Higher Risk Estimates Research Articles

Nomogram-Based Estimate of Axillary Nodal Involvement in ACOSOG Z0011 (Alliance): Validation and Association with Radiation Protocol Variations and Outcomes

Nomograms may be more accurate than experts at predicting risk. Our aim is to use two validated nomograms for axillary node involvement in breast cancer to assess whether protocol variations occurred in higher risk patients in ACOSOG Z0011. We used the M.D. Anderson (MDA) and Memorial Sloan-Kettering (MSK) nomograms to calculate the estimated risk of additional positive axillary nodes using sentinel lymph node biopsy and primary tumor surgery information. In the control arm, we compared findings of axillary dissection (AD) to nomogram-predicted estimates for validation. Logistic regression was used to evaluate whether nomogram-estimated higher risk of nodal involvement was associated with high tangent (HT) or supraclavicular (SCV) radiation field use for patients with known radiation field design. We included radiation fields in multivariate Cox models to evaluate associations with ten-year local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS). Of the 856 evaluable women enrolled, 552 (64.5%) had complete details for the MDA nomogram. Mean MDA risk estimate for patients in both treatment arms was 23.8%. For patients on the AD arm with positive nodes, the estimated risk was 25.9%. Estimated risk did not significantly differ between treatment arms (p-value 0.16). Higher risk estimate was associated with additional positive nodes in the AD arm (OR: 1.04, 95% CI:1.02-1.06, p<0.0001). 78/165 (47.3%) of evaluable patients in the pooled arms with known radiation fields received either HT(n=53) or SCV(n=25) radiation. We observed significant association with higher MDA nomogram estimated risk and SCV radiation (OR=1.07, 95%CI: 1.04-1.10,p<0.0001) but not HT (OR=0.99, 95%CI:0.96-1.02,p=0.52). On multivariable analysis, MDA nomogram estimate was associated with LRF (HR=1.05, 95%CI:1.02-1.08, p=0.003) but not DFS (HR-1.00, 95%CI:0.9901.02, p=0.54) or OS (HR=1.00, 95%CI:0.99-1.02, p=0.66). Receiving SCV radiation was associated with worse DFS (HR=1.83, 95%CI:0.77-4.36, p=0.045) and OS (HR=2.72, 95%CI:1.03-7.18, p=0.027) but not LRF (p=0.27) The MSK nomogram had similar associations for all endpoints. MDA and MSK nomogram risk estimates were associated with confirmed additional lymph node risk in ACOSOG Z011 in the AD arm and appeared balanced in both arms. Radiation oncologists’ use of SCV fields was associated with treating higher risk patients with a worse prognosis.

Body composition measurements and risk of hematological malignancies: A population-based cohort study during 20 years of follow-up

High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmö Diet and Cancer study conducted in Sweden between 1991–1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.

Sex-specific associations between adolescent categories of BMI with cardiovascular and non-cardiovascular mortality in midlife

ContextMost studies linking long-term consequences of adolescent underweight and obesity are limited to men.ObjectiveTo assess the sex-specific association of adolescent BMI with cardiovascular- and non-cardiovascular-related mortality in young adulthood and midlife.SettingA nationwide cohort.Participants927,868 women, 1,366,271 men.InterventionsMedical examination data at age 17, including BMI, were linked to the national death registry.Main outcomesDeath attributed to cardiovascular (CVD) and non-CVD causes.ResultsDuring 17,346,230 women-years and 28,367,431 men-years of follow-up, there were 451 and 3208 CVD deaths, respectively, and 6235 and 22,223 non-CVD deaths, respectively. Compared to low-normal BMI (18.5–22.0 kg/m2), underweight women had a lower adjusted risk for CVD mortality (Cox hazard ratio (HR) = 0.68; 95% CI 0.46–0.98) in contrast to underweight men (HR = 0.99; 0.88–1.13). The latter were at higher risk for non-CVD mortality (HR = 1.04; 1.00–1.09), unlike underweight women (HR = 1.01; 0.93–1.10). Findings, which persisted when the study sample was limited to those with unimpaired health, were accentuated for the obese with ≥ 30 years follow-up. Both sexes exhibited similarly higher risk estimates already in the high-normal BMI range (22.0 ≤ BMI < 25.0 kg/m2) with overall no interaction between sex and BMI (p = 0.62). Adjusted spline models suggested lower BMI values for minimal mortality risk among women (16.8 and 18.2 kg/m2) than men (18.8 and 20.0 kg/m2), for CVD and non-CVD death, respectively.ConclusionsUnderweight adolescent females have favorable cardiovascular outcomes in adulthood. Otherwise the risk patterns were similar between the sexes. The optimal BMI value for women and men with respect to future CVD outcomes is within or below the currently accepted low-normal BMI range.

