Thrombin Generation Assay in Hospitalized Nonsurgical Patients: A New Tool to Assess Venous Thromboembolism Risk?

BACKGROUND: Assessment of venous thromboembolism (VTE) risk is important to determine optimal primary prophylaxis in hospitalized patients. The Padua score helps to recognize patients with high VTE risk, but quantifying a VTE risk is often challenging in medical patients. Thrombin generation assay (TGA) reflects the pro-/anticoagulant balance and thus could help to better quantify VTE risk in medical hospitalized patients. AIM: To analyze the relation between TGA and VTE risk according to Padua score in medical hospitalized patients. METHODS: Between May and October 2013, 105 patients were included in an unselected cohort group of patients admitted to an internal medicine department in a large, university hospital. Within the 36 hours after admission and before any anticoagulant therapy, Padua score was calculated and sample for TGA was collected for each patient. Thrombin generation assay (velocity, peak, and endogenous thrombin potential [ETP]) was performed with 1 and 5 picomol/l (pM) tissue factor (TF) reagent. RESULTS: In patients with high Padua score (n = 29), velocity, peak, and ETP differed from patients with low Padua score. This difference was present at 1 and 5 pM TF, in ETP (P < .0001 and P = .003 respectively), in peak (P < .0001 in both conditions), and in velocity (P < .0001). According to multivariate analysis, myeloid disorders, older age, higher body mass index, myocardial infarction, C-reactive protein >5 mg/L, reduced mobility with bed rest significantly increased velocity 1 pM TF value. CONCLUSION: Single thrombin generation measurement could help to identify patients at risk of VTE in medical hospitalized patients.

Exercise-Induced Vasculitis: A Review with Illustrated Cases.

Although exercise-induced vasculitis (EIV) is usually misdiagnosed, it is not uncommon. Occurring mostly after prolonged exercise, especially in hot weather, EIV is an isolated cutaneous vasculitis with stereotypical presentation. This article reviews the clinical characteristics, treatments, and outcomes of EIV based on the published literature. We report 99 patients who developed EIV after walking, dancing, swimming, or hiking especially during hot weather, including the records of 16 patients with EIV treated at our hospital from 2007 to 2015. Erythematous or purpuric plaques arise on the lower legs, without the involvement of compression socks or stockings. Symptoms include itch, pain, and a burning sensation. EIV is an isolated cutaneous vasculitis. Lesions resolve spontaneously after 10 days. When triggering conditions persist, relapses are frequent (77.5 %). Histopathology demonstrates leukocytoclastic vasculitis in 95 % of cases with C3 or immunoglobulin M deposits in 88 and 46 % of cases, respectively. Blood investigations are negative. EIV appears to be a consequence of venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation. Both appear after prolonged and unusual exercise in hot weather. Treatment is not codified; topical corticosteroids may reduce symptoms and wearing light clothes might limit lesion occurrence.

e-Learning versus lecture-based courses in ECG interpretation for undergraduate medical students: a randomized noninferiority study.

OBJECTIVE: An ECG is pivotal for the diagnosis of coronary heart disease. Previous studies have reported deficiencies in ECG interpretation skills that have been responsible for misdiagnosis. However, the optimal way to acquire ECG interpretation skills is still under discussion. Thus, our objective was to compare the effectiveness of e-learning and lecture-based courses for learning ECG interpretation skills in a large randomized study. PARTICIPANTS AND METHODS: We conducted a prospective, randomized, controlled, noninferiority study. Participants were recruited from among fifth-year medical students and were assigned to the e-learning group or the lecture-based group using a computer-generated random allocation sequence. The e-learning and lecture-based groups were compared on a score of effectiveness, comparing the 95% unilateral confidence interval (95% UCI) of the score of effectiveness with the mean effectiveness in the lecture-based group, adjusted for a noninferiority margin. RESULTS: Ninety-eight students were enrolled. As compared with the lecture-based course, e-learning was noninferior with regard to the postcourse test score (15.1; 95% UCI 14.2; +∞), which can be compared with 12.5 [the mean effectiveness in the lecture-based group (15.0) minus the noninferiority margin (2.5)]. Furthermore, there was a significant increase in the test score points in both the e-learning and lecture-based groups during the study period (both P<0.0001). CONCLUSION: Our randomized study showed that the e-learning course is an effective tool for the acquisition of ECG interpretation skills by medical students. These preliminary results should be confirmed with further multicenter studies before the implementation of e-learning courses for learning ECG interpretation skills during medical school.

