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BackgroundPrimary aldosteronism is recognized as a severe form of renin-independent aldosteronism that results in excessive mineralocorticoid receptor (MR) activation.ObjectiveTo investigate whether a spectrum of subclinical renin-independent aldosteronism that increases risk for hypertension exists among normotensive persons.DesignCohort study.SettingNational community-based study.Participants850 untreated normotensive participants in MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity (PRA).MeasurementsLongitudinal analyses investigated whether aldosterone concentrations, in the context of physiologic PRA phenotypes (suppressed, ≤0.50 µg/L per hour; indeterminate, 0.51 to 0.99 µg/L per hour; unsuppressed, ≥1.0 µg/L per hour), were associated with incident hypertension (defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of antihypertensive medications). Cross-sectional analyses investigated associations between aldosterone and MR activity, assessed via serum potassium and urinary fractional excretion of potassium.ResultsA suppressed renin phenotype was associated with a higher rate of incident hypertension than other PRA phenotypes (incidence rates per 1000 person-years of follow-up: suppressed renin phenotype, 85.4 events [95% CI, 73.4 to 99.3 events]; indeterminate renin phenotype, 53.3 events [CI, 42.8 to 66.4 events]; unsuppressed renin phenotype, 54.5 events [CI, 41.8 to 71.0 events]). With renin suppression, higher aldosterone concentrations were independently associated with an increased risk for incident hypertension, whereas no association between aldosterone and hypertension was seen when renin was not suppressed. Higher aldosterone concentrations were associated with lower serum potassium and higher urinary excretion of potassium, but only when renin was suppressed.LimitationSodium and potassium were measured several years before renin and aldosterone.ConclusionSuppression of renin and higher aldosterone concentrations in the context of this renin suppression are associated with an increased risk for hypertension and possibly also with increased MR activity. These findings suggest a clinically relevant spectrum of subclinical primary aldosteronism (renin-independent aldosteronism) in normotension.Primary funding sourceNational Institutes of Health.

Aims: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24–28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria. Methods: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves. Results: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70–0.91). A PP pGCD59 cut‐off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9–100), specificity of 16.9% (95% CI: 9.8–26.3), positive predictive value of 22.1% (95% CI: 21.0–22.6), and negative predictive value of 100% (95% CI: 87.4–100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89–0.99) for the identification of PP glucose intolerance. Conclusion: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance. [ABSTRACT FROM AUTHOR]

The main purpose of many medical studies is to estimate the effects of a treatment or exposure on an outcome. However, it is not always possible to randomize the study participants to a particular treatment, therefore observational study designs may be used. There are major challenges with observational studies; one of which is confounding. Controlling for confounding is commonly performed by direct adjustment of measured confounders; although, sometimes this approach is suboptimal due to modeling assumptions and misspecification. Recent advances in the field of causal inference have dealt with confounding by building on classical standardization methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where new estimators were developed to overcome the limitations of the previous estimators (ie, nonparametric and parametric g-formula, inverse probability weighting, double-robust, and data-adaptive estimators). We illustrate the implementation of different methods using an empirical example from the Connors study based on intensive care medicine, and most importantly, we provide reproducible and commented code in Stata, R, and Python for researchers to adapt in their own observational study. The code can be accessed at https://github.com/migariane/Tutorial_Computational_Causal_Inference_Estimators. [ABSTRACT FROM AUTHOR]

Context: Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH. Objective: The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH). Methods: This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy (< 20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 hours of delivery. Results: We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P < .001). The odds of NH were higher in infants from mothers in tertile 3 of pGCD59 levels compared to those from mothers in tertile 1 (odds ratio [OR]: 2.41; 95% CI, 1.03-5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28; 95% CI, 0.96-5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI, 0.54-0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI, 0.56-0.78). Conclusion: Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH. [ABSTRACT FROM AUTHOR]

