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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/m(2), 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/m(2), 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

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 25 th to 75 th 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 P 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 P 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 P 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 P 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.

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.

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.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.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.TMs have a greater positive influence on several intermediate markers of patient behavior change compared to other categories of advice.TMs show promise as an approach for clinicians to discuss behavior change with patients efficiently and effectively.

Objective Situations with potential to motivate positive change in unhealthy behavior have been called ‘teachable moments’. Little is known about how they occur in the primary care setting. Methods Cross-sectional observational design. Audio-recordings collected during 811 physician–patient interactions for 28 physicians and their adult patients were analyzed using conversation analysis. Results Teachable moments were observed in 9.8% of the cases, and share three features: (1) the presence of a concern that is salient to the patient that is either obviously relevant to an unhealthy behavior, or through conversation comes to be seen as relevant; (2) a link that is made between the patient's salient concern and a health behavior that attempts to motivate the patient toward change; and (3) a patient response indicating a willingness to discuss and commit to behavior change. Additionally, we describe phenomena related to, but not teachable moments, including teachable moment attempts, missed opportunities, and health behavior advice. Conclusions Success of the teachable moment rests on the physician's ability to identify and explore the salience of patient concerns and recognize opportunities to link them with unhealthy behaviors. Practice implications The skills necessary for accomplishing teachable moments are well within the grasp of primary care physicians.

Background The widely recommended 5A's strategy for brief smoking cessation includes five tasks: Ask, Advise, Assess, Assist, and Arrange. Assessments of the 5A's have been limited to medical-record review and self-report. Using observational data, an instrument to assess the rate at which the 5A's are accomplished was developed. Methods The 5A's Direct Observation Coding scheme (5A-DOC) was developed using published 5A's guidelines and was refined using observed clinician–patient interactions. The development sample consisted of 46 audio-recorded visits of smokers with their physician ( n =5), collected in 2000. The 5A-DOC was next applied to a second sample of 131 visits with 28 physicians between 2005 and 2008. Inter-rater reliability was assessed and frequencies reported. Analyses were completed in 2008. Results Three observations shaped the development of the 5A-DOC: (1) patients accomplish 5A's tasks; (2) some communication actions accomplish multiple 5A's tasks simultaneously; and (3) sequence is important. Inter-rater agreement for identifying each task was moderate to excellent (kappa=0.58–1.0). When smoking status was established (Ask, n =78), 61% Assessed readiness, and 50% contained Assist. In all, 73% failed to complete the 5A's adequately. Conclusions Accounting for patient activity in smoking-cessation discussions is essential to accurately capture the degree to which the 5A's have been accomplished. The 5A-DOC can be applied to audio or transcript data to reliably assess which of the 5A's tasks have been accomplished. Clinician performance of the 5A's was modest, and findings suggest that clinician training should focus on Assess and the timing of this task, and alignment with patients' reported readiness.

Proton-decoupled Fourier transform nuclear magnetic resonance of natural abundance 13C was used to obtain spectra of ribonuclease A and its oxidized derivative at a set of pH values ranging from pH 1.40 to 6.72 at 45°. Observations on the native conformation were made at pH 4.14 and 6.55, and on the denatured conformation at pH 2.12 and below. In addition, the disrupted structure obtained by performic acid oxidation of the disulfide bonds was observed at several pH values. The loss of the native structure was associated with sharpening of the resonance bands. A tentative assignment was made for the unmodified ribonuclease A at pH 1.46 based on resonance positions of free amino acids and peptides. Although a good fit to the data was obtained, further development is required for unequivocal assignment. Partially relaxed spectra were used to obtain spin-lattice relaxation times (T1) for certain carbon types. These values are traced through several pH values for both ribonuclease A and its oxidized derivatives. Pairs of effective rotational correlation times (τeff) were derived from the T1 values of certain aliphatic resonances. By considering data from fluorescence depolarization experiments and observed line widths, it was possible to exclude one of the τeff values in the majority of cases. The results were interpreted in terms of increased segmental mobility in the denatured states, especially for α carbon nuclei that appear relatively restrained in the native state.

The natural abundance carbon 13 nuclear magnetic resonance spectra of the peptides l-valyl-l-leucyl-l-seryl-l-glutamylglycine, comprising the first 5 residues of the amino terminus of sperm whale myoglobin, l-leucyl-l-seryl-l-glutamic acid, and l-seryl-l-glutamylglycine have been recorded by continuous wave and pulsed Fourier transform techniques. Signal assignments were made by comparison of the peptides with each other and with the free amino acids, by the pH dependence of the chemical shifts, and by modification of the degree of proton decoupling in certain cases. The chemical shift dependence of specific carbon centers on their position in the oligopeptide sequences and the influence of the state of ionization of various groups on neighboring carbon sites were explored.

Proton-decoupled Fourier transform nuclear magnetic resonance of natural abundance 13C was used to obtain spectra of cyanoferrimyoglobins of harbor seal (Phoca vitulina) and sperm whale (Physeter catodon). These spectra were compared with those of hen egg white lysozyme and of bovine pancreatic ribonuclease A to show differences reflecting gross composition as well as differences tentatively attributable to more subtle conformational constraints. The cyanoferrimyoglobin spectra were much alike but not identical. Carboxymethylation of the native seal protein produced barely detectable changes at the chemical shift positions of the major adducts but no systematic alterations elsewhere in the spectrum. However, extensive modification of histidine and methionine residues by carboxymethylation of seal apomyoglobin in the presence of 8 m urea yielded a denatured product, judged by circular dichroism measurements, for which the 13C spectrum was sharp and characteristic of a denatured protein. This spectrum was used to tabulate tentative assignments. Partially relaxed spectra were used to obtain spin-lattice relaxation times (T1) for certain carbon types. These values are compared for the various myoglobin preparations mentioned above. The similarities between the native forms are striking. The denatured preparation gives many evidences of increased segmental mobility, especially for those nuclei that appear relatively restrained in the native state.