Sleeve Gastrectomy Compared with Gastric Bypass for Morbidly Obese Patients with End Stage Renal Disease: a Decision Analysis.

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/m2. 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/m2. 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.

The metabolic time line of pancreatic cancer: Opportunities to improve early detection of adenocarcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Enhanced metabolomic analysis identified metabolic pathways that may assist in differentiating PDCA stages that do not occur in a linear stepwise progression.

Prospective assessment of fibrinolysis in morbid obesity: tissue plasminogen activator resistance improves after bariatric surgery.

BACKGROUND: Morbid obesity is associated with an increased risk of thrombotic events, which has been attributed to increased thrombotic activity. Multiple mechanisms have been proposed to explain this increased risk, including an inflammatory state with upregulation of procoagulant and antifibrinolytic proteins. We therefore hypothesize that patients with morbid obesity are hypercoagulable and will revert to normal after bariatric surgery. OBJECTIVES: To evaluate changes in the hypercoagulable state after bariatric surgery. SETTING: University Hospital, Bariatric Center of Excellence, United States. METHODS: Thromboelastography (TEG) data were collected on 72 subjects with morbid obesity, with 36 who had 6 months of follow-up after bariatric surgery. TEG data of 75 healthy subjects (HS) without obesity, recent trauma or surgery, acute infection, or chronic conditions (e.g., liver, cardiovascular, or kidney disease; cancer; diabetes; autoimmune or inflammatory disorders; and disorders of coagulation) were used for comparison. TEG was performed alone and with the addition of 75 and 150 ng/mL tissue plasminogen activator (tPA) to quantify fibrinolysis resistance (tPA-challenged TEG). RESULTS: The bariatric surgery cohort had a median age of 40.5 years, a median body mass index of 44.6 kg/m2, and 90% female patients. Median body mass index reduced significantly 6 months post surgery but remained elevated compared with the HS group (31.4 versus 25.4 kg/m2, P < .0001). At 6 months post surgery, subjects had longer reaction time (mean difference, 1.3; P = .02), lower maximum amplitude (-2.4, P = .01), and increased fibrinolysis with low-dose (3.1, P < .0001) and high-dose tPA-challenged TEG (9, P < .0001). Compared with HS, the postsurgery TEG values were still more likely to be abnormal (all P < .05). CONCLUSIONS: Patients with morbid obesity form stronger clots more rapidly and are more resistant to fibrinolysis than subjects without obesity. Bariatric surgery significantly improved the hypercoagulable profile and fibrinolysis resistance of morbid obesity.

Persistent Homology for the Quantitative Evaluation of Architectural Features in Prostate Cancer Histology.

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.

Increase in post-reperfusion sensitivity to tissue plasminogen activator-mediated fibrinolysis during liver transplantation is associated with abnormal metabolic changes and increased blood product utilisation.

BACKGROUND: Increased systemic fibrinolytic activity can occur in liver transplant recipients after the donor graft is reperfused. However, it remains unclear whether this is related solely to tissue plasminogen activator (t-PA) levels or whether unique metabolic changes can alter t-PA activity and enhance fibrinolytic activity. We hypothesise that an increase in sensitivity to t-PA-mediated fibrinolysis (StF) following liver reperfusion is associated with specific metabolic abnormalities. MATERIALS AND METHODS: Liver transplant recipients had serial blood samples analysed with a modified thrombelastography assay using exogenous t-PA to measure sensitivity/resistance to fibrinolysis with the lysis 30 min after maximum clot strength (tLY30). Paired plasma samples were analysed with mass spectroscopy-based metabolomics. The tLY30 was correlated to metabolites using Spearman's rho. StF was defined as a tLY30 change of >8.5% from the anhepatic phase to 30 min after reperfusion based on the distribution of tLY30 in a healthy control population. RESULTS: StF occurred in 53% of patients. Cohorts had similar MELD scores (18 vs 16, p=0.876) and tLY30 at baseline (p=0.867) and anhepatic phase of surgery (p=0.463). Thirty min after reperfusion, the tLY30 was 73% in patient with StF vs 33% in those without StF 33% (p=0.006). StF was associated with increased red blood cell transfusions (p=0.035), during the first 2 hours of reperfusion. Nine metabolites demonstrated a correlation with tLY30 (p<0.05). DISCUSSION: StF is a transient event that resolves within 2 hours of graft reperfusion and is associated with increased blood product use. This phenomenon correlates with derangements in citric acid cycle, purine and amino acid metabolism. Future research is needed to determine whether these metabolites are biomarkers or mechanistically linked to increased sensitivity to t-PA-mediated fibrinolytic activity following graft reperfusion.

