured by poor family management). This appears to be because youth from high-risk families perceived their neighborhoods as high-risk, regardless of actual levels of risk (as reported by CKI). This study finds that the relationship between communities and adolescent behavior is complex and interacts with the family environment. PMID:25300758

Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

PubMed

Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

2017-10-01

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical utility of the Calgary Depression Scale for Schizophrenia in individuals at ultra-high risk of psychosis.

PubMed

Rekhi, Gurpreet; Ng, Wai Yee; Lee, Jimmy

2018-03-01

There is a pressing need for reliable and valid rating scales to assess and measure depression in individuals at ultra-high risk (UHR) of psychosis. The aim of this study was to examine the clinical utility of the Calgary Depression Scale for Schizophrenia (CDSS) in individuals at UHR of psychosis. 167 individuals at UHR of psychosis were included as participants in this study. The Structured Clinical Interview for DSM-IV Axis I Disorders, CDSS, Beck Anxiety Inventory and Global Assessment of Functioning were administered. A receiver operating characteristic (ROC) curve analysis and factor analyses were performed. Cronbach's alpha was computed. Correlations between CDSS factor scores and other clinical variables were examined. The median CDSS total score was 5.0 (IQR 1.0-9.0). The area under ROC curve was 0.886 and Cronbach's alpha was 0.855. A score of 7 on the CDSS yielded the highest sensitivity and specificity in detecting depression in UHR individuals. Exploratory factor analysis of the CDSS yielded two factors: depression-hopelessness and self depreciation-guilt, which was confirmed by confirmatory factor analysis. Further analysis showed that the depression-hopelessness factor predicted functioning; whereas the self depreciation-guilt factor was related to the severity of the attenuated psychotic symptoms. In conclusion, the CDSS demonstrates good psychometric properties when used to evaluate depression in individuals at UHR of psychosis. Our study results also support a two-factor structure of the CDSS in UHR individuals. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Scalable Clinical Decision Support for Individualized Cancer Risk Management | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

We will build a scalable clinical decision support (CDS) platform that helps clinicians and patients select cancer screening strategies that are best suited to each individual. This kind of CDS is important because increased evidence supports personalizing cancer screening decisions according to each individual's unique cancer risks. While a highly desired goal, individualizing screening at a population scale requires the implementation of patient-specific risk assessments for several types of cancer. This is quite challenging in today's overwhelmed primary care environment.

Risk factors for early myocardial infarction in South Asians compared with individuals in other countries.

PubMed

Joshi, Prashant; Islam, Shofiqul; Pais, Prem; Reddy, Srinath; Dorairaj, Prabhakaran; Kazmi, Khawar; Pandey, Mrigendra Raj; Haque, Sirajul; Mendis, Shanthi; Rangarajan, Sumathy; Yusuf, Salim

2007-01-17

South Asians have high rates of acute myocardial infarction (AMI) at younger ages compared with individuals from other countries but the reasons for this are unclear. To evaluate the association of risk factors for AMI in native South Asians, especially at younger ages, compared with individuals from other countries. Standardized case-control study of 1732 cases with first AMI and 2204 controls matched by age and sex from 15 medical centers in 5 South Asian countries and 10,728 cases and 12,431 controls from other countries. Individuals were recruited to the study between February 1999 and March 2003. Association of risk factors for AMI. The mean (SD) age for first AMI was lower in South Asian countries (53.0 [11.4] years) than in other countries (58.8 [12.2] years; P<.001). Protective factors were lower in South Asian controls than in controls from other countries (moderate- or high-intensity exercise, 6.1% vs 21.6%; daily intake of fruits and vegetables, 26.5% vs 45.2%; alcohol consumption > or =once/wk, 10.7% vs 26.9%). However, some harmful factors were more common in native South Asians than in individuals from other countries (elevated apolipoprotein B(100) /apolipoprotein A-I ratio, 43.8% vs 31.8%; history of diabetes, 9.5% vs 7.2%). Similar relative associations were found in South Asians compared with individuals from other countries for the risk factors of current and former smoking, apolipoprotein B100/apolipoprotein A-I ratio for the top vs lowest tertile, waist-to-hip ratio for the top vs lowest tertile, history of hypertension, history of diabetes, psychosocial factors such as depression and stress at work or home, regular moderate- or high-intensity exercise, and daily intake of fruits and vegetables. Alcohol consumption was not found to be a risk factor for AMI in South Asians. The combined odds ratio for all 9 risk factors was similar in South Asians (123.3; 95% confidence interval [CI], 38.7-400.2] and in individuals from other countries (125

Data-driven risk models could help target pipeline safety inspections

DOT National Transportation Integrated Search

2008-07-01

Federal safety agencies share a common problemthe : need to target resources effectively to reduce risk. One : way this targeting is commonly done is with a risk model : that uses safety data along with expert judgment to identify : and weight ris...

Observed changes in cardiovascular risk factors among high-risk middle-aged men who received lifestyle counselling: a 5-year follow-up.

PubMed

Siren, Reijo; Eriksson, Johan G; Vanhanen, Hannu

2016-12-01

To examine the long-term impact of health counselling among middle-aged men at high risk of CVD. An observational study with a 5-year follow-up. All men aged 40 years in Helsinki have been invited to a visit to evaluate CVD risk from 2006 onwards. A modified version of the North Karelia project risk tool (CVD risk score) served to assess the risk. High-risk men received lifestyle counselling based on their individual risk profile in 2006 and were invited to a follow-up visit in 2011. Of the 389 originally high-risk men, 159 participated in the follow-up visits in 2011. Based on their follow-up in relation the further risk communication, we divided the participants into three groups: primary health care, occupational health care and no control visits. Lifestyle and CVD risk score change. All groups showed improvements in lifestyles. The CVD risk score decreased the most in the group that continued the risk communication visits in their primary health care centre (6.1 to 4.8 [95% CI -1.6 to -0.6]) compared to those who continued risk communication visits in their occupational health care (6.0 to 5.4 [95% CI -1.3 to 0.3]), and to those with no risk communication visits (6.0 to 5.9 [95% CI -0.5 to 0.4]). These findings indicate that individualized lifestyle counselling improves health behaviour and reduces total CVD risk among middle-aged men at high risk of CVD. Sustained improvement in risk factor status requires ongoing risk communication with health care providers. KEY POINTS Studies of short duration have shown that lifestyle changes reduce the risk of cardiovascular disease among high-risk individuals. Sustaining these lifestyle changes and maintaining the lower disease risk attained can prove challenging. Cardiovascular disease (CVD) risk assessment and individualized health counselling for high-risk men, when implemented in primary health care, have the potential to initiate lifestyle changes that support risk reduction. Attaining a sustainable reduction in CVD

Event-Related Potentials: Search for Positive and Negative Child-Related Schemata in Individuals at Low and High Risk for Child Physical Abuse

ERIC Educational Resources Information Center

Milner, Joel S.; Rabenhorst, Mandy M.; McCanne, Thomas R.; Crouch, Julie L.; Skowronski, John J.; Fleming, Matthew T.; Hiraoka, Regina; Risser, Heather J.

2011-01-01

Objective: The present investigation used event-related potentials (ERPs, N400 and N300) to determine the extent to which individuals at low and high risk for child physical abuse (CPA) have pre-existing positive and negative child-related schemata that can be automatically activated by ambiguous child stimuli. Methods: ERP data were obtained from…

Do polypills lead to neglect of lifestyle risk factors? Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease.

PubMed

Selak, Vanessa; Bullen, Chris; Stepien, Sandrine; Arroll, Bruce; Bots, Michiel; Bramley, Dale; Cass, Alan; Grobbee, Diederick; Hillis, Graham S; Molanus, Barbara; Neal, Bruce; Patel, Anushka; Rafter, Natasha; Rodgers, Anthony; Thom, Simon; Tonkin, Andrew; Usherwood, Tim; Wadham, Angela; Webster, Ruth

2016-09-01

The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m(2), in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines. © The European Society of Cardiology 2016.

Individual microRNAs (miRNAs) display distinct mRNA targeting "rules".

PubMed

Wang, Wang-Xia; Wilfred, Bernard R; Xie, Kevin; Jennings, Mary H; Hu, Yanling Hu; Stromberg, Arnold J; Nelson, Peter T

2010-01-01

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using an assay we validated previously-a "RIP-Chip" experimental design. RIP-Chip data provided a list of mRNAs recruited into the AGO-miRNP in correlation to each miRNA. These experimentally identified miRNA targets were analyzed for complementary six nucleotide "seed" sequences within the transfected miRNAs. We found that miR-124 targets tended to have sequences in the 3'UTR that would be recognized by the 5' seed of miR-124, as described in previous studies. By contrast, miR-107 targets tended to have 'seed' sequences in the mRNA open reading frame, but not the 3' UTR. Further, mRNA targets of miR-128 and miR-320 are less enriched for 6-mer seed sequences in comparison to miR-107 and miR-124. In sum, our data support the importance of the 5' seed in determining binding characteristics for some miRNAs; however, the "binding rules" are complex, and individual miRNAs can have distinct sequence determinants that lead to mRNA targeting.

Between-airport heterogeneity in air toxics emissions associated with individual cancer risk thresholds and population risks

PubMed Central

2009-01-01

Background Airports represent a complex source type of increasing importance contributing to air toxics risks. Comprehensive atmospheric dispersion models are beyond the scope of many applications, so it would be valuable to rapidly but accurately characterize the risk-relevant exposure implications of emissions at an airport. Methods In this study, we apply a high resolution atmospheric dispersion model (AERMOD) to 32 airports across the United States, focusing on benzene, 1,3-butadiene, and benzo [a]pyrene. We estimate the emission rates required at these airports to exceed a 10-6 lifetime cancer risk for the maximally exposed individual (emission thresholds) and estimate the total population risk at these emission rates. Results The emission thresholds vary by two orders of magnitude across airports, with variability predicted by proximity of populations to the airport and mixing height (R2 = 0.74–0.75 across pollutants). At these emission thresholds, the population risk within 50 km of the airport varies by two orders of magnitude across airports, driven by substantial heterogeneity in total population exposure per unit emissions that is related to population density and uncorrelated with emission thresholds. Conclusion Our findings indicate that site characteristics can be used to accurately predict maximum individual risk and total population risk at a given level of emissions, but that optimizing on one endpoint will be non-optimal for the other. PMID:19426510

Predictors of Co-Occurring Risk Behavior Trajectories among Economically Disadvantaged African American Youth: Contextual and Individual Factors

PubMed Central

Sterrett, Emma M.; Dymnicki, Allison B.; Henry, David; Byck, Gayle; Bolland, John; Mustanski, Brian

2014-01-01

Purpose African American youth, particularly those from low-income backgrounds, evidence high rates of negative outcomes associated with three problem behaviors, conduct problems, risky sexual behavior, and substance use. This study used a contextually-tailored version of Problem Behavior Theory (PBT) to examine predictors of the simultaneous development of problem behaviors in this specific cultural group. Methods Socio-contextual and individual variables representing four PBT predictor categories, controls protection, support protection, models risk, and vulnerability risk, were examined as predictors of co-occurring problem behaviors among economically disadvantaged African American adolescents (n = 949). Specifically, the likelihood of following three classes of multiple problem behavior trajectories spanning ages 12 to 18, labeled the “early experimenters,” “increasing high risk-takers,” and “adolescent-limited” classes, as opposed to a “normative” class was examined. Results Among other findings, controls protection in the form of a more stringent household curfew at age 12 was related to a lower likelihood of being in the “early experimenters” and “increasing high risk-takers” classes. Conversely, vulnerability risk manifested as stronger attitudes of violence inevitability was associated with a higher likelihood of being in the “early experimenters” class. However, the PBT category of support protection was not associated with risk trajectory class. More distal neighborhood-level manifestations of PBT categories also did not predict co-occurring behavior problems. Conclusion Guided by an incorporation of contextually-salient processes into PBT, prevention programs aiming to decrease co-occurring problem behaviors among low-income African American adolescents would do well to target both proximal systems and psychological constructs related to perceived security throughout adolescence. PMID:24755141

Predictors of co-occurring risk behavior trajectories among economically disadvantaged African-American youth: contextual and individual factors.

PubMed

Sterrett, Emma M; Dymnicki, Allison B; Henry, David; Byck, Gayle R; Bolland, John; Mustanski, Brian

2014-09-01

African-American youth, particularly those from low-income backgrounds, evidence high rates of negative outcomes associated with three problem behaviors, conduct problems, risky sexual behavior, and substance use. This study used a contextually tailored version of problem behavior theory (PBT) to examine predictors of the simultaneous development of problem behaviors in this specific cultural group. Sociocontextual and individual variables representing four PBT predictor categories, controls protection, support protection, models risk, and vulnerability risk, were examined as predictors of co-occurring problem behaviors among economically disadvantaged African-American adolescents (n = 949). Specifically, the likelihood of following three classes of multiple problem behavior trajectories spanning ages 12-18, labeled the "early experimenters," "increasing high risk-takers," and "adolescent-limited" classes, as opposed to a "normative" class, was examined. Among other findings, controls protection in the form of a more stringent household curfew at age 12 was related to a lower likelihood of being in the "early experimenters" and "increasing high risk-takers" classes. Conversely, vulnerability risk manifested as stronger attitudes of violence inevitability was associated with a higher likelihood of being in the "early experimenters" class. However, the PBT category of support protection was not associated with risk trajectory class. More distal neighborhood-level manifestations of PBT categories also did not predict co-occurring behavior problems. Guided by an incorporation of contextually salient processes into PBT, prevention programs aiming to decrease co-occurring problem behaviors among low-income African-American adolescents would do well to target both proximal systems and psychological constructs related to perceived security throughout adolescence. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations.

PubMed

Selvarajah, Sharmini; Haniff, Jamaiyah; Kaur, Gurpreet; Guat Hiong, Tee; Bujang, Adam; Chee Cheong, Kee; Bots, Michiel L

2013-02-25

Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening.

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations

PubMed Central

2013-01-01

Background Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Methods Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. Results 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Conclusions Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening. PMID:23442728

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

PubMed

Itoh, Hiroshi; Komuro, Issei; Takeuchi, Masahiro; Akasaka, Takashi; Daida, Hiroyuki; Egashira, Yoshiki; Fujita, Hideo; Higaki, Jitsuo; Hirata, Ken-Ichi; Ishibashi, Shun; Isshiki, Takaaki; Ito, Sadayoshi; Kashiwagi, Atsunori; Kato, Satoshi; Kitagawa, Kazuo; Kitakaze, Masafumi; Kitazono, Takanari; Kurabayashi, Masahiko; Miyauchi, Katsumi; Murakami, Tomoaki; Murohara, Toyoaki; Node, Koichi; Ogawa, Susumu; Saito, Yoshihiko; Seino, Yoshihiko; Shigeeda, Takashi; Shindo, Shunya; Sugawara, Masahiro; Sugiyama, Seigo; Terauchi, Yasuo; Tsutsui, Hiroyuki; Ueshima, Kenji; Utsunomiya, Kazunori; Yamagishi, Masakazu; Yamazaki, Tsutomu; Yo, Shoei; Yokote, Koutaro; Yoshida, Kiyoshi; Yoshimura, Michihiro; Yoshimura, Nagahisa; Nakao, Kazuwa; Nagai, Ryozo

2018-06-01

Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL ( n = 2,518) or standard statin therapy targeting LDL-C 100-120 mg/dL ( n = 2,524). Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group ( P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67-1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31-0.88]; P = 0.01). Safety did not differ significantly between the two groups. We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation. © 2018 by the American Diabetes Association.

High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis.