Implantable cardioverter-defibrillator therapy and device-related complications in young patients with inherited cardiomyopathies or channelopathies: a 17-year cohort study.

To quantify appropriate and inappropriate therapy and complications related to implantable cardioverter-defibrillator (ICD) treatment in young patients receiving an ICD for a hereditary cardiomyopathy or channelopathy. This was a retrospective study including 117 consecutive patients who had received an ICD at Aarhus University Hospital, Denmark from 1 January 1999 to 31 December 2015. Patients were followed from the date of ICD implantation until migration, death, heart transplantation, or end of follow-up on 1 February 2017. Mean age at implantation was 30.5 ± 12.8 years, and the patients were followed for a mean period of 7.1 ± 4.4 years. The cumulative incidence at 1, 5, and 10 years was 17%, 29%, and 48% for appropriate ICD therapy, 6%, 13%, and 20% for inappropriate ICD therapy, and 7%, 18%, and 33% for device-related complications, respectively. Patients with an ICD implanted for secondary prevention had a higher risk of appropriate therapy compared with patients implanted for primary prevention [adjusted hazard ratio (HR) 5.18, 95% confidence interval (CI) 2.22-12.09; P < 0.01]. There was no difference in the risk of inappropriate therapy (adjusted HR 1.58, 95% CI 0.55-4.56; P = 0.40) or device-related complications (adjusted HR 1.22, 95% CI 0.56-2.68; P = 0.62) between patients with primary and secondary preventive indication. We observed high absolute risk estimates for appropriate ICD therapy in young patients with an ICD indicated by a hereditary cardiomyopathy or channelopathy. Also risks for inappropriate ICD therapy and device-related complications were significant.

Predictive value of coronary computed tomography angiography in asymptomatic individuals with diabetes mellitus: Systematic review and meta-analysis

BackgroundCoronary CT angiography (CTA) is generally not established as a screening tool for asymptomatic individuals. However, it is controversial whether this test may have a role for screening asymptomatic individuals with diabetes mellitus (DM) due to the high prevalence of asymptomatic coronary artery disease (CAD) in this subgroup. MethodsWe searched PubMed and EMBASE through May 2017 for studies that reported on the association between findings at coronary CTA and future cardiac events in asymptomatic individuals with DM. Summary hazard ratios for the presence of obstructive CAD (≥50% stenosis), presence of non-obstructive plaque (<50% stenosis), segment involvement score, and segment stenosis score were derived using a random effects regression model. I2 was calculated to quantify between-study heterogeneity and causing factors were identified using meta-regression. ResultsA total of 10 studies reporting on 5012 individuals with DM (median age: 62.3 years, median proportion of women: 40.5%) were included in the analysis. The presence of obstructive CAD on coronary CTA (vs. non-obstructive or no CAD) was associated with a significantly elevated risk for adverse events (summary HR: 4.07, 95% CI: 2.30 to 7.21). The estimated summary HR for non-obstructive plaque (vs. no CAD) was 2.17 (95% CI: 1.11 to 4.25). The pooled HRs per unit for segment stenosis score and segment involvement score were 1.44 (95% CI: 0.98 to 2.12), and 1.73 (95% CI: 1.07 to 2.80) respectively. On meta-regression analysis, we observed a trend towards a higher risk estimate in studies with a higher proportion of females (p = 0.1063). ConclusionThe presence and extent of CAD on coronary CTA are strong, independent predictors of cardiovascular events in asymptomatic individuals with DM despite heterogeneity between studies in endpoints, study population and length of follow-up.