Microfluidics contrasted to thrombelastography: perplexities in defining hypercoagulability.

BACKGROUND: Elevated clot strength (maximum amplitude [MA]) measured by thrombelastography (TEG) is associated with thrombotic complications. However, it remains unclear how MA translates to thrombotic risks, as this measurement is independent of time, blood flow, and clot degradation. We hypothesize that under flow conditions, increased clot strength correlates to time-dependent measurements of coagulation and resistance to fibrinolysis. MATERIALS AND METHODS: Surgical patients at high risk of thrombotic complications were analyzed with TEG and total thrombus-formation analysis system (T-TAS). TEG hypercoagulability was defined as an r <10.2 min, angle >59, MA >66 or LY30 <0.2% (based off of healthy control data, n = 141). The T-TAS AR and PL chips were used to measure clotting at arterial shear rates. T-TAS measurements include occlusion start time, occlusion time (OT), occlusion speed (OSp), and total clot generation (area under the curve). These measurements were correlated to TEG indices (R time, angle, MA, and LY30). Both T-TAS and TEG assays were challenged with tissue plasminogen activator (t-PA) to assess clot resistance to fibrinolysis. RESULTS: Thirty subjects were analyzed, including five controls. TEG-defined hypercoagulability by MA was detected in 52% of the inflammatory bowel disease/cancer patients; 0% was detected in the controls. There were no TEG measurements that significantly correlated with T-TAS AR and PL chip. However, in the presence of t-PA, T-TAS AR determined OSp to have an inverse relationship with TEG angle (-0.477, P = 0.012) and LY30 (-0.449, P = 0.019), and a positive correlation with R time (0.441 P = 0.021). In hypercoagulability determined by TEG MA, T-TAS PL had a significantly reduced OT (4:07 versus 6:27 min, P = 0.043). In hypercoagulability defined by TEG LY30, T-TAS PL had discordant findings, with a significantly prolonged OT (6:36 versus 4:30 min, P = 0.044) and a slower OSp (10.5 versus 19.0 kPa/min, P = 0.030). CONCLUSIONS: Microfluidic coagulation assessment with T-TAS has an overall poor correlation with most TEG measurements in a predominantly hypercoagulable patient population, except in the presence of t-PA. The one anticipated finding was an elevated MA having a shorter time to platelet-mediated microfluidic occlusion, supporting the role of platelets and hypercoagulability. However, hypercoagulability defined by LY30 had opposing results in which a low LY30 was associated with a longer PL time to occlusion and slower OSp. These discordant findings warrant ongoing investigation into the relationship between clot strength and fibrinolysis under different flow conditions.

Utility of Viscoelastic Assays Beyond Coagulation: Can Preoperative Thrombelastography Indices Predict Tumor Histology, Nodal Disease, and Resectability in Patients Undergoing Pancreatectomy?

