A quantitative exploration of gastrointestinal bleeding in intensive care unit patients

Background Quantitative assessments of the severity of bleeding in patients with bleeds within the gastrointestinal tract (GIB) are generally limited to blood tests like the hematocrit. The varied and irregular nature of the data collected during such observations makes it difficult in retrospective data analysis to characterize the complete course of bleeding. We intend to quantify the rate of blood loss over the course of an ICU stay, facilitating more precise analysis of retrospective data, and to use this quantification to examine questions about the effects of GIB. Methods and findings A population of 2,445 intensive care admissions across 2,266 patients with a diagnosis of GIB was studied. Using statistical techniques for smoothing data and accepted medical approaches for calculating blood loss, we are able to convert collections of individual laboratory readings that are difficult to understand into a simple, interpretable overview of the patient’s bleeding status over time. To demonstrate this method, we compare patients’ standard vital signs while bleeding heavily to times when they are not bleeding, finding a 3.0 ± 0.5% increase in heart rate, a 1.3 ± 0.4% decrease in systolic blood pressure and a 0.9 ± 0.5% decrease in diastolic blood pressure. After considering the effect of bleeding on standard vital signs, we demonstrate that patients with upper GIB have significantly elevated blood urea nitrogen levels while bleeding heavily, with a mean increase of 11.7 ± 7.2%, while patients with lower GIB do not, with a mean increase of 4.2 ± 6.6%. Conclusions This study introduces a novel method of processing retrospective laboratory data to characterize the course of bleeds within the gastrointestinal tract. This method is used to examine the direct effects of bleeding on a patient and can be deployed in future studies of bleeding using retrospective data

Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model

Background: Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. Methods and Findings: We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%–58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%–21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%–100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. Conclusions: Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts. Please see later in the article for the Editors' Summar

Directed avalanche processes with underlying interface dynamics

We describe a directed avalanche model; a slowly unloading sandbox driven by lowering a retaining wall. The directness of the dynamics allows us to interpret the stable sand surfaces as world sheets of fluctuating interfaces in one lower dimension. In our specific case, the interface growth dynamics belongs to the Kardar-Parisi-Zhang (KPZ) universality class. We formulate relations between the critical exponents of the various avalanche distributions and those of the roughness of the growing interface. The nonlinear nature of the underlying KPZ dynamics provides a nontrivial test of such generic exponent relations. The numerical values of the avalanche exponents are close to the conventional KPZ values, but differ sufficiently to warrant a detailed study of whether avalanche correlated Monte Carlo sampling changes the scaling exponents of KPZ interfaces. We demonstrate that the exponents remain unchanged, but that the traces left on the surface by previous avalanches give rise to unusually strong finite-size corrections to scaling. This type of slow convergence seems intrinsic to avalanche dynamics.Comment: 13 pages, 13 figure

An Interface View of Directed Sandpile Dynamics

We present a directed unloading sand box type avalanche model, driven by slowly lowering the retaining wall at the bottom of the slope. The avalanche propagation in the two dimensional surface is related to the space-time configurations of one dimensional Kardar-Parisi-Zhang (KPZ) type interface growth dynamics. We express the scaling exponents for the avalanche cluster distributions into that framework. The numerical results agree closely with KPZ scaling, but not perfectly.Comment: 4 pages including 5 figure

Estimates and predictors of health care costs of esophageal adenocarcinoma : A population-based cohort study

Background: Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. Methods: A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. Results: The mean net costs of EAC care per 30 patient-days were $1016 (95$955-$1078) in the initial phase,$669 (95% CI, $594-$743) in the continuing care phase, and $8678 (95$8217-$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007-2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70-74 years), and geographic region in the terminal phase. Conclusions: Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC

Development, Calibration, and Validation of a U.S. White Male Population-Based Simulation Model of Esophageal Adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has risen rapidly in the U.S. and western world. The aim of the study was to begin the investigation of this rapid rise by developing, calibrating, and validating a mathematical disease simulation model of EAC using available epidemiologic data.The model represents the natural history of EAC, including the essential biologic health states from normal mucosa to detected cancer. Progression rates between health states were estimated via calibration, which identified distinct parameter sets producing model outputs that fit epidemiologic data; specifically, the prevalence of pre-cancerous lesions and EAC cancer incidence from the published literature and Surveillance, Epidemiology, and End Results (SEER) data. As an illustrative example of a clinical and policy application, the calibrated and validated model retrospectively analyzed the potential benefit of an aspirin chemoprevention program.Model outcomes approximated calibration targets; results of the model's fit and validation are presented. Approximately 7,000 cases of EAC could have been prevented over a 30-year period if all white males started aspirin chemoprevention at age 40 in 1965.The model serves as the foundation for future analyses to determine a cost-effective screening and management strategy to prevent EAC morbidity and mortality