Background Risk Research Articles

Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set

Background and objectivePolygenic risk scores (PRSs) have been developed to identify men with the highest risk of prostate cancer. Our aim was to compare the performance of 16 PRSs in identifying men at risk of developing prostate cancer and then to evaluate the performance of the top-performing PRSs in differentiating individuals at risk of aggressive prostate cancer. MethodsFor this case-control study we downloaded 16 published PRSs from the Polygenic Score Catalog on May 28, 2021 and applied them to Michigan Genomics Initiative (MGI) patients. Cases were matched to the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to obtain granular clinical and pathological data. MGI prospectively enrolls patients undergoing surgery at the University of Michigan, and MUSIC is a multi-institutional registry that prospectively tracks demographic, treatment, and clinical variables. The predictive performance of each PRS was evaluated using the area under the covariate-adjusted receiver operating characteristic curve (aAUC), and the association between PRS and disease aggressiveness according to prostate biopsy data was measured using logistic regression. Key findings and limitationsWe included 18 050 patients in the analysis, of whom 15 310 were control subjects and 2740 were prostate cancer cases. The median age was 66.1 yr (interquartile range 59.9–71.6) for cases and 56.6 yr (interquartile range 42.6–66.7) for control subjects. The PRS performance in predicting the risk of developing prostate cancer according to aAUC ranged from 0.51 (95% confidence interval 0.51–0.53) to 0.67 (95% confidence interval 0.66–0.68). By contrast, there was no association between PRS and disease aggressiveness. Conclusions and clinical implicationsProstate cancer PRSs have modest real-world performance in identifying patients at higher risk of developing prostate cancer; however, they are limited in distinguishing patients with indolent versus aggressive disease. Patient summaryRisk scores using data for multiple genes (called polygenic risk scores) can identify men at higher risk of developing prostate cancer. However, these scores need to be refined to be able to identify men with the highest risk for clinically significant prostate cancer.

Women's reproductive risk score and healthy lifestyle modification in cardiovascular disease: Findings from the UK Biobank

Background and aimsReproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. MethodsThe RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0–1), intermediate lifestyle group (score: 2–3) and healthy lifestyle group (score: 4–5). ResultsEach point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. ConclusionsHigh RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy.

Arrhythmogenic Left Ventricular Cardiomyopathy: From Diagnosis to Risk Management.

Left ventricular arrhythmogenic cardiomyopathy (ALVC) is a rare and poorly characterized cardiomyopathy that has recently been reclassified in the group of non-dilated left ventricular cardiomyopathies. This review aims to summarize the background, diagnosis, and sudden cardiac death risk in patients presenting this cardiomyopathy. Although there is currently a lack of data on this condition, arrhythmogenic left ventricular dysplasia can be considered a specific disease of the left ventricle (LV). We have collected the latest evidence about the management and the risks associated with this cardiomyopathy. Left ventricular arrhythmogenic cardiomyopathy is still poorly characterized. ALVC is characterized by fibrofatty replacement in the left ventricular myocardium, with variable phenotypic expression. Diagnosis is based on a multiparametric approach, including cardiac magnetic resonance (CMR) and genetic testing, and is important for sudden cardiac death (SCD) risk stratification and management. Recent guidelines have improved the management of left ventricular arrhythmogenic cardiomyopathy. Further studies are necessary to improve knowledge of this cardiomyopathy.

Can Climate Shocks Make Vulnerable Subjects More Willing to Take Risks?

While economists in the past tended to assume that individual preferences, including risk preferences, are stable over time, a recent literature has developed and indicates that risk preferences respond to shocks, with mixed evidence on the direction of the responses. This paper utilizes a natural experiment with covariate (drought) and idiosyncratic shocks in combination with an independent field risk experiment. The risk experiment uses a Certainty Equivalent-Multiple Choice List approach and is played 1–2 years after the subjects were (to a varying degree) exposed to a covariate drought shock or idiosyncratic shocks for a sample of resource-poor young adults living in a risky semi-arid rural environment in Sub-Saharan Africa. The experimental approach facilitates a comprehensive assessment of shock effects on experimental risk premiums for risky prospects with varying probabilities of good and bad outcomes. The experiment also facilitates the estimation of the utility curvature in an Expected Utility (EU) model and, alternatively, separate estimation of probability weighting and utility curvature in three different Rank Dependent Utility models with a two-parameter Prelec probability weighting function. Our study is the first to comprehensively test the theoretical predictions of Gollier and Pratt (Econom J Econom Soc 64:1109–1123, 1996) versus Quiggin (Econ Theor 22(3):607–611, 2003). Gollier and Pratt (1996) build on EU theory and state that an increase in background risk will make subjects more risk averse while Quiggin (2003) states that an increase in background risk can enhance risk-taking in certain types of non-EU models. We find strong evidence that such non-EU preferences dominate in our sample.