Simple Summary: There are inequalities in cancer survival between patients with or without comorbidities. The healthcare pathway (i.e., diagnostic route) of a patient is thought to explain some of these inequalities. We explore how much of the effect of comorbidity on survival of patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) is explained by the diagnostic route (i.e., emergency diagnosis). We used mediation analysis to separate the effect of comorbidity on survival from its effect through diagnostic route. We found that, for DLBCL and FL, emergency diagnosis accounted for 24% and 16% of the inequalities in survival between comorbidity groups within 12 months since cancer diagnosis. This proportion reduced over time and was small after 5 years of follow up. Comorbidities can complicate the diagnosis and management of patients with DLBCL or FL. Our results show that greater research is needed to ensure patients with comorbidities have a timely diagnosis and will help to reduce the inequalities in cancer survival. Background: Socioeconomic inequalities in survival from non-Hodgkin lymphoma persist. Comorbidities are more prevalent amongst those in more deprived areas and are associated with diagnostic delay (emergency diagnostic route), which is also associated with poorer survival probability. We aimed to describe the effect of comorbidity on the probability of death mediated by diagnostic route (emergency vs. elective route) amongst patients with diffuse large B-cell (DLBCL) or follicular lymphoma (FL). Methods: We linked the English population-based cancer registry and hospital admission records (2005–2013) of patients aged 45–99 years. We decomposed the effect of comorbidity on survival into an indirect effect acting through diagnostic route and a direct effect not mediated by diagnostic route. Furthermore, we estimated the proportion of the comorbidity effect on survival mediated by diagnostic route. Results: For both DLBCL (n = 27,379) and FL (n = 14,043), those with any comorbidity, or living in more deprived areas, were more likely to experience diagnostic delay and poorer survival. The indirect effect of comorbidity on mortality through diagnostic route was highest at 12 months since diagnosis (DLBCL: Odds Ratio 1.10 [95% CI 1.07–1.13], FL: OR 1.09 [95% CI 1.04–1.14]). Within the first 12 months since diagnosis, emergency diagnostic route accounted for 24% (95% CI 17.5–29.5) and 16% (95% CI 6.0–25.6) of the comorbidity effect on mortality, for DLBCL and FL, respectively. Conclusion: Efforts to reduce diagnostic delay (emergency diagnosis) amongst patients with comorbidity would reduce inequalities in DLBCL and FL survival by 24% and 16%, respectively. Further public health programs and interventions are needed to reduce diagnostic delay amongst lymphoma patients with comorbidities. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the ability of second trimester plasma glycated CD59 (pGCD59), a novel biomarker, to predict the results of the 2 h 75 g oral glucose tolerance test at 24–28 weeks of gestation, employing the 2013 World Health Organisation criteria. This was a prospective study of 378 pregnant women. The ability of pGCD59 to predict gestational diabetes (GDM) was assessed using adjusted ROC curves for maternal age, BMI, maternal ethnicity, parity, previous GDM, and family history of diabetes. The pGCD59 levels were significantly higher in women with GDM compared to women with normal glucose tolerance (p = 0.003). The pGCD59 generated an adjusted AUC for identifying GDM cases of 0.65 (95%CI: 0.58–0.71, p < 0.001). The pGCD59 predicted GDM status diagnosed by a fasting glucose value of 5.1 mmol/L with an adjusted AUC of 0.74 (95%CI: 0.65–0.81, p < 0.001). Analysis of BMI subgroups determined that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC: 0.84 95%CI: 0.69–0.98) and BMI ≥ 40 kg/m2 (AUC: 0.96 95%CI: 0.86–0.99) categories. This study found that second trimester pGCD59 is a fair predictor of GDM status diagnosed by elevated fasting glucose independent of BMI and an excellent predictor of GDM in subjects with a very high BMI. [ABSTRACT FROM AUTHOR]

The influence of socioeconomic status (SES) on access to standard chemotherapy and/or monoclonal antibody therapy, and associated secular trends, relative survival, and excess mortality, among diffuse large B-cell lymphoma (DLBCL) patients is not clear. We conducted a Hong Kong population-based cohort study and identified adult patients with histologically diagnosed DLBCL between 2000 and 2018. We examined the association of SES levels with the odds and the secular trends of receipt of chemotherapy and/or rituximab. Additionally, we estimated the long-term relative survival by SES utilizing Hong Kong life tables. Among 4017 patients with DLBCL, 2363 (58.8%) patients received both chemotherapy and rituximab and 740 (18.4%) patients received chemotherapy alone, while 1612 (40.1%) and 914 (22.8%) patients received no rituximab or chemotherapy, respectively. On multivariable analysis, low SES was associated with lesser use of chemotherapy (odd ratio [OR] 0.44; 95% CI 0.34–0.57) and rituximab (OR 0.41; 95% CI 0.32–0.52). The socioeconomic disparity for either treatment showed no secular trend of change. Additionally, patients with low SES showed increased excess mortality, with a hazard ratio of 2.34 (95% CI 1.67–3.28). Improving survival outcomes for patients with DLBCL requires provision of best available medical care and securing access to treatment regardless of patients' SES. [ABSTRACT FROM AUTHOR]

