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Sökning: WFRF:(Segura Lidia)

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1.
  • Peterlongo, Paolo, et al. (författare)
  • Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
  • 2015
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 24:1, s. 308-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
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2.
  • Anderson, P., et al. (författare)
  • Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial
  • 2016
  • Ingår i: Addiction. - : WILEY-BLACKWELL. - 1360-0443 .- 0965-2140. ; 111:11, s. 1935-1945
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. Design: Cluster randomized factorial trial with 12-week implementation and measurement period. Setting: Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden. Participants: A total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden. Interventions: PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. Measurements: The primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period. Findings: During a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI = 1.13–1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI = 1.56–2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI = 1.77–3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI = 1.11–2.53). Conclusions: Providing primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption. © 2016 Society for the Study of Addiction
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3.
  • Hamdi, Yosr, et al. (författare)
  • Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
  • 2017
  • Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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4.
  • Keurhorst, M., et al. (författare)
  • Impact of primary healthcare providers' initial role security and therapeutic commitment on implementing brief interventions in managing risky alcohol consumption: a cluster randomised factorial trial
  • 2016
  • Ingår i: Implementation Science. - : BIOMED CENTRAL LTD. - 1748-5908. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Brief interventions in primary healthcare are cost-effective in reducing drinking problems but poorly implemented in routine practice. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation. Methods: In a cluster randomised factorial trial, 120 primary healthcare units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined. To explore the impact of initial role security and therapeutic commitment on implementing brief interventions, we performed multilevel linear regression analyses adapted to the factorial design. Results: Data from 746 providers from 120 PHCUs were included in the analyses. Baseline role security and therapeutic commitment were found not to influence implementation of brief interventions. Furthermore, there were no significant interactions between these characteristics and allocated implementation groups. Conclusions: The extent to which providers changed their brief intervention delivery following experience of different implementation strategies was not determined by their initial attitudes towards alcohol problems. In future research, more attention is needed to unravel the causal relation between practitioners' attitudes, their actual behaviour and care improvement strategies to enhance implementation science.
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5.
  • Anderson, Peter, et al. (författare)
  • Attitudes and Learning through Practice Are Key to Delivering Brief Interventions for Heavy Drinking in Primary Health Care: Analyses from the ODHIN Five Country Cluster Randomized Factorial Trial
  • 2017
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we test path models that study the interrelations between primary health care provider attitudes towards working with drinkers, their screening and brief advice activity, and their receipt of training and support and financial reimbursement. Study participants were 756 primary health care providers from 120 primary health care units (PHCUs) in different locations throughout Catalonia, England, The Netherlands, Poland, and Sweden. Our interventions were training and support and financial reimbursement to providers. Our design was a randomized factorial trial with baseline measurement period, 12-week implementation period, and 9-month follow-up measurement period. Our outcome measures were: attitudes of individual providers in working with drinkers as measured by the Short Alcohol and Alcohol Problems Perception Questionnaire; and the proportion of consulting adult patients (age 18+ years) who screened positive and were given advice to reduce their alcohol consumption (intervention activity). We found that more positive attitudes were associated with higher intervention activity, and higher intervention activity was then associated with more positive attitudes. Training and support was associated with both positive changes in attitudes and higher intervention activity. Financial reimbursement was associated with more positive attitudes through its impact on higher intervention activity. We conclude that improving primary health care providers screening and brief advice activity for heavy drinking requires a combination of training and support and on-the-job experience of actually delivering screening and brief advice activity.
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6.
  • Anderson, Peter, et al. (författare)
  • Delivery of Brief Interventions for Heavy Drinking in Primary Care: Outcomes of the ODHIN 5-Country Cluster Randomized Trial
  • 2017
  • Ingår i: Annals of family medicine (online). - : ANNALS FAMILY MEDICINE. - 1544-1709 .- 1544-1717. ; 15:4, s. 335-340
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE We aimed to test whether 3 strategies-training and support, financial reimbursement, and an option to direct screen-positive patients to an Internet-based method of giving brief advice-have a longer-term effect on primary care clinicians delivery of screening and advice to heavy drinkers operationalized with the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) tool. METHODS We undertook a cluster randomized factorial trial with a 12-week implementation period in 120 primary health care units throughout Catalonia, England, Netherlands, Poland, and Sweden. Units were randomized to 8 groups: care as usual (control); training and support alone; financial reimbursement alone; electronic brief advice alone; paired combinations of these conditions; and all 3 combined. The primary outcome was the proportion of consulting adult patients (aged 18 years and older) receiving intervention-screening and, if screen-positive, advice-at 9 months. RESULTS Based on the factorial design, the ratio of the log of the proportion of patients given intervention at the 9-month follow-up was 1.39 (95% CI, 1.03-1.88) in units that received training and support as compared with units that did not. Neither financial reimbursement nor directing screen-positive patients to electronic brief advice led to a higher proportion of patients receiving intervention. CONCLUSIONS Training and support of primary health care units has a lasting, albeit small, impact on the proportion of adult patients given an alcohol intervention at 9 months.
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7.