Coexistence of IgG4-related disease and tubercular lymphadenopathy in a rheumatoid arthritis patient

Extrapulmonary tuberculosis is a very common cause of generalised lymphadenopathy especially in tuberculosis endemic regions like India. A 33-year-old lady who had been diagnosed with rheumatoid arthritis 5 years back and had received treatment with biologicals including adalimumab presented with a 3 week history of persistent fever associated with significant weight loss and abdominal fullness. Investigations pointed towards a picture of tubercular aetiology although, a definite microbiological diagnosis was not possible at this stage. Patient also had an underlying subacute thyroiditis with diffusely increased uptake in Tc99 scan. Considering the background risk factor of use of biologicals and typical clinical presentation resembling tuberculosis, a decision to start antitubercular therapy was taken. The fever resolved but it recurred after 2 weeks and then after an extensive workup, the diagnosis of coexistent IgG4-related disease along with microbiological diagnosis of tuberculosis was established. This case highlights the importance of an active search for coexistent pathologies in cases of lymphadenopathy with insufficient response to standard therapy.

Index-tracking portfolio selection with background risk

Index-tracking portfolio selection with background risk

Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study)

Background and aimsConversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer.MethodsWe performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion.ResultsData were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.05, p = 0.0002), combined resection of adjacent organs [+/−] (OR 7.92, 95% CI 3.14–19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [−/+] (OR 4.46, 95% CI 2.01–9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99–1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54–8.04, p = 0.0028), combined resection of adjacent organs [+/−] (OR 5.96, 95% CI 2.15–16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [−/+] (OR 6.26, 95% CI 3.01–13.05, p < 0.0001).ConclusionsParticipation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients.Trial RegistrationThis study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Temporal changes in cumulative mortality risks of cancer, by occupation, in the working population of Japan from 1995 to 2020: a benchmark for radiation risk comparison

The purpose of this study was to provide benchmark data for discussing the tolerability of cancer risk associated with occupational radiation exposure. It focused on differences in cancer mortality risk by occupation among Japan’s working population and examined baseline cancer mortality risks and its variations from 1995 through 2020. Data were collected every five years from national vital statistics sources. By focusing on the same types of cancer among radiation induced effects, cumulative mortality risks were calculated for colorectal, lung, and breast cancer (females only) for those aged 15–74. The average cumulative mortality risk for the working population in Japan has decreased by 30%–60% over the past 25 years. Service workers and male managers were at an average risk, among all workers, while clerical workers and transportation and manufacturing workers had about half the average risk. The risks were higher for professionals and female managers, about 1.5–2 times the average for professionals and up to 5 times the average for female managers. The decrease in the average cancer mortality risk in the working population as a baseline suggests that risk tolerance in society might have changed over time. Since differences in mortality by occupation were confirmed, the usefulness of occupational data as a benchmark needs further investigation, as high-risk/low-risk occupations vary by country and region. The results of this study contribute to put radiation risks into perspective with the background risk of cancer.

How Risky is Online Sexting by Minors?

ABSTRACT What proportion of minors who engage in sexting find themselves involved in an episode of image abuse? The data come from a US nationally representative sample of 2639 respondents aged 18–28 reporting about experiences before the age of 18, of whom 23% had engaged in sexting as minors. Among those who sexted the rate of image abuse was 37%, a risk ratio of 13.2 compared to those who did not engage in sexting. For females who sexted the victimization rate was particularly high, but sexting increased risk for females and males. Among the minors who only sexted occasionally (vs those who sexted frequently) the rate of abuse was still high (35%) and the reduction in risk modest. When we controlled for other background and demographic risk factors like adversities and prior sexual abuse, it did not substantially reduce the large risk entailed with sexting. Various harm reduction strategies may be needed to supplement messages about dangers and risks.

Mediation of Psychological Capital in Youth Experiencing Homelessness.

