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Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention. Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Longitudinal observational data on patients can be used to investigate causal effects of time-varying treatments on time-to-event outcomes. Several methods have been developed for estimating such effects by controlling for the time-dependent confounding that typically occurs. The most commonly used is marginal structural models (MSM) estimated using inverse probability of treatment weights (IPTW) (MSM-IPTW). An alternative, the sequential trials approach, is increasingly popular, and involves creating a sequence of "trials" from new time origins and comparing treatment initiators and non-initiators. Individuals are censored when they deviate from their treatment assignment at the start of each "trial" (initiator or noninitiator), which is accounted for using inverse probability of censoring weights. The analysis uses data combined across trials. We show that the sequential trials approach can estimate the parameters of a particular MSM. The causal estimand that we focus on is the marginal risk difference between the sustained treatment strategies of "always treat" vs "never treat." We compare how the sequential trials approach and MSM-IPTW estimate this estimand, and discuss their assumptions and how data are used differently. The performance of the two approaches is compared in a simulation study. The sequential trials approach, which tends to involve less extreme weights than MSM-IPTW, results in greater efficiency for estimating the marginal risk difference at most follow-up times, but this can, in certain scenarios, be reversed at later time points and relies on modelling assumptions. We apply the methods to longitudinal observational data from the UK Cystic Fibrosis Registry to estimate the effect of dornase alfa on survival.

Structural equation models (SEMs) are widely used to handle multiequation systems that involve latent variables, multiple indicators, and measurement error. Maximum likelihood (ML) and diagonally weighted least squares (DWLS) dominate the estimation of SEMs with continuous or categorical endogenous variables, respectively. When a model is correctly specified, ML and DWLS function well. But, in the face of incorrect structures or nonconvergence, their performance can seriously deteriorate. Model implied instrumental variable, two stage least squares (MIIV-2SLS) estimates and tests individual equations, is more robust to misspecifications, and is noniterative, thus avoiding nonconvergence. This article is an overview and tutorial on MIIV-2SLS. It reviews the six major steps in using MIIV-2SLS: (a) model specification; (b) model identification; (c) latent to observed (L2O) variable transformation; (d) finding MIIVs; (e) using 2SLS; and (f) tests of overidentified equations. Each step is illustrated using a running empirical example from Reisenzein's (1986) randomized experiment on helping behavior. We also explain and illustrate the analytic conditions under which an equation estimated with MIIV-2SLS is robust to structural misspecifications. We include additional sections on MIIV approaches using a covariance matrix and mean vector as data input, conducting multilevel SEM, analyzing categorical endogenous variables, causal inference, and extensions and applications. Online supplemental material illustrates input code for all examples and simulations using the R package MIIVsem. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background Workplace absenteeism increases significantly during influenza epidemics. Sick leave records may facilitate more timely detection of influenza outbreaks, as trends in increased sick leave may precede alerts issued by sentinel surveillance systems by days or weeks. Sick leave data have not been comprehensively evaluated in comparison to traditional surveillance methods. The aim of this paper is to study the performance and the feasibility of using a detection system based on sick leave data to detect influenza outbreaks. Methods Sick leave records were extracted from private French health insurance data, covering on average 209,932 companies per year across a wide range of sizes and sectors. We used linear regression to estimate the weekly number of new sick leave spells between 2016 and 2017 in 12 French regions, adjusting for trend, seasonality and worker leaves on historical data from 2010 to 2015. Outbreaks were detected using a 95%-prediction interval. This method was compared to results from the French Sentinelles network, a gold-standard primary care surveillance system currently in place. Results Using sick leave data, we detected 92% of reported influenza outbreaks between 2016 and 2017, on average 5.88 weeks prior to outbreak peaks. Compared to the existing Sentinelles model, our method had high sensitivity (89%) and positive predictive value (86%), and detected outbreaks on average 2.5 weeks earlier. Conclusion Sick leave surveillance could be a sensitive, specific and timely tool for detection of influenza outbreaks.

PURPOSE With the availability of multigene panel testing (MGPT) for hereditary cancer risk assessment, clinicians need to assess the likelihood of pathogenic germline variants (PGVs) across numerous genes in parallel. This study's aim was to develop and validate a clinical prediction model (PREMMplus) for MGPT risk assessment. MATERIALS AND METHODS PREMMplus was developed in a single-institution cohort of 7,280 individuals who had undergone MGPT. Logistic regression models with Least Absolute Shrinkage and Selection Operator regularization were used to examine candidate predictors (age, sex, ethnicity, and personal/family history of 18 cancers/neoplasms) to estimate one's likelihood of carrying PGVs in 19 genes (broadly categorized by phenotypic overlap and/or relative penetrance: 11 category A [ APC, BRCA1/ 2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53] and eight category B genes [ ATM, BRIP1, CDKN2A, CHEK2, PALB2, PTEN, RAD51C, and RAD51D]). Model performance was validated in nonoverlapping data sets of 8,691 and 14,849 individuals with prior MGPT ascertained from clinic- and laboratory-based settings, respectively. RESULTS PREMMplus (score ≥ 2.5%) had 93.9%, 91.7%, and 89.3% sensitivity and 98.3%, 97.5%, and 97.8% negative-predictive value (NPV) for identifying category A gene PGV carriers in the development and validation cohorts, respectively. PREMMplus assessment (score ≥ 2.5%) had 89.9%, 85.6%, and 84.2% sensitivity and 95.0%, 93.5%, and 93.5% NPV, respectively, for identifying category A/B gene PGV carriers. Decision curve analyses support MGPT for individuals predicted to have ≥ 2.5% probability of a PGV. CONCLUSION PREMMplus accurately identifies individuals with PGVs in a diverse spectrum of cancer susceptibility genes with high sensitivity/NPV. Individuals with PREMMplus scores ≥ 2.5% should be considered for MGPT.

