Factors influencing the selection of an SGLT2i vs. a GLP-1RA as cardioprotective agent in patients with type 2 diabetes.

Purpose: Sodium glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardioprotective effects in people with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). In this patient group, there is treatment equipoise, from the standpoint of cardiovascular effect between these medication classes; however, factors associated with prescribing are poorly characterized.

Methods: We performed a retrospective real-world analysis by creating an electronic health record registry of people with type 2 diabetes and ASCVD (without additional indications for a specific cardioprotective class) who received a prescription for either an SGLT2i or GLP-1RA.

Predicting Hospital Readmission in Medicaid Patients With COPD Using Administrative and Claims Data.

Background: The goals of this study were to develop a model that predicts the risk of 30-d all-cause readmission in hospitalized Medicaid patients diagnosed with COPD and to create a predictive model in a retrospective study of a population cohort.

Methods: We analyzed 2016-2019 Medicaid claims data from 7 United States states. A was one in which either the admission diagnosis or the first or second clinical (discharge) diagnosis bore an International Classification of Diseases, Tenth Revision code for COPD.

Tutorial: Assessing the impact of nonignorable missingness on regression analysis using Index of Local Sensitivity to Nonignorability.

Data sets with missing observations are common in psychology research. One typically analyzes such data by applying statistical methods that rely on the assumption that the missing observations are missing at random (MAR). This assumption greatly simplifies analysis but is unverifiable from the data at hand, and assuming it incorrectly may lead to bias.

Predicting hospital readmission in Medicaid patients with diabetes using administrative and claims data.

Objectives: Readmission is common and costly for hospitalized Medicaid patients with diabetes. We aimed to develop a model predicting risk of 30-day readmission in Medicaid patients with diabetes hospitalized for any cause.

Study Design: Using 2016-2019 Medicaid claims from 7 US states, we identified patients who (1) had a diagnosis of diabetes or were prescribed any diabetes drug, (2) were hospitalized for any cause, and (3) were discharged to home or to a nonhospice facility.

Electronic phenotypes to distinguish clinician attention to high body mass index, hypertension, lipid disorders, fatty liver and diabetes in pediatric primary care: Diagnostic accuracy of electronic phenotypes compared to masked comprehensive chart review.

Background/objectives: Electronic phenotyping is a method of using electronic-health-record (EHR) data to automate identifying a patient/population with a characteristic of interest. This study determines validity of using EHR data of children with overweight/obesity to electronically phenotype evidence of clinician 'attention' to high body mass index (BMI) and each of four distinct comorbidities.

Methods: We built five electronic phenotypes classifying 2-18-year-old children with overweight/obesity (n = 17,397) by electronic/health-record evidence of distinct attention to high body mass index, hypertension, lipid disorders, fatty liver, and prediabetes/diabetes.

Sensitivity of estimands in clinical trials with imperfect compliance.

In clinical trials that are subject to noncompliance, the commonly used estimand is valid as a causal effect of treatment assignment but is sensitive to the level of compliance. An alternative estimand, the (), measures the average effect of treatment received in the latent subset of subjects who would comply with either assigned treatment. Because the principal stratum of compliers can vary with the circumstances of the trial, CACE too depends on the compliance fraction.

Survival of cancer survivors with a new pancreatic cancer diagnosis.

Background: Persons newly diagnosed with pancreas cancer and who have survived a previous cancer are often excluded from clinical trials, despite limited evidence about their prognosis. We examined the association between previous cancer and overall survival.

Methods: This US population-based cohort study included older adults (aged ≥66 years) diagnosed with pancreas cancer between 2005 and 2015 in the linked Surveillance, Epidemiology, and End Results-Medicare data.

PSA-Net: Deep learning-based physician style-aware segmentation network for postoperative prostate cancer clinical target volumes.

Purpose: Automatic segmentation of medical images with deep learning (DL) algorithms has proven highly successful in recent times. With most of these automation networks, inter-observer variation is an acknowledged problem that leads to suboptimal results. This problem is even more significant in segmenting postoperative clinical target volumes (CTV) because they lack a macroscopic visible tumor in the image.

Estimating the optimal timing of surgery by imputing potential outcomes.

Hypoplastic left heart syndrome is a congenital anomaly that is uniformly fatal in infancy without immediate treatment. The standard treatment consists of an initial Norwood procedure (stage 1) followed some months later by stage 2 palliation (S2P). The ideal timing of the S2P is uncertain.

