Multiple Risk Models Research Articles

Normalisation theory: Does it accurately describe temporal changes in adolescent drunkenness and smoking?

The multiple risk model postulates that accumulating risk factors increase adolescent drunkenness and smoking. The normalisation theory adds to this by arguing that the relation between accumulative risk and drunkenness and smoking is dependent on the distribution of these behaviours in the larger population. More concretely, normalisation theory predicts that: (i) when population level use increases, low risk adolescents will be more likely to use alcohol and cigarettes; and (ii) adolescents facing multiple risk factors will be equally likely to use alcohol and cigarettes, regardless of trends in population level use. The current study empirically tests these assumptions on five waves of nationally representative samples of Israeli Jewish youth. Five cross-sectional waves of data from the Israeli Health Behaviour in School-aged Children survey for Jewish 10th graders were used. Logistic regression models measured the impact of changes in population level use across waves on drunkenness and smoking, and their association with differing levels of risk factors. Between zero and two risk factors, the risk of drunkenness and smoking increases for each additional risk factor. When reaching two risk factors, added risk does not significantly increase the likelihood of smoking and drunkenness. Changes in population level drunkenness and smoking did not systematically relate to changes in the individual level relationship between risk factors and smoking and drunkenness. The pattern of results in this study provides strong evidence for the multiple risk factor model and inconsistent evidence for the normalisation theory. [Sznitman SR, Zlotnick C, Harel-Fisch Y. Normalisation theory: Does it accurately describe temporal changes in adolescent drunkenness and smoking? Drug Alcohol Rev 2016;35:424-432].

Exposure to Single and Multiple Risks of Youngsters in Their Early Career in Britain: Continuous or Cumulative Disadvantage?

A plethora of studies raised concerns about the rising inequality on the labour market since the mid 1980s and especially also during the current crisis. In this paper we examine how low-skilled young men and women of 16 to 35 years of age fare with respect to their income and employment security over their career using panel data for Britain covering the early 1990s to the late 2000s. The main question is whether low-skilled youngsters are able to recover from their lower entry-level of security or that their disadvantage accelerates due to being exposed to adverse events and statuses over the career? A brief review of globalization, insider-outsider, tournament and stratification theories renders some support to the idea of cumulative disadvantage. The novelty of the approach is in studying the longer-term or career effects of exposure to single and multiple life course risks. The single risk results confirm the literature that low-skilled youngsters face continuous disadvantage instead of cumulative disadvantage implying that they recover but that the gap with the high skilled is never closed. The multiple risk models however reveal a mixed picture of cumulative disadvantage with respect to employment security and continuous disadvantage with respect to income security.

Beyond Bayesian vs. VaRR Dilemma to Empirical Model Risk Management: How to Manage Risk (After Risk Management Has Failed) for Hedge Funds

In aftermath of the Financial Crisis, some risk management practitioners advocate wider adoption of Bayesian inference to replace Value-at-Risk (VaR) models for minimizing risk failures (Borison & Hamm, 2010). They claim reliance of Bayesian inference on subjective judgment, the key limitation of Bayesian methodology as underscored by statisticians (Kass & Raftery, 1995; Kruschke, 2011; Lynch, 2007), as the most significant advantage compared with VaR (Christoffersen, 2012). Despite its well-known limitations, just like all other quantitative models (Derman, 1996; Morini, 2011), VaR – [mostly] non-Bayesian and [increasingly] Bayesian – continues to be a key methodological foundation of risk management and regulation related risk modeling practices in global Finance (Danielsson et al., 2014; Zangari, 1996). Bayesian inference modeling and VaR modeling frameworks are outlined to facilitate model risk management (Derman, 1996; Morini, 2011; US Fed & OCC, 2011) for minimizing risk of any model – Bayesian, VaR, or Bayesian VaR. VaR frameworks are empirically applied for hedge fund risk modeling (Darbyshire & Hampton, 2012, 2014) of a multi-asset fund of funds portfolio of a large Wall Street investment bank. Multiple risk models and measures with transparent assumptions to cross-validate convergent findings across multiple levels of risk analysis are examined for empirical model risk management.