Assessment of DNA damages in lymphocytes of agricultural workers exposed to pesticides by comet assay in a cross-sectional study

Purpose: To assess the predictive power of the comet assay in the context of occupational exposure to pesticides.Materials and methods: The recruited subjects completed a structured questionnaire and gave a blood sample. Exposure to pesticides was measured by means of an algorithm based on Dosemeci’s work (Agricultural Health Study). Approximately 50 images were analyzed for each sample via fluorescence microscopy. The extent of DNA damage was estimated by tail moment (TM) and is the product of tail DNA (%) and tail Length.Results: Crude significant risks (odds ratios, ORs) for values higher than the 75th percentile of TM were observed among the exposed subjects (score > 1). The frequency of some confounding factors (sex, age and smoking) was significantly higher among the exposed workers. A significant dose–effect relationship was observed between TM and exposure score. Significant high-risk estimates (ORs), adjusted by the studied confounding factors, among exposure to pesticides and TM, % tail DNA and tail length were confirmed using unconditional logistic regression models.Conclusions: The adjusted associations (ORs) between the comet parameters and exposure to pesticides were significant. The sensitivity of the comet test was low (41%), the specificity (89%) and the predictive positive value (0.77) were found acceptable.

Validated Alzheimer\u2019s Disease Risk Index (ANU-ADRI) is associated with smaller volumes in the default mode network in the early 60s

Strong evidence is available suggesting that effective reduction of exposure to demonstrated modifiable risk factors in mid-life or before could significantly decrease the incidence of Alzheimer’s disease (AD) and delay its onset. A key ingredient to achieving this goal is the reliable identification of individuals at risk well before they develop clinical symptoms. The aim of this study was to provide further neuroimaging evidence of the effectiveness of a validated tool, the ANU Alzheimer’s Disease Risk Index, for the assessment of future risk of cognitive decline. Participants were 461 (60–64 years, 48% female) community-living individuals free of dementia at baseline. Associations between risk estimates obtained with the ANU-ADRI, total and regional brain volumes including in the default mode network (DMN) measured at the same assessment and diagnosis of MCI/dementia over a 12-year follow-up were tested in a large sample of community-living individuals free of dementia at baseline. Higher risk estimates on the ANU-ADRI were associated with lower cortical gray matter and particularly in the DMN. Importantly, difference in participants with high and low risk scores explained 7–9% of the observed difference in gray matter volume. In this sample, every one additional risk point on the ANU-ADRI was associated with an 8% increased risk of developing MCI/dementia over a 12-year follow-up and this association was partly mediated by a sub-region of the DMN. Risk of cognitive decline assessed with a validated instrument is associated with gray matter volume, particularly in the DMN, a region known to be implicated in the pathological process of the disease.

Labour-market marginalisation after mental disorders among young natives and immigrants living in Sweden

BackgroundThe aim was to investigate the associations between mental disorders and three different measures of labour-market marginalisation, and differences between native Swedes and immigrants.MethodsThe study comprised 1,753,544 individuals, aged 20–35 years, and resident in Sweden 2004. They were followed 2005–2011 with regard to disability pension, sickness absence (≥90 days) and unemployment (≥180 days). Immigrants were born in Western countries (Nordic countries, EU, Europe outside EU or North-America/Oceania), or in non-Western countries (Africa, Asia or South-America). Mental disorders were grouped into seven subgroups based on a record of in- or specialised outpatient health care 2001–2004. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed by Cox regression models with both fixed and time-dependent covariates and competing risks. We also performed stratified analyses with regard to labour-market attachment.ResultsIndividuals with mental disorders had a seven times higher risk of disability pension, a two times higher risk of sickness absence, and a 20% higher risk of unemployment than individuals without mental disorders. Individuals with personality disorders and schizophrenia/non-affective psychoses had highest risk estimates for having disability pension and long-term sickness absence, while the risk estimates of long-term unemployment were similar among all subgroups of mental disorders. Among persons with mental disorders, native Swedes had higher risk estimates for disability pension (HR:6.6; 95%CI:6.4–6.8) than Western immigrants (4.8; 4.4–5.2) and non-Western immigrants (4.8; 4.4–5.1), slightly higher risk estimates for sickness absence (2.1;2.1–2.2) than Western (1.9;1.8–2.1), and non-Western (1.9;1.7–2.0) immigrants but lower risk estimates for unemployment (1.4;1.3–1.4) than Western (1.8;1.7–1.9) and non-Western immigrants (2.0;1.9–2.1). There were similar risk estimates among sub-regions within both Western and non-Western countries. Stratification by labour-market attachment showed that the risk estimates for immigrants were lower the more distant individuals were from gainful employment.ConclusionsMental disorders were associated with all three measures of labour-market marginalisation, strongest with subsequent disability pension. Native Swedes had higher risk estimates for both disability pension and sickness absence, but lower risk estimates for unemployment than immigrants. Previous labour-market attachment explained a great part of the association between immigrant status and subsequent labour-market marginalisation.