Effect of Extrinsic and Intrinsic Stressors on Clinical Skills Performance in Third-Year Medical Students.

BACKGROUND: Both enhancements and impairments of clinical performance due to acute stress have been reported, often as a function of the intensity of an individual's response. According to the broader stress literature, peripheral or extrinsic stressors (ES) and task-contingent or intrinsic stressors (IS) can be distinguished within a stressful situation. The objective of this study was to assess the impact of IS and ES on clinical performance. METHOD: A prospective randomized crossover study was undertaken with third-year medical students conducting two medical experiences with simulated patients. The effects of severity of the disease (IS) and the patient's aggressiveness (ES) were studied. A total of 109 students were assigned to four groups according to the presence of ES and IS. Subjective stress and anxiety responses were assessed before and after each experience. The students' clinical skills, diagnostic accuracy and argumentation were assessed as clinical performance measures. Sex and student-perceived cognitive difficulty of the task were considered as adjustment variables. RESULTS: Both types of stressors improved clinical performance. IS improved diagnostic accuracy (regression parameter ß = 9.7, p = 0.004) and differential argumentation (ß = 5.9, p = 0.02), whereas ES improved clinical examination (ß = 12.3, p < 0.001) and communication skills (ß = 15.4, p < 0.001). The student-perceived cognitive difficulty of the task was a strong deleterious factor on both stress and performance. CONCLUSION: In simulated consultation, extrinsic and intrinsic stressors both have a positive but different effect on clinical performance.

[Validation of a screening tool toward a geriatric comprehensive assessment during a non geriatric consultation: the geriatric warning test]. / Validation d'un outil d'orientation vers une évaluation gériatrique standardisée en consultation de spécialité non gériatrique: le test d'alerte gériatrique.

Comprehensive geriatric assessment (CGA) is a validated method but is time consuming and must be performed by several professional. It is useful to elaborate a screening tool, which allows the elderly to CGA. The aim of this study is to validate the Geriatric Warning Test (GWT), a 6-questions form: 1) Did your patient consult or did hospitalize for a fall in the last 3 months? 2) Did your patient lose weight or did he loose the appetite? 3) Has your patient difficulties to see or listen? 4) Does your patient need help in the everyday life? 5) Has your patient a change of the cognitive functions? 6) Does your patient need a geriatric evaluation for one or several any reason that those cited previously? During a prospective observational study, a doctor non-geriatrician practitioner informed the GWT during a consultation of vascular medicine. All the patients aged 70 or more years old had an EGS after the consultation. An EGS was considered as necessary if 2 propositions and essential if 3 propositions were present from a 10 propositions list. The relevance of the TAG was analysed when one then 2 questions were informed during the consultation. The CGA was judged as necessary with a positive predictive value (PPV) of 81,8% and a negative predictive value (NPV) of 87,5%, when a single question is sufficient to indicate the CGA, and respectively of 76,5 and 53,9% when 2 questions of the GWT are taken into account. For an essential CGA (3 propositions), the PPV and NPV are 40,9 and 100%, by taking a single question of the GWT and 47,1 and 92,3% with 2 questions. A single positive question of the GWT must be used to propose an EGS during a non geriatric consultation.

Stress responses in medical students in ambulatory and in-hospital patient consultations.