BACKGROUND: Hypercoagulability and malignancy have been linked since the 1860s. However, the impact of different neoplasms on multiple components of the coagulation system remains poorly understood. Thrombelastography (TEG) enables measurement of coagulation incorporating clotting through fibrinolysis. We hypothesize that specific TEG indices that are associated with hypercoagulability can be appreciated in patients with adenocarcinoma undergoing pancreatic resection. STUDY DESIGN: Blood samples were obtained from patients undergoing pancreatic resection before surgical incision and assayed with TEG. The 4 indices of coagulation measured by TEG included in the analysis were R time, angle, maximum amplitude, and lysis at 30 minutes. Patient tumor type, nodal disease, and mass resectability were contrasted with TEG indices. RESULTS: One hundred patients were enrolled over 18 months. The majority (63%) of patients had adenocarcinoma. Patients with adenocarcinoma had increased angle compared with other lesions (49 degrees [interquartile range {IQR} 37 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.011). When excluding patients that underwent neoadjuvant therapy, patients with adenocarcinoma had shorter R times (13 minutes [IQR 9 to 16 minutes] vs 14 minutes [IQR 12 to 18 minutes]; p = 0.051), steeper angles (49 degrees [IQR 40 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.010), and higher maximum amplitude (67 mm [IQR 61 to 69 mm] vs 62 mm [IQR 57 to 67 mm]; p = 0.017). Nodal disease was associated with a significantly increased angle (49 degrees [IQR 42 to 59 degrees] vs 40 degrees [IQR 32 to 50 degrees]; p = 0.002) and maximum amplitude (64 mm [IQR 61 to 69 mm] vs 62 mm [IQR 56 to 67 mm]; p = 0.017). Patients who underwent successful mass resection had longer R times (14 minutes [IQR 11 to 17 minutes] vs 10 minutes [IQR 9 to 15]; p = 0.033) and shorter angles (44 degrees [IQR 35 to 55 degrees] vs 58 degrees [IQR 45 to 66 degrees]; p = 0.025). CONCLUSIONS: Patients with adenocarcinoma undergoing pancreatic resection have multiple TEG abnormalities consistent with hypercoagulability. These TEG outputs are associated with tumor type, nodal disease, and probability of a successful resection. The use of preoperative TEG has the potential to aid surgeon and patient discussions on anticipated disease burden and prognosis before resection.

Thrombin Provokes Degranulation of Platelet α-Granules Leading to the Release of Active Plasminogen Activator Inhibitor-1 (PAI-1).

BACKGROUND: The balance of fibrinolytic mediators is crucial to the survival of the critically ill patient, with tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) playing significant roles. While elevated levels of PAI-1 are associated with increased morbidity and mortality, the source of this PAI-1 remains elusive. Platelets contain 90% of circulating plasma PAI-1, however, their ability to release active PAI-1 is controversial. We hypothesize platelets contain active PAI-1 in α-granules capable of immediate degranulation when exposed to high concentrations of thrombin. METHODS: In vitro apheresis platelets were stimulated with thrombin (1 IU/mL, 5 IU/mL) followed by the collection of supernatant (5-120 min). Supernatant and lysate PAI-1 was measured by ELISA. The experiment was repeated in the presence of t-PA followed by measurement of t-PA:PAI-1 complex measurement by ELISA. Finally, healthy whole blood underwent dilution with control and thrombin-treated platelet lysate followed by thrombelastography (TEG) in a t-PA-stimulated TEG. RESULTS: Thrombin provoked immediate near-complete degranulation of PAI-1 from α-granules (median 5m 5 IU/mL thrombin 125.1 ng/mL, 1 IU/mL thrombin 114.9 ng/mL, control 9.9 ng/mL). The released PAI-1 rapidly complexed with t-PA, with a 4-fold increase in complex formation in the thrombin-treated supernatant. Conversely, PAI-1 in the control lysate demonstrated a 6-fold increase in complex formation compared with thrombin lysate. Last, control platelet lysate inhibited t-PA-induced fibrinolysis by TEG (median LY30 control 15m 7.9%), while thrombin-treated platelet lysates, after PAI-1 degranulation, were unable to affect the fibrinolysis profile (median LY30 5 IU/mL 28.5%, 1 IU/mL 12.4%). CONCLUSION: Thrombin provokes rapid α-degranulation of active PAI-1, capable of complexing with t-PA and neutralizing t-PA-induced fibrinolysis by TEG.

Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: Prognostic, level III.

Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation.

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.

Thrombelastography indicates limitations of animal models of trauma-induced coagulopathy.

BACKGROUND: 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 with 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 before experimentation. Citrated native TEGs were conducted on each whole blood sample within 2 h of collection. The clot initiation (R-time, minutes), angle (degrees), maximum amplitude (MA; millimeter), and lysis 30 min after MA (LY30; percentage) 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 Kruskal-Wallis test with alpha adjusted with a Bonferroni correction for multiple comparisons (alpha = 0.016). RESULTS: Median R-time (clot initiation) was 14.65 min (IQR: 13.2-16.3 min) for humans, 5.7 min (4.9-8.8) for pigs, and 5.2 min (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° (interquartile range [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 with 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 mm (70.4-75.5) for pigs, and 66.5 mm (56.5-68.6) for rats. Humans had reduced MA compared with 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). CONCLUSIONS: 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 trauma-induced coagulopathy 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.

Development of a Measure of Incremental Behavior Change Toward Smoking Cessation.

INTRODUCTION: A reliable measure capable of detecting progression towards smoking cessation would be valuable for evaluating and optimizing the effectiveness of low- to moderate-intensity cessation interventions, such as brief advice in the primary care setting. This article presents the development and evaluation of a brief self-report measure of Incremental Behavior Change toward Smoking cessation (IBC-S). METHODS: Sequential samples of 411 and 399 adult smokers completed items representing a spectrum of behavioral and cognitive changes antecedent to smoking cessation. The dimensionality, fit, range of difficulty, and reliability of items were evaluated using factor analysis and Rasch modeling. RESULTS: The final 15-item IBC-S measure met fit criteria and demonstrated acceptable reliability. Participants with a significant change in IBC-S score were over four times more likely to report cessation at 6-week follow-up (OR 4.37, 95% CI 1.83-10.42). CONCLUSION: The IBC-S is brief, reliable and associated with self-report of smoking reduction and cessation. IMPLICATIONS: This article presents the psychometric evaluation of a measure to assess a spectrum of behaviors and cognitions antecedent to smoking cessation. The findings indicate that the items show good measurement properties and good potential as a sensitive measure to evaluate interventions. This measure provides an alternative outcome for interventions that are designed to move individuals towards cessation attempts.

Intimate Partner Violence and Barriers to Cervical Cancer Screening: A Gynecologic Oncology Fellow Research Network Study.

OBJECTIVES: The aims of the study were to examine barriers to cervical cancer screening among women who have experienced intimate partner violence (IPV) and accessed domestic violence shelters, to compare barriers among those up-to-date (UTD) and not UTD on screening, and to evaluate acceptability of human papillomavirus self-sampling. MATERIALS AND METHODS: This is a cross-sectional survey in which domestic violence shelters in Ohio were identified and women completed an anonymous survey assessing UTD screening status, barriers related to screening, history of IPV, intention to follow up on abnormal screening, and acceptability of self-sampling. Characteristics of UTD and not UTD women were compared using Mann-Whitney U tests. RESULTS: A total of 142 women from 11 shelters completed the survey. Twenty-three percent of women were not UTD. Women who were not UTD reported more access-related barriers (mean = 2.2 vs 1.8; p = .006). There was no difference in reported IPV-related barriers between women who were not UTD and those who are UTD (mean = 2.51 in not UTD vs 2.24 in UTD; p = .13). Regarding future screening, of the women who expressed a preference, more women not UTD preferred self-sampling than UTD women (32% vs 14%; p = .05). CONCLUSIONS: In this study, access-related barriers were more commonly reported among women not UTD with screening. Addressing these barriers at domestic violence shelters may improve screening among not UTD women. Self-sampling may also be one feasible approach to support screening in this population.

Geo-Referenced, Abundance Calibrated Ocean Distribution of Chinook Salmon (Oncorhynchus tshawytscha) Stocks across the West Coast of North America.

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.

Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock.