Occupational COPD and job exposure matrices: a systematic review and meta-analysis.

BackgroundThe association between occupational exposure and COPD reported previously has mostly been derived from studies relying on self-reported exposure to vapors, gases, dust, or fumes (VGDF), which could be subjective and prone to biases. The aim of this study was to assess the strength of association between exposure and COPD from studies that derived exposure by job exposure matrices (JEMs).MethodsA systematic search of JEM-based occupational COPD studies published between 1980 and 2015 was conducted in PubMed and EMBASE, followed by meta-analysis. Meta-analysis was performed using a random-effects model, with results presented as a pooled effect estimate with 95% confidence intervals (CIs). The quality of study (risk of bias and confounding) was assessed by 13 RTI questionnaires. Heterogeneity between studies and its possible sources were assessed by Egger test and meta-regression, respectively.ResultsIn all, 61 studies were identified and 29 were included in the meta-analysis. Based on JEM-based studies, there was 22% (pooled odds ratio =1.22; 95% CI 1.18–1.27) increased risk of COPD among those exposed to airborne pollutants arising from occupation. Comparatively, higher risk estimates were obtained for general populations JEMs (based on expert consensus) than workplace-based JEM were derived using measured exposure data (1.26; 1.20–1.33 vs 1.14; 1.10–1.19). Higher risk estimates were also obtained for self-reported exposure to VGDF than JEMs-based exposure to VGDF (1.91; 1.72–2.13 vs 1.10; 1.06–1.24). Dusts, particularly biological dusts (1.33; 1.17–1.51), had the highest risk estimates for COPD. Although the majority of occupational COPD studies focus on dusty environments, no difference in risk estimates was found for the common forms of occupational airborne pollutants.ConclusionOur findings highlight the need to interpret previous studies with caution as self-reported exposure to VGDF may have overestimated the risk of occupational COPD.

Individual and Neighborhood Socioeconomic Status and the Association between Air Pollution and Cardiovascular Disease.

Background:Long-term fine particulate matter (PM2.5) exposure is linked with cardiovascular disease, and disadvantaged status may increase susceptibility to air pollution-related health effects. In addition, there are concerns that this association may be partially explained by confounding by socioeconomic status (SES).Objectives:We examined the roles that individual- and neighborhood-level SES (NSES) play in the association between PM2.5 exposure and cardiovascular disease.Methods:The study population comprised 51,754 postmenopausal women from the Women’s Health Initiative Observational Study. PM2.5 concentrations were predicted at participant residences using fine-scale regionalized universal kriging models. We assessed individual-level SES and NSES (Census-tract level) across several SES domains including education, occupation, and income/wealth, as well as through an NSES score, which captures several important dimensions of SES. Cox proportional-hazards regression adjusted for SES factors and other covariates to determine the risk of a first cardiovascular event.Results:A 5 μg/m3 higher exposure to PM2.5 was associated with a 13% increased risk of cardiovascular event [hazard ratio (HR) 1.13; 95% confidence interval (CI): 1.02, 1.26]. Adjustment for SES factors did not meaningfully affect the risk estimate. Higher risk estimates were observed among participants living in low-SES neighborhoods. The most and least disadvantaged quartiles of the NSES score had HRs of 1.39 (95% CI: 1.21, 1.61) and 0.90 (95% CI: 0.72, 1.07), respectively.Conclusions:Women with lower NSES may be more susceptible to air pollution-related health effects. The association between air pollution and cardiovascular disease was not explained by confounding from individual-level SES or NSES.Citation:Chi GC, Hajat A, Bird CE, Cullen MR, Griffin BA, Miller KA, Shih RA, Stefanick ML, Vedal S, Whitsel EA, Kaufman JD. 2016. Individual and neighborhood socioeconomic status and the association between air pollution and cardiovascular disease. Environ Health Perspect 124:1840–1847; http://dx.doi.org/10.1289/EHP199

Urbanisation and geographic variation of overweight and obesity in India: a cross-sectional analysis of the Indian Demographic Health Survey 2005-2006.