Identifying hereditary cancer: Genetic counseling and cancer risk assessment

The goal of cancer genetic counseling, risk assessment, and testing is to identify individuals and families at risk for hereditary cancer, such that targeted management strategies can be used to reduce associated morbidity and mortality. Involvement of a qualified cancer genetic service provider helps to ensure that at-risk individuals identified and offered appropriate education, risk assessment, genetic testing, and follow-up risk management strategies. There are multiple screening and hereditary risk models available to help the clinician identify who needs to be referred to cancer genetic counseling and to facilitate the cancer risk assessment process. Genetic testing should only be pursued with fully informed consent in the context of pretest counseling to ensure that the individual understands the benefits, risks, and limitations of genetic testing, possible results, and their implications. Incorporating psychosocial assessment throughout the counseling session may assist the individual in their understanding of genetic testing in the context of their support resources and coping mechanisms and may help with decision making. There is a growing public awareness of and interest in cancer genetic testing, as well as increasing complexity of available testing options and results. It is therefore essential that cancer genetic professionals, primary care providers, and oncology practitioners work together to ensure that genetic testing for hereditary cancer syndromes is used in the most appropriate and effective way.

From temporal processing to developmental language disorders: mind the gap.

The 'rapid temporal processing' and the 'temporal sampling framework' hypotheses have been proposed to account for the deficits in language and literacy development seen in specific language impairment and dyslexia. This paper reviews these hypotheses and concludes that the proposed causal chains between the presumed auditory processing deficits and the observed behavioural manifestation of the disorders are vague and not well established empirically. Several problems and limitations are identified. Most data concern correlations between distantly related tasks, and there is considerable heterogeneity and variability in performance as well as concerns about reliability and validity. Little attention is paid to the distinction between ostensibly perceptual and metalinguistic tasks or between implicit and explicit modes of performance, yet measures are assumed to be pure indicators of underlying processes or representations. The possibility that diagnostic categories do not refer to causally and behaviourally homogeneous groups needs to be taken seriously, taking into account genetic and neurodevelopmental studies to construct multiple-risk models. To make progress in the field, cognitive models of each task must be specified, including performance domains that are predicted to be deficient versus intact, testing multiple indicators of latent constructs and demonstrating construct reliability and validity.

Individual Patient Data Of Conditional Survival Analysis In a Large Cohort Of 816 Multiple Myeloma (MM) Patients Constitutes a Different Way To Identify Patients With Extended Life Expectancy