Analysis of local sensitivity to nonignorability with missing outcomes and predictors.

The ISNI (index of sensitivity to local nonignorability) method quantifies local sensitivity of parametric inferences to nonignorable missingness in an outcome variable. Here we extend ISNI to the situations where both outcomes and predictors can be missing and where the missingness mechanism can be either parametric or semi-parametric. We define the quantity MinNI (minimum nonignorability) to be an approximation to the norm of the smallest value of the transformed nonignorability that gives a nonnegligible displacement of the estimate of the parameter of interest.

Survival of patients newly diagnosed with colorectal cancer and with a history of previous cancer.

Patients with previous cancer are often excluded from clinical trials despite limited evidence about their prognosis. We examined the effect of previous cancer on overall and colorectal cancer (CRC)-specific survival of patients newly diagnosed with CRC. This population-based cohort study from the U.

COVID-19 associated mortality and cardiovascular disease outcomes among US women veterans.

The burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. We conducted an observational study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We assembled a retrospective cohort from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020.

Survival of women diagnosed with breast cancer and who have survived a previous cancer.

Purpose: Many women diagnosed with breast cancer have survived previous cancer; yet little is known about the impact of previous cancer on overall and cancer-specific survival.

Methods: This population-based cohort study using SEER-Medicare data included women (age ≥ 66 years) diagnosed with breast cancer between 2005 and 2015. Separately by breast cancer stage, we estimated effect of previous cancer on overall survival using Cox regression and on cause-specific survival using competing risk regression; all survival analyses adjusted for covariates.

Approach to Managing a Postmenopausal Patient.

The case of a symptomatic, postmenopausal woman is presented and a full discussion of the approach to her management is discussed. Pertinent guidelines and scientific evidence are emphasized as support for the recommendations.

Estimating the optimal timing of surgery from observational data.

Infants with hypoplastic left heart syndrome require an initial Norwood operation, followed some months later by a stage 2 palliation (S2P). The timing of S2P is critical for the operation's success and the infant's survival, but the optimal timing, if one exists, is unknown. We attempt to identify the optimal timing of S2P by analyzing data from the Single Ventricle Reconstruction Trial (SVRT), which randomized patients between two different types of Norwood procedure.

Flexible, rule-based dose escalation: The cohort-sequence design.

Phase I oncology trials seek to acquire preliminary information on the safety of novel treatments. In current practice, most such trials employ rule-based designs that determine whether to escalate the dose using data from the current dose only. The most popular of these, the 3 + 3, is simple and familiar but inflexible and inefficient.

Underlying Breast Cancer Risk and Menopausal Hormone Therapy.

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk.

Statistical modeling and prediction of clinical trial recruitment.

Real-time prediction of clinical trial accrual can support logistical planning, ensuring that studies meet but do not exceed sample size targets. We describe a novel, simulation-based prediction method that is founded on a realistic model for the underlying processes of recruitment. The model reflects key features of enrollment such as the staggered initiation of new centers, heterogeneity in enrollment capacity, and declining accrual within centers.

Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin.

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro.

Measuring the Impact of Nonignorable Missingness Using the R Package isni.

Background And Objective: The popular assumption of ignorability simplifies analyses with incomplete data, but if it is not satisfied, results may be incorrect. Therefore it is necessary to assess the sensitivity of empirical findings to this assumption. We have created a user-friendly and freely available software program to conduct such analyses.

Glucocorticoid Receptor Mutations and Hypersensitivity to Endogenous and Exogenous Glucocorticoids.

Background: The glucocorticoid receptor (GR) consists of two alternatively spliced isoforms: GRα, which activates gene transcription, and GRβ, a dominant-negative receptor. Theoretically, inactivating variants of GRβ could result in glucocorticoid hypersensitivity.

Design: A 46-year-old woman presented for evaluation of adrenal insufficiency prompted by low plasma cortisol levels and multiple unexplained symptoms but without clinical evidence of glucocorticoid insufficiency.

Statistical justification of expansion cohorts in phase 1 cancer trials.

Background: Phase I cancer trials increasingly incorporate dose-expansion cohorts (DECs), reflecting a growing demand to acquire more information about investigational drugs. Protocols commonly fail to provide a sample-size justification or analysis plan for the DEC. In this study, we develop a statistical framework for the design of DECs.