PubMed

de Ronde, Maurice W J; Kok, Maayke G M; Moerland, Perry D; Van den Bossche, Jan; Neele, Annette E; Halliani, Amalia; van der Made, Ingeborg; de Winther, Menno P J; Meijers, Joost C M; Creemers, Esther E; Pinto-Sietsma, Sara-Joan

2017-08-01

The risk of developing cardiovascular disease (CVD) is twice as high among smoking individuals compared to non-smokers. Monocytes are involved in smoking-related atherosclerotic plaque formation. In this study, we investigated whether smokers with an increased risk of developing CVD can be identified on the basis of monocyte-derived miRNA expression levels. We performed a miRNA microarray experiment on isolated monocytes from smoking, former smoking and non-smoking individuals in a cohort of patients with premature CVD and healthy controls (Cohort I, n = 76). We found miR-124-3p to be heterogeneously expressed among all smoking individuals, whereas expression was low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that among smoking individuals an increase in miR-124-3p is associated with an increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72 95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium score ≥ 80 th percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This was not observed among former smokers or non-smoking individuals. Flow cytometric analysis demonstrated that high miR-124-3p expression was associated with upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in an upregulation of CD206 surface expression on monocytes. High miR-124-3p expression is associated with an increased risk of subclinical atherosclerosis in smoking individuals and with an altered monocyte phenotype. This may suggest that miR-124-3p identifies which smoking individuals are susceptible to the atherogenic effects of smoking. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemometric analysis for extraction of individual fluorescence spectrum and lifetimes from a target mixture

NASA Technical Reports Server (NTRS)

Hallidy, William H. (Inventor); Chin, Robert C. (Inventor)

1999-01-01

The present invention is a system for chemometric analysis for the extraction of the individual component fluorescence spectra and fluorescence lifetimes from a target mixture. The present invention combines a processor with an apparatus for generating an excitation signal to transmit at a target mixture and an apparatus for detecting the emitted signal from the target mixture. The present invention extracts the individual fluorescence spectrum and fluorescence lifetime measurements from the frequency and wavelength data acquired from the emitted signal. The present invention uses an iterative solution that first requires the initialization of several decision variables and the initial approximation determinations of intermediate matrices. The iterative solution compares the decision variables for convergence to see if further approximation determinations are necessary. If the solution converges, the present invention then determines the reduced best fit error for the analysis of the individual fluorescence lifetime and the fluorescence spectrum before extracting the individual fluorescence lifetime and fluorescence spectrum from the emitted signal of the target mixture.

Individual and family characteristics associated with BRCA1/2 genetic testing in high-risk families.

PubMed

Katapodi, Maria C; Northouse, Laurel L; Milliron, Kara J; Liu, Guipeng; Merajver, Sofia D

2013-06-01

Little is known about family members' interrelated decisions to seek genetic testing for breast cancer susceptibility. The specific aims of this cross-sectional, descriptive, cohort study were (i) to examine whether individual and family characteristics have a direct effect on women's decisions to use genetic testing for hereditary susceptibility to breast cancer and (ii) to explore whether family characteristics moderate the relationships between individual characteristics and the decision to use genetic testing. Participants were women (>18 years old) who (i) received genetic testing for hereditary breast cancer and who agreed to invite one of their female relatives into the study and (ii) female relatives who had NOT obtained genetic testing and were identified by pedigree analysis as having >10% chances of hereditary susceptibility to breast cancer. The final sample consisted of 168 English-speaking, family dyads who completed self-administered, mailed surveys with validated instruments. Multivariate conditional logistic regression analyses showed that the proposed model explained 62% of the variance in genetic testing. The factors most significantly associated with genetic testing were having a personal history of cancer; perceiving genetic testing to have more benefits than barriers; having greater family hardiness; and perceiving fewer negative consequences associated with a breast cancer diagnosis. No significant interaction effects were observed. Findings suggest that both individual and family characteristics are associated with the decision to obtain genetic testing for hereditary breast cancer; hence, there is a need for interventions that foster a supportive family environment for patients and their high-risk relatives. Copyright © 2012 John Wiley & Sons, Ltd.

Early identification and high-risk strategies for bipolar disorder.

PubMed

Correll, Christoph U; Penzner, Julie B; Lencz, Todd; Auther, Andrea; Smith, Christopher W; Malhotra, Anil K; Kane, John M; Cornblatt, Barbara A

2007-06-01

To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD). Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies. Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies. Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.

A retrospective study of recurrent chlamydia infection in men and women: is there a role for targeted screening for those at risk?

PubMed

Evans, C; Das, C; Kinghorn, G

2009-03-01

Chalmydia trachomatis remains the commonest sexually transmitted infection (STI) in the UK. This study identifies those at risk of recurrent infection (RI) attending a central genitourinary clinic, time to subsequent reinfection and duration of at-risk behaviour for the consideration of targeted chlamydia screening. From 1995 to 2005, a total of 14,011 patients' were diagnosed with chlamydia and 1743 (12.4%) had RI, classified as a repeat infection greater than three months after initial diagnosis. Individual risk factors for both sexes include young age <25, two or more partners and failure to attend for test of cure (TOC) and previous STI. Men of non-White ethnicity, symptoms and those self-referred were also at risk. Combined risk factors for both sexes were non-White ethnicity, symptoms, young age, previous STI and two or more partners. Attendance for TOC considerably reduced RI rates in men (odds ratio [OR] = 0.549; 95% confidence interval [CI] 0.359-0.840). Mean time to first and last reinfection in men was 1.91 and 2.49 years, in women 1.76 and 1.92 years. One in eight individuals with chlamydia infection are at risk of RI, the majority of which will occur within two years of initial presentation. These individuals have identifiable risk factors facilitating targeted re-screening, enhanced follow-up and support for behavioural change.

Economic evaluation of targeted cancer interventions: critical review and recommendations.

PubMed

Elkin, Elena B; Marshall, Deborah A; Kulin, Nathalie A; Ferrusi, Ilia L; Hassett, Michael J; Ladabaum, Uri; Phillips, Kathryn A

2011-10-01

Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

[Research and application: scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population].

PubMed

Wang, W J

2016-07-06

There is a large population at high risk for diabetes in China, and there has been a dramatic increase in the incidence of diabetes in the country over the past 30 years. Interventions targeting the individual risk factors of diabetes can effectively prevent diabetes; these include factors such as an unhealthy diet, lack of physical activity, overweight, and obesity, among others. Evaluation of related knowledge, attitudes, and behaviors before and after intervention using appropriate scales can measure population demands and the effectiveness of interventions. Scientificity and practicability are basic requirements of scale development. The theoretical basis and measuring items of a scale should be consistent with the theory of behavior change and should measure the content of interventions in a standardized and detailed manner to produce good validity, reliability, and acceptability. The scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population is a tool for demand evaluation and effect evaluation of lifestyle intervention that has good validity and reliability. Established by the National Center for Chronic and Noncommunicable Disease Control and Prevention, its use can help to decrease the Chinese population at high risk for diabetes through targeted and scientifically sound lifestyle interventions. Future development of intervention evaluation scales for useing in high-risk populations should consider new factors and characteristics of the different populations, to develop new scales and modify or simplify existing ones, as well as to extend the measurement dimensions to barriers and supporting environment for behaviors change.

Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

PubMed

Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith

2017-09-01

Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P < 0.00001), as was OS (HR = 0.90, CI 0.85-0.97; P = 0.003). The absolute differences in EFS at 5 and 10 years were 3.5% and 2.7%, and for OS were 3.0% and 2.8% respectively in favour of IFN-α. There was no evidence that the benefit of IFN-α differed depending on dose or duration of treatment, or by age, gender, site of primary tumour, disease stage, Breslow thickness, or presence of clinical nodes. Only for ulceration was there evidence of an interaction (test for heterogeneity: P = 0.04 for EFS; P = 0.002 for OS); only patients with ulcerated tumours appeared to obtain benefit from IFN-α. This meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting Persons With or At High Risk for Chronic Obstructive Pulmonary Disease by State-based Surveillance

PubMed Central

Pleasants, Roy A.; Heidari, Khosrow; Wheaton, Anne G.; Ohar, Jill A.; Strange, Charlie; Croft, Janet B.; Liao, Winston; Mannino, David M.; Kraft, Monica

2015-01-01

The Behavioral Risk Factor Surveillance System (BRFSS) survey is used to estimate chronic obstructive pulmonary disease (COPD) prevalence and could be expanded to describe respiratory symptoms in the general population and to characterize persons with or at high risk for the disease. Tobacco duration and respiratory symptom questions were added to the 2012 South Carolina BRFSS. Data concerning sociodemographics, chronic illnesses, health behaviors, and respiratory symptoms were collected in 9438 adults ≥ 35 years-old. Respondents were categorized as having COPD, high risk, or low risk for the disease. High risk was defined as no self-reported COPD, ≥ 10 years’ tobacco use, and ≥ 1 respiratory symptom (frequent productive cough or shortness of breath (SOB), or breathing problems affecting activities). Prevalence of self-reported and high-risk COPD were 9.1% and 8.0%, respectively. Overall, 17.3%, 10.6%, and 5.2% of all respondents reported activities limited by breathing problems, frequent productive cough, and frequent SOB, respectively. The high-risk group was more likely than the COPD group to report a productive cough and breathing problems limiting activities as well as being current smokers, male, and African-American. Health impairment was more severe in the COPD than the high-risk group, and both were worse than the low-risk group. Conclusions Persons at high risk for COPD share many, but not all, of the characteristics of persons diagnosed with the disease. Additional questions addressing smoking duration and respiratory symptoms in the BRFSS identifies groups at high risk for having or developing COPD who may benefit from smoking cessation and case-finding interventions. PMID:26367193

Radiation Risk Assessment of the Individual Astronaut: A Complement to Radiation Interests at the NIH

NASA Technical Reports Server (NTRS)

Richmond, Robert C.

2004-01-01

Predicting human risks following exposure to space radiation is uncertain in part because of unpredictable distribution of high-LET and low-dose-derived damage amongst cells in tissues, unknown synergistic effects of microgravity upon gene- and protein-expression, and inadequately modeled processing of radiation-induced damage within cells to produce rare and late-appearing malignant cancers. Furthermore, estimation of risks of radiogenic outcome within small numbers of astronauts is not possible using classic epidemiologic study. It therefore seems useful to develop strategies of risk-assessment based upon large datasets acquired from correlated biological models useful for resolving radiogenic risk-assessment for irradiated individuals. In this regard, it is suggested that sensitive cellular biodosimeters that simultaneously report 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the biomolecular risk of malignant transformation be developed in order to resolve these NASA-specific challenges. Multiparametric cellular biodosimeters could be developed using analyses of gene-expression and protein-expression whereby large datasets of cellular response to radiation-induced damage are analyzed for markers predictive for acute response as well as cancer-risk. A new paradigm is accordingly addressed wherein genomic and proteomic datasets are registered and interrogated in order to provide statistically significant dose-dependent risk estimation in individual astronauts. This evaluation of the individual for assessment of radiogenic outcomes connects to NIH program in that such a paradigm also supports assignment of a given patient to a specific therapy, the diagnosis of response of that patient to therapy, and the prediction of risks accumulated by that patient during therapy - such as risks incurred by scatter and neutrons produced during high-energy Intensity-Modulated Radiation Therapy

High-risk behaviour in hypomanic states.

PubMed

Fletcher, Kathryn; Parker, Gordon; Paterson, Amelia; Synnott, Howe

2013-08-15

Risk-taking behaviours during hypomanic states are recognised, however the high-risk nature of some behaviours-including the potential for harm to both the individual and others-has not been detailed in the research literature. The current study examines risk-taking behaviours and their consequences (including their potential for impairment) in those with a bipolar II condition. Participants were recruited from the Sydney-based Black Dog Institute Depression Clinic. Diagnostic assignment of bipolar II disorder was based on clinician judgement and formal DSM-IV criteria. Participants completed a series of detailed questions assessing previous risk-taking behaviours during hypomanic states. The sample comprised a total of 93 participants. Risk-taking behaviours during hypomania included spending significant amounts of money, excessive alcohol or drug use, dangerous driving and endangering sexual activities. Key consequences included interpersonal conflict, substantial financial burden and feelings of guilt, shame and remorse. Despite recognition of the risks and consequences associated with hypomanic behaviours, less than one-fifth of participants agreed that hypomania should be treated because of the associated risks. Study limitations included a cross-sectional design, reliance on self-report information, lack of controlling for current mood state, and comprised a tertiary referral sample that may be weighted to more severe cases. Findings may therefore not be generalisable and require replication. Risk-taking behaviours during hypomania are common, and often linked with serious consequences. Whilst hypomania is often enjoyed and romanticised by patients-leading to ambivalence around treatment of such states-careful consideration of the impact of risk-taking behaviour is necessary, while the study raises the question as to what is 'impairment' in hypomania. Findings should advance clinical management by identifying those high-risk behaviours that would benefit from

The Violence Risk Scale: Predictive Validity and Linking Changes in Risk with Violent Recidivism in a Sample of High-Risk Offenders with Psychopathic Traits

ERIC Educational Resources Information Center

Lewis, Kathy; Olver, Mark E.; Wong, Stephen C. P.

2013-01-01

The Violence Risk Scale (VRS) uses ratings of static and dynamic risk predictors to assess violence risk, identify targets for treatment, and assess changes in risk following treatment. The VRS was rated pre- and posttreatment on a sample of 150 males, mostly high-risk violent offenders many with psychopathic personality traits. These individuals…

Exploring individual adaptations to an anterior cruciate ligament injury prevention programme.

PubMed

Fox, Aaron S; Bonacci, Jason; McLean, Scott G; Saunders, Natalie

2018-01-01

Individual responses to anterior cruciate ligament injury prevention programmes (ACL IPPs) have received little attention. This study examined the effects of an ACL IPP on neuromuscular control and lower limb biomechanics during landing at the group and individual levels. Sixteen female athletes were randomly allocated to training (n=8) or control (n=8) groups. Electromyography, and three-dimensional kinematic and kinetic data were collected during landing at two testing sessions. Repeated measures ANOVA and effect sizes (Cohen's d) examined the effect of the IPP at the group and individual levels. A sub-group analysis comparing the effect of the IPP on 'high-' (i.e. large peak knee abduction moment at baseline) versus 'low-risk' individuals was also conducted. At the group level; the IPP increased activation of the medial hamstrings prior to landing (p<0.001; d=0.264) and the medial gastrocnemius at landing (p<0.001; d=0.426), and increased hip external rotation early after initial contact (p<0.001; d=0.476). Variable adaptations were seen across individuals within the training group for all variables (p<0.001). The IPP had a large effect in reducing frontal plane knee moments for 'high-risk' individuals (d>0.91), however these results did not reach statistical significance (p>0.05). The IPP induced adaptations during landing, however, individual data revealed dissimilar responses to the programme. Individuals displaying a pre-existing high-risk strategy may incur greater benefits from IPPs, yet only if the programme targets the relevant high-risk strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia.

PubMed

Dodell-Feder, David; Delisi, Lynn E; Hooker, Christine I

2014-06-01

Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN's hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia

PubMed Central

Dodell-Feder, David; DeLisi, Lynn E.; Hooker, Christine I.

2014-01-01

Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN’s hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning. PMID:24768131

The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: a randomized controlled trial.

PubMed

Hernáez, Álvaro; Castañer, Olga; Goday, Alberto; Ros, Emilio; Pintó, Xavier; Estruch, Ramón; Salas-Salvadó, Jordi; Corella, Dolores; Arós, Fernando; Serra-Majem, Lluis; Martínez-González, Miguel Ángel; Fiol, Miquel; Lapetra, José; de la Torre, Rafael; López-Sabater, M Carmen; Fitó, Montserrat

2017-09-01

Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation increased (+6.46%, p = 0.007), the degree of LDL oxidative modifications decreased (-36.3%, p<0.05), estimated LDL particle size augmented (+3.06%, p = 0.021), and LDL particles became cholesterol-rich (+2.41% p = 0.013) relative to the low-fat control diet. LDL lipoproteins became less cytotoxic for macrophages only relative to baseline (-13.4%, p = 0.019). No significant effects of the TMD-Nuts intervention on LDL traits were observed versus the control diet. Adherence to a TMD, particularly when enriched with virgin olive oil, decreased LDL atherogenicity in high cardiovascular risk individuals. The development of less atherogenic LDLs could contribute to explaining some of the cardioprotective benefits of this dietary pattern. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic antibody targeting of individual Notch receptors.