BackgroundPrior analyses have advocated that mortality from major cancer has declined reflecting continuing progress in cancer prevention, early detection and treatment. Survival estimates are typically presented as the probability of surviving a given length of time after the diagnosis. In contrast, conditional survival describes the probabilities of surviving y additional years given patients survived x years. Conditional survival provides additional information about how the risk of death may change over time, taking into account, how long someone has already survived. In multiple myeloma, many prognostic parameters have been proposed to predict survival, but results on conditional survival are lacking. MethodsWe evaluated 816 consecutive multiple myeloma patients treated at our department between 1997-2011 with almost complete long-term follow-up. Patients' data were assessed via electronic medical record (EMR) retrieval within an innovative research data warehouse. Our platform, the University of Freiburg Translational Research Integrated Database Environment (U-RIDE), acquires and stores all patient data contained in the EMR at our hospital and provides immediate advanced text searching capacity. In an initial step, we assessed age, gender, disease stage (Durie&Salmon [D&S]), time of death and last follow-up. Moreover, we determined 5-year conditional survival as the probability of surviving at least 5 more years as a function of years a patient had already survived since initial diagnosis (i.e. 5-year conditional survival for those, who survived 0, 1, 2, 3, 4 and 5 years after initial diagnosis). Five year conditional survival was stratified according to gender, stage, age and other risk variables. ResultsThe OS probabilities at 5-/10-years were 50% and 25%, respectively. The 5-year-conditional survival remained constant over the years (50%, even at 5 years). As expected, D&S stage I vs. II+III showed different 5-year conditional survival estimates of 75% vs. 42%, respectively for those who survived 1 year after diagnosis. Similarly, age subgroups <60, 60-70 and >70 years showed notably different 5-year conditional survival estimates, but also remained constant over the course of time with ∼63%, 51% and 27%, respectively. Via multivariable Cox model including gender, admission period (<2001, 2001-2007, >2007), age and disease stage by D&S, the latter two were of statistical significance (p<0.001).To distinctively identify long-term survivors via conditional survival, we performed a comprehensive analysis of various prognostic factors, including disease-related factors, such as single components of the D&S (e.g. hemoglobin, calcium, creatinine and osteolyses) and International Staging System, laboratory variables (e.g. LDH, type of paraprotein) and host-related risks. The latter includes comorbid conditions, such as performance status and organ function. Via multivariable analysis, we identified an impaired Karnofsky Performance Status <80%, ≥2 osteolyses, hemoglobin <10g/dl, ß2-microglobulin ≥5.5mg/l and LDH ≥200U/l as significant additional risk factors (Table 1). Extensive cytogenetic analyses are currently included in our risk assessment (according to Moreau P. ASH 2012:#598 and Avet-Loiseau H. JCO 2012).Table 1Multivariable Cox proportional hazard model incorporating the covariables selected by boostingVariablesHR95%- CIp-valueKPS (%)80-100<8012.4-1.01-5.680.05Osteolyses<2≥212.17-1.52-3.10<0.001Hemoglobin≤10>1010.58-0.4-0.840.004ß2-MG<5.5≥5.511.73-1.08-2.770.02LDH<200≥20011.39-1.01-1.920.05eGFR≥9060-89<6011.221.28-0.79-1.870.76-2.140.88Albumin<3.5≥3.510.87-0.61-1.230.42Lung diseaseno-mildmoderate-severe11.31-0.87-1.980.20Freiburg Comorbidity Index01-0.691-31.210.47-3.08ISSI-II1-0.77III1.070.68-1.68 ConclusionsConditional survival analyses constitute an attractive tool to predict outcome, supplements existing measures and may guide cancer survivors in planning their future. Our ongoing risk assessment via inclusion of additional variables and cytogenetics aims to define long- vs. short-term survivors in a multiple myeloma specific risk model and should help to provide clinically relevant prognostic information (e.g accurate estimate of cause-specific survival), and to implement preventive and interventional strategies. Disclosures:No relevant conflicts of interest to declare.

Less is More: Evidence from International Asset Pricing Models

We revisit financial market integration and study the impact of multiple risk factors and model specification on inference. Our tests exploit a method correct in finite sample that jointly assesses coefficient significance and detects identification problems. Results on four countries show that multiple sources of risk in international asset pricing models lead to lack of identification and spurious inference. We find that domestic factor models are well identified which is not the case for global and international models. Nonetheless, domestic models do not provide a base for testing financial market integration. Given that constraint, the best-identified international model includes few factors and reveals that financial integration varies over time and across countries.

Conditional Survival Analysis in a Large Cohort of Multiple Myeloma Patients Provides Detailed Information about Long-Term Survival and Constitutes a Different Way to Identify Patients with Extended Life Expectancy