There are few if any reports regarding the role of lifetime waterpipe smoking in the etiology of multiple sclerosis (MS). In a population-based incident case-control study conducted in Tehran, Iran, we investigated the association between waterpipe smoking and MS, adjusted for confounders. Cases (n  = 547) were patients aged 15–50 years identified from the Iranian Multiple Sclerosis Society between 2013 and 2015. Population-based controls (n  = 1,057) were persons aged 15–50 years recruited through random digit telephone dialing. A doubly robust estimation method, the targeted maximum likelihood estimator (TMLE), was used to estimate the marginal risk ratio and odds ratio for the association between waterpipe smoking and MS. The estimated risk ratio and odds ratio were both 1.70 (95% confidence interval: 1.34, 2.17). The population attributable fraction was 21.4% (95% confidence interval: 4.0, 38.8). Subject to the limitations of case-control studies in interpreting associations causally, these results suggest that waterpipe use, or strongly related but undetermined factors, increases the risk of MS. Further epidemiologic studies, including nested case-control studies, are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The management regarding metastatic colorectal cancer throughout Europe is not well known. To draw a European comparison of the management and prognosis of metastatic colorectal cancers. Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model. Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P<0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients <70 or ≥80 years at diagnosis. Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations. [ABSTRACT FROM AUTHOR]

Abstract Background In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. Methods We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. Results This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. Conclusion This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.

Background: Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain. Methods: We conducted a multilevel population-based cohort study, including CRC cases for the period 2011– 2013. The study time-to-event outcome was death, and the primary exposure was CRC patients' socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation. Results: Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0– 110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1– 2.3). Conclusions: We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups. [ABSTRACT FROM AUTHOR]

Numerous studies have analysed the effect of comorbidity on cancer outcomes, but evidence on the association between multimorbidity and short-term mortality among colorectal cancer patients is limited. We aimed to assess this association and the most frequent patterns of multimorbidity associated with a higher short-term mortality risk among colorectal cancer patients in Spain. Data were obtained from two Spanish population-based cancer registries and electronic health records. We estimated the unadjusted cumulative incidence of death by comorbidity status at 6 months and 1 year. We used a flexible parametric model to derive the excess mortality hazard ratios (HRs) for multimorbidity after adjusting for sex, age at diagnosis, cancer stage and treatment. We estimated the adjusted cumulative incidence of death by comorbidity status and identified multimorbidity patterns. Among the study participants, 1,048 cases were diagnosed with cancers of the colon and rectum, 2 cases with cancer of the anus with overlapping sites of the rectum and 11 cases with anal adenocarcinomas but treated as colorectal cancer patients. Among 1,061 colorectal cancer patients, 171 (16.2%) died before 6 months, 246 (23.3%) died before the 1-year follow-up, and 324 (30.5%) had multimorbidity. Patients with multimorbidity had two times higher mortality risk than those without comorbidities at 6 months (adjusted HR: 2.04; 95% confidence interval [CI]: 1.30–3.20, p = 0.002). The most frequent multimorbidity pattern was congestive heart failure + diabetes. However, patients with rheumatologic disease + diabetes had two times higher 1-year mortality risk than those without comorbidities (HR: 2.23; 95% CI: 1.23–4.07, p = 0.008). Multimorbidity was a strong independent predictor of short-term mortality at 6 months and 1 year among the colorectal cancer patients in Spain. The identified multimorbidity pattern was consistent. Our findings might help identify patients at a higher risk for poor cancer and treatment outcomes. • Multimorbidity was a strong predictor of short-term mortality in colorectal cancer. • Patients with multimorbidity had twice higher mortality risk than those without. • The most frequent multimorbidity pattern was congestive heart failure + diabetes. • Our findings can help identify patients at a higher risk for poor cancer outcomes. [ABSTRACT FROM AUTHOR]