Radiofrequency ablation (RFA) is one of the effective therapeutic modalities in patients with hepatocellular carcinoma (HCC). However, there is no proper method to evaluate the HCC response to RFA. This study aimed to establish and validate a clinical prediction model based on dual-energy computed tomography (DECT) quantitative-imaging parameters, clinical variables, and CT texture parameters.We enrolled 63 patients with small HCC. Two to four weeks after RFA, we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients' clinical baseline variables. DECT images were manually segmented, and 56 CT texture features were extracted. We used LASSO algorithm for feature selection and data dimensionality reduction; logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters; we then added texture features to build a clinical-texture model based on clinical model.A total of six optimal CT texture analysis (CTTA) features were selected, which were statistically different between patients with or without tumor progression (P0.05). When clinical variables and DECT-quantitative parameters were included, the clinical models showed that albumin-bilirubin grade (ALBI) [odds ratio (OR) = 2.77, 95% confidence interval (CI): 1.35-6.65, P = 0.010], λDECT-quantitative parameters, CTTA, and clinical variables were helpful in predicting HCC progression after RFA. The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.

Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders.To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia.We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was0.001 with standard error0.001, indicating good discrimination and excellent calibration.The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

Background. The purpose of this study was to investigate the risk factors of left atrial (LA) or left atrial appendage (LAA) thrombi in patients with nonvalvular atrial fibrillation (NVAF) and to establish and validate relevant predictive models. It might improve thromboembolic risk stratification in patients with NVAF. Methods. This study retrospectively included 1210 consecutive patients with NVAF undergoing transesophageal echocardiography (TEE), of whom 139 patients had thrombi in LA or in LAA. Through literature review and the ten events per variable (10EPV) principle, 13 variables were finally identified for inclusion in multivariate analysis. Models were constructed by multivariate logistic stepwise regression and least absolute shrinkage and selection operator (lasso) regression. Results. After logistic regression, five variables (AF type, age, B-type natriuretic peptide, E/e’ ratio, and left atrial diameter) were finally screened out as model 1. After Lasso regression, AF type, age, gender, B-type natriuretic peptide, E/e’ ratio, left atrial diameter, and left ventricular ejection fraction were finally screened as model 2. After comparing the two models, the simpler model 1 was finally selected. The area under the ROC curve (AUC) of the model 1 was 0.865 (95% CI: 0.838–0.892), the Hosmer–Lemeshow test = 0.898, and the AUC = 0.861 after internal validation. The clinical decision curve showed that the new clinical prediction model could achieve a net clinical benefit when the expected threshold was between 0 and 0.6. Conclusion. This study constructed a new clinical prediction model of LA or LAA thrombi, with a higher discriminative degree than the CHADS2 and CHA2DS2-VASc scoring systems (AUC: 0.865 vs. 0.643; AUC: 0.865 vs 0.652).

Tuberculosis (TB) is recognized as being a major public health concern owing to its increase in Qinghai, China. In this study, we aimed to estimate the long-term effects of meteorological variables on TB incidence and construct an advanced hybrid model with seasonal autoregressive integrated moving average (SARIMA) and a neural network nonlinear autoregression (SARIMAX-NNARX) by integrating meteorological factors and evaluating the model fitting and prediction effect. During 2005-2017, TB experienced an upward trend with obvious periodic and seasonal characteristics, peaking in spring and winter. The results showed that TB incidence was positively correlated with average relative humidity (ARH) with a 2-month lag (β = 1.889, p = 0.003), but negatively correlated with average atmospheric pressure (AAP) with a 1-month lag (β = - 1.633, p = 0.012), average temperature (AT) with a 2-month lag (β = - 0.093, p = 0.027), and average wind speed (AWS) with a 0-month lag (β = - 13.221, p = 0.033), respectively. The SARIMA (3,1,0)(1,1,1)

To demonstrate improvements in the precision of inverse probability-weighted estimators by use of auxiliary variables, i.e., determinants of the outcome that are independent of treatment, missingness or selection.First with simulated data, and then with public data from the National Health and Nutrition Examination Survey (NHANES), we estimated the mean of a continuous outcome using inverse probability weights to account for informative missingness. We assessed gains in precision resulting from the inclusion of auxiliary variables in the model for the weights. We compared the performance of robust and nonparametric bootstrap variance estimators in this setting.We found that the inclusion of auxiliary variables reduced the empirical variance of inverse probability-weighted estimators. However, that reduction was not captured in standard errors computed using the robust variance estimator, which is widely used in weighted analyses due to the non-independence of weighted observations. In contrast, a nonparametric bootstrap estimator properly captured the precision gain.Epidemiologists can leverage auxiliary data to improve the precision of weighted estimators by using bootstrap variance estimation, or a closed-form variance estimator that properly accounts for the estimation of the weights, in place of the standard robust variance estimator.

Several prognostic models such as the Palliative Performance Scale (PPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) have been developed to complement clinician's prediction of survival (CPS). However, few studies with large scales have been conducted to show which prognostic tool had better performance than CPS in patients with weeks of survival.We aimed to compare the prognostic performance of the PPS, PPI, PaP, and CPS in inpatients admitted to palliative care units (PCUs).This study was part of a multi-center prospective observational study involving patients admitted to PCUs in Japan. We computed their prognostic performance using the area under the receiver operating characteristics curve (AUROC) and calibration plots for seven, 14-, 30- and 60-day survival.We included 1896 patients with a median overall survival of 19 days. The AUROC was 73% to 84% for 60-day and 30-day survival, 75% to 84% for 14-day survival, and 80% to 87% for seven-day survival. The calibration plot demonstrated satisfactory agreement between the observational and predictive probability for the four indices in all timeframes. Therefore, all four prognostic indices showed good performance. CPS and PaP consistently had significantly better performance than the PPS and PPI from one-week to two-month timeframes.The PPS, PPI, PaP, and CPS had relatively good performance in patients admitted to PCUs with weeks of survival. CPS and PaP had significantly better performance than the PPS and PPI. CPS may be sufficient for experienced clinicians while PPS may help to improve prognostic confidence for inexperienced clinicians.