Abstract 4982 Introduction:Prior analyses have advocated that mortality from major cancer has declined reflecting continuing progress in cancer prevention, early detection and treatment. Survival estimates are typically presented as the probability of surviving a given length of time after the diagnosis. In contrast, conditional survival describes the probabilities of surviving y additional years given patients survived x years. Conditional survival provides additional information about how the risk of death may change over time, taking into account, how long someone has already survived. In multiple myeloma many prognostic parameters have been proposed to predict survival, but results on conditional survival are still lacking. Methods:We evaluated 816 consecutive multiple myeloma patients treated at our department between 1997–2011. Patients’ data were assessed via electronic medical record (EMR) retrieval within an innovative research data warehouse. Our platform, the University of Freiburg Translational Research Integrated Database Environment (U-RIDE), acquires and stores all patient data contained in the EMR at our hospital and provides immediate advanced text searching capacity. In an initial step, we assessed age, gender, disease stage (Durie&Salmon [D&S]), time of death and last follow-up. Moreover, we determined 5-year conditional survival as the probability of surviving at least 5 more years as a function of years a patient had already survived since initial diagnosis (i. e. 5-year conditional survival for those, who survived 0, 1, 2, 3, 4 and 5 years after initial diagnosis). Five year conditional survival was stratified according to gender, stage, age and other risk variables. Results:The OS probabilities at 5- and 10- years were 50% and 25%, respectively. The 5-year conditional survival probabilities remained almost constant over the years a patient had already survived after initial diagnosis (∼53%). According to baseline variables, conditional survival estimates showed no gender differences. As expected, D&S stage I vs. stage II+III showed substantially different 5-year conditional survival estimates over the years for those who survived 1 year after initial diagnosis (75% vs. 42%, respectively). Similarly, age subgroups <60, 60–70 and >70 years showed notably different 5-year conditional survival estimates, but also remained constant over the course of time with ∼63%, 51% and 27%, respectively. The multivariable Cox model, including gender, year of admission (before 2001, 2001–2007 and after 2007), D&S (stage II-III) and age (>70 years) showed increased hazard ratio (HR) for both latter groups of 2. 2 (95% CI 1. 8–2. 7; <0. 0001) and 3. 5 (95% CI: 2. 7–4. 4, <0. 0001), respectively. Ongoing analyses aim to distinctively identify long-term survivors via conditional survival. In order to obtain a comprehensive analysis of relevant prognostic factors, we have focused on variables with high degree of completeness. These include disease-related factors, such as single components of the D&S (e. g. hemoglobin, calcium, creatinine and osteolyses) and International Staging System, laboratory variables (e. g. LDH, type of paraprotein) and host-related risk factors. The latter include comorbid conditions such as performance status and organ function. Of note, over the study period, admission of patients <60 years decreased from 60% to 34%, but increased for those ≥70 years from 10% to 35%, respectively, illustrating that not only young and fit, but also elderly patients are increasingly treated within large referral and university centers and that patient cohorts and risks do not remain constant over time. Conclusions:In this study, involving a large cohort of multiple myeloma patients, analyses stratified by age and stage revealed substantially different conditional survival estimates. Conditional survival seems an attractive tool to predict outcome over time, supplements existing measures and may guide cancer survivors in planning their future. The combination of the main prognostic factors of the ongoing analysis in a multiple myeloma specific risk model, may define long-term survivors via conditional survival more distinctively and will be presented at the meeting. Disclosures:No relevant conflicts of interest to declare.

Using multiple risk models with preventive interventions

An ideal preventive intervention would have negligible side effects and could be applied to the entire population, thus achieving maximal preventive impact. Unfortunately, many interventions have adverse effects and beneficial effects. For example, tamoxifen reduces the risk of breast cancer by about 50% and the risk of hip fracture by 45%, but increases the risk of stroke by about 60%; other serious adverse effects include endometrial cancer and pulmonary embolus. Hence, tamoxifen should only be given to the subset of the population with high enough risks of breast cancer and hip fracture such that the preventive benefits outweigh the risks. Recommendations for preventive use of tamoxifen have been based primarily on breast cancer risk. Age-specific and race-specific rates were considered for other health outcomes, but not risk models. In this paper, we investigate the extent to which modeling not only the risk of breast cancer, but also the risk of stroke, can improve the decision to take tamoxifen. These calculations also give insight into the relative benefits of improving the discriminatory accuracy of such risk models versus improving the preventive effectiveness or reducing the adverse risks of the intervention. Depending on the discriminatory accuracies of the risk models, there may be considerable advantage to modeling the risks of more than one health outcome.

