Abstract Objective “Teachable moments” have been proposed as events or circumstances which can lead individuals to positive behavior change. However, the essential elements of teachable moments have ...not been elucidated. Therefore, we undertook a comprehensive review of the literature to uncover common definitions and key elements of this phenomenon. Methods Using databases spanning social science and medical disciplines, all records containing the search term “teachable moment* ” were collected. Identified literature was then systematically reviewed and patterns were derived. Results Across disciplines, ‘teachable moment’ has been poorly developed both conceptually and operationally. Usage of the term falls into three categories: (1) “teachable moment” is synonymous with “opportunity” (81%); (2) a context that leads to a higher than expected behavior change is retrospectively labeled a ‘teachable moment’ (17%); (3) a phenomenon that involves a cueing event that prompts specific cognitive and emotional responses (2%). Conclusion The findings suggest that the teachable moment is not necessarily unpredictable or simply a convergence of situational factors that prompt behavior change but suggest the possible creation of a teachable moment through clinician–patient interaction. Practice implications Clinician–patient interaction may be central to the creation of teachable moments for health behavior change.
Introduction Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared with physiologic ...fibrinolysis after trauma. Animal models have not reproduced these changes. We hypothesize rodents have a shutdown phenotype that require an exogenous profibrinolytic to differentiate mechanisms that promote or inhibit fibrinolysis. Methods Fibrinolysis resistance was assessed by thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA) titrations in whole blood. There were 3 experimental groups: (1) tissue injury (laparotomy/bowel crush), (2) shock (hemorrhage to mean arterial pressure of 20 mmHg), and (3) control (arterial cannulation and tracheostomy). Baseline and 30-minute postintervention blood samples were collected, and assayed with TEG challenged with taurocholic acid (TUCA). Results Rats were resistant to exogenous tPA; the percent clot remaining 30 minutes after maximum amplitude (CL30) at 150 ng/mL ( P = .511) and 300 ng/mL ( P = .931) was similar to baseline, whereas 600 ng/mL ( P = .046) provoked fibrinolysis. Using the TUCA challenge, the percent change in CL30 from baseline was increased in tissue injury compared with control ( P = .048.), whereas CL30 decreased in shock versus control ( P = .048). tPA increased in the shock group compared with tissue injury ( P = .009) and control ( P = .012). Conclusion Rats have an innate fibrinolysis shutdown phenotype. The TEG TUCA challenge is capable of differentiating changes in clot stability with rats undergoing different procedures. Tissue injury inhibits fibrinolysis, whereas shock promotes tPA-mediated fibrinolysis.
The current system for evaluating prostate cancer architecture is the Gleason grading system which divides the morphology of cancer into five distinct architectural patterns, labeled 1 to 5 in ...increasing levels of cancer aggressiveness, and generates a score by summing the labels of the two most dominant patterns. The Gleason score is currently the most powerful prognostic predictor of patient outcomes; however, it suffers from problems in reproducibility and consistency due to the high intra-observer and inter-observer variability amongst pathologists. In addition, the Gleason system lacks the granularity to address potentially prognostic architectural features beyond Gleason patterns. We evaluate prostate cancer for architectural subtypes using techniques from topological data analysis applied to prostate cancer glandular architecture. In this work we demonstrate the use of persistent homology to capture architectural features independently of Gleason patterns. Specifically, using persistent homology, we compute topological representations of purely graded prostate cancer histopathology images of Gleason patterns 3,4 and 5, and show that persistent homology is capable of clustering prostate cancer histology into architectural groups through a ranked persistence vector. Our results indicate the ability of persistent homology to cluster prostate cancer histopathology images into unique groups with dominant architectural patterns consistent with the continuum of Gleason patterns. In addition, of particular interest, is the sensitivity of persistent homology to identify specific sub-architectural groups within single Gleason patterns, suggesting that persistent homology could represent a robust quantification method for prostate cancer architecture with higher granularity than the existing semi-quantitative measures. The capability of these topological representations to segregate prostate cancer by architecture makes them an ideal candidate for use as inputs to future machine learning approaches with the intent of augmenting traditional approaches with topological features for improved diagnosis and prognosis.
Fibrinolysis shutdown (SD) is an independent risk factor for increased mortality in trauma. High levels of plasminogen activator inhibitor-1 (PAI-1) directly binding tissue plasminogen activator ...(t-PA) is a proposed mechanism for SD; however, patients with low PAI-1 levels present to the hospital with a rapid TEG (r-TEG) LY30 suggestive SD. We therefore hypothesized that two distinct phenotypes of SD exist, one, which is driven by t-PA inhibition, whereas another is due to an inadequate t-PA release in response to injury.