The purpose of this study was to establish a clinical prediction model for the differential diagnosis of pulmonary cystic echinococcosis (CE) and pulmonary abscess according to computed tomography (CT)-based radiomics signatures and clinical indicators. This is a retrospective single-centre study. A total of 117 patients, including 53 with pulmonary CE and 64 with pulmonary abscess, were included in our study and were randomly divided into a training set (n = 95) and validation set (n = 22). Radiomics features were extracted from CT images, a radiomics signature was constructed, and clinical indicators were evaluated to establish a clinical prediction model. Finally, a model combining imaging radiomics features and clinical indicators was constructed. The performance of the nomogram, radiomics signature and clinical prediction model was evaluated and validated with the training and test datasets, and then the three models were compared. The radiomics signature of this study was established by 25 features, and the radiomics nomogram was constructed by using clinical factors and the radiomics signature. Finally, the areas under the receiver operating characteristic curve (AUCs) for the training set and test set were 0.970 and 0.983, respectively. Decision curve analysis showed that the radiologic nomogram was better than the clinical prediction model and individual radiologic characteristic model in differentiating pulmonary CE from pulmonary abscess. The radiological nomogram and models based on clinical factors and individual radiomics features can distinguish pulmonary CE from pulmonary abscess and will be of great help to clinical diagnoses in the future.

Background Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results Models were developed and integrated into a web-app (https://neurosurgery.shinyapps.io/fuseml/) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59–0.74], back pain (0.72, 95%CI: 0.64–0.79), and leg pain (0.64, 95%CI: 0.54–0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk–benefit estimation, truly impacting clinical practice in the era of “personalized medicine” necessitates more robust tools in this patient population.

Although risk stratification of patients with acute decompensated heart failure (HF) is important, it is unknown whether machine learning (ML) or conventional statistical models are optimal. We developed ML algorithms to predict 7-day and 30-day mortality in patients with acute HF and compared these with an existing logistic regression model at the same timepoints.Patients presenting to one of 86 hospitals, who were either admitted to hospital or discharged home directly from the emergency department, were randomly selected using stratified random sampling. ML approaches, including neural networks, random forest, XGBoost, and the Lasso, were compared with a validated logistic regression model for discrimination and calibration.Among 12,608 patients in our analysis, lasso regression (c-statistic 0.774; 95% CI, 0.743, 0.806) performed better than other ML models for 7-day mortality but did not outperform the baseline logistic regression model (0.794; 95% CI, 0.789, 0.800). For 30-day mortality, XGBoost performed better than other ML models (c-statistic 0.759; 95% CI; 0.740, 0.779), but was not significantly better than logistic regression (c-statistic 0.755; 95% CI, 0.750, 0.762). Logistic regression demonstrated better calibration at 7 days (calibration-in-the-large 0.017; 95% CI, -0.657, 0.692, and calibration slope 0.954; 95% CI, 0.769, 1.139), and at 30 days (-0.026; 95% CI, -0.374, 0.322, and 0.964; 95% CI, 0.831, 1.098), and best Brier scores, compared to ML approaches.Logistic regression was comparable to ML in discrimination, but was superior to ML algorithms in calibration overall. ML algorithms for prognosis should routinely report calibration metrics in addition to discrimination.

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow-up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan-Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the current literature, most regression models for estimating cure rates assume proportional hazards (PH) between different subgroups. It turns out that the estimation of cure rates for subgroups is highly sensitive to this assumption, so more flexible models are needed, especially when this PH assumption is clearly violated. We propose a new cure model to simultaneously incorporate both PH and non-PH scenarios for different covariates. We develop a stable and easily implementable iterative procedure for parameter estimation through maximization of the nonparametric likelihood function. The covariance matrix is estimated by adding perturbation weights to the estimation procedure. In simulation studies, the proposed method provides unbiased estimation for the regression coefficients, survival curves, and cure rates given covariates, while existing models are biased. Our model is applied to a study of stage III soft tissue sarcoma and provides trustworthy estimation of cure rates for different treatment and demographic groups.

This work aimed to explore the application value of computed tomography (CT)-based radiomics in predicting changes in tumor regression during radiotherapy for nasopharyngeal carcinoma. In this work, 144 patients with nasopharyngeal carcinoma who underwent concurrent chemoradiotherapy (CCRT) in our hospital from January 2015 to December 2021 were selected. The patients were divided into a radiosensitive group (79 cases) and an insensitive group (65 cases) according to the tumor volume shrinkage during radiotherapy. The 3D Slicer 4.10.2 software was used to delineate the tumor region of interest (ROI), and a total of 1223 radiomics features were extracted using the radiomics module under the software. After between-group and within-group consistency tests, one-way ANOVA, and LASSO dimensionality reduction, three omics features were finally selected for the establishment of predictive models. At the same time, the age, gender, tumor T stage and N stage, hemoglobin, and albumin of the patients were collected to establish a clinical prediction model. The results showed that compared with logistic regression, decision tree, random forest, and AdaBoost models, the SVM model based on CT radiomics features had the best performance in predicting tumor regression changes during tumor radiotherapy (training group area under the receiver operating characteristic curve (AUC): 0.840 (95% confidence interval (CI): 0.764–0.916); validation group: AUC: 0.810 (95% CI: 0.676–0.944)). Compared with the supported vector machine (SVM) prediction model based on clinical features, the SVM model based on radiomics features had better performance in predicting the change of retraction during tumor radiotherapy (training group: omics feature SVM model AUC: 0.84, clinical feature SVM model: 0.78; validation group: omics feature SVM model AUC: 0.8, clinical feature SVM model: 0.58, P = 0.044). Based on the radiomics characteristics and clinical characteristics of patients, a nomo prediction map was established, and the calibration curve shows good consistency, which can be visualized to assist clinical judgment. In this work, the prediction model composed of CT-based radiomic features combined with clinical features can accurately predict withdrawal changes during tumor radiotherapy, ensuring the accuracy of treatment planning, and minimizing the number of CT scans during radiotherapy.

Recurrent event data with a terminal event commonly arise in many longitudinal follow-up studies. This article proposes a class of dynamic semiparametric transformation models for the marginal mean functions of the recurrent events with a terminal event, where some covariate effects may be time-varying. An estimation procedure is developed for the model parameters, and the asymptotic properties of the resulting estimators are established. In addition, relevant significance tests are suggested for examining whether or not covariate effects vary with time, and a model checking procedure is presented for assessing the adequacy of the proposed models. The finite sample performance of the proposed estimators is examined through simulation studies, and an application to a medical cost study of chronic heart failure patients is provided.