PubMed

Wu, Yan; Cain-Hom, Carol; Choy, Lisa; Hagenbeek, Thijs J; de Leon, Gladys P; Chen, Yongmei; Finkle, David; Venook, Rayna; Wu, Xiumin; Ridgway, John; Schahin-Reed, Dorreyah; Dow, Graham J; Shelton, Amy; Stawicki, Scott; Watts, Ryan J; Zhang, Jeff; Choy, Robert; Howard, Peter; Kadyk, Lisa; Yan, Minhong; Zha, Jiping; Callahan, Christopher A; Hymowitz, Sarah G; Siebel, Christian W

2010-04-15

The four receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth. Ligand binding triggers a conformational change in the receptor negative regulatory region (NRR) that enables ADAM protease cleavage at a juxtamembrane site that otherwise lies buried within the quiescent NRR. Subsequent intramembrane proteolysis catalysed by the gamma-secretase complex liberates the intracellular domain (ICD) to initiate the downstream Notch transcriptional program. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer, making the Notch pathway a compelling target for new drugs. Although gamma-secretase inhibitors (GSIs) have progressed into the clinic, GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways and cause intestinal toxicity, attributed to dual inhibition of Notch1 and 2 (ref. 11). To elucidate the discrete functions of Notch1 and Notch2 and develop clinically relevant inhibitors that reduce intestinal toxicity, we used phage display technology to generate highly specialized antibodies that specifically antagonize each receptor paralogue and yet cross-react with the human and mouse sequences, enabling the discrimination of Notch1 versus Notch2 function in human patients and rodent models. Our co-crystal structure shows that the inhibitory mechanism relies on stabilizing NRR quiescence. Selective blocking of Notch1 inhibits tumour growth in pre-clinical models through two mechanisms: inhibition of cancer cell growth and deregulation of angiogenesis. Whereas inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, inhibition of either receptor alone reduces or avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors. Our studies emphasize the value of paralogue-specific antagonists in dissecting the contributions of distinct Notch receptors to

Extrapolating non-target risk of Bt crops from laboratory to field.

PubMed

Duan, Jian J; Lundgren, Jonathan G; Naranjo, Steve; Marvier, Michelle

2010-02-23

The tiered approach to assessing ecological risk of insect-resistant transgenic crops assumes that lower tier laboratory studies, which expose surrogate non-target organisms to high doses of insecticidal proteins, can detect harmful effects that might be manifested in the field. To test this assumption, we performed meta-analyses comparing results for non-target invertebrates exposed to Bacillus thuringiensis (Bt) Cry proteins in laboratory studies with results derived from independent field studies examining effects on the abundance of non-target invertebrates. For Lepidopteran-active Cry proteins, laboratory studies correctly predicted the reduced field abundance of non-target Lepidoptera. However, laboratory studies incorporating tri-trophic interactions of Bt plants, herbivores and parasitoids were better correlated with the decreased field abundance of parasitoids than were direct-exposure assays. For predators, laboratory tri-trophic studies predicted reduced abundances that were not realized in field studies and thus overestimated ecological risk. Exposure to Coleopteran-active Cry proteins did not significantly reduce the laboratory survival or field abundance of any functional group examined. Our findings support the assumption that laboratory studies of transgenic insecticidal crops show effects that are either consistent with, or more conservative than, those found in field studies, with the important caveat that laboratory studies should explore all ecologically relevant routes of exposure.

Anticipating Early Fatality: Friends', Schoolmates' and Individual Perceptions of Fatality on Adolescent Risk Behaviors

PubMed Central

Soller, Brian; Williams, Kristi

2015-01-01

Past research indicates that anticipating adverse outcomes, such as early death (fatalism), is associated positively with adolescents' likelihood of engaging in risky behaviors. Health researchers and criminologists have argued that fatalism influences present risk taking in part by informing individuals' motivation for delaying gratification for the promise of future benefits. While past findings highlight the association between the anticipation of early death and a number of developmental outcomes, no known research has assessed the impact of location in a context characterized by high perceptions of fatality. Using data from Add Health and a sample of 9,584 adolescents (51 % female and 71 % white) nested in 113 schools, our study builds upon prior research by examining the association between friends', school mates', and individual perceptions of early fatality and adolescent risk behaviors. We test whether friends' anticipation of being killed prior to age 21 or location in a school where a high proportion of the student body subscribes to attitudes of high fatality, is associated with risky behaviors. Results indicate that friends' fatalism is positively associated with engaging in violent delinquency, non-violent delinquency, and drug use after controlling for individual covariates and prior individual risk-taking. Although friends' delinquency accounts for much of the effect of friends' fatalism on violence, none of the potential intervening variables fully explain the effect of friends' fatalism on youth involvement in nonviolent delinquency and drug use. Our results underscore the importance of friendship contextual effects in shaping adolescent risk-taking behavior and the very serious consequences perceptions of fatality have for adolescents' involvement in delinquency and drug use. PMID:23828725

Beyond the patient: the broader impact of genetic discrimination among individuals at risk of Huntington disease.

PubMed

Bombard, Yvonne; Palin, JoAnne; Friedman, Jan M; Veenstra, Gerry; Creighton, Susan; Bottorff, Joan L; Hayden, Michael R

2012-03-01

We aimed to address gaps in current understanding of the scope and impact of discrimination, by examining a cohort of individuals at-risk for Huntington disease (HD), to describe the prevalence of concern for oneself and one's family in multiple domains; strategies used to mitigate discrimination; and the extent to which concerns relate to experiences. We conducted a cross-sectional survey of 293 individuals at-risk for HD (80% response rate); 167 respondents were genetically tested and 66 were not. Fear of discrimination was widespread (86%), particularly in the insurance, family and social settings. Approximately half of concerned individuals experienced discrimination (40-62%, depending on genetic status). Concern was associated with "keeping quiet" about one's risk of HD or "taking action to avoid" discrimination. Importantly, concern was highly distressing for some respondents (21% for oneself; 32% for relatives). Overall, concerned respondents with high education levels, who discovered their family history at a younger age, and those who were mutation-positive were more likely to report experiences of discrimination than others who were concerned. Concerns were rarely attributed to genetic test results alone. Concern about genetic discrimination is frequent among individuals at-risk of HD and spans many settings. It influences behavioral patterns and can result in high levels of self-rated distress, highlighting the need for practice and policy interventions. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

A Framework for Widespread Replication of a Highly Spatially Resolved Childhood Lead Exposure Risk Model

PubMed Central

Kim, Dohyeong; Galeano, M. Alicia Overstreet; Hull, Andrew; Miranda, Marie Lynn

2008-01-01

Background Preventive approaches to childhood lead poisoning are critical for addressing this longstanding environmental health concern. Moreover, increasing evidence of cognitive effects of blood lead levels < 10 μg/dL highlights the need for improved exposure prevention interventions. Objectives Geographic information system–based childhood lead exposure risk models, especially if executed at highly resolved spatial scales, can help identify children most at risk of lead exposure, as well as prioritize and direct housing and health-protective intervention programs. However, developing highly resolved spatial data requires labor-and time-intensive geocoding and analytical processes. In this study we evaluated the benefit of increased effort spent geocoding in terms of improved performance of lead exposure risk models. Methods We constructed three childhood lead exposure risk models based on established methods but using different levels of geocoded data from blood lead surveillance, county tax assessors, and the 2000 U.S. Census for 18 counties in North Carolina. We used the results to predict lead exposure risk levels mapped at the individual tax parcel unit. Results The models performed well enough to identify high-risk areas for targeted intervention, even with a relatively low level of effort on geocoding. Conclusions This study demonstrates the feasibility of widespread replication of highly spatially resolved childhood lead exposure risk models. The models guide resource-constrained local health and housing departments and community-based organizations on how best to expend their efforts in preventing and mitigating lead exposure risk in their communities. PMID:19079729

Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness Analysis.

PubMed

Jarmul, Jamie; Pletcher, Mark J; Hassmiller Lich, Kristen; Wheeler, Stephanie B; Weinberger, Morris; Avery, Christy L; Jonas, Daniel E; Earnshaw, Stephanie; Pignone, Michael

2018-04-01

It is unclear whether testing for novel risk factors, such as a cardiovascular genetic risk score (cGRS), improves clinical decision making or health outcomes when used for targeting statin initiation in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was to estimate the cost-effectiveness of cGRS testing to inform clinical decision making about statin initiation in individuals with low-to-intermediate (2.5%-7.5%) 10-year predicted risk of ASCVD. We evaluated the cost-effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4 test/treat strategies: treat all, treat none, test/treat if cGRS is high, and test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and 7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained. Under base case assumptions for statin disutility and cost, the preferred strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions; for example, when statins cost $15 per month and statin disutility is 0.013 (ie, willing to trade 3 months of life in perfect health to avoid 20 years of statin therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000 per quality-adjusted life-year gained) is to test and treat if cGRS is intermediate or high. Overall, the results were not sensitive to assumptions about statin efficacy and harms. Testing for a 27-single-nucleotide polymorphism cGRS is generally not a cost-effective approach for targeting statin therapy in the primary prevention of ASCVD for low- to intermediate-risk patients. © 2018 American Heart Association, Inc.

Incorporating Multiple Secondary Targets into Learning Trials for Individuals with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Nottingham, Casey L.; Vladescu, Jason C.; Kodak, Tiffany; Kisamore, April N.

2017-01-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary…

A Preliminary Controlled Comparison of Programs Designed to Reduce Risk of Eating Disorders Targeting Perfectionism and Media Literacy

ERIC Educational Resources Information Center

Wilksch, Simon M.; Durbridge, Mitchell R.; Wade, Tracey D.

2008-01-01

The study aims to find out whether programs targeting perfectionism and media literacy are more effective than control classes in reducing eating disorder risk factors. Finding reveals that perfectionism programs are well suited to individuals of mid- to late adolescent age and shows the importune of making prevention programs developmentally…

Attitudinal and behavioral characteristics predict high risk sexual activity in rural Tanzanian youth.

PubMed

Aichele, Stephen R; Borgerhoff Mulder, Monique; James, Susan; Grimm, Kevin

2014-01-01

The incidence of HIV infection in rural African youth remains high despite widespread knowledge of the disease within the region and increasing funds allocated to programs aimed at its prevention and treatment. This suggests that program efficacy requires a more nuanced understanding of the profiles of the most at-risk individuals. To evaluate the explanatory power of novel psychographic variables in relation to high-risk sexual behaviors, we conducted a survey to assess the effects of psychographic factors, both behavioral and attitudinal, controlling for standard predictors in 546 youth (12-26 years of age) across 8 villages in northern Tanzania. Indicators of high-risk sexual behavior included HIV testing, sexual history (i.e., virgin/non-virgin), age of first sexual activity, condom use, and number of lifetime sexual partners. Predictors in the statistical models included standard demographic variables, patterns of media consumption, HIV awareness, and six new psychographic features identified via factor analyses: personal vanity, family-building values, ambition for higher education, town recreation, perceived parental strictness, and spending preferences. In a series of hierarchical regression analyses, we find that models including psychographic factors contribute significant additional explanatory information when compared to models including only demographic and other conventional predictors. We propose that the psychographic approach used here, in so far as it identifies individual characteristics, aspirations, aspects of personal life style and spending preferences, can be used to target appropriate communities of youth within villages for leading and receiving outreach, and to build communities of like-minded youth who support new patterns of sexual behavior.

Premorbid functional development and conversion to psychosis in clinical high-risk youths

PubMed Central

Tarbox, Sarah I.; Addington, Jean; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Heinssen, Robert; Mcglashan, Thomas H.; Woods, Scott W.

2014-01-01

Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention. PMID:24229556

Formal thought disorder in people at ultra-high risk of psychosis

PubMed Central

Weinstein, Sara; Stahl, Daniel; Day, Fern; Valmaggia, Lucia; Rutigliano, Grazia; De Micheli, Andrea; Fusar-Poli, Paolo; McGuire, Philip

2017-01-01

Background Formal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear. Aims Examine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis. Method The Thought and Language Index (TLI) was used to assess 24 ultra-high-risk participants, 16 people with first-episode psychosis and 13 healthy controls. Ultra-high-risk individuals were followed up for a mean duration of 7 years (s.d.=1.5) to determine the relationship between formal thought disorder at baseline and transition to psychosis. Results TLI scores were significantly greater in the ultra-high-risk group compared with the healthy control group (effect size (ES)=1.2), but lower than in people with first-episode psychosis (ES=0.8). Total and negative TLI scores were higher in ultra-high-risk individuals who developed psychosis, but this was not significant. Combining negative TLI scores with attenuated psychotic symptoms and basic symptoms predicted transition to psychosis (P=0.04; ES=1.04). Conclusions TLI is beneficial in evaluating formal thought disorder in ultra-high-risk participants, and complements existing instruments for the evaluation of psychopathology in this group. Declaration of interests None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28713586

Perceived risks and use of psychotherapy via telemedicine for patients at risk for suicide.

PubMed

Gilmore, Amanda K; Ward-Ciesielski, Erin F

2017-01-01

Introduction Suicide is a major public health problem and its human, emotional, and economic costs are significant. Individuals in rural areas are at highest risk for suicide. However, telemedicine services are typically not rendered to individuals who are actively suicidal. The goals of the current study were to identify the risks of using telemedicine for mental healthcare from the perspective of licensed mental health providers and to determine factors associated with the use of telemedicine with patients who are at high risk for suicide. Methods A total of 52 licensed mental health providers were recruited online through several professional organization listservs and targeted emails. Providers completed online questionnaires regarding demographics, caseload of suicidal patients, perceived risks for using telemedicine with patients at risk for suicide, attitudes towards telemedicine, and use of telemedicine with patients at risk for suicide. Results Three key perceived risks associated with using telemedicine were identified, including assessment, lack of control over patient, and difficulties triaging patients if needed. It was also found that individuals who had more positive attitudes towards telemedicine, younger providers, and more experienced providers were more likely to use telemedicine with patients who are at high risk for suicide. Discussion To our knowledge, this is the first study to examine the perceived risks and use of telemedicine with patients at high risk for suicide. It is essential to continue this line of research to develop protocols for the provision of evidence-based therapy via telemedicine for this high-risk group.

HIV/Sexually Transmitted Infection Prevention Messaging: Targeting Root Causes of Sexual Risk Behavior.

PubMed

Manhart, Lisa E; Epstein, Marina; Bailey, Jennifer A; Hill, Karl G; Haggerty, Kevin P; Catalano, Richard F

2016-02-01

Sexual risk behaviors (SRBs) often lead to sexually transmitted infections (STI), yet little is known about what drives SRB and whether this differs by sex. Participants (n = 920; 75% white) were drawn from the Raising Healthy Children study, enrolled in 1993 and 1994 in grades 1 to 2, and followed up through age 24/25 years. Lifetime STI diagnosis was defined by self-report or seropositivity for Chlamydia trachomatis or herpes simplex virus 2. Multivariable models assessed individual (social skills, behavioral disinhibition) and environmental factors (family involvement, school bonding, antisocial friends) predictive of STI diagnosis as mediated by 3 proximal SRB (sex under the influence of drugs or alcohol, condom use, lifetime number of sex partners). Twenty-five percent of participants had ever had an STI. All SRBs differed by sex (P < 0.001), and female participants were more likely to have had an STI (P < 0.001). Behavioral disinhibition and antisocial friends in adolescence were associated with more SRB for both sexes, whereas social skills were associated with less SRB in female but more in male participants. Considering SRB and individual and environmental factors together, lifetime number of sex partners (adjusted relative risk [ARR], 1.04per partner; 95% confidence interval [CI], 1.03-1.05) and inconsistent condom use (ARR, 1.10per year; 95% CI, 1.04-1.16) were associated with increased risk of STI, whereas social skills were associated with decreased risk of STI (ARR, 0.84; 95% CI, 0.75-0.93). Behavioral disinhibition seemed to drive SRB, but family involvement mitigated this in several cases. Adolescent environmental influences and individual characteristics drive some SRB and may be more effective targets for STI/HIV prevention interventions than proximal risk behaviors.