COMPLIANCE, OPPOSITION, AND BEHAVIOR PROBLEMS IN TODDLERS BORN PRETERM OR LOW BIRTHWEIGHT.

Although children born preterm or low birth weight (PT LBW) are more likely to exhibit behavior problems compared to children born at term, developmental and family processes associated with these problems are unclear. We examined trajectories of maternal depressive symptoms in relation to toddler compliance and behavior problems in families with PT LBW infants. A total of 177 infants (93 boys, 84 girls) and their mothers enrolled in the study during the infant's NICU stay. Data were collected at five time points across 2 years. Assessments of maternal depressive symptoms were conducted at all time points, and toddler compliance and opposition to maternal requests and behavior problems were assessed at 2 years. Toddlers born earlier with more health problems to mothers whose depressive symptoms increased over time exhibited the most opposition to maternal requests during a cleanup task at 24 months, consistent with multiple risk models. Mothers with elevated depression symptoms reported more behavior problems in their toddlers. The study has implications for family-based early intervention programs seeking to identify PT LBW infants at highest risk for problem behaviors.

Managing unintentional dwelling fire risk

In this paper, we examine the management of unintentional dwelling fire risk through the development of a geographical information system (GIS) for dwelling fire prevention support based upon an 18-month case study in a UK fire and rescue service. Previous research into causal factors in unintentional dwelling fire incidents was used to guide the development of a multiple linear regression risk model for dwelling fire incidents that was the basis of the GIS developed. The GIS provided a more detailed analysis of unintentional dwelling fire risk factors, and enabled more targeted fire prevention activities for the identified at-risk social groups.

Cumulative versus Multiple-Risk Models in the Prediction of Anxiety Symptoms

The present study aimed to advance understanding of the cumulative and incremental influences of anxiety sensitivity, behavioral inhibition, and interpretive and judgment biases on anxiety outcomes in a large sample of emerging adults (N = 862; mean age = 18.75 years, SD = 1.04). Participants completed a battery of questionnaires assessing the constructs of interest and cumulative- and multiple-risk models were tested. Linear, hierarchical regression analyses showed that cumulative- and multiple-risk models significantly predicted anxiety outcomes, although the statistical prediction offered by the latter model was superior. Additionally, variability in each risk factor significantly predicted anxiety outcomes after controlling for the total number of risks, supporting the value of the severity of risk to the prediction of anxiety outcomes. Findings, implications for intervention, and limitations are discussed.

Predicting Adverse Outcomes After Complex Cancer Surgery

Predicting Adverse Outcomes After Complex Cancer Surgery

Concurrent changes in conduct problems and depressive symptoms in early adolescents: a developmental person-centered approach.

The co-occurrence of conduct problems (CP) and depressive symptoms (DS) is an important topic in developmental psychopathology; however, research in this area is still in its early stages. Using data from a school-based longitudinal sample of 2,453 adolescents with five waves from Grade 6 to 9, we examined the prevalence, etiology, and consequences of the co-occurrence of CP and DS. A person-centered approach, general growth mixture modeling, was applied to obtain CP and DS trajectory groups. The risk factors and consequences of the co-occurrence problem were examined using the trajectory groups. As hypothesized in a nonclinical sample, a small proportion of boys (8.8%) and girls (3.7%) reported to be high in both CP and DS over time. Among the adolescents with the highest level of CP, only 6.3% of the boys and 6.0% of the girls experienced the highest level of DS. However, among those with the highest level of DS trajectories, 42.9% of the boys and 10.2% of the girls reported the highest level of CP, indicating a gender-specific risk of the co-occurrence problem for depressed boys. Psychosocial and family factors were identified as vulnerable precursors to co-occurring CP and DS, a finding in line with the multiple domain risk model for CP and the transactional model for DS. The study also found that adolescents with the co-occurrence problem were more similar to those with "pure DS" than those with "pure CP" in academic adjustment at the ninth grade.