We examined the nationwide geographic variation of overweight and obesity in India, as well as a range of potential correlates of excess body fat. We conducted cross-sectional analyses of the 2005-2006 Indian Demographic Health Survey (IDHS), based on 161,050 individuals (age range 18-54 years). Multivariate logistic regression models were used to determine odds ratios (OR) of overweight and obesity compared to normal weight with associated correlates. The overall prevalence was 12.4% for overweight, 3.2% for obesity, and 26.5% for underweight. After multivariate adjustment, obesity was nearly thrice more likely in urban areas than in rural (OR 2.73, 95% CI 2.53-2.94). Women were 2.71 times more likely to be obese than men (95% CI 2.50-2.95). Better socioeconomic status was significantly associated with overweight and obesity. Overweight (OR 1.38, 95% CI 1.31-1.47) and obesity (OR 1.46, 95% CI 1.32-1.61) were most likely to occur in India's Southern zone, when controlled for confounding factors. High-risk estimates for overweight/obesity in urban settings, along with socioeconomic prowess in India and the resulting nutritional transition make a compelling case for public health policy on healthy lifestyles to avert the growing burden of non-communicable diseases associated with overweight/obesity.

Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data: a population- and insurance-based cohort.

Clinical trials and few observational studies report increased hyperkalemia risks in heart failure patients receiving aldosterone blockers in addition to standard therapy. The aim of this study is to assess the hyperkalemia risk and combined use of spironolactone and long-term ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB) therapy for heart failure in a real-life setting of a heterogeneous population. Using claims data of the statutory health insurance fund AOK, covering 30% of the German population, we performed a nested case-control study in a cohort of heart failure patients receiving continuous ACE/ARB therapy (n = 1,491,894). Hyperkalemia risk associated with concurrent use of spironolactone and ACE/ARB was calculated by conditional logistic regression in 1062 cases and 10,620 risk-set-sampling-matched controls. Risk of hyperkalemia in heart failure patients was significantly associated with spironolactone use (odds ratio (OR) (95% confidence interval (CI)) = 13.59 (11.63-15.88) in all and 11.05 (8.67-14.08) in those with information on New York Heart Association (NYHA) stage of disease). In the NYHA subpopulation, higher risk estimates were observed in short-term as compared with long-term users (OR (95%CI) = 13.00 (9.82-17.21) and 9.12 (6.78-12.26), respectively). Moreover, the association was stronger in older (≥70 years of age) as compared with younger patients (<70 years of age) (OR (95%CI) = 12.32 (9.35-16.23) and 8.73 (5.05-15.08), respectively), although interaction was not significant (pinteraction = 0.07). Hyperkalemia risk associated with combined use of spironolactone and ACE/ARB is much stronger in real-life practice than observed in clinical trials. Careful potassium level monitoring in concomitant users of spironolactone and ACE/ARB is necessary.

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease.

Foot and mouth disease risk assessment in Mongolia—Local expertise to support national policy

To address weaknesses in the current foot and mouth disease (FMD) control system and to inform the formulation of a national control strategy, Mongolia conducted two separate risk assessments, one for the Eastern region which in the past has seen re-current introductions of infection, and one for the Western region, where freedom from disease had been demonstrated over several years until FMD was re-introduced in 2013. The risk assessment was conducted in three stages: first local experts developed entry, exposure and consequence pathways during separate workshops in both regions, then data was collected, compiled and analysed, and finally, during a second workshop local experts provided risk estimations for both regions and identified recommendations for risk management. Risk estimates for each pathway were individually recorded, which ensured that views of all experts were equally represented in the risk estimation and which allowed assessing possible impact of different factors related to the background of participating local experts on risk estimates. Entry risk pathways with highest risk estimates were related to livestock movements and in the consequence assessment due to direct contacts. Uncertainty, for which disagreement between participants acted as a proxy, was high in entry pathways and in the assessment of effectiveness of control measures.The risk assessment was conducted with local experts who had no previous risk assessment experience. Through their involvement in the whole process however, they assumed a high level of ownership and despite lively discussions for some risk pathways, a high level of agreement was achieved and credible results were communicated to decision makers. Especially valuable were the derived recommendations. Through the risk assessment the local experts gained a thorough understanding of the FMD risk which resulted in sensible and realistic recommendations, which, if implemented, can lead to a sustainable strengthening of the Mongolian capacities to prevent, control and eradicate FMD. The process was underlined by extensive field data collection, which helped to address important data gaps and therefore to improve quality and reliability of findings. The Mongolian veterinary authority was very committed to the risk assessment and several recommendations have already been integrated in the revision of the national FMD strategy.