Evaluation of Promotional Materials To Promote Low-Dose Computed Tomography (LDCT) Screening to High-Risk Consumers and Health Care Providers.

PubMed

Hudson, Janella N; Quinn, Gwendolyn P; Wilson, Lauren E; Simmons, Vani N

2017-03-11

Low-dose computed tomography (LDCT) screening is a promising screening modality for increasing the detection rate of early stage lung cancers among high-risk individuals. Despite being recommended by the US Preventative Services Task Force, uptake of LDCT remains low. The objective of the current study was to gather feedback from high-risk consumers and health care providers on LDCT promotional materials. Focus group discussions were conducted with high-risk individuals (8 focus groups; N = 38) and primary care providers (9 focus groups; N = 23). Participants reviewed existing LDCT promotional materials to assess their perceptions of media materials created to publicize LDCT. Data were analyzed using the constant comparative method. Several key themes emerged from focus groups that can be used to inform development of future LDCT promotional materials. High-risk (HR) participants expressed greater receptivity for promotional materials that did not further stigmatize lung cancer and/or smoking and expressed preferences for materials that clearly outlined the risks/benefits of screening. Primary care providers (PCPs) offered suggestions to facilitate the referral process such as diagnostic codes and requested a design that clearly outlined eligibility criteria. A clear and thorough explanation of LDCT eligibility, cost, harms, and benefits was of chief importance for both PCP and HR audiences. Given that PCPs and HR audiences are not well informed on the specifics of LDCT screening eligibility and insurance coverage, creating provider and patient education opportunities will aid in shared decision-making opportunities. Promotional materials that meet the needs of the target audience are needed to facilitate discussions of risks/benefits of screening with HR individuals.

Adolescents with high periodontal risk in Public Dental Service.

PubMed

Jansson, Leif; Adler, Lottie; Jonés, Catarina

2013-01-01

The purpose of the present study was to investigate the prevalence of adolescents with high periodontal risk and to identify factors with influence on the decision to refer a patient to a specialist clinic of Periodontology, on compliance rate and on treatment outcome. The investigation was conducted as a retrospective study on adolescents at age 13-17. In total, clinical examinations and risk evaluations according to caries- and periodontal risk were performed on 50347 adolescents in general dentistry at ages 13, 15 and 17 in 2007. Individuals with a high periodontal risk were included in the present investigation. A high periodontal risk was defined as presence of sites with periodontal pocket depths >6mm and loss of periodontal tissue support. Multiple logistic regression analyses were adopted to calculate the influence of the potential predictors on the investigated dependent variables. In total, 0.5% of the adolescents were found to have high periodontal risk. The diagnosis local periodontitis and the number of periodontal pockets with probing depths >6 mm were positively and significantly correlated to referral to a periodontist. Eighteen percent dropped out before the treatment was completed. Smokers had a significantly lower compliance than non-smokers. The success rate was significantly lower for individuals with many periodontal pockets and for those with the diagnosis local periodontitis. The prevalence of adolescents classified as having high periodontal risk was low. A large frequency of subjects dropped out before the periodontal treatment was completed, especially at the specialist clinics.

Hypertension update and cardiovascular risk reduction in physically active individuals and athletes.

PubMed

Oliveira, Leonardo P J; Lawless, Christine E

2010-04-01

Hypertension is a prevalent disease worldwide. Its inadequate treatment leads to major cardiovascular complications, such as myocardial infarction, stroke, and heart failure. These conditions decrease life expectancy and are a substantial cost burden to health care systems. Physically active individuals and professional athletes are not risk free for developing this condition. Although the percentage of persons affected is substantially lower than the general population, these individuals still need to be thoroughly evaluated and blood pressure targets monitored to allow safe competitive sports participation. Regarding treatment, lifestyle modification measures should be routinely emphasized to athletes and active individuals with the same importance as for the general population. Medication treatment can be complicated because of restrictions by athletic organizations and possible limitations on maximal exercise performance. In addition, the choice of an antihypertensive drug should be made with consideration for salt and water losses that routinely occur in athletes, as well as preservation of exercise performance and endothelial function. First-line therapies for athletes and physically active individuals may be different from the general population. Some authorities believe that blocking the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is more beneficial compared with diuretics because of ACE inhibitors and ARBs being able to avoid salt and water losses. Dihydropyridine calcium channel blockers (CCBs) are another reasonable choice. Despite effects on heart rate, nondihydropyridine CCBs do not appear to impair exercise performance. beta-Blockers are not used as a first-line therapy in athletes because of effects on exercise and prohibition by the National Collegiate Athletic Association and World Anti-Doping Agency in certain sports. In this article, we address the evidence on hypertension

Tuberculosis testing among populations with high HIV risk in Tijuana, Baja California, Mexico

PubMed Central

Velasquez, Michele G.; Laniado-Laborin, Rafael; Rodwell, Timothy C.; Cerecer, Paris; Lozada, Remedios; Cuevas-Mota, Jazmine; Burgos, Jose Luis; Garfein, Richard S.

2013-01-01

Objective To assess the prevalence of prior tuberculin skin testing (TST) among populations at risk for HIV infection in Tijuana, Mexico, and to identify factors associated with TST. Methods Sex workers, injection drug users, noninjecting drug users, and homeless persons ≥ 18 years old were recruited by using targeted sampling for risk assessment interviews and serologic testing for HIV and Mycobacterium tuberculosis infection. Univariate and multivariate logistic regression were used to identify correlates of self-reported TST history. Results Of 502 participants, 38.0% reported prior TST, which was associated with previous incarceration in the United States of America [odds ratio (OR) = 13.38; 95% confidence interval (CI) = 7.37–24.33] and injection drug use (OR = 1.99; 95% CI = 1.27–3.11). Positive results on serologic tests for M. tuberculosis infection (57%) and HIV (4.2%) were not associated with a prior TST. Conclusions A history of TST was lower in HIV-positive participants even though TST is indicated for persons with HIV in Mexico. Fewer than half the individuals at high risk for HIV in this study had a history of TST; however, TST was fairly common among those individuals with a prior history of incarceration. Increased tuberculosis screening is needed for populations at risk of contracting HIV in Tijuana, particularly those outside of criminal justice settings. PMID:22910722

Tuberculosis testing among populations with high HIV risk in Tijuana, Baja California, Mexico.

PubMed

Velasquez, Michele G; Laniado-Laborin, Rafael; Rodwell, Timothy C; Cerecer, Paris; Lozada, Remedios; Cuevas-Mota, Jazmine; Burgos, Jose Luis; Garfein, Richard S

2012-07-01

To assess the prevalence of prior tuberculin skin testing (TST) among populations at risk for HIV infection in Tijuana, Mexico, and to identify factors associated with TST. Sex workers, injection drug users, noninjecting drug users, and homeless persons > 18 years old were recruited by using targeted sampling for risk assessment interviews and serologic testing for HIV and Mycobacterium tuberculosis infection. Univariate and multivariate logistic regression were used to identify correlates of self-reported TST history. Of 502 participants, 38.0% reported prior TST, which was associated with previous incarceration in the United States of America [odds ratio (OR) = 13.38; 95% confidence interval (CI) = 7.37-24.33] and injection drug use (OR = 1.99; 95% CI = 1.27- 3.11). Positive results on serologic tests for M. tuberculosis infection (57%) and HIV (4.2%) were not associated with a prior TST. A history of TST was lower in HIV-positive participants even though TST is indicated for persons with HIV in Mexico. Fewer than half the individuals at high risk for HIV in this study had a history of TST; however, TST was fairly common among those individuals with a prior history of incarceration. Increased tuberculosis screening is needed for populations at risk of contracting HIV in Tijuana, particularly those outside of criminal justice settings.

Can healthy, young adults uncover personal details of unknown target individuals in their dreams?

PubMed

Smith, Carlyle

2013-01-01

We investigated the possibility that undergraduate college students could incubate dreams containing information about unknown target individuals with significant life problems. In Experiment 1, students provided two baseline dreams. They were then exposed to a photo of an individual and invited to dream about a health problem (unknown to them and the experimenter) of that individual and asked to provide two more dreams. From a class of 65 students, 12 dreamers volunteered dreams about the unknown target. In Experiment 2, 66 students were asked to dream about the life problems of a second individual, simply by looking at the photo (experimental group). Another 56 students were exposed to this same paradigm, but the photo that they examined was computer generated and the target individual was fictitious (control group). The dream elements were objectively scored with categories devised using the Hall-Van de Castle system as a model. Data were ordinal, and the nonparametric Wilcoxon signed rank test was used to examine preincubation (baseline) versus postincubation (photo examination and incubation) dream content in Experiment 1. In Experiment 2, a Z score for proportions was used to compare differences in frequency of devised categories between experimental and control groups. In Experiment 1, the comparison of postincubation dreams (all categories combined) was significant compared with the preincubation dreams (Z = 2.09, P = .036). The postincubation dreams reflected the health problem of the target. In Experiment 2, the proportion of scored categories in experimental and control groups were compared at the preincubation and postincubation conditions. The proportions of "Combined" (all categories) was very significantly larger at the postincubation condition (Z = 6.27, P < .00001). The groups did not differ at the preincubation condition (Z = -1.12, not significant). Individual postincubation condition comparisons of the experimental versus control groups revealed

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

Physical activity barriers and motivators among high-risk employees.

PubMed

Paguntalan, John C; Gregoski, Mathew

2016-11-22

Worksite wellness programs offer an ideal setting to target high-risk sedentary workers to improve health status. Lack of physical activity is associated with increased risk for coronary heart disease and mortality. Despite the risks, the number of sedentary workers is increasing. This study examined the perceived barriers and motivators for physical activity among employees at high-risk for coronary heart disease. A purposive sample of 24 high-risk workers participating in a wellness program in rural South Carolina were enrolled in the study. Qualitative data was obtained through semi-structured face-to-face interviews. Grounded theory was used to analyze qualitative data, and identify overarching themes. Physical limitations due to pain and weakness, lack of motivation, and lack of time emerged as the main barriers to physical activity. Family relationships were reported as the strongest motivator along with social support and potential health benefits. Findings highlight the unique experience of high-risk workers with physical activity. The findingsunderscore the need to design and implement effective interventions specifically designed to meet the needs of high-risk employees.

Targeting trachoma control through risk mapping: the example of Southern Sudan.

PubMed

Clements, Archie C A; Kur, Lucia W; Gatpan, Gideon; Ngondi, Jeremiah M; Emerson, Paul M; Lado, Mounir; Sabasio, Anthony; Kolaczinski, Jan H

2010-08-17

Trachoma is a major cause of blindness in Southern Sudan. Its distribution has only been partially established and many communities in need of intervention have therefore not been identified or targeted. The present study aimed to develop a tool to improve targeting of survey and control activities. A national trachoma risk map was developed using Bayesian geostatistics models, incorporating trachoma prevalence data from 112 geo-referenced communities surveyed between 2001 and 2009. Logistic regression models were developed using active trachoma (trachomatous inflammation follicular and/or trachomatous inflammation intense) in 6345 children aged 1-9 years as the outcome, and incorporating fixed effects for age, long-term average rainfall (interpolated from weather station data) and land cover (i.e. vegetation type, derived from satellite remote sensing), as well as geostatistical random effects describing spatial clustering of trachoma. The model predicted the west of the country to be at no or low trachoma risk. Trachoma clusters in the central, northern and eastern areas had a radius of 8 km after accounting for the fixed effects. In Southern Sudan, large-scale spatial variation in the risk of active trachoma infection is associated with aridity. Spatial prediction has identified likely high-risk areas to be prioritized for more data collection, potentially to be followed by intervention.

Delay discounting, risk-taking, and rejection sensitivity among individuals with Internet and Video Gaming Disorders.

PubMed

Weinstein, Aviv; Abu, Hodaya Ben; Timor, Ayelet; Mama, Yaniv

2016-12-01

Background and aims There is a previous evidence for impulsivity in individuals with Internet and Video Gaming Disorders. The aim of this study was to examine whether Internet and video game addictions are associated with experiential delay discounting, risk-taking, and sensitivity to social rejection using computerized tasks and questionnaires. Methods Twenty participants (mean age 24, SD = 1.55) with high score on the Problematic Online Gaming Questionnaire (POGQ) were compared with 20 participants (mean age 24.8, SD = 1.34) with low score on the POGQ. They performed on computerized Balloon Analog Risk Task and Experiential Delay discounting Task (EDT), and filled in the sensitivity to social rejection questionnaire. Results Participants with high POGQ scores had lower measures of delay discounting, higher measures of risk-taking, and higher measures of sensitivity to social rejection compared with participants with low POGQ scores. Discussion The results of this study support the previous evidence of risk-taking and provide new evidence for difficulties in delay discounting and sensitivity to social rejection among those who score high on Internet and video games. Conclusions The results suggest that Internet- and video game-addicted individuals seek immediate gratification and cannot wait for later reward. Furthermore, these individuals spend time in the virtual world, where they feel safe, and avoid social interactions presumably due to fears of social rejection.

Contact Networks in a Wildlife-Livestock Host Community: Identifying High-Risk Individuals in the Transmission of Bovine TB among Badgers and Cattle

PubMed Central

Böhm, Monika; Hutchings, Michael R.; White, Piran C. L.

2009-01-01

through complex contact networks. Targeting testing or preventive measures at high-contact groups and individuals within livestock populations would enhance the effectiveness and efficiency of disease management strategies. PMID:19401755

Emotional Encoding Context Leads to Memory Bias in Individuals with High Anxiety

PubMed Central

Fernandes, Myra A.

2017-01-01

We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects) using a deep or shallow encoding instruction (between-subjects). Following study, in Test 1, participants completed separate recognition test blocks for the words overlayed onto the negative and the neutral contexts. Following this, in Test 2, participants completed a recognition test for the foils from each Test 1 block. We found a significant three-way interaction on Test 2, such that individuals with high anxiety who initially studied target words using a shallow encoding instruction, demonstrated significantly elevated memory for foils that were contained within the negative Test 1 block. Results show that during retrieval (Test 1), participants re-entered the mode of processing (negative or neutral) engaged at encoding, tainting the encoding of foils with that same mode of processing. The findings suggest that individuals with high relative to low anxiety, adopt a particularly salient negative retrieval mode, and this creates a downstream bias in encoding and subsequent retrieval of otherwise neutral information. PMID:29280957

Emotional Encoding Context Leads to Memory Bias in Individuals with High Anxiety.

PubMed

Lee, Christopher; Fernandes, Myra A

2017-12-27

We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects) using a deep or shallow encoding instruction (between-subjects). Following study, in Test 1, participants completed separate recognition test blocks for the words overlayed onto the negative and the neutral contexts. Following this, in Test 2, participants completed a recognition test for the foils from each Test 1 block. We found a significant three-way interaction on Test 2, such that individuals with high anxiety who initially studied target words using a shallow encoding instruction, demonstrated significantly elevated memory for foils that were contained within the negative Test 1 block. Results show that during retrieval (Test 1), participants re-entered the mode of processing (negative or neutral) engaged at encoding, tainting the encoding of foils with that same mode of processing. The findings suggest that individuals with high relative to low anxiety, adopt a particularly salient negative retrieval mode, and this creates a downstream bias in encoding and subsequent retrieval of otherwise neutral information.