Youth who experience homelessness engage in behaviors that place them at high risk for disease and injury. Despite their health risk behaviors, these youth display psychological capital, positive attributes of hope, efficacy, resilience, and optimism that motivate them to engage in health-promoting behaviors such as safer sex. However, this array of positive psychological attributes has not been studied in this vulnerable population. The specific aim of this analysis was to determine whether factors of psychological capital mediated the relationship between background risk factors (e.g., race/ethnicity, educational attainment, reason for being homeless, sexual abuse history, and HIV status) and outcomes of condom intention, safer sex behaviors, and life satisfaction among youth who participated in a longitudinal intervention study. Using a Solomon four-group design, 602 youth were recruited from drop-in centers in two large cities (Columbus, Ohio, and Austin, Texas) to participate in a brief intervention that included outcomes of enhanced communication skills, goal setting, safer sex behaviors, drug refusal skills, and life satisfaction. Using an autoregressive, cross-lagged, longitudinal mediation model, we tested the direct and indirect effects of background factors, psychological capital, and intervention outcomes. Models were tested for the intervention group alone and the total sample. There were no significant direct or indirect effects of background factors on intervention outcomes among the intervention group, and the model fit was poor. There were also no significant mediating paths via factors of psychological capital and poor model fit for the combined group. Findings provide important information about intrinsic strengths of youth experiencing homelessness and psychological capital as a significant construct for understanding health behaviors among disadvantaged and underserved youth. The lack of significant mediation effects may have been due, in part, to the lack of a robust measure of psychological capital. Further study with various background factors and outcomes would contribute further to our understanding of how best to support this population.

Optimal insurance with counterparty and additive background risk

AbstractIn this paper, we explore how to design the optimal insurance contracts when the insured faces insurable, counterparty, and additive background risk simultaneously. The target is to minimize the mean-variance of the insured’s loss. By utilizing the calculus of variations, an implicit characterization of the optimal ceded loss function is given. An explicit structure of the optimal ceded loss function is also provided by making full use of its implicit characterization. We further derive a much simpler solution when these three kinds of risk have some special dependence structures. Finally, we give a numerical example to illustrate our results.

Research on the Portfolio of Chinese Photovoltaic Enterprises

Two models to reduce potential risks in photovoltaic enterprises are introduced in this paper to demonstrate the problem that the price of silicon is dropping sharply today. Based on the portfolio theories, the first model is created by the use of Mean-variance model which is traditional and functional. As an improvement, the second model, the Mean-semivariance model takes not only the financial marketing risks but also the background risks into consideration. The data is collected by iFind from three different enterprises. Despite having a large production scale, each enterprise is separated from each other. The calculations indicate that the paper contains a figure that contains the weights of two stocks from two different enterprises. The figure displays the distinction between the effective and inefficient portfolios. Among the efficient portfolios, some of them own a high level of Sharpe ratio while having a low level of deviation, indicating that upstream industries could invest in both upstream industries, and midstream industries in order to weaken the risks brought by the price drop of silicon. This paper will assist investors in making better investment decisions using portfolio theories.

Contrasting risk preferences in the shadow of volcanic background risk: a field experiment in Arequipa, Perú

ABSTRACT We investigate the divergence in risk preferences between individuals exposed to background risk and those who are not, using a field experiment conducted in Arequipa, Peru. Arequipa, a city located in close proximity to the El Misti volcano, is constantly threatened by lahars – mudflows originating from this volcano. Our study combines experimenta l assessments of risk tolerance and patience with a targeted survey designed to assess residents’ awareness of their exposure to risks. Our primary finding reveals that residents living in hazard-prone areas exhibit higher levels of risk tolerance compared to their counterparts in safer zones. To address concerns about causality, we employ instrumental variable (IV) regressions and conduct stability analyses of coefficients. We subsequently discuss our findings in the context of the literature on preference adaptation.