Ethical survey of high cholesterol and risk estimation for familial hypercholesterolemia in 6320 students of ages from 6 to 19 years

Ethical survey of high cholesterol and risk estimation for familial hypercholesterolemia in 6320 students of ages from 6 to 19 years

Optimized outcome prediction in breast cancer by combining the 70-gene signature with clinical risk prediction algorithms.

Clinical guidelines for breast cancer treatment differ in their selection of patients at a high risk of recurrence who are eligible to receive adjuvant systemic treatment (AST). The 70-gene signature is a molecular tool to better guide AST decisions. The aim of this study was to evaluate whether adding the 70-gene signature to clinical risk prediction algorithms can optimize outcome prediction and consequently treatment decisions in early stage, node-negative breast cancer patients. A 70-gene signature was available for 427 patients participating in the RASTER study (cT1-3N0M0). Median follow-up was 61.6 months. Based on 5-year distant-recurrence free interval (DRFI) probabilities survival areas under the curve (AUC) were calculated and compared for risk estimations based on the six clinical risk prediction algorithms: Adjuvant! Online (AOL), Nottingham Prognostic Index (NPI), St. Gallen (2003), the Dutch National guidelines (CBO 2004 and NABON 2012), and PREDICT plus. Also, survival AUC were calculated after adding the 70-gene signature to these clinical risk estimations. Systemically untreated patients with a high clinical risk estimation but a low risk 70-gene signature had an excellent 5-year DRFI varying between 97.1 and 100 %, depending on the clinical risk prediction algorithms used in the comparison. The best risk estimation was obtained in this cohort by adding the 70-gene signature to CBO 2012 (AUC: 0.644) and PREDICT (AUC: 0.662). Clinical risk estimations by all clinical algorithms improved by adding the 70-gene signature. Patients with a low risk 70-gene signature have an excellent survival, independent of their clinical risk estimation. Adding the 70-gene signature to clinical risk prediction algorithms improves risk estimations and therefore might improve the identification of early stage node-negative breast cancer patients for whom AST has limited value. In this cohort, the PREDICT plus tool in combination with the 70-gene signature provided the best risk prediction.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-2954-2) contains supplementary material, which is available to authorized users.

Abstract P086: Urbanization and Geographic Variation of Overweight/Obesity in India: the 2005-06 India Demographic Health Survey

Background: Obesity and overweight are considered to be the fifth leading risk factor for deaths worldwide. In India, the prevalence of overweight and obesity is growing, along with an ongoing nutritional transition as more people adopt urban lifestyles or migrate to urban areas for economic opportunities. Objective: This study examined the geographic variation of overweight/obesity in India, as well as a wide range of potential risk factors and correlates of overweight-obesity, including socio-demographics and level of urbanization. Methods: We conducted cross-sectional analyses of the 2005-06 India Demographic Health Survey (DHS), using anthropometric data from 161,050 individuals to determine prevalence of obesity and overweight, and demographics with regards to urban or rural settings. We then used a multivariate logistic regression model to determine the odds of combined overweight and obesity in urban settings as adjusted for age, sex, education level, standard of living, religion and zone for 111,730 individuals (after excluding underweight subjects [BMI &lt; 18.5] and missing cases) for India overall, and then for each zone separately. Results: The overall prevalence of combined overweight/obesity (BMI ≥ 25) was 15.5%. The odds of overweight/obesity in urban settings after adjusting for confounders as age, sex, education level, standard of living, religion and zone were nearly twice that of rural settings (OR 1.95, 95% CI: 1.88-2.02). We also found significant associations between overweight/obesity and higher education (OR 2.11 95% CI: 2.62-2.87), and higher standard of living (OR 6.71 95% CI: 6.25-7.21). Individuals from the southern zone were most likely to be overweight/obese when compared to the northern zone in multivariate analyses (OR 1.44, 95% CI: 1.36-1.52). While urban settings were consistently and significantly associated with higher risks of overweight/obesity across all zones, the risk was highest for individuals from the eastern zone (OR 2.57, 95% CI: 2.30-2.87). Conclusions: The results demonstrate significant associations between overweight/obesity and urbanization in India, with high risk estimates for overweight/obesity in urban settings even for the least urban zones. Socioeconomic prowess and the resulting nutritional transition in India make a compelling case for administrative policy on nutrition and healthy lifestyles to avert future burden of non-communicable diseases associated with overweight/obesity.