Individualization of a Manualized Pressure Ulcer Prevention Program: Targeting Risky Life Circumstances Through a Community-Based Intervention for People with Spinal Cord Injury

PubMed Central

Vaishampayan, Ashwini; Clark, Florence; Carlson, Mike; Blanche, Erna Imperatore

2012-01-01

Purpose To sensitize practitioners working with individuals with spinal cord injury to the complex life circumstances that are implicated in the development of pressure ulcers, and to document the ways that interventions can be adapted to target individual needs. Methods Content analysis of weekly fidelity/ quality control meetings that were undertaken as part of a lifestyle intervention for pressure ulcer prevention in community-dwelling adults with spinal cord injury. Results Four types of lifestyle-relevant challenges to ulcer prevention were identified: risk-elevating life circumstances, communication difficulties, equipment problems, and individual personality issues. Intervention flexibility was achieved by changing the order of treatment modules, altering the intervention content or delivery approach, or going beyond the stipulated content. Conclusion Attention to recurrent types of individual needs, along with explicit strategies for tailoring manualized interventions, has potential to enhance pressure ulcer prevention efforts for adults with spinal cord injury. Target audience This continuing education article is intended for practitioners interested in learning about a comprehensive, context-sensitive, community-based pressure ulcer prevention program for people with spinal cord injury. Objectives After reading this article, the reader should be able to: Describe some of the contextual factors that increase pressure ulcer risk in people with spinal cord injury living in the community.Distinguish between tailored and individualized intervention approaches.Identify the issues that must be taken into account to design context-sensitive, community-based pressure ulcer prevention programs for people with spinal cord injury.Describe approaches that can be used to individualize manualized interventions. PMID:21586911

Back and upper extremity disorders among enlisted U.S. Marines: burden and individual risk factors.

PubMed

Huang, G D; Feuerstein, M; Arroyo, F

2001-11-01

Although musculoskeletal disorders of the low back and upper extremities can affect military readiness, little is known about their extent and risk factors in the U.S. Marine Corps. Using the Defense Medical Epidemiology and Defense Medical Surveillance System databases, back and upper extremity diagnostic categories were among the top four sources of outpatient visits and duty limitation among enlisted Marines. Back disorders were also found to be the fifth most common cause for lost time. Subsequently, high-risk occupations were identified, age-related trends for clinic visit rates were determined, and rate ratios were computed for the top 15 low back and upper extremity diagnoses among enlisted Marines from 1997 through 1998. Occupational categories with the highest rates of musculoskeletal-related outpatient visits included image interpretation, auditing and accounting, disturbsing, surveillance/target acquisition, and aircraft launch equipment. Significantly increasing linear trends in rates across age groups were found for most diagnoses. For 1998, age-specific rate ratios indicated significantly higher rates for most low back and upper extremity disorders for females; lower rank (i.e., E1-E4) was also a risk, but for fewer diagnoses. The findings emphasize the need to identify modifiable (e.g., work-related, individual) risk factors and to develop focused primary and secondary prevention programs for musculoskeletal disorders in the Marine Corps. Subsequently, these efforts can assist in reducing associated effects, maximizing resource utilization, and enhancing operational readiness.

Risk-Based Evaluation of Total Petroleum Hydrocarbons in Vapor Intrusion Studies

PubMed Central

Brewer, Roger; Nagashima, Josh; Kelley, Michael; Heskett, Marvin; Rigby, Mark

2013-01-01

This paper presents a quantitative method for the risk-based evaluation of Total Petroleum Hydrocarbons (TPH) in vapor intrusion investigations. Vapors from petroleum fuels are characterized by a complex mixture of aliphatic and, to a lesser extent, aromatic compounds. These compounds can be measured and described in terms of TPH carbon ranges. Toxicity factors published by USEPA and other parties allow development of risk-based, air and soil vapor screening levels for each carbon range in the same manner as done for individual compounds such as benzene. The relative, carbon range makeup of petroleum vapors can be used to develop weighted, site-specific or generic screening levels for TPH. At some critical ratio of TPH to a targeted, individual compound, the overwhelming proportion of TPH will drive vapor intrusion risk over the individual compound. This is particularly true for vapors associated with diesel and other middle distillate fuels, but can also be the case for low-benzene gasolines or even for high-benzene gasolines if an adequately conservative, target risk is not applied to individually targeted chemicals. This necessitates a re-evaluation of the reliance on benzene and other individual compounds as a stand-alone tool to evaluate vapor intrusion risk associated with petroleum. PMID:23765191

Individualized Fracture Risk Feedback and Long-term Benefits After 10 Years.

PubMed

Wu, Feitong; Wills, Karen; Laslett, Laura L; Riley, Malcolm D; Oldenburg, Brian; Jones, Graeme; Winzenberg, Tania

2018-02-01

This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term. This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25-44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires. From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (β=0.023, 95% CI=0.005, 0.041 g/cm 2 ) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking). Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis. Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights

A study on negative and depressive symptom prevalence in individuals at ultra-high risk for psychosis.

PubMed

Azar, Marleine; Pruessner, Marita; Baer, Lawrence H; Iyer, Srividya; Malla, Ashok K; Lepage, Martin

2016-09-21

Negative symptoms are known to be present in the prodromal stage of psychotic disorders, yet little is known about their prevalence. Studies examining the presence of negative symptoms in ultra-high risk (UHR) populations have shown some limitations, notably failing to control depression. The objective of this study was to examine the prevalence of negative symptoms in the presence of significant levels of depression and in the absence of such symptoms (primary negative symptoms) over 1 year and to examine differences in negative symptoms in psychosis converters and non-converters. Participants were 123 individuals at UHR for the development of psychosis receiving follow-up for a period of 2 years. Negative symptoms and depression were measured using the Scale for the Assessment of Negative Symptoms and the Montgomery-Asberg Depression Scale at baseline, 6 and 12 months post-admission. At baseline, the prevalence of negative symptoms and primary negative symptoms was 76.4% and 32.7%, respectively. Whereas the prevalence of negative symptoms was significantly decreased at 6 months, the prevalence of primary negative symptoms was similar at all time points. Negative symptoms at baseline were not different between later converters and non-converters to psychosis. Our findings confirm the presence of secondary and primary negative symptoms in individuals at UHR, but suggest a differential trajectory of both measures over time. Future studies should include larger UHR groups and focus on the investigation of intra-individual changes in primary negative symptoms over time and further explore their potential role for psychosis conversion. © 2016 John Wiley & Sons Australia, Ltd.

Diagnosis and Management of High Risk Group for Gastric Cancer

PubMed Central

Yoon, Hyuk; Kim, Nayoung

2015-01-01

Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer.

PubMed

Donà, Maria Gabriella; Benevolo, Maria; Latini, Alessandra; Rollo, Francesca; Colafigli, Manuela; Frasca, Mirko; Zaccarelli, Mauro; Giglio, Amalia; Moretto, Domenico; Pescarmona, Edoardo; Cristaudo, Antonio; Giuliani, Massimo

2018-04-25

Anal cytology may be useful for evaluating lesions associated with human papillomavirus (HPV) in individuals at increased risk for anal cancer. Liquid-based cytology was used to assess anal cytological lesions among human immunodeficiency virus (HIV)-infected and HIV-uninfected men who have sex with men (MSM). The Linear Array HPV genotyping test was used for HPV detection. This cross-sectional study included 1021 MSM, of whom 388 were HIV-infected (38.0%). Anal cytological lesions (atypical squamous cells of undetermined significance or more severe [ASCUS+]) were observed in 32.5% and 53.2% of the HIV-uninfected and HIV-infected individuals, respectively (P < .0001). The highest ASCUS + prevalence was observed among ≥45-year-old HIV-uninfected MSM (37.3%) and 25-to 29-year-old HIV-infected MSM (66.7%). High-grade squamous intraepithelial lesions (HSILs) peaked in ≥ 45-year-old HIV-uninfected subjects and 35- to 39-year-old HIV-infected subjects. Individuals with anal infections with high-risk (HR) HPV types were 3 to 4 times more likely to have an ASCUS + report. An HPV-16 and/or HPV-18 infection increased the odds of HSIL or more severe cytology (HSIL+) for HIV-infected MSM almost 4 times. MSM concurrently infected with HR and low-risk HPVs were significantly more likely to have low-grade squamous intraepithelial lesions or more severe cytology (LSIL+) than those infected with only HR types. No significant associations were found between cytological abnormalities and the HIV load and nadir and current CD4 + counts. The prevalence of anal cytological lesions is high in MSM, even in HIV-infected individuals treated with combined antiretroviral therapy. In these subjects, HSILs occur more frequently and at a younger age in comparison with HIV-uninfected counterparts. Specific diagnostic procedures should be implemented to manage individuals at increased risk for anal cancer with an abnormal anal Papanicolaou test. Cancer Cytopathol 2018. �

Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany; Kisamore, April N

2017-07-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target. © 2017 Society for the Experimental Analysis of Behavior.

A Danish diabetes risk score for targeted screening: the Inter99 study.

PubMed

Glümer, Charlotte; Carstensen, Bendix; Sandbaek, Annelli; Lauritzen, Torsten; Jørgensen, Torben; Borch-Johnsen, Knut

2004-03-01

To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765-0.838) for the first half of the Inter99 population, 0.761 (0.720-0.803) for the second half of the Inter99 population, and 0.803 (0.721-0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P<0.0001). We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.

Temporal association of cannabis use with symptoms in individuals at clinical high risk for psychosis.

PubMed

Corcoran, Cheryl M; Kimhy, David; Stanford, Arielle; Khan, Shamir; Walsh, Julie; Thompson, Judy; Schobel, Scott; Harkavy-Friedman, Jill; Goetz, Ray; Colibazzi, Tiziano; Cressman, Victoria; Malaspina, Dolores

2008-12-01

Cannabis use is reported to increase the risk for psychosis, but no prospective study has longitudinally examined drug use and symptoms concurrently in clinical high risk cases. We prospectively followed for up to 2 years 32 cases who met research criteria for prodromal psychosis to examine the relationship between substance use and clinical measures. Cases with a baseline history of cannabis use (41%) were older, but did not differ in clinical measures. Longitudinal assessments showed these cases had significantly more perceptual disturbances and worse functioning during epochs of increased cannabis use that were unexplained by concurrent use of other drugs or medications. These data demonstrate that cannabis use may be a risk factor for the exacerbation of subthreshold psychotic symptoms, specifically perceptual disturbances, in high risk cases.

Subgroups at high risk for ischaemic heart disease:identification and validation in 67 000 individuals from the general population

PubMed Central

Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Dyson, Greg; Haase, Christiane L; Benn, Marianne; Nordestgaard, Børge G; Sing, Charles F

2015-01-01

Background The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects. Methods PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS). Results In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS. Conclusions PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population. PMID:25361584

Increasing colorectal cancer screening among individuals in the carpentry trade: test of risk communication interventions.

PubMed

Lipkus, Isaac M; Skinner, Celette Sugg; Dement, John; Pompeii, Lisa; Moser, Barry; Samsa, Gregory P; Ransohoff, David

2005-05-01

Individuals in the carpentry trade, due to lifestyle habits and occupational exposures, may be at above-average risk for colorectal cancer (CRC). Based on the literature which suggests that increasing perceived risk motivates behavior change, we report on the effectiveness of four risk-communication interventions targeted to increase initial, yearly and repeat fecal occult screening (FOBT) among carpenters (N = 860) over a 3-year period. Our 2 x 2 factorial design intervention study varied two dimensions of providing CRC risk factor information: (1) type of risk factor-one set of interventions emphasized three basic risk factors (age, family history and polyps); the other set emphasized a comprehensive set of risk factors including basic, lifestyle, and occupational factors, and (2) tailoring/not tailoring risk factor information. Participants were provided FOBTs. Outcomes were the proportion of returned FOBTs. Varying the amount and intensity of delivering CRC risk factors information affected neither risk perceptions nor initial, yearly, or repeat screening. However, yearly and repeat screening rates were greater among participants who received interventions addressing comprehensive set of risk factors, especially with increasing age. Tailoring on several CRC risk factors appears insufficient to increase and sustain elevated perceptions of CRC risks to promote screening.

Impact of Neurocognition on Social and Role Functioning in Individuals at Clinical High Risk for Psychosis

PubMed Central

Carrión, Ricardo E.; Goldberg, Terry E.; McLaughlin, Danielle; Auther, Andrea M.; Correll, Christoph U.; Cornblatt, Barbara A.

2011-01-01

Objective Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. Method A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Results Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. Conclusions These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning. PMID:21536691

Impact of neurocognition on social and role functioning in individuals at clinical high risk for psychosis.

PubMed

Carrión, Ricardo E; Goldberg, Terry E; McLaughlin, Danielle; Auther, Andrea M; Correll, Christoph U; Cornblatt, Barbara A

2011-08-01

Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning.

Bridging the gap between individual-level risk for HIV and structural determinants: using root cause analysis in strategic planning.

PubMed

Willard, Nancy; Chutuape, Kate; Stines, Stephanie; Ellen, Jonathan M

2012-01-01

HIV prevention efforts have expanded beyond individual-level interventions to address structural determinants of risk. Coalitions have been an important vehicle for addressing similar intractable and deeply rooted health-related issues. A root cause analysis process may aid coalitions in identifying fundamental, structural-level contributors to risk and in identifying appropriate solutions. For this article, strategic plans for 13 coalitions were analyzed both before and after a root cause analysis approach was applied to determine the coalitions' strategic plans potential impact and comprehensiveness. After root cause analysis, strategic plans trended toward targeting policies and practices rather than on single agency programmatic changes. Plans expanded to target multiple sectors and several changes within sectors to penetrate deeply into a sector or system. Findings suggest that root cause analysis may be a viable tool to assist coalitions in identifying structural determinants and possible solutions for HIV risk.

"For all my family's sake, I should go and find out": an Australian report on genetic counseling and testing uptake in individuals at high risk of breast and/or ovarian cancer.

PubMed

Wakefield, Claire E; Ratnayake, Paboda; Meiser, Bettina; Suthers, Graeme; Price, Melanie A; Duffy, Jessica; Tucker, Kathy

2011-06-01

Despite proven benefits, the uptake of genetic counseling and testing by at-risk family members of BRCA1 and BRCA2 mutation carriers remains low. This study aimed to examine at-risk individuals' reported reasons for and against familial cancer clinic (FCC) attendance and genetic testing. Thirty-nine telephone interviews were conducted with relatives of high-risk mutation carriers, 23% (n = 9) of whom had not previously attended an FCC. Interview responses were analyzed using the frameworks of Miles and Huberman. The reasons most commonly reported for FCC attendance were for clarification of risk status and to gain access to testing. While disinterest in testing was one reason for FCC nonattendance, several individuals were unaware of their risk (n = 3) or their eligibility to attend an FCC (n = 2), despite being notified of their risk status through their participation in a large-scale research project. Individuals' reasons for undergoing testing were in line with that reported elsewhere; however, concerns about discrimination and insurance were not reported in nontestees. Current guidelines regarding notifying individuals discovered to be at increased risk in a research, rather than clinical setting, take a largely nondirective approach. However, this study demonstrates that individuals who receive a single letter notifying them of their risk may not understand/value the information they receive.

Risk Factors and Therapeutic Targets in Pancreatic Cancer

PubMed Central

Wörmann, Sonja Maria; Algül, Hana

2013-01-01

Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc., increase the potential for acquiring genetic mutations that may result in PC. Another hallmark of PC is its poor response to radio- and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signaling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches. PMID:24303367

Exploratory analysis of social cognition and neurocognition in individuals at clinical high risk for psychosis.

PubMed

Yong, Emma; Barbato, Mariapaola; Penn, David L; Keefe, Richard S E; Woods, Scott W; Perkins, Diana O; Addington, Jean

2014-08-15

Neurocognition and social cognition are separate but related constructs known to be impaired in schizophrenia. The aim of this study was to extend the current knowledge of the relationship between social cognition and neurocognition in individuals at clinical high risk (CHR) of developing psychosis by examining, in a large sample, the associations between a wide range of neurocognitive tasks and social cognition. Participants included 136 young people at CHR. Specific domains within neurocognition and social cognition were compared using Spearman correlations. Results showed that poor theory of mind correlated with low ratings on a wide range of neurocognitive tasks. Facial affect was more often associated with low ratings on spatial working memory and attention. These results support a link between neurocognition and social cognition even at this early stage of potential psychosis, with indication that poorer performance on social cognition may be associated with deficits in attention and working memory. Understanding these early associations may have implications for early intervention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Health-risk appraisal with or without disease management for worksite cardiovascular risk reduction.