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.

A randomized trial to evaluate primary care clinician training to use the Teachable Moment Communication Process for smoking cessation counseling.

OBJECTIVE: To implement and evaluate the impact of a Teachable Moment Communication Process (TMCP) training intervention on clinicians' smoking cessation counseling behaviors in practice. METHOD: Using a group randomized trial, 31 community-based, primary care clinicians in Northeast Ohio received either TMCP training or an attention control (2010-2012). TMCP training consisted of two, three-hour sessions involving didactic instruction, skill practice with standardized patients, and coaching. Clinician performance of TMCP elements was assessed by coding audio-recordings of routine visits with smokers at baseline and post-intervention (n=806). RESULTS: Baseline performance of all TMCP elements was similar in the two groups. After the intervention, TMCP-trained clinicians were more often observed advising patients to quit while linking smoking to the patient's concern (58% vs. 44%, p=0.01), expressing optimism (36% vs. 3%, p<0.001), expressing partnership (40% vs. 12%, p=0.003) and eliciting the patient's readiness to quit (84% vs. 65%, p=0.006) than clinicians in the comparison group. TMCP-trained clinician responses were also better aligned with patients' expressed readiness to quit smoking than comparison group clinicians (p<0.001). CONCLUSION: The intervention significantly changed the content of clinicians' smoking cessation communication in ways consistent with the TMCP model for health behavior change.

How well do physician and patient visit priorities align?

This study found that there is alignment between a patient's reason for a visit and the physician's main concern 69% of the time. Less than fully aligned priorities were associated with insurance status and the number of problems addressed.

Transitions, realignments, and focus shifts: possibilities for biopsychosocial care in the electronic health record era.

The healthcare system in the United States is currently evolving in response to a diverse range of inter-related economic and political pressures. In this article, we discuss three important macro-level transitions (volume to value, clinician-centric to patient-centered care, and individual to population) and their implications for the practice of medicine, health information technology (HIT), and clinical training. Specifically, challenges and opportunities for advancing the use of the biopsychosocial model in clinical practice and teaching in this new, electronic health record (EHR) era of medicine are highlighted. While much work needs to be done to leverage the potential of EHR/HIT systems, their potential to improve population health and patient experience while controlling the costs of care is great. As primary care clinicians and behavioral scientists navigating this changing healthcare landscape, we should continue to strive to deliver high-quality, patient-centered care. Insisting that future generations of EHR/HIT systems support a biopsychosocial approach is part of this mission.

Creating a culture of inquiry in family medicine.

BACKGROUND AND OBJECTIVES: Strengthening the contribution of reflective practice and new knowledge generation to the learning relationships forged during graduate and undergraduate medical training offers a possibility to create a climate more conducive to the recruitment and retention of family physicians. The Culture of Inquiry (CI) fellowship, an immersive, experientially based training program, combines didactic instruction, workshops, and mentoring to develop the capacity of family medicine's teachers to imagine, implement, and disseminate clinically relevant research and stimulate collaborations with those whom they train. This article outlines the CI fellowship program, summarizes its outcomes, and offers insights about programmatic features contributing to its success. METHODS: The Department of Family Medicine and Community Health at Case Western Reserve University selected CI fellows from interested local family physicians who train residents and medical students. Over 10 months, with 10% effort expected from fellows, the CI fellowship exposed each fellow to the entire research process and provided technical and logistical support for the design and completion of two research projects. Quantitative and qualitative program evaluation were used to assess outcomes. RESULTS: Scholarly productivity of fellows exceeded expectations. Collaborations with students and residents produced a ripple effect that amplified the fellowship's impact by strengthening those relationships crucial to the creation of a culture of inquiry among family medicine's teachers, learners, and practitioners. CONCLUSIONS: The CI fellowship represents a highly replicable program to connect committed and interested clinicians to research mentors with the goal of increasing scholarship and creating a growing culture of inquiry in family medicine.

Teachable moments for health behavior change and intermediate patient outcomes.

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.