  • Anderson, Peter, et al. (författare)
  • Impact of practice, provider and patient characteristics on delivering screening and brief advice for heavy drinking in primary healthcare: Secondary analyses of data from the ODHIN five-country cluster randomized factorial trial
  • 2017
  • Ingår i: European Journal of General Practice. - : TAYLOR & FRANCIS LTD. - 1381-4788 .- 1751-1402. ; 23:1, s. 241-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The implementation of primary healthcare-based screening and advice that is effective in reducing heavy drinking can be enhanced with training. Objectives: Undertaking secondary analysis of the five-country ODHIN study, we test: the extent to which practice, provider and patient characteristics affect the likelihood of patients being screened and advised; the extent to which such characteristics moderate the impact of training in increasing screening and advice; and the extent to which training mitigates any differences due to such characteristics found at baseline. Methods: A cluster randomized factorial trial involving 120 practices, 746 providers and 46 546 screened patients from Catalonia, England, the Netherlands, Poland, and Sweden. Practices were randomized to receive training or not to receive training. The primary outcome measures were the proportion of adult patients screened, and the proportion of screen-positive patients advised. Results: Nurses tended to screen more patients than doctors (OR = 3.1; 95% CI: 1.9, 4.9). Screenpositive patients were more likely to be advised by doctors than by nurses (OR = 2.3; 95% CI: 1.4, 4.1), and more liable to be advised the higher their risk status (OR = 1.9; 95% CI: 1.3, 2.7). Training increased screening and advice giving, with its impact largely unrelated to practice, provider or patient characteristics. Training diminished the differences between doctors and nurses and between patients with low or high-risk status. Conclusions: Training primary healthcare providers diminishes the negative impacts that some practice, provider and patient characteristics have on the likelihood of patients being screened and advised.
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8.
  • Bendtsen, Preben, et al. (författare)
  • Implementing referral to an electronic alcohol brief advice website in primary healthcare: results from the ODHIN implementation trial
  • 2016
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055 .- 2044-6055. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The objective of the present study was to explore whether the possibility of offering facilitated access to an alcohol electronic brief intervention (eBI) instead of delivering brief face-to-face advice increased the proportion of consulting adults who were screened and given brief advice. Design The study was a 12-week implementation study. Sixty primary healthcare units (PHCUs) in 5 jurisdictions (Catalonia, England, the Netherlands, Poland and Sweden) were asked to screen adults who attended the PHCU for risky drinking. Setting A total of 120 primary healthcare centres from 5 jurisdictions in Europe. Participants 746 individual providers (general practitioners, nurses or other professionals) participated in the study. Primary outcome Change in the proportion of patients screened and referred to eBI comparing a baseline 4-week preimplementation period with a 12-week implementation period. Results The possibility of referring patients to the eBI was not found to be associated with any increase in the proportion of patients screened. However, it was associated with an increase in the proportion of screen-positive patients receiving brief advice from 70% to 80% for the screen-positive sample as a whole (pamp;lt;0.05), mainly driven by a significant increase in brief intervention rates in England from 87% to 96% (pamp;lt;0.01). The study indicated that staff displayed a low level of engagement in this new technology. Staff continued to offer face-to-face advice to a larger proportion of patients (54%) than referral to eBI (38%). In addition, low engagement was seen among the referred patients; on average, 18% of the patients logged on to the website with a mean log-on rate across the different countries between 0.58% and 36.95%. Conclusions Referral to eBI takes nearly as much time as brief oral advice and might require more introduction and training before staff are comfortable with referring to eBI.
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9.
  • Bendtsen, Preben, et al. (författare)
  • Professionals Attitudes Do Not Influence Screening and Brief Interventions Rates for Hazardous and Harmful Drinkers: Results from ODHIN Study
  • 2015
  • Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP): Policy B - Oxford Open Option D. - 0735-0414 .- 1464-3502. ; 50:4, s. 430-437
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine the relation between existing levels of alcohol screening and brief intervention rates in five European jurisdictions and role security and therapeutic commitment by the participating primary healthcare professionals. Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psychologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities as part of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment. The only significant but small relationship was found between role security and screening rate in a multilevel logistic regression analysis adjusted for occupation of the provider, number of eligible patients and the random effects of jurisdictions and primary health care units (PHCU). No significant relationship was found between role security and brief intervention rate nor between therapeutic commitment and screening rate/brief intervention rate. The proportion of patients screened varied across jurisdictions between 2 and 10%. The findings show that the studied factors (role security and therapeutic commitment) are not of great importance for alcohol screening and BI rates. Given the fact that screening and brief intervention implementation rate has not changed much in the last decade in spite of increased policy emphasis, training initiatives and more research being published, this raises a question about what else is needed to enhance implementation.
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10.
  • Keurhorst, Myrna N., et al. (författare)
  • Implementing training and support, financial reimbursement, and referral to an internet-based brief advice program to improve the early identification of hazardous and harmful alcohol consumption in primary care (ODHIN) : study protocol for a cluster randomized factorial trial
  • 2013
  • Ingår i: Implementation Science. - : BioMed Central. - 1748-5908 .- 1748-5908. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe European level of alcohol consumption, and the subsequent burden of disease, is high compared to the rest of the world. While screening and brief interventions in primary healthcare are cost-effective, in most countries they have hardly been implemented in routine primary healthcare. In this study, we aim to examine the effectiveness and efficiency of three implementation interventions that have been chosen to address key barriers for improvement: training and support to address lack of knowledge and motivation in healthcare providers; financial reimbursement to compensate the time investment; and internet-based counselling to reduce workload for primary care providers.Methods/designIn a cluster randomized factorial trial, data from Catalan, English, Netherlands, Polish, and Swedish primary healthcare units will be collected on screening and brief advice rates for hazardous and harmful alcohol consumption. The three implementation strategies will be provided separately and in combination in a total of seven intervention groups and compared with a treatment as usual control group. Screening and brief intervention activities will be measured at baseline, during 12 weeks and after six months. Process measures include health professionals’ role security and therapeutic commitment of the participating providers (SAAPPQ questionnaire). A total of 120 primary healthcare units will be included, equally distributed over the five countries. Both intention to treat and per protocol analyses are planned to determine intervention effectiveness, using random coefficient regression modelling.DiscussionEffective interventions to implement screening and brief interventions for hazardous alcohol use are urgently required. This international multi-centre trial will provide evidence to guide decision makers.
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