PubMed

Maron, David J; Forbes, Barbara L; Groves, Jay R; Dietrich, Mary S; Sells, Patrick; DiGenio, Andres G

2008-01-01

Worksite health promotion programs use health risk appraisal (HRA) surveys to identify employees at increased risk, then provide a range of interventions to encourage high-risk individuals to improve their health. Our objective was to determine how the intensity of intervention after HRA affected cardiovascular risk after 1 year, comparing individual follow-up counseling with environmental supports. 133 employees of Vanderbilt University with cardiovascular risk factors were randomly assigned to worksite HRA plus targeted disease management (DM group) or HRA plus information about worksite health promotion programs (HRA group). The DM group received longitudinal individualized counseling for risk reduction, whereas the HRA group members received one feedback session about their risk factors and information about free worksite health promotion programs. The main outcome measure was the difference between groups in the change in average Framingham risk score from baseline to 1 year. There was no significant baseline difference between groups in the Framingham risk score. Among DM participants, the mean (SD) Framingham risk score decreased by 22.6%; among HRA participants, the mean score rose by 4.3% (P = .017 for the difference between groups). In this study of employees with cardiovascular risk factors, HRA followed by individual counseling was more effective than providing information about free worksite health promotion programs.

Individual versus systemic risk and the Regulator's Dilemma.

PubMed

Beale, Nicholas; Rand, David G; Battey, Heather; Croxson, Karen; May, Robert M; Nowak, Martin A

2011-08-02

The global financial crisis of 2007-2009 exposed critical weaknesses in the financial system. Many proposals for financial reform address the need for systemic regulation--that is, regulation focused on the soundness of the whole financial system and not just that of individual institutions. In this paper, we study one particular problem faced by a systemic regulator: the tension between the distribution of assets that individual banks would like to hold and the distribution across banks that best supports system stability if greater weight is given to avoiding multiple bank failures. By diversifying its risks, a bank lowers its own probability of failure. However, if many banks diversify their risks in similar ways, then the probability of multiple failures can increase. As more banks fail simultaneously, the economic disruption tends to increase disproportionately. We show that, in model systems, the expected systemic cost of multiple failures can be largely explained by two global parameters of risk exposure and diversity, which can be assessed in terms of the risk exposures of individual actors. This observation hints at the possibility of regulatory intervention to promote systemic stability by incentivizing a more diverse diversification among banks. Such intervention offers the prospect of an additional lever in the armory of regulators, potentially allowing some combination of improved system stability and reduced need for additional capital.

Individual versus systemic risk and the Regulator's Dilemma

PubMed Central

Beale, Nicholas; Rand, David G.; Battey, Heather; Croxson, Karen; May, Robert M.; Nowak, Martin A.

2011-01-01

The global financial crisis of 2007–2009 exposed critical weaknesses in the financial system. Many proposals for financial reform address the need for systemic regulation—that is, regulation focused on the soundness of the whole financial system and not just that of individual institutions. In this paper, we study one particular problem faced by a systemic regulator: the tension between the distribution of assets that individual banks would like to hold and the distribution across banks that best supports system stability if greater weight is given to avoiding multiple bank failures. By diversifying its risks, a bank lowers its own probability of failure. However, if many banks diversify their risks in similar ways, then the probability of multiple failures can increase. As more banks fail simultaneously, the economic disruption tends to increase disproportionately. We show that, in model systems, the expected systemic cost of multiple failures can be largely explained by two global parameters of risk exposure and diversity, which can be assessed in terms of the risk exposures of individual actors. This observation hints at the possibility of regulatory intervention to promote systemic stability by incentivizing a more diverse diversification among banks. Such intervention offers the prospect of an additional lever in the armory of regulators, potentially allowing some combination of improved system stability and reduced need for additional capital. PMID:21768387

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

PubMed

Murchie, Brent; Tandon, Kanwarpreet; Hakim, Seifeldin; Shah, Kinchit; O'Rourke, Colin; Castro, Fernando J

2017-04-01

Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

Risk factors for knee replacement due to primary osteoarthritis, a population based, prospective cohort study of 315,495 individuals.

PubMed

Apold, Hilde; Meyer, Haakon E; Nordsletten, Lars; Furnes, Ove; Baste, Valborg; Flugsrud, Gunnar B

2014-06-23

Osteoarthritis (OA) of the knee is a common and disabling condition. We wanted to investigate the modifiable risk factors Body Mass Index (BMI) and physical activity, using knee replacement (KR) as a marker for severely symptomatic disease, focusing on the interaction between these risk factors. 315,495 participants (mean age 43.0 years) from national health screenings were followed prospectively with respect to KR identified by linkage to the Norwegian Arthroplasty Register. Data were analysed by Cox proportional hazard regression. During 12 years of follow up 1,323 individuals received KR for primary OA. There was a dose-response relationship between BMI and heavy labour, and later KR. Comparing the highest versus the lowest quarter of BMI, the relative risk was 6.2 (95% CI: 4.2-9.0) in men and 11.1 (95% CI: 7.8-15.6) in women. Men reporting intensive physical activity at work had a relative risk of 2.4 (95% CI: 1.8-3.2) versus men reporting sedentary activity at work, the corresponding figure in women being 2.3 (95% CI: 1.7-3.2). The effect of BMI and physical activity at work was additive. The heaviest men with the most strenuous work had a RR of 11.7 (95% CI: 5.9-23.1) compared to the ones with the lowest BMI and most sedentary work. For women the corresponding RR was 15.8 (95% CI: 8.2-30.3). There was no association between physical activity during leisure and KR. We found that a high BMI and intensive physical activity at work both contribute strongly to the risk of having a KR. As the two risk factors seem to act independently, people with strenuous physical work with a high BMI are at particularly high risk for severely disabling OA of the knee, and should be targeted with effective preventive measures.

Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.

PubMed

Bosse, Kristopher R; Raman, Pichai; Zhu, Zhongyu; Lane, Maria; Martinez, Daniel; Heitzeneder, Sabine; Rathi, Komal S; Kendsersky, Nathan M; Randall, Michael; Donovan, Laura; Morrissy, Sorana; Sussman, Robyn T; Zhelev, Doncho V; Feng, Yang; Wang, Yanping; Hwang, Jennifer; Lopez, Gonzalo; Harenza, Jo Lynne; Wei, Jun S; Pawel, Bruce; Bhatti, Tricia; Santi, Mariarita; Ganguly, Arupa; Khan, Javed; Marra, Marco A; Taylor, Michael D; Dimitrov, Dimiter S; Mackall, Crystal L; Maris, John M

2017-09-11

We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

2017 Taiwan lipid guidelines for high risk patients.

PubMed

Li, Yi-Heng; Ueng, Kwo-Chang; Jeng, Jiann-Shing; Charng, Min-Ji; Lin, Tsung-Hsien; Chien, Kuo-Liong; Wang, Chih-Yuan; Chao, Ting-Hsing; Liu, Ping-Yen; Su, Cheng-Huang; Chien, Shih-Chieh; Liou, Chia-Wei; Tang, Sung-Chun; Lee, Chun-Chuan; Yu, Tse-Ya; Chen, Jaw-Wen; Wu, Chau-Chung; Yeh, Hung-I

2017-04-01

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C <55 mg/dL can be considered in ACS patients with DM. After treating LDL-C to target, non-HDL-C can be considered as a secondary target for patients with TG ≥ 200 mg/dL. The suggested non-HDL-C target is < 100 mg/dL in ACS and CAD patients. For patients with ischemic stroke or transient ischemic attack presumed to be of atherosclerotic origin, statin therapy is beneficial and LDL-C < 100 mg/dL is the suggested target. For patients with symptomatic carotid stenosis or intracranial arterial stenosis, in addition to antiplatelets and blood pressure control, LDL

Increase in physical activity and cardiometabolic risk profile change during lifestyle intervention in primary healthcare: 1-year follow-up study among individuals at high risk for type 2 diabetes.

PubMed

Kujala, Urho M; Jokelainen, Jari; Oksa, Heikki; Saaristo, Timo; Rautio, Nina; Moilanen, Leena; Korpi-Hyövälti, Eeva; Saltevo, Juha; Vanhala, Mauno; Niskanen, Leo; Peltonen, Markku; Tuomilehto, Jaakko; Uusitupa, Matti; Keinänen-Kiukaannemi, Sirkka

2011-01-01

Objectives To investigate the association between increase in physical activity and changes in cardiometabolic risk factors during a lifestyle intervention programme in routine clinical settings. Design Prospective follow-up. Setting 400 primary healthcare centres and occupational healthcare outpatient clinics in Finland. Participants Individuals at high risk for type 2 diabetes identified in the implementation project of the national diabetes prevention programme (FIN-D2D) and participating in baseline and 1-year follow-up visits. Final study group comprised the 1871 non-diabetic participants who responded at follow-up visit to a question on stability versus increase of physical activity. Interventions Lifestyle intervention. Primary outcome measures Cardiometabolic risk factors (body composition, blood pressure and those measured from fasting venous blood samples) measured at baseline and follow-up visits. Results Of the participants, 310 (16.6% of all responders) reported at follow-up having clearly increased their physical activity during the past year, while 1380 (73.8%) had been unable to increase their physical activity. Those who increased their activity decreased their weight by 3.6 kg (95% CI 2.9 to 4.3, age and sex adjusted, p<0.001) and waist circumference by 3.6 cm (95% CI 2.9 to 4.3, p<0.001) more than those who did not increase their activity. Similarly, those who increased their physical activity had greater reductions in total cholesterol (group difference in reduction 0.17 mmol/l, 95% CI 0.06 to 0.28, p=0.002), low-density lipoprotein cholesterol (0.16 mmol/l, 95% CI 0.06 to 0.26, p=0.001), low-density lipoprotein/high-density lipoprotein ratio (0.17, 95% CI 0.08 to 0.25, p<0.001) as well as fasting glucose (0.09 mmol/l, 95% CI 0.03 to 0.15, p=0.004) and 2 h glucose levels (0.36 mmol/l, 95% CI 0.17 to 0.55, p=0.023) than those who did not increase their physical activity. Conclusion Increasing physical activity seems to be an important feature of

Community participatory physical activity intervention targets children at high risk for obesity

USDA-ARS?s Scientific Manuscript database

This community participatory research evaluated the feasibility of a summer soccer and nutrition education program to increase physical activity (PA) in rural Mississippi Delta children at high risk of obesity and previously not exposed to soccer. Children aged 4-12 were recruited through school and...

Targeting Trachoma Control through Risk Mapping: The Example of Southern Sudan

PubMed Central

Clements, Archie C. A.; Kur, Lucia W.; Gatpan, Gideon; Ngondi, Jeremiah M.; Emerson, Paul M.; Lado, Mounir; Sabasio, Anthony; Kolaczinski, Jan H.

2010-01-01

Background Trachoma is a major cause of blindness in Southern Sudan. Its distribution has only been partially established and many communities in need of intervention have therefore not been identified or targeted. The present study aimed to develop a tool to improve targeting of survey and control activities. Methods/Principal Findings A national trachoma risk map was developed using Bayesian geostatistics models, incorporating trachoma prevalence data from 112 geo-referenced communities surveyed between 2001 and 2009. Logistic regression models were developed using active trachoma (trachomatous inflammation follicular and/or trachomatous inflammation intense) in 6345 children aged 1–9 years as the outcome, and incorporating fixed effects for age, long-term average rainfall (interpolated from weather station data) and land cover (i.e. vegetation type, derived from satellite remote sensing), as well as geostatistical random effects describing spatial clustering of trachoma. The model predicted the west of the country to be at no or low trachoma risk. Trachoma clusters in the central, northern and eastern areas had a radius of 8 km after accounting for the fixed effects. Conclusion In Southern Sudan, large-scale spatial variation in the risk of active trachoma infection is associated with aridity. Spatial prediction has identified likely high-risk areas to be prioritized for more data collection, potentially to be followed by intervention. PMID:20808910

High-risk regions and outbreak modelling of tularemia in humans.

PubMed

Desvars-Larrive, A; Liu, X; Hjertqvist, M; Sjöstedt, A; Johansson, A; Rydén, P

2017-02-01

Sweden reports large and variable numbers of human tularemia cases, but the high-risk regions are anecdotally defined and factors explaining annual variations are poorly understood. Here, high-risk regions were identified by spatial cluster analysis on disease surveillance data for 1984-2012. Negative binomial regression with five previously validated predictors (including predicted mosquito abundance and predictors based on local weather data) was used to model the annual number of tularemia cases within the high-risk regions. Seven high-risk regions were identified with annual incidences of 3·8-44 cases/100 000 inhabitants, accounting for 56·4% of the tularemia cases but only 9·3% of Sweden's population. For all high-risk regions, most cases occurred between July and September. The regression models explained the annual variation of tularemia cases within most high-risk regions and discriminated between years with and without outbreaks. In conclusion, tularemia in Sweden is concentrated in a few high-risk regions and shows high annual and seasonal variations. We present reproducible methods for identifying tularemia high-risk regions and modelling tularemia cases within these regions. The results may help health authorities to target populations at risk and lay the foundation for developing an early warning system for outbreaks.

Can variation in HIV/STD-related risk be explained by individual SES? Findings from female sex workers in a rural Chinese county.

PubMed

Fang, Xiaoyi; Li, Xiaoming; Yang, Hongmei; Hong, Yan; Stanton, Bonita; Zhao, Ran; Dong, Baiqing; Liu, Wei; Zhou, Yuejiao; Liang, Shaoling

2008-03-01

Low socioeconomic status (SES) has been linked to HIV and sexually transmitted disease (STD) at a macro level because the majority of new cases of HIV infection in the world have been reported in underdeveloped or developing countries. However, empirical data on the relationship between individual SES and HIV/STD related risk have been mixed. Employing quantitative data from 454 female sex workers (FSWs), this study was designed to examine the profile of the study sample in terms of their individual SES, HIV/STD-related sexual risk across work locations with different social, cultural, and economic conditions; and to examine the relationship between work location and HIV-related risk behaviors, controlling for individual SES. We have shown in the current study that both SES and HIV/STD-related risk behaviors significantly differed by work location. However, the difference in individual SES was not sufficient to explain the difference of HIV/STD-related risk across the work locations. The findings underscore the need for effective prevention intervention efforts targeting FSWs in rural areas. Based on the findings, we also suggest that HIV/STD intervention efforts among FSWs should take the social and cultural contextual factors of their working environment (and sexual risks) into consideration.

Can variation in HIV/STD-related risk be explained by individual SES? Findings from female sex workers in a rural Chinese county

PubMed Central

Fang, Xiaoyi; Li, Xiaoming; Yang, Hongmei; Hong, Yan; Stanton, Bonita; Zhao, Ran; Dong, Baiqing; Liu, Wei; Zhou, Yuejiao; Liang, Shaoling

2007-01-01

Low socioeconomic status (SES) has been linked to HIV and sexually transmitted disease (STD) at a macro level because the majority of new cases of HIV infection in the world have been reported in underdeveloped or developing countries. However, empirical data on the relationship between individual SES and HIV/STD related risk have been mixed. Employing quantitative data from 454 female sex workers, this study was designed to examine the profile of the study sample in terms of their individual SES, HIV/STD-related sexual risk across work locations with different social, cultural and economic conditions; and examine the relationship between work location and HIV-related risk behaviors, controlling for individual SES. We have shown in the current study that both SES and HIV/STD-related risk behaviors significantly differed by work location. However, the difference in individual SES was not sufficient to explain the difference of HIV/STD-related risk across the work locations. The findings underscore the need for effective prevention intervention efforts targeting female sex workers in rural area. Based on the findings, we also suggest that HIV/STD intervention efforts among female sex workers should take the social and cultural contextual factors of their working environment (and sexual risks) into consideration. PMID:18350430

Community-based randomized controlled trial of diabetes prevention study for high-risk individuals of type 2 diabetes: lifestyle intervention using web-based system.