CONTEXT: Little is known about health professionals' responses to acute stressors encountered in the clinical environment. The goal of this study was to measure the subjective and physiological stress responses of medical students to consultations in familiar (in-hospital) and unfamiliar (ambulatory) settings. We hypothesised that: (i) providing a consultation in an unfamiliar setting would result in increased stress responses in medical students, and (ii) some differences in stress responses according to gender might become apparent. METHODS: A quantitative cross-over study was conducted over a 6-month period. Participating students were invited to provide consultations to patients in an ambulatory setting. In order to provide a control condition, each student was required to conduct a similar consultation (without reporting back to the patient) with an in-hospital patient during his or her rotation in internal medicine. Pre- and post-consultation subjective and physiological responses were measured using a visual analogue scale (VAS), the State-Trait Anxiety Inventory (STAI), a cognitive appraisal scale and salivary cortisol levels. RESULTS: All of the subjective and physiological stress responses were greater in the ambulatory setting than the in-hospital setting. There was an effect of gender on the responses. Women showed greater pre-consultation subjective stress levels in the ambulatory setting, whereas men exhibited greater physiological stress levels in the ambulatory setting. No correlations were observed between subjective and cortisol responses. CONCLUSIONS: Ambulatory consultations are more stressful for medical students than consultations carried out in the more familiar in-hospital setting. Further studies should be conducted to investigate the nature of the stressors in this particular environment, to explore the possible explanations for a gender effect, and to explore the effects of these stress responses on students' diagnostic skills.

Exploring how students think: a new method combining think-aloud and concept mapping protocols.

OBJECTIVES: A key element of medical competence is problem solving. Previous work has shown that doctors use inductive reasoning to progress from facts to hypotheses and deductive reasoning to move from hypotheses to the gathering of confirmatory information. No individual assessment method has been designed to quantify the use of inductive and deductive procedures within clinical reasoning. The aim of this study was to explore the feasibility and reliability of a new method which allows for the rapid identification of the style (inductive or deductive) of clinical reasoning in medical students and experts. METHODS: The study included four groups of four participants. These comprised groups of medical students in Years 3, 4 and 5 and a group of specialists in internal medicine, all at a medical school with a 6-year curriculum in France. Participants were asked to solve four clinical problems by thinking aloud. The thinking expressed aloud was immediately transcribed into concept maps by one or two 'writers' trained to distinguish inductive and deductive links. Reliability was assessed by estimating the inter-writer correlation. The calculated rate of inductive reasoning, the richness score and the rate of exhaustiveness of reasoning were compared according to the level of expertise of the individual and the type of clinical problem. RESULTS: The total number of maps drawn amounted to 32 for students in Year 4, 32 for students in Year 5, 16 for students in Year 3 and 16 for experts. A positive correlation was found between writers (R = 0.66-0.93). Richness scores and rates of exhaustiveness of reasoning did not differ according to expertise level. The rate of inductive reasoning varied as expected according to the nature of the clinical problem and was lower in experts (41% versus 67%). CONCLUSIONS: This new method showed good reliability and may be a promising tool for the assessment of medical problem-solving skills, giving teachers a means of diagnosing how their students think when they are confronted with clinical problems.

Lethal limb ischaemia in leukaemia. Case report and review of the literature.

Several disturbances of the coagulation system are associated with malignancies of the hematopoietic system. The primary mechanisms of these are disseminated intravascular coagulation and hyperviscosity. As such, bleeding or thrombotic events are often encountered and, occasionally, they may even be the inaugural symptom of leukaemia. The lack of a diagnostic tool that would enable a rapid diagnosis of a hematopoietic malignancy, which may present initially as, for example, a coagulation disorder (arterial or venous thrombotic event and/or haemorrhage), can have dramatic consequences. The treatment of choice for this clinical condition is chemotherapy associated with leukopheresis with the aim of obtaining a rapid cytoreduction. We report here a case relevant to this situation and attempt to assess current knowledge on the ethiopathogenesis and treatment of coagulation abnormalities in leukaemia. Our report highlights the imperative need for immediate haematological diagnosis despite the non-specific presentation.

[Abdominal aortic involvement in active giant cell (temporal) arteritis: a study of 20 patients by Doppler ultrasonography and computed tomographic angiography]. / Fréquence de l'atteinte de l'aorte abdominale au diagnostic de maladie de Horton : étude de 20 patients par échographie-Doppler et angiotomodensitométrie.