Personalized medicine aims to tailor medical decisions based on patient-specific characteristics. Advances in data capturing techniques such as electronic health records dramatically increase the availability of comprehensive patient profiles, promoting the rapid development of optimal treatment rule (OTR) estimation methods. An archetypal OTR estimation approach is the outcome weighted learning, where OTR is determined under a weighted classification framework with clinical outcomes as the weights. Although outcome weighted learning has been extensively studied and extended, existing methods are susceptible to irregularities of outcome distributions such as outliers and heavy tails. Methods that involve modeling of the outcome are also sensitive to model misspecification. We propose a contrast weighted learning (CWL) framework that exploits the flexibility and robustness of contrast functions to enable robust OTR estimation for a wide range of clinical outcomes. The novel value function in CWL only depends on the pairwise contrast of clinical outcomes between patients irrespective of their distributional features and supports. The Fisher consistency and convergence rate of the estimated decision rule via CWL are established. We illustrate the superiority of the proposed method under finite samples using comprehensive simulation studies with ill-distributed continuous outcomes and ordinal outcomes. We apply the CWL method to two datasets from clinical trials on idiopathic pulmonary fibrosis and COVID-19 to demonstrate its real-world application.

The introduction of the alternative model of personality disorders in the fifth edition of the

Prior research has shown that cancer risk varies by geography, but scan statistics methods for identifying cancer clusters in case-control studies have been limited in their ability to identify multiple clusters and adjust for participant-level risk factors. We develop a method to identify geographic patterns of breast cancer odds using the Wisconsin Women's Health Study, a series of 5 population-based case-control studies of female Wisconsin residents aged 20-79 enrolled in 1988-2004 (cases=16,076, controls=16,795). We create sets of potential clusters by overlaying a 1 km grid over each county-neighborhood and enumerating a series of overlapping circles. Using a two-step approach, we fit a penalized binomial regression model to the number of cases and trials in each grid cell, penalizing all potential clusters by the least absolute shrinkage and selection operator (Lasso). We use BIC to select the number of clusters, which are included in a participant-level logistic regression model. We identify 15 geographic clusters, resulting in 23 areas of unique geographic odds ratios. After adjustment for known risk factors, confidence intervals narrowed but breast cancer odds ratios did not meaningfully change; one additional hotspot was identified. By considering multiple overlapping spatial clusters simultaneously, we discern gradients of spatial odds across Wisconsin.

Tuberculous (TBE) and malignant (MPE) pleural effusions present with similar lymphocytic exudates. As TBE is an inflammatory and hypersensitivity process, we hypothesized that echographic septation may be more prevalent in TBE than in MPE, potentially serving as a good clinical predictor for TBE.A total of 183 TBE and 266 MPE patients were recruited retrospectively. Multivariate logistic regression was performed to determine significant predictors for TBE.TBE diagnosis was confirmed histologically (caseating granuloma) in 84.7% of the cases, while MPE was biopsy-proven in 63.9% of the cases. Echographic septation was more evident in TBE than in MPE (46.5% vs. 8.2%, p 0.001). Multivariate logistic regression analysis showed that male sex, serum leucocyte count ≤9 × 10Echographic septation may potentially facilitate discrimination between TBE and MPE as part of a clinical prediction model. Prospective validation of this prediction model in an external cohort is anticipated.

Continuous-time hidden Markov models are an attractive approach for disease modeling because they are explainable and capable of handling both irregularly sampled, skewed and sparse data arising from real-world medical practice, in particular to screening data with extensive followup. Most applications in this context consider time-homogeneous models due to their relative computational simplicity. However, the time homogeneous assumption is too strong to accurately model the natural history of many diseases including cancer. Moreover, cancer risk across the population is not homogeneous either, since exposure to disease risk factors can vary considerably between individuals. This is important when analyzing longitudinal datasets and different birth cohorts. We model the heterogeneity of disease progression and regression using piece-wise constant intensity functions and model the heterogeneity of risks in the population using a latent mixture structure. Different submodels under the mixture structure employ the same types of Markov states reflecting disease progression and allowing both clinical interpretation and model parsimony. We also consider flexible observational models dealing with model over-dispersion in real data. An efficient, scalable Expectation-Maximization algorithm for inference is proposed with the theoretical guaranteed convergence property. We demonstrate our method’s superior performance compared to other state-of-the-art methods using synthetic data and a real-world cervical cancer screening dataset from the Cancer Registry of Norway. Moreover, we present two model-based risk stratification methods that identify the risk levels of individuals.

Many hearing aid (HA) users receive limited benefit from amplification, especially when trying to understand speech in noise, and they often report hearing-related residual activity limitations. Current HA fitting strategies are typically based on pure-tone hearing thresholds only, even though suprathreshold factors have been linked to aided outcomes. Furthermore, clinical measures of speech perception such as word recognition scores (WRSs) are performed without frequency-specific amplification, likely resulting in suboptimal speech audibility and thus inaccurate estimates of suprathreshold hearing abilities. Corresponding measures with frequency-specific amplification ("aided") would likely improve such estimates and enable more accurate aided outcome prediction. Here, we investigated potential links between either unaided WRSs or aided WRSs measured at several above-conversational levels and two established HA outcome measures: The Hearing-In-Noise Test (HINT) and the International Outcome Inventory for Hearing Aids (IOI-HA).Thirty-seven older individuals with bilateral hearing impairments participated. Two conditions were tested: unaided and aided, with all stimuli presented over headphones. In the unaided condition, the most comfortable level (MCL) for the presented speech stimuli, WRS at MCL+10 dB as well as uncomfortable levels (UCLs) for narrowband noise stimuli were measured. In the aided condition, all stimuli were individually amplified according to the "National Acoustic Laboratories-Revised, Profound" fitting rule. Aided WRSs were then measured using an Interacoustics Affinity system at three above-conversational levels, allowing for the maximum aided WRS as well as the presence of "rollover" in the performance-intensity function to be estimated. Multivariate data analyses were performed to examine the relations between the HINT (measured using a simulated HA with the NAL-RP amplification) or IOI-HA scores (for the participants' own HAs) and various potential predictors (age, pure-tone average hearing loss, unaided WRS, aided WRS, rollover presence [ROp], and UCL).Aided WRSs predicted the HINT scores better than any other predictor and were also the only significant predictor of the IOI-HA scores. In addition, UCL and ROp in the aided WRSs were significant predictors of the HINT scores and competed for variance in the statistical models. Neither age nor pure-tone average hearing loss could predict the two aided outcomes.Aided WRSs can predict HA outcome more effectively than unaided WRSs, age or pure-tone audiometry and could be relatively easily implemented in clinical settings. More research is necessary to better understand the relations between ROp, UCL and speech recognition at above-conversational levels.

