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

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

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

Quality of life in patients with various Barrett's esophagus associated health states

BACKGROUND: The management of Barrett's esophagus (BE), particularly high grade dysplasia (HGD), is an area of much debate and controversy. Surgical esophagectomy, intensive endoscopic surveillance and mucosal ablative techniques, especially photodynamic therapy (PDT), have been proposed as possible management strategies. The purpose of this study was to determine the health related quality of life associated with Barrett's esophagus and many of the pivotal health states associated with Barrett's HGD management. METHODS: 20 patients with Barrett's esophagus were enrolled in a pilot survey study at a large urban hospital. The utility of Barrett's esophagus without dysplasia (current health state) as well as various health states associated with HGD management (hypothetical states as the subject did not have HGD) were measured using a validated health utility instrument (Paper Standard Gamble). These specific health states were chosen for the study because they are considered pivotal in Barrett's HGD decision making. Information regarding Barrett's HGD was presented to the subject in a standardized format that was designed to be easily comprehendible. RESULTS: The average utility scores (0–1 with 0 = death and 1 = perfect health) for the various Barrett's esophagus associated states were: BE without dysplasia-0.95; Post-esophagectomy for HGD with dysphagia-0.92; Post-PDT for HGD with recurrence uncertainty-0.93; Post-PDT for HGD with recurrence uncertainty and dysphagia-0.91; Intensive endoscopic surveillance for HGD-0.90. CONCLUSION: We present the scores for utilities associated with Barrett's esophagus as well as various states associated with the management of HGD. The results of our study may be useful in advising patients and providers regarding expected outcomes of the various HGD management strategies as well as providing utility scores for future cost-effectiveness analyses

Disparities in cancer outcomes across age, sex, and race/ethnicity among patients with pancreatic cancer

Abstract Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early‐stage and late‐stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received. We used logistic regression to compare differences in treatment received across age, sex, and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian, and 2% Hispanic. Median age was 75; 56% were female and 53% had late‐stage cancer. Among early‐stage patients in the adjusted Cox model, older patient subgroups had worse survival compared with ages 66–69 (HR > 1.1, P 69); no survival differences existed between sexes. Black (HR = 1.1, P = 0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with White. Among late‐stage cancer patients, patients over age 84 had worse survival than those aged 66–69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had worse survival than females; there were no racial/ethnic differences. Older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC patients; these disparities persist after adjusting for differences in demographic and clinical characteristics

Screening for Pancreatic Adenocarcinoma in BRCA2 Mutation Carriers: Results of a Disease Simulation Model

Background: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. Methods: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. Findings: One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with ≥ 3 FDRs, annual screening starting at an earlier age (i.e. 35–40) was optimal. Interpretation Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. Funding American Cancer Society – New England Division – Ellison Foundation Research Scholar Grant (RSG-15-129-01-CPHPS)

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

Background & Aims: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol’s chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. Methods: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. Results: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%–66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%–57%) could have been spared any biopsy. Conclusions: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708

Radiofrequency Ablation of Barrett's Esophagus Reduces Esophageal Adenocarcinoma Incidence and Mortality in a Comparative Modeling Analysis

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