Integrating Stress Scenarios into Risk Quantification Models

We enhance the method of integrating scenarios proposed in Ergashev (2012) into risk models. In particular, we provide additional theoretical insights of the method with focus on stress testing Value-at-Risk models. We extend the application of the method, which is originally proposed for scenario analysis in the operational risk context, to market and credit risks. We provide detailed application guidance of the method for market, credit, and operational risks. The method (i) ensures that a stressed model produces a higher risk estimate than the model based on historical data only and (ii) does not require assumptions on stressed loss distributions, thereby simplifying the scenario generation process.

Maternal Asthma and Use of Antiasthmatic Drugs in Early Pregnancy and Congenital Malformations in the Offspring

Objectives: To investigate the risk of congenital malformations in infants born of women who had used antiasthmatic drugs in early pregnancy. Methods: Data were obtained from the Swedish Medical Birth Register for 1996-2011. Information on drug use was based on midwife interviews towards the end of the first trimester. Presence of congenital malformations was ascertained from three national health registers. Risk estimates were made with Mantel-Haenszel odds ratios after adjustment for delivery year, maternal age, parity, smoking, and body mass index. Consideration was taken to concomitantly used drugs. Results: Among more than 1.5 million women who gave birth, 2.9% reported the use of antiasthmatics. These women had characteristics which distinguished them from other women who gave birth and they more often than these used other drugs than antiasthmatics. These differences seemed to affect malformation risk only little. The risk for a major malformation was slightly but significantly increased (odds ratio=1.09, 95% confidence interval 1.03-1.12), specifically this was seen for cardiovascular defects, median cleft palate, and pyloric stenosis. There was no specific association with specific drugs or drug groups, the highest risk estimate was seen for women who used only one drug and notably a short-acting adrenergic or used three or more antiasthmatic drug groups. Conclusion: The absolute risk for a congenital malformation in infants born of women using antiasthmatics is low and some evidence indicates that it is due to underlying asthma. A good control of asthma seems important and scare of teratogenicity of the common antiasthmatic drugs should not prevent adequate use.

Particulate phase polycyclic aromatic hydrocarbons in the ambient atmosphere of a protected and ecologically sensitive area in a tropical megacity

This study reports, for the first time, the profiles and source analysis of 16 US EPA priority polycyclic aromatic hydrocarbons (PAHs) associated with PM10 (particulate matter with aerodynamic diameter ≤10μm) at a protected and ecologically sensitive area – the Yamuna Biodiversity Park – located in the megacity Delhi, India. Weekly PM10 sampling was carried out at this location for 1 year (2009–2010) and the annual mean PM10 level was found to be ∼9 times the World Health Organization limit. Seasonal variation of PAHs (range 37.2–74.0ngm−3) was significant with winter values being 72% and 68% higher than summer and monsoon respectively. Principal component analysis coupled with multiple linear regression identified diesel, natural gas and lubricating oil combustion (49.5%), wood combustion (25.4%), gasoline (15.5%) and coal combustion (9.6%) sources for the observed PAHs. Heavy traffic on the national highway and arterial roads and domestic emissions from suburban households in the vicinity of the park appeared to have significantly affected its air quality. A substantial portion (∼55%) of the aerosol PAH load was comprised of carcinogenic species, which yielded a considerably high lifetime inhalation cancer risk estimate (8.7E−04). If considered as a conservative lower-bound estimate, this risk translates into ∼211 excess cancer cases for lifetime inhalation exposure to the observed PAH concentrations in Delhi.