Substantive model compatible multiple imputation (SMC-MI) is a relatively novel imputation method that is particularly useful when the analyst's model includes interactions, non-linearities, and/or partially observed random slope variables.Here we thoroughly investigate a SMC-MI strategy based on joint modeling of the covariates of the analysis model. We provide code to apply the proposed strategy and we perform an extensive simulation work to test it in various circumstances. We explore the impact on the results of various factors, including whether the missing data are at the individual or cluster level, whether there are non-linearities and whether the imputation model is correctly specified. Finally, we apply the imputation methods to the motivating example data.SMC-JM appears to be superior to standard JM imputation, particularly in presence of large variation in random slopes, non-linearities, and interactions. Results seem to be robust to slight mis-specification of the imputation model for the covariates. When imputing level 2 data, enough clusters have to be observed in order to obtain unbiased estimates of the level 2 parameters.SMC-JM is preferable to standard JM imputation in presence of complexities in the analysis model of interest, such as non-linearities or random slopes.

To analyze the prevalence trend of Sjögren's syndrome in the Department of Immunology and Rheumatology of Nanjing Zhongda Hospital from January 2015 to December 2019, and compare the application of SARIMA model and Holt-Winters model in predicting the number of cases of Sjögren's syndrome.All of the data from the Department of Immunology and Rheumatology of Nanjing Zhongda Hospital were collected. The number of monthly cases from January 2015 to December 2019 was regarded as the training set, and it was used to establish the SARIMA model and Holt-Winters model. The number of monthly incidences from January 2020 to December 2020 was regarded as the test set, and it was used to check the model performance.The optimal model of SARIMA is ARIMA (0,1,1) (2,1,1)Holt-Winters addition model produces better prediction accuracy of the model.

Cure models are a class of time-to-event models where a proportion of individuals will never experience the event of interest. The lifetimes of these so-called cured individuals are always censored. It is usually assumed that one never knows which censored observation is cured and which is uncured, so the cure status is unknown for censored times. In this paper, we develop a method to estimate the probability of cure in the mixture cure model when some censored individuals are known to be cured. A cure probability estimator that incorporates the cure status information is introduced. This estimator is shown to be strongly consistent and asymptotically normally distributed. Two alternative estimators are also presented. The first one considers a competing risks approach with two types of competing events, the event of interest and the cure. The second alternative estimator is based on the fact that the probability of cure can be written as the conditional mean of the cure status. Hence, nonparametric regression methods can be applied to estimate this conditional mean. However, the cure status remains unknown for some censored individuals. Consequently, the application of regression methods in this context requires handling missing data in the response variable (cure status). Simulations are performed to evaluate the finite sample performance of the estimators, and we apply them to the analysis of two datasets related to survival of breast cancer patients and length of hospital stay of COVID-19 patients requiring intensive care.

When estimating path coefficients among psychological constructs measured with error, structural equation modeling (SEM), which simultaneously estimates the measurement and structural parameters, is generally regarded as the gold standard. In practice, however, researchers usually first compute composite scores or factor scores, and use those as observed variables in a path analysis, for purposes of simplifying the model or avoiding model convergence issues. Whereas recent approaches, such as reliability adjustment methods and factor score regression, has been proposed to mitigate the bias induced by ignoring measurement error in composite/factor scores with continuous indicators, those approaches are not yet applicable to models with categorical indicators. In this article, we introduce the two-stage path analysis (2S-PA) with definition variables as a general framework for path modeling to handle categorical indicators, in which estimation of factor scores and path coefficients are separated. It thus allows for different estimation methods in the measurement and the structural path models and easier diagnoses of violations of model assumptions. We conducted three simulation studies, ranging from latent regression to mediation analysis with categorical indicators, and showed that 2S-PA generally produced similar estimates to those using SEM in large samples, but gave better convergence rates, less standard error bias, and better control of Type I error rates in small samples. We illustrate 2S-PA using data from a national data set, and show how researchers can implement it in Mplus and OpenMx. Possible extensions and future directions of 2S-PA are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Many clinical trials repeatedly measure several longitudinal outcomes on patients. Patient follow-up can discontinue due to an outcome-dependent event, such as clinical diagnosis, death, or dropout. Joint modeling is a popular choice for the analysis of this type of data. Using example data from a prodromal Alzheimer's disease trial, we propose a new type of multivariate joint model in which longitudinal brain imaging outcomes and memory impairment ratings are allowed to be associated both with time to open-label medication and dropout, and where the brain imaging outcomes may also directly affect the memory impairment ratings. Existing joint models for multivariate longitudinal outcomes account for the correlation between the longitudinal outcomes through the random effects, often by assuming a multivariate normal distribution. However, for these models, it is difficult to interpret how the longitudinal outcomes affect each other. We model the dependence between the longitudinal outcomes differently so that a first longitudinal outcome affects a second one. Specifically, for each longitudinal outcome, we use a linear mixed-effects model to estimate its trajectory, where, for the second longitudinal outcome, we include the linear predictor of the first outcome as a time-varying covariate. This facilitates an easy and direct interpretation of the association between the longitudinal outcomes and provides a framework for latent mediation analysis to understand the underlying biological processes. For the trial considered here, we found that part of the intervention effect is mediated through hippocampal brain atrophy. The proposed joint models are fitted using a Bayesian framework via MCMC simulation.

Summary Marginal structural models (MSMs), which adopt inverse probability treatment weighting in the estimating equations, are powerful tools to estimate the causal effects of time-varying exposures in the presence of time-dependent confounders. Motivated by the Conservation of Hearing Study (CHEARS) Audiology Assessment Arm (AAA) where repeated hearing measurements were clustered by study participants, time, and testing sites, we propose two methods to account for the multilevel correlation structure when fitting the MSMs. The first method directly models the covariance of the repeated outcomes when solving the weighted generalized estimating equations for MSMs, while the second two-stage analysis approach fits cluster-specific MSMs first and then combines the estimated parameters using mixed-effects meta-analysis. Finite sample simulation results suggest that our methods can obtain less biased and more efficient estimates of the parameters by accounting for the multilevel correlation. Moreover, we explore the effects of using fixed- or mixed-effects model to estimate the treatment probability on the parameter estimates of the MSMs in the presence of unmeasured cluster-level confounders. Lastly, we apply our methods to the CHEARS AAA data set, to estimate the causal effects of aspirin use on hearing loss.