Trauma activations from our Level I center between 2014 and 2016 with blood collected within an hour of injury were analyzed with r-TEG and a modified TEG assay to quantify fibrinolysis sensitivity using exogenous t-PA (t-TEG). Using the existing r-TEG thresholds for SD (<0.9%), physiologic (LY30 0.9-2.9%), and hyperfibrinolysis (LY30 > 2.9%) patients were stratified into phenotypes. A t-TEG LY30 greater than 95th percentile of healthy volunteers (n = 140) was classified as t-PA hypersensitive and used to subdivide phenotypes. A nested cohort had t-PA and PAI-1 activity levels measured in addition to proteomic analysis of additional fibrinolytic regulators.
This study included 398 patients (median New Injury Severity Score, 18), t-PA-Sen was present in 27% of patients. Shutdown had the highest mortality rate (20%) followed by hyperfibinolysis (16%) and physiologic (9% p = 0.020). In the non-t-PA hypersensitive cohort, SD had a fivefold increase in mortality (15%) compared with non-SD patients (3%; p = 0.003) which remained significant after adjusting for Injury Severity Score and age (p = 0.033). Overall t-PA activity (p = 0.002), PAI-1 (p < 0.001), and t-PA/PAI-1 complex levels (p = 0.006) differed between the six phenotypes, and 54% of fibrinolytic regulator proteins analyzed (n = 19) were significantly different.
In conclusion, acute fibrinolysis SD is not caused by a single etiology, and is clearly associated with PAI-1 activity. The differential phenotypes require an ongoing investigation to identify the optimal resuscitation strategy for these patients.
Prognostic, level III.
Understanding seasonal migration and localized persistence of populations is critical for effective species harvest and conservation management. Pacific salmon (genus Oncorhynchus) forecasting models ...predict stock composition, abundance, and distribution during annual assessments of proposed fisheries impacts. Most models, however, fail to account for the influence of biophysical factors on year-to-year fluctuations in migratory distributions and stock-specific survival. In this study, the ocean distribution and relative abundance of Chinook salmon (O. tshawytscha) stocks encountered in the California Current large marine ecosystem, U.S.A were inferred using catch-per-unit effort (CPUE) fisheries and genetic stock identification data. In contrast to stock distributions estimated through coded-wire-tag recoveries (typically limited to hatchery salmon), stock-specific CPUE provides information for both wild and hatchery fish. Furthermore, in contrast to stock composition results, the stock-specific CPUE metric is independent of other stocks and is easily interpreted over multiple temporal or spatial scales. Tests for correlations between stock-specific CPUE and stock composition estimates revealed these measures diverged once proportional contributions of locally rare stocks were excluded from data sets. A novel aspect of this study was collection of data both in areas closed to commercial fisheries and during normal, open commercial fisheries. Because fishing fleet efficiency influences catch rates, we tested whether CPUE differed between closed area (non-retention) and open area (retention) data sets. A weak effect was indicated for some, but not all, analyzed cases. Novel visualizations produced from stock-specific CPUE-based ocean abundance facilitates consideration of how highly refined, spatial and genetic information could be incorporated in ocean fisheries management systems and for investigations of biogeographic factors that influence migratory distributions of fish.
Abstract Background Massive transfusion (MT) is frequently required during liver transplantation. Risk stratification of transplant patients at risk for MT is an appealing concept but remains poorly ...developed. Thrombelastography (TEG) has recently been shown to reduce mortality when used for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for MT. Material and methods Liver transplant patients had blood drawn before surgical incision and assayed via TEG. Preoperative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after MA) were correlated to red blood cell units, plasma (fresh frozen plasma), cryoprecipitate, and platelets during the first 24 h after surgery and tested for their performance using a receiver-operating characteristic curve. Results Twenty-eight patients were included in the analysis with a median Model for End-Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated with MT (defined as ≥10 red blood cell units/24 h) were a low MA ( P < 0.001) and low angle ( P = 0.014). A high international normalized ratio of prothrombin time ( P = 0.003) and low platelet count ( P = 0.007) were also associated with MT. MA had the highest area under the curve (0.861) followed by international normalized ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of 90% and specificity of 72% to predict a MT. MA was the only coagulation variable that correlated strongly to all blood products transfused. Conclusions TEG MA has a high predictability of MT during liver transplantation. The use of TEG preoperatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a MT.
Abstract Objective Teachable moments (TM) are opportunities created through physician–patient interaction and used to encourage patients to change unhealthy behaviors. We examine the effectiveness of ...TMs to increase patients’ recall of advice, motivation to modify behavior, and behavior change. Methods A mixed-method observational study of 811 patient visits to 28 primary care clinicians used audio-recordings of visits to identify TMs and other types of advice in health behavior change talk. Patient surveys assessed smoking, exercise, fruit/vegetable consumption, height, weight, and readiness for change prior to the observed visit and 6-weeks post-visit. Results Compared to other identified categories of advice (i.e. missed opportunities or teachable moment attempts), recall was greatest after TMs occurred (83% vs. 49–74%). TMs had the greatest proportion of patients change in importance and confidence and increase readiness to change; however differences were small. TMs had greater positive behavior change scores than other categories of advice; however, this pattern was statistically non-significant and was not observed for BMI change. Conclusion TMs have a greater positive influence on several intermediate markers of patient behavior change compared to other categories of advice. Practice implications TMs show promise as an approach for clinicians to discuss behavior change with patients efficiently and effectively.