OBJECTIVE: This study used Doppler ultrasonography and computed tomographic angiography (CTA) to assess the prevalence of abdominal aortic lesions that suggested abdominal aortitis at diagnosis of giant-cell or temporal arteritis (GCA). We also evaluated the contribution of these 2 techniques to diagnosis. METHODS: This single-center study included patients admitted to the internal medicine department of the Nantes (France) University Hospital, between May 1999 and May 2002 at the time of their diagnosis with biopsy-proven GCA. In the 8 weeks after diagnosis, patients underwent a thorough workup, including the collection of clinical and laboratory data. Imaging tests for each patient included Doppler ultrasonography and a CTA scan of the abdominal aorta, looking for aneurysms, ectasia, and thickening of the aortic wall. RESULTS: This study included 20 patients (17 women, mean age 73.9+/-7.2 years, mean CRP=116+/-75.9mg/L). Doppler ultrasonography suggested aortitis in 8 cases (40%): 7 patients (35%) had a hypoechoic halo, 3 (15%) a small aneurysm (diameter < 30mm), and 2 (10%) both. CTA scans of the aorta showed aortitis in 5 cases (25%), all with abnormal thickening of the aortic wall. CTA did not identify any aneurysms. Overall, abdominal aortitis was suspected in 10 patients (50%). CONCLUSION: At the time of GCA diagnosis, both Doppler ultrasonography and CTA can detect morphological abnormalities of the abdominal aorta. Here they suggested asymptomatic abdominal aortitis in half the patients. Doppler ultrasonography appears more effective for detecting aortic aneurysms, while CTA seems helpful for the diagnosis of parietal thickening. The risk factors associated with abdominal aortitis in GCA remain to be identified.

D-dimers, thrombin-antithrombin complexes, and risk factors for thromboembolism in hospitalized patient.

INTRODUCTION: There is lack of data about the correlation between hemostatic markers and the clinical and biological risk factors (RFs) for venous thromboembolism (VTE) in medical inpatients without suspicion of acute VTE. MATERIAL AND METHODS: To evaluate the coagulation activation status in patients with current known RFs for VTE, the authors measured 2 markers of hypercoagulability, thrombin antithrombin (TAT) complexes and D-dimers, at day 1 in 165 patients hospitalized in internal medicine wards without suspected acute VTE. All known RFs for VTE were systematically assessed at admission and classified in a chronological way as permanent or transient. RESULTS: Surprisingly, TAT values followed a multimodal distribution. D-dimers showed a normal distribution after a logarithmic transformation (P = .34, Shapiro-Wilk test). Interestingly, a significant progression in D-dimer levels was found according to the chronological classification of RFs. D-dimer variations on multivariate analysis (not applicable for TAT because of the multimodal distribution) correlated independently with a recent inability to walk and an increase in C reactive protein level more than 10 mg/L. CONCLUSIONS: (a) this study is the first to describe the variations of hypercoagulability markers according to a systematic screening of RFs for VTE in inpatients without suspicion of acute VTE, (b) TAT appeared as a less relevant marker of hypercoagulability than D-dimers in internal medicine inpatients, (d) the chronological classification of RFs identified clearly groups at risk for the prethrombotic state, and (d) an increased hypercoagulability state was demonstrated in patients with an association between a recent immobility and increased inflammatory markers.

Acute posttraumatic ischemia of the limbs: algodystrophy or related syndrome? A prospective study on a series of 25 patients.

The aim of this study was to present clinical and paraclinical features of a rarely studied vascular syndrome that usually occurs after a minor traumatic injury. The prospective study of 25 patients identified a group of young subjects, mainly women, generally with history of vascular hyperactivity to cold, showing disseminated pain in a limb always combined with vasospasm, consecutive to a minor traumatic injury in general, and simulating acute ischemia of a limb. The patients' arterial and microcirculatory flows were restored after warming, which proved that they were suffering from intense, reversible but pathological vasospasm, because of its duration, diffusion, intensity, and disproportion as to the triggering event. The symptoms may recur, but they respond to physiotherapy. Patients' follow-up showed that microcirculatory function remains abnormal sometime after the initial episode with, in particular, an exacerbation of the venoarteriolar reflex.