Implementing an innovative consent form: the PREDICT experience

BackgroundIn the setting of coronary angiography, generic consent forms permit highly variable communication between patients and physicians. Even with the existence of multiple risk models, clinicians have been unable to readily access them and thus provide patients with vague estimations regarding risks of the procedure.MethodsWe created a web-based vehicle, PREDICT, for embedding patient-specific estimates of risk from validated multivariable models into individualized consent documents at the point-of-care. Beginning August 2006, outpatients undergoing coronary angiography at the Mid America Heart Institute received individualized consent documents generated by PREDICT. In February 2007 this approach was expanded to all patients undergoing coronary angiography within the four Kansas City hospitals of the Saint Luke's Health System. Qualitative research methods were used to identify the implementation challenges and successes with incorporating PREDICT-enhanced consent documents into routine clinical care from multiple perspectives: administration, information systems, nurses, physicians, and patients.ResultsMost clinicians found usefulness in the tool (providing clarity and educational value for patients) and satisfaction with the altered processes of care, although a few cardiologists cited delayed patient flow and excessive patient questions. The responses from administration and patients were uniformly positive. The key barrier was related to informatics.ConclusionThis preliminary experience suggests that successful change in clinical processes and organizational culture can be accomplished through multidisciplinary collaboration. A randomized trial of PREDICT consent, leveraging the accumulated knowledge from this first experience, is needed to further evaluate its impact on medical decision-making, patient compliance, and clinical outcomes.

Advanced Heart Failure: A Call to Action

Despite improvements in medical therapy for heart failure, more than 250,000 people die in the United States as a result of heart failure each year. There are multiple risk factors and models that have been created to identify these people, yet there has not been a significant impact on outcomes or change in the therapies for these patients. The authors review the available therapies for patients with advanced heart failure and the various risk models available to predict morbidity and mortality and present simple "office predictors" that could be used to potentially predict patients who would benefit from these therapies.

Investing in movies

Investment managers are becoming increasingly interested in intellectual property as an asset class, and a large part of this intellectual property is filmed content created by the major movie studios. We have collected reliable information about the creative content and financial performance of feature films, and used this data to better understand the returns to investing in movies. We describe the valuation context of feature films and list the important factors influential in explaining financial returns. These factors are then used to build a quantitative, multiple factor valuation and risk model of the asset class.

Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome

Circadian symptom manifestation in the evening and night is one of the main characteristics of restless legs syndrome (RLS). Although the inverse temporal course of corticosteroid rhythm and RLS symptom severity is obvious, this relationship has yet to be studied. We investigated the effect of late-evening application of exogenous cortisol (hydrocortisone) on sensory leg discomfort (SLD), one of the main complaints of patients with RLS. Ten untreated patients with idiopathic RLS participated in the study. Change of SLD was rated on a visual analogue scale during the 60 minutes resting period of the so-called Suggested Immobilization Test. Patients received either hydrocortisone 40 mg or placebo (saline) IV in random order in a double-blind crossover design, with 1 week between the experiments. Severity of SLD was lower during hydrocortisone infusion than during placebo (p = 0.032). Though blind to the experimental condition, 5 of the 10 patients experienced improvement in symptoms during hydrocortisone administration, but no patient felt an amelioration during the placebo condition. Our data indicate a probable physiologic relationship between evening and early night hour restless legs syndrome symptom increase and low cortisol level.

Commentary: Multiple Risk Models in Pediatric Research--Considering the Context that Shapes Children's Health

Commentary: Multiple Risk Models in Pediatric Research--Considering the Context that Shapes Children's Health

Comparison of Mortality Risk for Electrocardiographic Abnormalities in Men and Women With and Without Coronary Heart Disease (from the Cardiovascular Health Study)

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.