The Cox proportional hazards model is commonly used to estimate the association between time-to-event and covariates. Under the proportional hazards assumption, covariate effects are assumed to be constant in the follow-up period of study. When measurement error presents, common estimation methods that adjust for an error-contaminated covariate in the Cox proportional hazards model assume that the true function on the covariate is parametric and specified. We consider a semiparametric partly linear Cox model that allows the hazard to depend on an unspecified function of an error-contaminated covariate and an error-free covariate with time-varying effect, which simultaneously relaxes the assumption on the functional form of the error-contaminated covariate and allows for nonconstant effect of the error-free covariate. We take a Bayesian approach and approximate the unspecified function by a B-spline. Simulation studies are conducted to assess the finite sample performance of the proposed approach. The results demonstrate that our proposed method has favorable statistical performance. The proposed method is also illustrated by an application to data from the AIDS Clinical Trials Group Protocol 175.

Human microbiome research has become a hot-spot in health and medical research in the past decade due to the rapid development of modern high-throughput. Typical data in a microbiome study consisting of the operational taxonomic unit counts may have over-dispersion and/or structural zero issues. In such cases, negative binomial models can be applied to address the over-dispersion issue, while zero-inflated negative binomial models can be applied to address both issues. In practice, it is essential to know if there is zero-inflation in the data before applying negative binomial or zero-inflated negative binomial models because zero-inflated negative binomial models may be unnecessarily complex and difficult to interpret, or may even suffer from convergence issues if there is no zero-inflation in the data. On the other hand, negative binomial models may yield invalid inferences if the data does exhibit excessive zeros. In this paper, we develop a new test for detecting zero-inflation resulting from a latent class of subjects with structural zeros in a negative binomial regression model by directly comparing the amount of observed zeros with what would be expected under the negative binomial regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Intensive simulation studies are conducted to investigate the performance of the new test and compare it with the classical Wald, likelihood ratio, and score tests. The tests are also applied to human gut microbiome data to test latent class in microbial genera.

Covariate modeling is an important opportunity for pharmacometrics to influence decision making in drug development. The stepwise covariate model (SCM) building procedure is the most common method for covariate model development. Despite its advantages, the traditional SCM method is known to have long runtimes and the suboptimal ability to select relevant covariates, especially in more complex phase III settings. In this work, two alternative approaches are presented: SCM+, which introduces the "adaptive scope reduction" and changes to general estimation settings, and "stage-wise filtering," which groups covariates into categories based on their importance (mechanistic, structural, and exploratory). The three methods (SCM, SCM+, and SCM+ with stage-wise filtering) are applied to data from a simulated phase III population pharmacokinetic study and are compared in terms of efficiency and relevance. The two SCM+ methods were considerably more efficient than the traditional SCM: the number of function evaluations was reduced by 70% for SCM+ and by 76% for SCM+ with stage-wise filtering compared to SCM; the corresponding number of executed models was reduced by 44% for SCM+ and 70% for SCM+ with stage-wise filtering. In addition, among the three methods, SCM+ with stage-wise filtering selected the highest number of relevant covariates. Given the improved efficiency and ability to select relevant covariates shown in this work, the use of SCM+ and stage-wise filtering can greatly increase the efficiency of covariate modeling in drug development, which will ultimately facilitate more timely support for decision making.

Ecological momentary assessment and other modern data collection technologies facilitate research on both within-subject and between-subject variability of health outcomes and behaviors. For such intensively measured longitudinal data, Hedeker et al extended the usual two-level mixed-effects model to a two-level mixed-effects location scale (MELS) model to accommodate covariates' influence as well as random subject effects on both mean (location) and variability (scale) of the outcome. However, there is a lack of existing standardized effect size measures for the MELS model. To fill this gap, our study extends Rights and Sterba's framework of

International audience; In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work, we explain how joint models can be extended to the framework of a latent quantity measured over time by indicators of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each observation of the indicators through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time stopped by the occurrence of death.

To evaluate the usefulness of a published clinical decision support tool to predict the likelihood of a retrievable inferior vena cava (IVC) filter being maintained as a permanent device.This multicenter retrospective cohort study included 1498 consecutive patients (852 men and 646 women; median age, 60 years; range, 18-98 years) who underwent retrievable IVC filter insertion between January 2012 and December 2019. The indications for IVC filtration, baseline neurologic disease, history of venous thromboembolism (VTE), and underlying malignancy were recorded. Accuracy, sensitivity, and specificity of a published clinical support tool were calculated to determine the usefulness of the tool.The majority of filters (1271/1498 [85%]) were placed for VTE with a contraindication to anticoagulation. A history of VTE was present in 811 of 1498 patients (54%) patients; underlying malignancy in 531 of 1498 patients (35%), and neurological disease in 258 of 1498 patients (17%). Of the 1498 filters, 456 (30%) were retrieved, 276 (18%) were maintained as permanent devices on follow-up, and 766 (51%) filters were not retrieved. The accuracy of the clinical prediction model was 61%, sensitivity was 60%, and specificity was 62%.A previously published clinical decision support tool to predict permanence of IVC filters had modest usefulness in the examined population; this factor should be taken into account when using this clinical decision support tool outside of the original study population. Future studies are required to refine the predictive capability of IVC filter decision support tools for broader use across different patient populations.