PubMed

Cha, Seon-Ah; Lim, Sun-Young; Kim, Kook-Rye; Lee, Eun-Young; Kang, Borami; Choi, Yoon-Hee; Yoon, Kun-Ho; Ahn, Yu-Bae; Lee, Jin-Hee; Ko, Seung-Hyun

2017-05-05

The trend of increasing numbers of patients with type 2 diabetes emphasizes the need for active screening of high-risk individuals and intensive lifestyle modification (LSM). The community-based Korean Diabetes Prevention Study (C-KDPS) is a randomized controlled clinical trial to prevent type 2 diabetes by intensive LSM using a web-based program. The two public healthcare centers in Korea are involved, and 420 subjects are being recruited for 6 months and will be followed up for 22 months. The participants are allocated randomly to intensive LSM (18 individual sessions for 24 weeks) and usual care (control group). The major goals of the C-KDPS lifestyle intervention program are: 1) a minimum of 5-7% loss of initial body weight in 6 months and maintenance of this weight loss, 2) increased physical activity (≥ 150 min/week of moderate intensity activity), 3) balanced healthy eating, and 4) quitting smoking and alcohol with stress management. The web-based program includes education contents, video files, visit schedules, and inter-communicable keeping track sites. Primary outcomes are the diagnoses of newly developed diabetes. A 75-g oral glucose tolerance test with hemoglobin A1c level determination and cardiovascular risk factor assessment is scheduled at 6, 12, 18, and 22 months. Active screening of high-risk individuals and an effective LSM program are an essential prerequisite for successful diabetes prevention. We hope that our C-KDPS program can reduce the incidence of newly developed type 2 diabetes and be implemented throughout the country, merging community-based public healthcare resources and a web-based system. Clinical Research Information Service (CRIS), Republic of Korea (No. KCT0001981 ). Date of registration; July 28, 2016.

Hazard identification and risk assessment for biologics targeting the immune system.

PubMed

Weir, Andrea B

2008-01-01

Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection

PubMed Central

Lutzky, Viviana P.; Ratnatunga, Champa N.; Smith, Daniel J.; Kupz, Andreas; Doolan, Denise L.; Reid, David W.; Thomson, Rachel M.; Bell, Scott C.; Miles, John J.

2018-01-01

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts. PMID:29942313

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection.

PubMed

Lutzky, Viviana P; Ratnatunga, Champa N; Smith, Daniel J; Kupz, Andreas; Doolan, Denise L; Reid, David W; Thomson, Rachel M; Bell, Scott C; Miles, John J

2018-01-01

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts.

Balance training reduces falls risk in older individuals with type 2 diabetes.

PubMed

Morrison, Steven; Colberg, Sheri R; Mariano, Mira; Parson, Henri K; Vinik, Arthur I

2010-04-01

This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes.

Balance Training Reduces Falls Risk in Older Individuals With Type 2 Diabetes

PubMed Central

Morrison, Steven; Colberg, Sheri R.; Mariano, Mira; Parson, Henri K.; Vinik, Arthur I.

2010-01-01

OBJECTIVE This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50–75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. RESULTS Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. CONCLUSIONS Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes. PMID:20097781

Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia

PubMed Central

Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B.; Loewy, Rachel; Vinogradov, Sophia

2016-01-01

BACKGROUND Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target. METHODS 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures. RESULTS We observed signifcant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed inter-individual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20–40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. CONCLUSIONS There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of inter-individual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. PMID:27617637

Duration of attenuated positive and negative symptoms in individuals at clinical high risk: Associations with risk of conversion to psychosis and functional outcome

PubMed Central

Carrión, Ricardo E.; Demmin, Docia; Auther, Andrea M.; McLaughlin, Danielle; Olsen, Ruth; Lencz, Todd; Correll, Christoph U.; Cornblatt, Barbara A.

2016-01-01

Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability. PMID:27424062

Attachment style and suicide behaviors in high risk psychiatric inpatients following hospital discharge: The mediating role of entrapment.

PubMed

Li, Shuang; Galynker, Igor I; Briggs, Jessica; Duffy, Molly; Frechette-Hagan, Anna; Kim, Hae-Joon; Cohen, Lisa J; Yaseen, Zimri S

2017-11-01

Insecure attachment is associated with suicidal behavior. This relationship and its possible mediators have not been examined in high-risk psychiatric inpatients with respect to the critical high-risk period following hospital discharge. Attachment styles and perception of entrapment were assessed in 200 high-risk adult psychiatric inpatients hospitalized following suicidal ideation or suicide attempt. Suicidal behaviors were evaluated with the Columbia Suicide Severity Rating Scale at 1-2 months post-discharge. Associations between different attachment styles and suicidal behaviors were assessed and mediation of attachment effects by entrapment was modeled. Fearful attachment was associated with post-discharge suicidal behavior and there was a trend-level negative association for secure attachment. In addition, entrapment mediated the relationship between fearful attachment and suicidal behavior. The current study highlights the mediating role of perceptions of entrapment in the contribution of fearful attachment to suicidal behavior in high-risk patients, suggesting entrapment as potential therapeutic target to prevent suicidal behavior in these individuals. Further research is warranted to establish the mechanisms by which entrapment experiences emerge in patients with insecure attachment styles. Copyright © 2017 Elsevier B.V. All rights reserved.

Awareness of Individual Cardiovascular Risk Factors and Self-Perception of Cardiovascular Risk in Women.

PubMed

Monsuez, Jean-Jacques; Pham, Tai; Karam, Nicole; Amar, Laurence; Chicheportiche-Ayache, Corinne; Menasché, Philippe; Desnos, Michel; Dardel, Paul; Weill, Isabelle

2017-09-01

Cardiovascular risk factors (CVRFs) self-perception by women may be inaccurate. A questionnaire was completed anonymously Online by women who self-reported their personal CVRF levels including age, weight, contraceptive use, menopausal status, smoking, diet and physical activities. Self-perceived risk was matched to actual cardiovascular risk according to the Framingham score. Among 5,240 young and middle-aged women with a high educational level, knowledge of personal CVRFs increased with age, from 51-90% for blood pressure (BP), 22-45% for blood glucose and 15-47% for blood cholesterol levels, between 30 and 65 years, respectively. This knowledge was lower for smoking compared with nonsmoking women: 62.5% vs. 74.5% for BP (P < 0.001), 22.7% vs. 33.8% for blood glucose (P < 0.001), 21.9% vs. 32.0% for cholesterol levels (P < 0.001). Knowledge of BP level was reduced among women using an estrogen-progestogen contraception (56.8% vs. 62.1%, P = 0.0031) and even more reduced among smokers (52.2%, P < 0.001). Conversely, women with leisure-time physical or sportive activity (60.5%), were less overweight or obese (22.4% vs. 34.2%, P < 0.001). They reported better knowledge of BP (72.4% vs. 68.3%, P < 0.001), blood cholesterol (31.1% vs. 26.4%, P < 0.001) and glucose levels (32.7% vs. 27.8%, P < 0.001). Self-perceived cardiovascular risk was rated low by 1,279 (20.4%), moderate by 3,710 (63.3%) and high by 893 (16.3%) women. Among 3,386 women tested using the Framingham score, 40.8% were at low, 25.2% at moderate and 33.8% at high risk. Knowledge of CVRFs and self-perception of individual risk are inaccurate in women. Educational interventions should be emphasized. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients.

PubMed

Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

2015-08-01

Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Communication of uncertainty regarding individualized cancer risk estimates: effects and influential factors.

PubMed

Han, Paul K J; Klein, William M P; Lehman, Tom; Killam, Bill; Massett, Holly; Freedman, Andrew N

2011-01-01

To examine the effects of communicating uncertainty regarding individualized colorectal cancer risk estimates and to identify factors that influence these effects. Two Web-based experiments were conducted, in which adults aged 40 years and older were provided with hypothetical individualized colorectal cancer risk estimates differing in the extent and representation of expressed uncertainty. The uncertainty consisted of imprecision (otherwise known as "ambiguity") of the risk estimates and was communicated using different representations of confidence intervals. Experiment 1 (n = 240) tested the effects of ambiguity (confidence interval v. point estimate) and representational format (textual v. visual) on cancer risk perceptions and worry. Potential effect modifiers, including personality type (optimism), numeracy, and the information's perceived credibility, were examined, along with the influence of communicating uncertainty on responses to comparative risk information. Experiment 2 (n = 135) tested enhanced representations of ambiguity that incorporated supplemental textual and visual depictions. Communicating uncertainty led to heightened cancer-related worry in participants, exemplifying the phenomenon of "ambiguity aversion." This effect was moderated by representational format and dispositional optimism; textual (v. visual) format and low (v. high) optimism were associated with greater ambiguity aversion. However, when enhanced representations were used to communicate uncertainty, textual and visual formats showed similar effects. Both the communication of uncertainty and use of the visual format diminished the influence of comparative risk information on risk perceptions. The communication of uncertainty regarding cancer risk estimates has complex effects, which include heightening cancer-related worry-consistent with ambiguity aversion-and diminishing the influence of comparative risk information on risk perceptions. These responses are influenced by

Prevalence of Pubic Hair Grooming-Related Injuries and Identification of High-Risk Individuals in the United States.

PubMed

Truesdale, Matthew D; Osterberg, E Charles; Gaither, Thomas W; Awad, Mohannad A; Elmer-DeWitt, Molly A; Sutcliffe, Siobhan; Allen, Isabel; Breyer, Benjamin N

2017-11-01

Pubic hair grooming is a common practice that can lead to injury and morbidity. To identify demographic and behavioral risk factors associated with pubic hair grooming-related injuries to characterize individuals with high risk of injury and develop recommendations for safe grooming practices. This cross-sectional study conducted a national survey of noninstitutionalized US adults (aged 18-65 years). The web-based survey was conducted through a probability-based web panel designed to be representative of the US population. Data were collected in January 2014 and analyzed from August 1, 2016, through February 1, 2017. Grooming-related injury history (yes or no), high-frequency injuries (>5 lifetime injuries), and injury requiring medical attention. Among the 7570 participants who completed the survey (4198 men [55.5%] and 3372 women [44.5%]; mean (SD) age, 41.9 [18.9] years), 5674 of 7456 (76.1%) reported a history of grooming (66.5% of men and 85.3% of women [weighted percentages]). Grooming-related injury was reported by 1430 groomers (weighted prevalence, 25.6%), with more women sustaining an injury than men (868 [27.1%] vs 562 [23.7%]; P = .01). Laceration was the most common injury sustained (818 [61.2%]), followed by burn (307 [23.0%]) and rashes (163 [12.2%]). Common areas for grooming-related injury for men were the scrotum (378 [67.2%]), penis (196 [34.8%]), and pubis (162 [28.9%]); for women, the pubis (445 [51.3%]), inner thigh (340 [44.9%]), vagina (369 [42.5%]), and perineum (115 [13.2%]). After adjustment for age, duration of grooming, hairiness, instrument used, and grooming frequency, men who removed all their pubic hair 11 times or more during their lifespan had an increased risk for grooming injury (adjusted odds ratio [AOR], 1.97; 95% CI, 1.28-3.01; P = .002) and were prone to repeated high-frequency injuries (AOR, 3.89; 95% CI, 2.01-7.52; P < .001) compared with groomers who did not remove all their pubic hair. Women who removed all

General intellectual functioning as a buffer against theory-of-mind deficits in individuals at ultra-high risk for psychosis.

PubMed

Hur, Ji-Won; Byun, Min Soo; Shin, Na Young; Shin, Ye Seul; Kim, Sung Nyun; Jang, Joon Hwan; Kwon, Jun Soo

2013-09-01

The influence of neurocognition, including general intelligence, on theory of mind (ToM) among patients with schizophrenia spectrum disorder is controversial. The purpose of the present study was to identify the influences of the non-ToM cognition and general intelligence on ToM performance in individuals at ultra-high risk (UHR) for psychosis. Fifty-five UHR subjects and 58 healthy controls (HCs) completed neurocognitive, verbal, and nonverbal ToM tasks. UHR individuals showed poorer performance in the two verbal ToM tasks, the false-belief task and the strange-story tasks. Moreover, the UHR subjects displayed poorer recall on the interference list of the verbal learning test. Linear regression analysis revealed that neurocognitive functioning, including executive functioning, working memory, and general intelligence, accounted for significant amounts of the variance in the results for UHR individuals: 20.4% in the false-belief task, 44.0% in the strange-story task, and 49.0% in the nonverbal cartoon task. Neurocognition, including general intelligence, was not a significant contributor to performance on ToM tasks in HCs. ToM deficits were not noted in UHR individuals with above-average IQ scores (≥ 110) compared with UHR subjects with IQ scores less than 110, who displayed significant differences on all ToM tasks compared with HCs. The present results suggest that ToM deficits in UHR individuals are complex and may be influenced by non-ToM cognition. Our findings are discussed in relation to the role of neurocognitive abilities in ToM-related impairments in UHR individuals. Copyright © 2013 Elsevier B.V. All rights reserved.

Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation.

PubMed

Engdahl, Johan; Holmén, Anders; Rosenqvist, Mårten; Strömberg, Ulf

2013-08-03

In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP=1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake.

Is a Risky Lifestyle Always "Risky"? The Interaction between Individual Propensity and Lifestyle Risk in Adolescent Offending: A Test in Two Urban Samples

ERIC Educational Resources Information Center

Svensson, Robert; Pauwels, Lieven

2010-01-01

This study examines the effects on adolescent offending of lifestyle risk and the individual propensity to offend. It is assumed that lifestyle risk will have a more important effect on offending for those individuals with high levels of individual propensity, whereas for individuals with low levels of individual propensity it is assumed that a…

Targeted Self-Management of Epilepsy and Mental Illness for individuals with epilepsy and psychiatric comorbidity.

PubMed

Sajatovic, Martha; Tatsuoka, Curtis; Welter, Elisabeth; Perzynski, Adam T; Colon-Zimmermann, Kari; Van Doren, Jamie R; Bukach, Ashley; Lawless, Mary Ellen; Ryan, Eleanor R; Sturniolo, Katherine; Lhatoo, Samden

2016-11-01

Serious mental illness is disproportionately common in people with epilepsy and contributes to complications and mortality. Few care approaches specifically target individuals who have epilepsy and severe mental illness. We used an iterative process to refine an existing intervention and tested the novel intervention, Targeted Self-Management for Epilepsy and Mental Illness (TIME) in individuals with epilepsy and comorbid mental illness (E-MI). The TIME intervention was developed with input from a community advisory board and then tested for feasibility, acceptability, and preliminary efficacy in people with E-MI, using a 16-week prospective, randomized controlled design comparing TIME (N=22) vs. treatment as usual (TAU, N=22). Primary outcome was change in depressive symptoms, assessed by the Montgomery Asberg Depression Rating Scale (MADRS). Secondary assessments included global psychiatric symptom severity, seizure frequency, sleep patterns, quality of life, stigma, social support, and self-efficacy. There were 44 individuals enrolled, mean age 48.25 (SD=11.82) with 25 (56.8%) African-Americans. The majority (N=31, 70.5%) were unemployed, and most (N=41, 95.5%) had annual income individuals (18 in TIME, 18 in TAU) assessed at 12weeks and 35 individuals (19 in TIME, 16 in TAU) assessed at 16weeks. There was a significant effect for MADRS (p=0.036; effect size of 0.70), with lower MADRS at 16weeks in TIME, while TAU MADRS did not change. Differences between most secondary measures were not statistically significant. The TIME intervention engages individuals to actively participate in self-management and can reduce depression in E-MI. Given the high morbidity and mortality associated with epilepsy complicated by serious mental illness, additional research is needed to better identify how TIME might be implemented in routine care settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Substance use and regional gray matter volume in individuals at high risk of psychosis.