The Value of Negative Urinary Dipstick Tests for Haematuria in Patients Undergoing Surveillance for Low-grade Ta Urothelial Cancer: A Two-stage Prospective Clinical Study in 524 Patients

Background and objectiveThe risk of first recurrence beyond 5 yr for patients with low-grade (LG) Ta non–muscle-invasive bladder cancer (NMIBC) is low enough to consider discontinuing cystoscopic surveillance at that point. However, a positive urinary dipstick test for haematuria (UDH) during and beyond the period of cystoscopic surveillance can disrupt plans to cease surveillance because the association between UDH positivity and recurrence in LG Ta NMIBC is unknown. In a two-stage study, we evaluated this association and explored the role of UDH negativity in predicting the absence of recurrence. MethodsBecause of previously demonstrated changes in recurrence patterns over time, two prospective cohorts were assessed: an “exploratory” cohort (January 2007–March 2008) and a “validation” cohort (November 2017–August 2018). UDH was performed before flexible cystoscopy. Patient, operative, and surveillance data have been recorded prospectively using standard pro forma sheets since 1978 in our institution. Only patients with primary LG Ta pTa NMIBC were included for analysis. Key findings and limitationsWe assessed 231 patients in the exploratory group and 293 in the validation group. The proportion of smokers (67% vs 70%; p = 0.5) and mean follow-up (72.2 vs 79.9 mo; p = 0.2) were similar between the groups. The recurrence rate was higher in the exploratory group (19% vs 11%; p = 0.009), as was the UDH positivity rate (37% vs 11%; p < 0.001). The specificity and negative predictive value were 64% and 83% in the exploratory group, and 90% and 90%, respectively, in the validation group. These values increased further for the subgroup with solitary primary tumours the subgroup without recurrence for 3 yr. Conclusions and clinical implicationsUDH negativity has a high probability of being associated with the absence of recurrence in small LG Ta NMIBC and could be an inexpensive adjunct during surveillance. Ongoing validation, which started in 2019, is being performed in a now-nationalised Scottish protocol in which UDH replaces cystoscopy in years 2 and 4 for patients in the low-risk group. Patient summaryWe investigated the accuracy of a dipstick test for blood in the urine for patients undergoing surveillance for low-grade noninvasive bladder cancer. We found that a negative dipstick test result was highly associated with the absence of tumour recurrence, particularly for patients with the lowest risk. These findings have been introduced into a national protocol designed to reduce the frequency of telescopic inspection of the bladder during surveillance to reduce the burden for patients.

The Hospital Frailty Risk Score Independently Predicts Postoperative Outcomes in Glioblastoma Patients

Background and ObjectiveThe Hospital Frailty Risk Score (HFRS) was recently introduced as a tool for quantifying patient frailty using ICD-10 codes. The utility of HFRS has not yet been evaluated. The objective of the study is to determine the utility of HFRS in predicting surgical outcomes following resection of GBM and compare its prognostic ability to other validated indices, such as the American Society of Anesthesiologists (ASA) physical status classification and Charlson Comorbidity Index (CCI). MethodsA retrospective analysis was conducted using a GBM patient database (2017 to 2019) at a single institution. HFRS was calculated using ICD-10 codes. Bivariate logistic regression was used to model the prognostic ability of each frailty index, and model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Multivariate linear and logistic regression models were used to assess for significant associations between HFRS and continuous and binary postoperative outcomes, respectively. Results263 GBM patients were included in the study. HFRS had a significantly greater AUROC when compared to ASA (p=0.016) and CCI (p=0.037) for predicting 30-day readmission. On multivariate analysis, HFRS was significantly and independently associated with hospital length of stay (LOS) (p=0.0038), nonroutine discharge (p=0.018) and 30-day readmission (p=0.0051). ConclusionHFRS has utility in predicting postoperative outcomes for GBM patients and more effectively predicts 30-day readmission than other frailty indices. HFRS may be used as a tool for optimizing clinical decision-making to reduce adverse post-operative outcomes among GBM patients.

Optimal Insurance with Background Risk under the Ambiguity and Belief Heterogeneity Structure

Optimal Insurance with Background Risk under the Ambiguity and Belief Heterogeneity Structure

Optimal Insurance Design under Different Dependency Structures of Insurable Risk and Background Risk

Optimal Insurance Design under Different Dependency Structures of Insurable Risk and Background Risk

Multiplicative Background Risk and Risk Taking

Multiplicative Background Risk and Risk Taking

Adição da Troponina Ultrassensível à Avaliação de Risco Perioperatório Melhora a Capacidade Preditiva de Morte em Pacientes Submetidos à Cirurgia Não Cardíaca

Abstract Background Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. Objective Evaluate the incremental power of troponin to the usual risk stratification Methods A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. Results Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p&lt;0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. Conclusion The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.

State-dependent background risk and optimal prevention in a two-period model

State-dependent background risk and optimal prevention in a two-period model