There is lack of information about predictive variables for pneumonia mortality in the Mexican population.To identify a model for predictive variables for mortality in adults hospitalized with community acquired pneumonia (CAP).Case-control study of patients hospitalized with CAP. The cases were incident cases with CAP that died during hospitalization and controls were those that did not die. The patients were followed during the study time until the discharge or outcome of each patient. The association between the independent variables (clinical, severity indices for pneumonia) with the outcome variable (in-hospital mortality) was evaluated by logistic regression.The model of associated variables with mortality were stratified age from 50-70 years (odds ratio [OR] 2.35; 95% confidence interval [95% CI: 1.06-5.17) and age70 years (OR: 2.75; 95% CI: 1.18-6.37), woman (OR: 2.05; 95% CI: 1.11-3.8), antecedent of arterial hypertension (OR: 0.40; 95% CI: 0.20-0.80), tachycardia (OR: 2.68; 95% CI: 1.16-6.17), tachypnea (OR: 2.85; 95% CI: 1.54-5.29), leukocytes ≥ 12,000 (OR: 2.17; 95% CI: 1.21-3.87) and urea nitrogen30 mg/dL (OR: 4.85; 95% CI: 2.55-9.24).The proposed risk model is easy to document with clinical history and routine clinical laboratory variables.Existe escasa información sobre variables predictoras para mortalidad por neumonía en población mexicana.Identificar un modelo de variables predictoras para mortalidad en adultos hospitalizados por neumonía adquirida en la comunidad (NAC).Estudio de casos y controles de pacientes hospitalizados por NAC. Los casos fueron pacientes con NAC que fallecieron durante la hospitalización y los controles fueron pacientes que no fallecieron. Los pacientes se siguieron durante el tiempo de estudio hasta el egreso o el desenlace de cada uno. La asociación entre las variables independientes (clínicas, índices de gravedad para neumonía) con la variable desenlace (muerte hospitalaria) se evaluó mediante regresión logística.Las variables asociadas a mortalidad fueron la edad estratificada de 50-70 años (odds ratio [OR] 2.35; intervalo de confianza del 95% [IC 95%]: 1.06-5.17) y70 años (OR 2.75; IC 95%: 1.18-6.37), ser mujer (OR 2.05; IC 95%: 1.11-3.8), antecedente de hipertensión arterial (OR 0.40; IC 95%: 0.20-0.80), taquicardia (OR 2.68; IC 95%: 1.16-6.17), taquipnea (OR 2.85; IC 95%: 1.54-5.29), leucocitos ≥ 12,000 (OR 2.17; IC 95%: 1.21-3.87) y nitrógeno de la urea30 mg/dl (OR 4.85; IC 95%: 2.55-9.24).El modelo de riesgo que se propone es fácil de documentar con la historia clínica y las pruebas de laboratorio habituales.

Objective: Generalized linear models (GLMs) such as logistic and Poisson regression are among the most common statistical methods for modeling binary and count outcomes. Though single-coefficient tests (odds ratios, incidence rate ratios) are the most common way to test predictor-outcome relations in these models, they provide limited information on the magnitude and nature of relations with outcomes. We assert that this is largely because they do not describe direct relations with quantities of interest (QoIs) such as probabilities and counts. Shifting focus to QoIs makes several nuances of GLMs more apparent.Method: To bolster interpretability of these models, we provide a tutorial on logistic and Poisson regression and suggestions for enhancements to current reporting practices for predictor-outcome relations in GLMs.Results: We first highlight differences in interpretation between traditional linear models and GLMs, and describe common misconceptions of GLMs. In particular, we highlight that link functions A) introduce non-constant relations between predictors and outcomes and B) make predictor-QoI relations dependent on other covariates. Each of these properties causes interpretation of GLM coefficients to diverge from interpretations of linear models. Next, we argue for a more central focus on QoIs (probabilities and counts). Finally, we propose and provide graphics and tables, with sample R code, for enhancing presentation and interpretation of QoIs.Conclusions: By improving present practices in the reporting of predictor-outcomerelations in GLMs, we hope to maximize the amount of actionable information generated by statistical analyses and provide a tool for building a cumulative science of substance use disorders.Public Health Significance: We propose several enhancements to current reporting practices for statistical analyses of binary outcomes (e.g., psychiatric diagnoses) and count outcomes (e.g., number of alcoholic drinks consumed). We encourage researchers to interpret results in terms of quantities of interest (probabilities for binary models, counts for count models) and provide a tutorial and R code for implementing these analyses. Doing so can provide richer information about a statistical analysis, make study results easier for research consumers to understand, and facilitate comparison of results across studies.

In X-ray computed tomography (CT) an important objective is to reduce the radiation dose without significantly degrading the image quality. Compressed sensing (CS) enables the radiation dose to be reduced by producing diagnostic images from a limited number of projections. However, conventional CS-based algorithms are computationally intensive and time-consuming. We propose a new algorithm that accelerates the CS-based reconstruction by using a fast pseudopolar Fourier based Radon transform and rebinning the diverging fan beams to parallel beams. The reconstruction process is analyzed using a maximum-a-posterior approach, which is transformed into a weighted CS problem. The weights involved in the proposed model are calculated based on the statistical characteristics of the reconstruction process, which is formulated in terms of the measurement noise and rebinning interpolation error. Therefore, the proposed method not only accelerates the reconstruction, but also removes the rebinning and interpolation errors. Simulation results are shown for phantoms and a patient. For example, a 512 × 512 Shepp-Logan phantom when reconstructed from 128 rebinned projections using a conventional CS method had 10% error, whereas with the proposed method the reconstruction error was less than 1%. Moreover, computation times of less than 30 sec were obtained using a standard desktop computer without numerical optimization.

Objectives. To determine the number of excess deaths (i.e., those exceeding historical trends after accounting for COVID-19 deaths) occurring in Florida during the COVID-19 pandemic. Methods. Using seasonal autoregressive integrated moving average time-series modeling and historical mortality trends in Florida, we forecasted monthly deaths from January to September of 2020 in the absence of the pandemic. We compared estimated deaths with monthly recorded total deaths (i.e., all deaths regardless of cause) during the COVID-19 pandemic and deaths only from COVID-19 to measure excess deaths in Florida. Results. Our results suggest that Florida experienced 19 241 (15.5%) excess deaths above historical trends from March to September 2020, including 14 317 COVID-19 deaths and an additional 4924 all-cause, excluding COVID-19, deaths in that period. Conclusions. Total deaths are significantly higher than historical trends in Florida even when accounting for COVID-19–related deaths. The impact of COVID-19 on mortality is significantly greater than the official COVID-19 data suggest.