Aortic involvement in recent-onset giant cell (temporal) arteritis: a case-control prospective study using helical aortic computed tomodensitometric scan.

OBJECTIVE: The prevalence of the involvement of large vessels in giant cell arteritis (GCA) is 3-13%. Aortitis is the most serious complication of GCA. Computed tomodensitometric (CT) scan allows analysis of both the aortic wall and endoluminal part of the aorta. Therefore, we conducted a study using CT scan to analyze aortic abnormalities in patients with recent-onset GCA. METHODS: This prospective controlled study compared patients with biopsy-proven GCA with a matched control group based on sex, age, and cardiovascular risk factors. During the 4-week period following diagnosis of GCA, patients underwent an aortic CT scan. The aortic imaging results were blindly compared between both groups. RESULTS: From January 5, 1998 to January 11, 1999, 22 patients and 22 controls were screened by CT scan for aortic involvement. Thickening of the aortic wall was more frequent among patients than controls (45.4% versus 13.6%; P = 0.02). Aortic thickening (mean 3.3 mm) was located on the ascending part of the thoracic aorta in 22.7% of the patients, with no evidence of thickening in the controls (P = 0.05). Thickening of the abdominal aortic wall was noted in 27.3% of the patients and none of the controls (P = 0.02). CONCLUSION: This study suggests that inflammatory aortic thickening, detected by CT scan, occurs frequently at the time of diagnosis of GCA, and that this condition predominantly occurs on the ascending part of the aorta.

Buttock claudication disclosing a thrombosis of the superior left gluteal artery: Report of a case diagnosed by a selective arteriography of the iliac artery, and cured by per-cutaneous stenting.

We report on a case of left buttock claudication, occurring consistently after 150 meters walking, and disappearing after a short rest. As magnetic resonance angiography (MRA) did not show any explanation for this claudication, a selective angiography of left internal iliac artery was requested, which clearly identified a tight stenosis of the onset of the left superior gluteal artery. A per-cutaneous angioplasty together with stenting of this artery, induced a prompt and complete relief of pain at the three months follow-up visit.

Development of an experimental model of pre-thrombosis in rats based on Wessler's principle using a calibrated venous stasis.

We have developed a model of a pre-thrombotic state in rats based on venous stasis induced by partial ligature of the inferior vena cava. The degree of stenosis was calibrated by using variations in upstream venous pressure. Different degrees of stasis were tested in order to obtain a pre-thrombotic state. Increasing doses of thromboplastin were infused. The thrombogenic potential of this model was evaluated by measuring thrombus weight and by the increase in levels of thrombin-antithrombin complexes. A pre-thrombotic state was induced by 2 h of exposure to a 40% stasis obtained by increasing by 40% the upstream venous pressure (mean thrombus weight, 0.2 +/- 0.6 mg). In these conditions of stasis, low doses of thromboplastin induced venous thrombosis (mean weight, 23 +/- 20 mg; P < 0.05). The increase in thrombus size was correlated to the rise in thrombin-antithrombin levels (r = 0.53, P < 0.001). In conclusion, we have developed the first animal model in which venous stasis can be calibrated by varying the degree of stenosis of the inferior vena cava. This model could be used to study the kinetics of biological markers of hypercoagulability, to study the pathogeny of thrombosis or to evaluate the therapeutic efficacy of new drugs in pre-clinical trials.

[Risk factors for maternal thromboembolism: clinical predisposition]. / Facteurs de risque de la maladie thrombo-embolique maternelle. Facteurs cliniques pré-existants.

Predisposing clinical features in pregnant women are poorly evaluated in the literature. Several factors are undeniable, for example extrinsic compression of the iliac vein (Cockett syndrome), post phlebitis disease, varicose vein disease, and, for most patients, unquantifiable risk factors. Careful assessment of the overall sensitivity to venous thrombosis, on the basis of history taking (patient and family), will allow better assessment of the predisposition to thromboembolism.