Background: Cancer treatment and outcomes can be influenced by tumor characteristics, patient overall health status, and comorbidities. While previous studies have analyzed the influence of comorbidity on cancer outcomes, limited information is available regarding factors associated with the increased prevalence of comorbidities and multimorbidity among patients with colorectal cancer in Spain. Patients and Methods: This cross-sectional study obtained data from all colorectal cancer cases diagnosed in two Spanish provinces in 2011 from two population-based cancer registries and electronic health records. We calculated the prevalence of comorbidities according to patient and tumor factors, identified factors associated with an increased prevalence of comorbidity and multimorbidity, analyzed the association between comorbidities and time-to-surgery, and developed an interactive web application (https://comcor.netlify.com/). Results: The most common comorbidities were diabetes (23.6%), chronic obstructive pulmonary disease (17.2%), and congestive heart failure (14.5%). Among all comorbidities, 52% of patients were diagnosed at more advanced stages (stage III/IV). Patients with advanced age, restricted performance status or who were disabled, obese, and smokers had a higher prevalence of multimorbidity. Patients with multimorbidity had a longer time-to-surgery than those without comorbidity (17 days, 95% confidence interval: 3– 29 days). Conclusion: We identified a consistent pattern of factors associated with a higher prevalence of comorbidities and multimorbidity at diagnosis and an increased time-to-surgery among patients with colorectal cancer with multimorbidity in Spain. This pattern may provide insights for further etiological and preventive research and help to identify patients at a higher risk for poorer cancer outcomes and suboptimal treatment. [ABSTRACT FROM AUTHOR]

Introduction Stillbirth, one of the urgent concerns of preventable perinatal deaths, has wide-reaching consequences for society. We studied secular stillbirth trends by maternal socioeconomic status (SES) in Spain. Methods We developed a population-based observational study, including 4 083 919 births during 2007–15. We estimate stillbirth rates and secular trends by maternal SES. We also evaluated the joint effect of maternal educational attainment and the Human Development Index (HDI) of women's country of origin on the risk of stillbirth. The data and statistical analysis can be accessed for reproducibility in a GitHub repository: https://github.com/migariane/Stillbirth Results We found a consistent pattern of socioeconomic inequalities in the risk of delivering a stillborn, mainly characterized by a persistently higher risk, over time, among women with lower SES. Overall, women from countries with low HDIs and low educational attainments had approximately a four times higher risk of stillbirth (RR: 4.44; 95%CI: 3.71–5.32). Furthermore, we found a paradoxical reduction of the stillbirth gap over time between the highest and the lowest SESs, which is mostly due to the significant and increasing trend of stillbirth risk among highly educated women of advanced maternal age. Conclusion Our findings highlight no improvement in stillbirth rates among women of lower SES and an increasing trend among highly educated women of advanced maternal age over recent years. Public health policies developing preventive programmes to reduce stillbirth rates among women with lower SES are needed as well as the necessity of further study to understand the growing trend of age-related stillbirths among highly educated women in Spain. [ABSTRACT FROM AUTHOR]

Background: Scientific literature has provided clear evidence of the profound impact of sexual violence on women's health, such as somatic disorders and mental adverse outcomes. However, consequences related to obstetric complications are not yet completely clarified. This study aimed to assess the association of lifetime exposure to intimate partner sexual violence with eclampsia.Methods: We considered all the seven Demographic and Health Surveys (DHS) that included data on sexual violence and on signs and symptoms suggestive of eclampsia for women of reproductive age (15-49 years). We computed unadjusted and adjusted odds ratios (OR) to evaluate the risk of suggestive eclampsia by ever subjected to sexual violence. A sensitivity analysis was conducted restricting the study population to women who had their last live birth over the 12 months before the interview.Results: Self-reported experience of sexual violence ranged from 3.7% in Mali to 9.2% in India while prevalence of women reporting signs and symptoms compatible with eclampsia ranged from 14.3% in Afghanistan to 0.7% in the Philippines. Reported sexual violence was associated with a 2-fold increased odd of signs and symptoms suggestive of eclampsia in the pooled analysis. The sensitivity analysis confirmed the strength of the association between sexual violence and eclampsia in Afghanistan and in India.Conclusions: Women and girls in low-and-middle-income countries are at high risk of sexual violence, which may represent a risk factor for hypertensive obstetric complication. Accurate counseling by health care providers during antenatal care consultations may represent an important opportunity to prevent adverse outcomes during pregnancy. [ABSTRACT FROM AUTHOR]