PubMed

Stone, James M; Bhattacharyya, Sagnik; Barker, Gareth J; McGuire, Philip K

2012-02-01

Individuals with an at risk mental state (ARMS) are at greatly increased risk of developing a psychotic illness. Risk of transition to psychosis is associated with regionally reduced cortical gray matter volume. There has been considerable interest in the interaction between psychosis risk and substance use. In this study we investigate the relationship between alcohol, cannabis and nicotine use with gray matter volume in ARMS subjects and healthy volunteers. Twenty seven ARMS subjects and 27 healthy volunteers took part in the study. All subjects underwent volumetric MRI imaging. The relationship between regional gray matter volume and cannabis use, smoking, and alcohol use in controls and ARMS subjects was analysed using voxel-based morphometry. In any region where a significant relationship with drug was present, data were analysed to determine if there was any group difference in this relationship. Alcohol intake was inversely correlated with gray matter volume in cerebellum, cannabis intake was use was inversely correlated with gray matter volume in prefrontal cortex and tobacco intake was inversely correlated with gray matter volume in left temporal cortex. There were no significant interactions by group in any region. There is no evidence to support the hypothesis of increased susceptibility to harmful effects of drugs and alcohol on regional gray matter in ARMS subjects. However, alcohol, tobacco and cannabis at low to moderate intake may be associated with lower gray matter in both ARMS subjects and healthy volunteers-possibly representing low-level cortical damage or change in neural plasticity. Copyright © 2011 Elsevier B.V. All rights reserved.

Clustering of lifestyle risk behaviours among residents of forty deprived neighbourhoods in London: lessons for targeting public health interventions.

PubMed

Watts, P; Buck, D; Netuveli, G; Renton, A

2016-06-01

Clustering of lifestyle risk behaviours is very important in predicting premature mortality. Understanding the extent to which risk behaviours are clustered in deprived communities is vital to most effectively target public health interventions. We examined co-occurrence and associations between risk behaviours (smoking, alcohol consumption, poor diet, low physical activity and high sedentary time) reported by adults living in deprived London neighbourhoods. Associations between sociodemographic characteristics and clustered risk behaviours were examined. Latent class analysis was used to identify underlying clustering of behaviours. Over 90% of respondents reported at least one risk behaviour. Reporting specific risk behaviours predicted reporting of further risk behaviours. Latent class analyses revealed four underlying classes. Membership of a maximal risk behaviour class was more likely for young, white males who were unable to work. Compared with recent national level analysis, there was a weaker relationship between education and clustering of behaviours and a very high prevalence of clustering of risk behaviours in those unable to work. Young, white men who report difficulty managing on income were at high risk of reporting multiple risk behaviours. These groups may be an important target for interventions to reduce premature mortality caused by multiple risk behaviours. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cardiovascular risk

PubMed Central

Payne, Rupert A

2012-01-01

Cardiovascular disease is a major, growing, worldwide problem. It is important that individuals at risk of developing cardiovascular disease can be effectively identified and appropriately stratified according to risk. This review examines what we understand by the term risk, traditional and novel risk factors, clinical scoring systems, and the use of risk for informing prescribing decisions. Many different cardiovascular risk factors have been identified. Established, traditional factors such as ageing are powerful predictors of adverse outcome, and in the case of hypertension and dyslipidaemia are the major targets for therapeutic intervention. Numerous novel biomarkers have also been described, such as inflammatory and genetic markers. These have yet to be shown to be of value in improving risk prediction, but may represent potential therapeutic targets and facilitate more targeted use of existing therapies. Risk factors have been incorporated into several cardiovascular disease prediction algorithms, such as the Framingham equation, SCORE and QRISK. These have relatively poor predictive power, and uncertainties remain with regards to aspects such as choice of equation, different risk thresholds and the roles of relative risk, lifetime risk and reversible factors in identifying and treating at-risk individuals. Nonetheless, such scores provide objective and transparent means of quantifying risk and their integration into therapeutic guidelines enables equitable and cost-effective distribution of health service resources and improves the consistency and quality of clinical decision making. PMID:22348281

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

PubMed

Cressman, Sonya; Peacock, Stuart J; Tammemägi, Martin C; Evans, William K; Leighl, Natasha B; Goffin, John R; Tremblay, Alain; Liu, Geoffrey; Manos, Daria; MacEachern, Paul; Bhatia, Rick; Puksa, Serge; Nicholas, Garth; McWilliams, Annette; Mayo, John R; Yee, John; English, John C; Pataky, Reka; McPherson, Emily; Atkar-Khattra, Sukhinder; Johnston, Michael R; Schmidt, Heidi; Shepherd, Frances A; Soghrati, Kam; Amjadi, Kayvan; Burrowes, Paul; Couture, Christian; Sekhon, Harmanjatinder S; Yasufuku, Kazuhiro; Goss, Glenwood; Ionescu, Diana N; Hwang, David M; Martel, Simon; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Tsao, Ming-Sound; Lam, Stephen

2017-08-01

Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and

Developmental Dyslexia: Predicting Individual Risk

ERIC Educational Resources Information Center

Thompson, Paul A.; Hulme, Charles; Nash, Hannah M.; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J.

2015-01-01

Background: Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. Methods: The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6…

Sirolimus enhances remission induction in patients with high risk acute myeloid leukemia and mTORC1 target inhibition.

PubMed

Kasner, Margaret T; Mick, Rosemarie; Jeschke, Grace R; Carabasi, Matthew; Filicko-O'Hara, Joanne; Flomenberg, Neal; Frey, Noelle V; Hexner, Elizabeth O; Luger, Selina M; Loren, Alison W; Mangan, James K; Wagner, John L; Weiss, Mark; Carroll, Martin; Perl, Alexander E

2018-04-02

Background Mammalian Target of Rapamycin Complex 1 (mTORC1) inhibitors enhance chemotherapy response in acute myelogenous leukemia (AML) cells in vitro. However whether inhibiting mTORC1 enhances clinical response to AML chemotherapy remains controversial. We previously optimized measurement of mTORC1's kinase activity in AML blasts during clinical trials using serial phospho-specific flow cytometry of formaldehyde-fixed whole blood or marrow specimens. To validate mTORC1 as a therapeutic target in AML, we performed two clinical trials combining an mTORC1 inhibitor (sirolimus) and MEC (mitoxantrone, etoposide, cytarabine) in patients with relapsed, refractory, or untreated high-risk AML. Methods Flow cytometric measurements of ribosomal protein S6 phosphorylation (pS6) were performed before and during sirolimus treatment to determine whether mTORC1 inhibition enriched for chemotherapy response. Results In 51 evaluable subjects, the overall response rate (ORR) to the combination regimen was 47% (95% confidence interval 33-61%, 33% CR, 2% CRi, 12% PR) and similar toxicity to historic experience with MEC alone. 37 subjects had baseline pS6 measured pre-sirolimus, of whom 27 (73%) exhibited mTORC1 activity. ORR was not significantly different between subjects with and without baseline mTORC1 activity (52% vs 40%, respectively, p = 0.20). The ORR among subjects with baseline target activation and mTORC1 inhibition during therapy was 71% (12/17) compared to 20% (2/10) in subjects without target inhibition. Conclusions Fixed, whole blood pS6 by flow cytometry may be a predictive biomarker for clinical response to mTORC1 inhibitor-based regimens. These data provide clinical confirmation that mTORC1 activation mediates chemotherapy resistance in patients with AML.

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

PubMed Central

Copenhaver, Michael M.; Tunku, Noor; Ezeabogu, Ifeoma; Potrepka, Jessica; Zahari, Muhammad Muhsin A.; Kamarulzaman, Adeeba; Altice, Frederick L.

2011-01-01

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated. PMID:21860786

[Genetic tests in oncology: from identification of high risk groups to therapy].

PubMed

Sgambato, Alessandro; Ripani, Maurizio; Romano Spica, Vincenzo

2010-01-01

The development of genetic epidemiology in oncology has made possible more frequent analysis of high risk groups, allowing the development of promising susceptibility indicators. The main public health implications include screening and new perspectives for pharmacogenetics and nutrigenomics. The study of genetic variants allows the evaluation of individual risk of developing a disease and has important implications in primary and secondary prevention programs. The analysis of somatic mutations present in tumour cells may contribute to selecting the optimal treatment on an individual basis and to reducing the occurrence of adverse effects of chemotherapy. The authors give a summary of the state of the art of this field and analyze the potential applications of genetic tests in oncology, from identification of high risk groups to defining individualized therapies with particular emphasis on implications for prevention.

Accounting for individualized competing mortality risks in estimating postmenopausal breast cancer risk.

PubMed

Schonberg, Mara A; Li, Vicky W; Eliassen, A Heather; Davis, Roger B; LaCroix, Andrea Z; McCarthy, Ellen P; Rosner, Bernard A; Chlebowski, Rowan T; Hankinson, Susan E; Marcantonio, Edward R; Ngo, Long H

2016-12-01

Accurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death. We included 73,066 women who completed the 2004 Nurses' Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors) and 7 risk factors for non-breast cancer death (comorbidities, functional dependency) and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women's Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years). Within 5 years, 1.8 % of NHS participants were diagnosed with breast cancer (vs. 2.0 % in WHI-ES, p = 0.02), and 6.6 % experienced non-breast cancer death (vs. 5.2 % in WHI-ES, p < 0.001). Using a model selection procedure which incorporated the Akaike Information Criterion, c-statistic, statistical significance, and clinical judgement, our final model included 9 breast cancer risk factors, 5 comorbidities, functional dependency, and mammography use. The model's c-statistic was 0.61 (95 % CI [0.60-0.63]) in NHS and 0.57 (0.55-0.58) in WHI-ES. On average, our model under predicted breast cancer in WHI-ES (E/O 0.92 [0.88-0.97]). We developed a novel prediction model that factors in postmenopausal women's individualized competing risks of non-breast cancer death when estimating breast cancer risk.

Accounting for individualized competing mortality risks in estimating postmenopausal breast cancer risk

PubMed Central

Schonberg, Mara A.; Li, Vicky W.; Eliassen, A. Heather; Davis, Roger B.; LaCroix, Andrea Z.; McCarthy, Ellen P.; Rosner, Bernard A.; Chlebowski, Rowan T.; Hankinson, Susan E.; Marcantonio, Edward R.; Ngo, Long H.

2016-01-01

Purpose Accurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death. Methods We included 73,066 women who completed the 2004 Nurses’ Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors), 7 risk factors for non-breast cancer death (comorbidities, functional dependency), and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women’s Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years). Results Within 5 years, 1.8% of NHS participants were diagnosed with breast cancer (vs. 2.0% in WHI-ES, p=0.02) and 6.6% experienced non-breast cancer death (vs. 5.2% in WHI-ES, p<0.001). Using a model selection procedure which incorporated the Akaike Information Criterion, c-statistic, statistical significance, and clinical judgement, our final model included 9 breast cancer risk factors, 5 comorbidities, functional dependency, and mammography use. The model’s c-statistic was 0.61 (95% CI [0.60–0.63]) in NHS and 0.57 (0.55–0.58) in WHI-ES. On average our model under predicted breast cancer in WHI-ES (E/O 0.92 [0.88–0.97]). Conclusions We developed a novel prediction model that factors in postmenopausal women’s individualized competing risks of non-breast cancer death when estimating breast cancer risk. PMID:27770283

High-risk diagnosis, social stress, and parent-child relationships: A moderation model.

PubMed

Bentley, Eryn; Millman, Zachary B; Thompson, Elizabeth; Demro, Caroline; Kline, Emily; Pitts, Steven C; DeVylder, Jordan E; Smith, Melissa Edmondson; Reeves, Gloria; Schiffman, Jason

2016-07-01

Stress is related to symptom severity among youth at clinical high-risk (CHR) for psychosis, although this relation may be influenced by protective factors. We explored whether the association of CHR diagnosis with social stress is moderated by the quality of parent-child relationships in a sample of 96 (36 CHR; 60 help-seeking controls) adolescents and young adults receiving mental health services. We examined self-reported social stress and parent-child relationships as measured by the Behavior Assessment System for Children, Second Edition (BASC-2), and determined CHR status from the clinician-administered Structured Interview for Psychosis-Risk Syndrome (SIPS). The social stress subscale, part of the clinical domain of the BASC-2, assesses feelings of stress and tension in personal relationships and the relations with parents subscale, part of the adaptive domain of the BASC-2, assesses perceptions of importance in family and quality of parent-child relationship. There was a modest direct relation between risk diagnosis and social stress. Among those at CHR, however, there was a significant relation between parent-child relationships and social stress (b=-0.73, t[92]=-3.77, p<0.001, f(2)=0.15) that was not observed among non-CHR individuals, suggesting that a positive parent-child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent-child relationships might be relevant for adolescents and young adults at clinical high-risk for psychosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

PubMed

Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

2016-11-01

Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO 2 ) target range (85-92%) from April 2011. Lower SpO 2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO 2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

Social relationships in young adults at ultra high risk for psychosis.

PubMed

Robustelli, Briana L; Newberry, Raeana E; Whisman, Mark A; Mittal, Vijay A

2017-01-01

Studies suggest that individuals with schizophrenia have smaller social networks and less satisfying relationships. However, much is still unknown about the typical quantity and quality of social relationships in young adults during the ultra high-risk (UHR) period. Investigating these relationships holds significant importance for improving understanding of etiological processes, mapping the social environment, and highlighting treatment targets in a critical period. A total of 85 participants (44 UHR and 41 healthy controls) completed measures examining the participants' social relationships, social support, and loneliness. Mean differences between the UHR and healthy control participants and associations between social relationships and symptoms and functioning were examined. Results indicated significant differences between groups on several indices. Specifically, the UHR youth reported fewer close friends, less diverse social networks, less perceived social support, poorer relationship quality with family and friends, and more loneliness. Notably, within the UHR group, being lonely and having fewer and worse quality relationships was associated with greater symptom severity and lower overall functioning. This study suggests that youth at high-risk of developing psychosis have fewer and poorer quality social relationships. Interventions that focus on increasing the quantity and quality of young adults' social networks may be beneficial for this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Social Relationships in Young Adults at Ultra High Risk For Psychosis

PubMed Central

Robustelli, Briana L.; Newberry, Raeana E.; Whisman, Mark A.; Mittal, Vijay A.

2016-01-01

Studies suggest that individuals with schizophrenia have smaller social networks and less satisfying relationships. However, much is still unknown about the typical quantity and quality of social relationships in young adults during the ultra high-risk (UHR) period. Investigating these relationships holds significant importance for improving understanding of etiological processes, mapping the social environment, and highlighting treatment targets in a critical period. A total of 85 participants (44 UHR and 41 healthy controls) completed measures examining the participants’ social relationships, social support, and loneliness. Mean differences between the UHR and healthy control participants and associations between social relationships and symptoms and functioning were examined. Results indicated significant differences between groups on several indices. Specifically, the UHR youth reported fewer close friends, less diverse social networks, less perceived social support, poorer relationship quality with family and friends, and more loneliness. Notably, within the UHR group, being lonely and having fewer and worse quality relationships was associated with greater symptom severity and lower overall functioning. This study suggests that youth at high-risk of developing psychosis have fewer and poorer quality social relationships. Interventions that focus on increasing the quantity and quality of young adults’ social networks may be beneficial for this population. PMID:27987484

Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

DOE PAGES

Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R.; ...

2016-07-15

Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here in this research, we investigate mesoporous silica nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayermore » composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSN and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index <0.1) on MSN cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and reverified their monodispersity and stability. Then, using intravital imaging in the CAM, we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. In conclusion, overall we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and

Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

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

Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R.