Introduction
The use of bariatric surgery has increased for morbidly obese patients with end stage renal disease (ESRD) for whom listing on the waitlist is often restricted until a certain BMI ...threshold is achieved. Effective weight loss for this population improves access to life-saving renal transplantation. However, it is unclear whether sleeve gastrectomy (SG) vs Roux-en-Y gastric bypass (RYGB) is a more effective therapy for these patients.
Methods
A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with ESRD who were deemed ineligible to be waitlisted for renal transplantation unless they achieved a BMI less than 35 kg/m
2
. Life expectancy following weight management (MWM), RYGB, and SG were estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m
2
. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review.
Results
RYGB improved survival compared with SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 1.3 additional years of life compared with patient’s who underwent SG and 2.6 additional years of life compared with MWM.
Conclusions
RYGB improves access to renal transplantation and thereby increases long-term survival compared with SG and MWM. The use of SG may be incongruent with the goal of improving access to renal transplantation for morbidly obese patients.
A reliable biomarker to detect pancreatic ductal adenocarcinoma (PDAC) continues to be elusive. With employing metabolomics we hypothesize that a broader analysis of systemic blood can differentiate ...different stages of PDAC.
Patients undergoing pancreatic resection had plasma samples grouped by diagnosis and assayed with mass spectrometry. 10 per group neuroendocrine (PNET), intraductal papillary mucinous neoplasm (IPMN), localized PDAC, locally advanced PDAC, and metastatic were analyzed to assess if metabolites could delineation different stages of adenocarcinoma.
Of the 215 metabolites measured, four had a stronger correlation to disease burden than CA19-9. However, none of these metabolites differentiated stepwise progression in malignancy. Principal component analysis identified five metabolic components. Each cancer cohort was characterized by a unique combination of components, two components were predictors of PDCA stages.
Enhanced metabolomic analysis identified metabolic pathways that may assist in differentiating PDCA stages that do not occur in a linear stepwise progression.
Abstract Introduction Thrombelastography (TEG) has been used to characterize the coagulation changes associated with injury and shock. Animal models developed to investigate trauma - induced ...coagulopathy (TIC) have failed to produce excessive bleeding. We hypothesize that a native TEG will demonstrate marked differences in humans compared to these experimental models, which explains the difficulties in reproducing a clinically relevant coagulopathy in animal models. Methods Whole blood was collected from 138 healthy human volunteers, 25 swine and 66 Sprague Dawley rats prior to experimentation. Citrated native TEGs were conducted on each whole blood sample within 2 hours of collection. The clot initiation (R-time, min), angle (degrees), MA (mm), and LY30 (%) were analyzed and contrasted between species with data represented as the median and 25th to 75th quartile range. Difference between species was conducted with a Kruskall Wallis test with alpha adjusted with a Bonferroni correction for multiple comparisons (alpha = 0.016). Results Median R-Time (clot initiation) 14.65 min (IQR: 13.2-16.3 min) for humans, 5.7 (4.9-8.8) for pigs, and 5.2 (4.4-6) for rodents. Humans had longer R-Times than both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats (p= 0.4439). Angle (fibrin cross-linking) was 42.3 degrees (IQR: 37.5-50.2) for humans, 71.7 (64.3-75.6) for pigs, and 61.8 (56.8-66.7) for rats. Humans had reduced Angle compared to both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats (p=0.6052). MA (clot strength) was 55.5 mm (IQR: 52.0-59.5 for humans, 72.5 (70.4-75.5) for pigs, and 66.5 (56.5-68.6) for rats. Humans had reduced MA compared to both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats (p=0.0161). LY30 (fibrinolysis) was 1.5 % (IQR: 0.975-2.5) for humans, 3.3 (1.9-4.3) for pigs, and 0.5 (0.1-1.2) for rats. Humans had a lesser LY30 than pigs (p=0.0062) and a greater LY30 than rats (p<0.0001), and pigs had a greater LY30 than rats (p<0.0001). Conclusion Humans, swine, and rodents have distinctly different coagulation systems, when evaluated by citrated native TEG. Animals are hypercoagulable with rapid clotting times and clots strengths nearly 50% stronger than humans. These coagulation differences indicate the limitations of previous models of TIC in producing coagulation abnormalities associated with increased bleeding. The inherent hypercoagulable baseline tendencies of these animals may result in subclinical biochemical changes that are not detected by conventional TEG and should be taken into consideration when extrapolated to clinical medicine.