Context. Patients with adrenocortical tumors have been frequently observed to have nonadrenal neoplasia. Objective. To investigate whether patients with benign adrenocortical tumors have a higher likelihood of having nonadrenal neoplasia detected. Design and Participants. Case-control study of patients with benign adrenocortical tumors (cases; n = 400) and normal adrenal glands (controls; n = 400), who underwent repeated abdominal cross-sectional imaging. Main Outcomes. Primary analyses: association between case-control status and benign abdominal neoplasia detected via cross-sectional imaging. Secondary analyses: association between case-control status and tumors detected via other imaging modalities. Results. The mean interval of abdominal imaging was 4.7 (SD = 3.8) years for cases and 5.9 (4.8) years for controls. Cases were more likely to have detected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas (8.5% vs. 4.5%, adjusted OR = 2.22, 95% CI (1.11, 4.63)) compared with controls. In secondary analyses, cases were more likely to have detected thyroid nodules (25.5% vs. 17.0%, adjusted OR = 1.77, 95% CI (1.15, 2.74)), hyperparathyroidism or parathyroid adenomas (3.5% vs. 1.3%, adjusted OR = 3.00, 95% CI (1.00, 11.64)), benign breast masses (6.0% vs. 3.3%, adjusted OR = 3.25, 95% CI (1.28, 8.78)), and benign prostatic hyperplasia (20.5% vs. 5.3%, adjusted OR = 3.20, 95% CI (1.14, 10.60)). Using a composite outcome, cases had higher odds of detection of the composite of IPMN, thyroid nodules, parathyroid tumors, benign breast masses, and prostate hyperplasia (adjusted OR = 2.36, 95% CI: 1.60, 3.50) when compared with controls. Conclusions. Patients with benign adrenocortical tumors had higher odds of detected pancreatic IPMN, as well as thyroid nodules, parathyroid tumors, benign breast masses, and prostate hyperplasia compared with patients with normal adrenal glands. These associations may have important implications for patient care and healthcare economics, regardless of whether they reflect incidental discoveries due to imaging detection or frequency bias, or a common risk for developing multiple neoplasia. [ABSTRACT FROM AUTHOR]

When estimating the average effect of a binary treatment (or exposure) on an outcome, methods that incorporate propensity scores, the G-formula, or targeted maximum likelihood estimation (TMLE) are preferred over naïve regression approaches, which are biased under misspecification of a parametric outcome model. In contrast propensity score methods require the correct specification of an exposure model. Double-robust methods only require correct specification of either the outcome or the exposure model. Targeted maximum likelihood estimation is a semiparametric double-robust method that improves the chances of correct model specification by allowing for flexible estimation using (nonparametric) machine-learning methods. It therefore requires weaker assumptions than its competitors. We provide a step-by-step guided implementation of TMLE and illustrate it in a realistic scenario based on cancer epidemiology where assumptions about correct model specification and positivity (ie, when a study participant had 0 probability of receiving the treatment) are nearly violated. This article provides a concise and reproducible educational introduction to TMLE for a binary outcome and exposure. The reader should gain sufficient understanding of TMLE from this introductory tutorial to be able to apply the method in practice. Extensive R-code is provided in easy-to-read boxes throughout the article for replicability. Stata users will find a testing implementation of TMLE and additional material in the Appendix S1 and at the following GitHub repository: https://github.com/migariane/SIM-TMLE-tutorial. [ABSTRACT FROM AUTHOR]

Receiver operating characteristic (ROC) analysis is used for comparing predictive models in both model selection and model evaluation. ROC analysis is often applied in clinical medicine and social science to assess the tradeoff between model sensitivity and specificity. After fitting a binary logistic or probit regression model with a set of independent variables, the predictive performance of this set of variables can be assessed by the area under the curve (AUC) from an ROC curve. An important aspect of predictive modeling (regardless of model type) is the ability of a model to generalize to new cases. Evaluating the predictive performance (AUC) of a set of independent variables using all cases from the original analysis sample often results in an overly optimistic estimate of predictive performance. One can use K-fold cross-validation to generate a more realistic estimate of predictive performance in situations with a small number of observations. AUC is estimated iteratively for k samples (the "test" samples) that are independent of the sample used to predict the dependent variable (the "training" sample). cvauroc implements k-fold cross-validation for the AUC for a binary outcome after fitting a logit or probit regression model, averaging the AUCs corresponding to each fold, and bootstrapping the cross-validated AUC to obtain statistical inference and 95% confidence intervals. Furthermore, cvauroc optionally provides the cross-validated fitted probabilities for the dependent variable or outcome, contained in a new variable named fit; the sensitivity and specificity for each of the levels of the predicted outcome, contained in two new variables named sen and spe; and the plot of the mean cross-validated AUC and k-fold ROC curves. [ABSTRACT FROM AUTHOR]