Summary There has been increased interest in using prior information in statistical analyses. For example, in rare diseases, it can be difficult to establish treatment efficacy based solely on data from a prospective study due to low sample sizes. To overcome this issue, an informative prior to the treatment effect may be elicited. We develop a novel extension of the conjugate prior of Chen and Ibrahim (2003) that enables practitioners to elicit a prior prediction for the mean response for generalized linear models, treating the prediction as random. We refer to the hierarchical prior as the hierarchical prediction prior (HPP). For independent and identically distributed settings and the normal linear model, we derive cases for which the hyperprior is a conjugate prior. We also develop an extension of the HPP in situations where summary statistics from a previous study are available. The HPP allows for discounting based on the quality of individual level predictions, and simulation results suggest that, compared to the conjugate prior and the power prior, the HPP efficiency gains (e.g., lower mean squared error) where predictions are incompatible with the data. An efficient Monte Carlo Markov chain algorithm is developed. Applications illustrate that inferences under the HPP are more robust to prior-data conflict compared to selected nonhierarchical priors.

In biomedical studies, survival data with a cure fraction (the proportion of subjects cured of disease) are commonly encountered. The mixture cure and bounded cumulative hazard models are two main types of cure fraction models when analyzing survival data with long-term survivors. In this article, in the framework of the Cox proportional hazards mixture cure model and bounded cumulative hazard model, we propose several estimators utilizing pseudo-observations to assess the effects of covariates on the cure rate and the risk of having the event of interest for survival data with a cure fraction. A variable selection procedure is also presented based on the pseudo-observations using penalized generalized estimating equations for proportional hazards mixture cure and bounded cumulative hazard models. Extensive simulation studies are conducted to examine the proposed methods. The proposed technique is demonstrated through applications to a melanoma study and a dental data set with high-dimensional covariates.

Factorial trials offer an efficient method to evaluate multiple interventions in a single trial, however the use of additional treatments can obscure research objectives, leading to inappropriate analytical methods and interpretation of results. We define a set of estimands for factorial trials, and describe a framework for applying these estimands, with the aim of clarifying trial objectives and ensuring appropriate primary and sensitivity analyses are chosen. This framework is intended for use in factorial trials where the intent is to conduct "two-trials-in-one" (ie, to separately evaluate the effects of treatments A and B), and is comprised of four steps: (i) specifying how additional treatment(s) (eg, treatment B) will be handled in the estimand, and how intercurrent events affecting the additional treatment(s) will be handled; (ii) designating the appropriate factorial estimator as the primary analysis strategy; (iii) evaluating the interaction to assess the plausibility of the assumptions underpinning the factorial estimator; and (iv) performing a sensitivity analysis using an appropriate multiarm estimator to evaluate to what extent departures from the underlying assumption of no interaction may affect results. We show that adjustment for other factors is necessary for noncollapsible effect measures (such as odds ratio), and through a trial re-analysis we find that failure to consider the estimand could lead to inappropriate interpretation of results. We conclude that careful use of the estimands framework clarifies research objectives and reduces the risk of misinterpretation of trial results, and should become a standard part of both the protocol and reporting of factorial trials.

The existence of items not susceptible to the event of interest is of both theoretical and practical importance. Although researchers may provide, for example, biological, medical, or sociological evidence for the presence of such items (cured), statistical models performing well under the existence or not of a cured proportion, frequently offer a necessary flexibility. This work introduces a new reparameterization of a flexible family of cure models, which not only includes among its special cases, the most studied cure models (such as the mixture, bounded cumulative hazard, and negative binomial cure model) but also classical survival models (ie, without cured items). One of the main properties of the proposed family, apart from its computationally tractable closed form, is that the case of zero cured proportion is not found at the boundary of the parameter space, as it typically happens to other families. A simulation study examines the (finite) performance of the suggested methodology, focusing to the estimation through EM algorithm and model discrimination, by the aid of the likelihood ratio test and Akaike information criterion; for illustrative purposes, analysis of two real life datasets (on recidivism and cutaneous melanoma) is also carried out.

Personalised fracture plates manufactured using 3D printing offer an improved treatment option for unstable pelvic ring fractures that may not be adequately secured using off-the-shelf components. To design fracture plates that secure the bone fragments in their pre-fracture positions, the fractures must be reduced virtually using medical imaging-based reconstructions, a time-consuming process involving segmentation and repositioning of fragments until surface congruency is achieved. This study compared statistical shape models (SSMs) and contralateral mirroring as automated methods to reconstruct the hemipelvis using varying amounts of bone surface geometry. The training set for the geometries was obtained from pelvis CT scans of 33 females. The root-mean-squared error (RMSE) was quantified across the entire surface of the hemipelvis and within specific regions, and deviations of pelvic landmarks were computed from their positions in the intact hemipelvis. The reconstruction of the entire hemipelvis surfaced based on contralateral mirroring had an RMSE of 1.21 ± 0.29 mm, whereas for SSMs based on the entire hemipelvis surface, the RMSE was 1.11 ± 0.29 mm, a difference that was not significant (p = 0.32). Moreover, all hemipelvis reconstructions based on the full or partial bone geometries had RMSEs and landmark deviations from contralateral mirroring that were significantly lower (p

High-dimensional inference is one of fundamental problems in modern biomedical studies. However, the existing methods do not perform satisfactorily. Based on the Markov property of graphical models and the likelihood ratio test, this article provides a simple justification for the Markov neighborhood regression method such that it can be applied to statistical inference for high-dimensional generalized linear models with mixed features. The Markov neighborhood regression method is highly attractive in that it breaks the high-dimensional inference problems into a series of low-dimensional inference problems. The proposed method is applied to the cancer cell line encyclopedia data for identification of the genes and mutations that are sensitive to the response of anti-cancer drugs. The numerical results favor the Markov neighborhood regression method to the existing ones.

In the analysis for competing risks data, regression modeling of the cause-specific hazard functions has been usually conducted using the same time scale for all event types. However, when the true time scale is different for each event type, it would be appropriate to specify regression models for the cause-specific hazards on different time scales for different event types. Often, the proportional hazards model has been used for regression modeling of the cause-specific hazard functions. However, the proportionality assumption may not be appropriate in practice. In this article, we consider the additive risk model as an alternative to the proportional hazards model. We propose predictions of the cumulative incidence functions under the cause-specific additive risk models employing different time scales for different event types. We establish the consistency and asymptotic normality of the predicted cumulative incidence functions under the cause-specific additive risk models specified on different time scales using empirical processes and derive consistent variance estimators of the predicted cumulative incidence functions. Through simulation studies, we show that the proposed prediction methods perform well. We illustrate the methods using stage III breast cancer data obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute.