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Examines the effectivity of mixed-format curriculum in supporting the learning behaviors to characterize skills of medical students. Effectivity of problem-based learning (PBL) and medical ethics in developing learning skills; Use of the Cognitive Behavior Survey; Comparison between mixed traditional and PBL curriculum.

ABSTRACT. In a prospective study of the growth and neuropsychologic function of hemophilic subjects, 333 boys, median age of 12.3 years, had baseline neurologic examinations. The study population included 207 individuals (62%) who were seropositive for human immunodeficiency virus type 1 (HIV-1). Overall results indicated that 11% had abnormalities of cranial nerve function, 17% had abnormal deep tendon reflexes, 23% had abnormal strength, 25% had abnormal coordination, and 31% had abnormal tone, bulk, or range of motion. By contrast, 2% or fewer displayed abnormal movements or had abnormal pain or vibratory sensation, or altered mental status. Abnormalities were more common in older hemophilic subjects (eg, 67 [38%] of 177 subjects is greater than or less than 12 years of age had abnormal tone, bulk, or range of motion vs 36 [23%] of 156 subjects < 12 years of age). When compared with regard to HIV-1 status, HIV-seronegative and HIV-seropositive subjects did not differ with regard to head circumference or the frequency of abnormalities of cranial nerve function, sensation, muscle strength, or coordination. However, deep tendon reflexes and tone, bulk, or range of motion were more frequently abnormal in HIV-1-seropositive individuals. More HIV-1-positive subjects had at least one increased deep tendon reflex (13/207 [6.3%] vs 1/126 [0.8%] in seronegatives) and more had non-hemophilia-related decreases in muscle bulk (7/207 [3.4%] vs 0/126 in seronegatives). These results indicate that hemophilia causes substantial neurologic dysfunction and that certain findings, such as changes in muscle-stretch reflexes or muscle bulk, may also... [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel. Methods: We randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial was terminated prematurely when the sponsor lost financing. Results: We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34, 95% confidence interval [CI], 0.18 to 0.63; P<0.001). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13; 95% CI, 0.03 to 0.56; P=0.001). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omeprazole and 5.7% with placebo (hazard ratio with omeprazole, 0.99; 95% CI, 0.68 to 1.44; P=0.96); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole. Conclusions: Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Funded by Cogentus Pharmaceuticals; ClinicalTrials.gov number, NCT00557921.) N Engl J Med 2010;363:1909-17. [ABSTRACT FROM AUTHOR]

The weak peroxisome proliferator activated receptor-α (PPAR-α) agonists gemfibrozil and fenofibrate achieve only small increases in high-density lipoprotein (HDL) cholesterol. CP-778,875 is a more potent PPAR-α agonist developed to produce greater HDL cholesterol increases. This randomized, multicenter, double-blinded, placebo-controlled study evaluated the efficacy and safety of CP-778,875 in subjects with mixed dyslipidemia and type 2 diabetes. Eight-six subjects with low HDL cholesterol (≤45 mg/dl for men and ≤55 mg/dl for women) and increased triglycerides (150 to 500 mg/dl) who had coexisting type 2 diabetes were randomized. Subjects received CP-778,875 doses of 0.5, 2, or 6 mg/day or placebo for 6 weeks. Any other lipid-altering therapy was stopped at screening. The primary end point was percent change in HDL cholesterol from baseline. The 2-mg/day dose of CP-778,875 significantly increased HDL cholesterol by 14%. The 2-mg dose also increased concentrations of apolipoprotein (apo) A-I, HDL2 cholesterol, and HDL3 cholesterol by 13%, 12%, and 19%, respectively. An unusual dose–response pattern was observed in that at 6 mg/day CP-778,875 only increased HDL cholesterol by 3% and decreased HDL2 cholesterol by 24%. Fasting triglyceride levels were significantly decreased to a similar extent (26%) by all 3 doses of CP-778,875. CP-778,875 significantly increased homocysteine levels. There was no significant relation between change in homocysteine and change in apoA-I or HDL cholesterol. No subjects developed myopathy. In conclusion, CP-778,875 2 mg/day significantly increased HDL cholesterol, significantly lowered fasting triglycerides, and increased apoA-I and HDL subfractions. The clinical relevance of the increase in homocysteine levels is unknown. [Copyright &y& Elsevier]

ABSTRACT. To determine the effects of hemophilia and human immunodeficiency virus (HIV) infection on the nervous system, the authors examined the relationship of brain magnetic resonance imaging (MRI) findings to immunologic function and neurologic examination findings. Baseline examinations included physical and neurologic examination, immunologic and virologic testing, and MRI of the brain. On neurologic examination, muscle atrophy was considered to be related to hemophilia if adjacent joints had arthropathy due to bleeding. Muscle atrophy was considered non-hemophilia-related if unrelated to arthropathy or if muscle atrophy was diffuse. Subjects were boys aged 6 to 19 years, enrolled in a multicenter study of the effects of hemophilia and HIV infection on growth and development, all with congenital coagulopathies requiring factor infusions. Three hundred ten subjects had complete data including neurologic examination, T-cell subsets, HIV antibodies, and MRI. Subjects with HIV infection whose CD4[sup +] counts were <200/micro L were compared with subjects with HIV infection and CD4[sup +] counts is greater than or equal to 200/micro L and with HIV-negative subjects, all of whom had CD4[sup +] counts >200/micro L. MRI studies were normal in 230. Abnormal MRI studies were more frequent in HIV-positive subjects with CD4[sup +] counts <200 (29.4% abnormal compared with 17% in HIV-positive subjects with CD4[sup +] counts is greater than or equal to 200 and 15.3% in HIV-negative subjects). Diffuse atrophy accounted for most of the excess abnormalities in HIV-positive subjects with CD4[sup +] counts <200 (77.3% of abnormal scans). Diffuse atrophy on MRI was associated with decreased... [ABSTRACT FROM AUTHOR]

Background-The balance between benefit (ischemia protection) and risk (bleeding) is a key consideration in choosing the intensity of antiplatelet therapy for patients with acute coronary syndromes. The goals of this analysis were to identify baseline characteristics that independently predict bleeding and to determine how bleeding events impact the subsequent mortality in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-T1MI 38). Methods and Results-Multivariable Cox regression analyses adjusted for treatment, baseline, and procedural variables were used to determine the predictors for serious (TIMI major or minor) bleeding. To analyze the hazard ratio and time dependency of bleeding on mortality, we used iterative day-to-day landmark analyses after the bleed. From the 13 420 patients with acute coronary syndromes included in this analysis, 534 (4.0%) experienced a serious bleeding event. Variables with the highest strength of association with risk of serious bleeding were female sex, use of a glycoprotein Jib/lila inhibitor, duration of intervention, age, assignment to prasugrel, regional characteristics, admission diagnosis of ST-elevation myocardial infarction, femoral access for angiography, creatinine clearance, hypercholesterolemia, and arterial hypertension. Serious bleeding was associated with a significantly increased adjusted hazard ratio of 5.84 (95% confidence interval 4.11 to 8.29) for mortality. However, the hazard ratio did not differ statistically from baseline risk by 40 days after the bleeding event. Conclusions-The major predictors of serious bleeding were a combination of patient and procedural characteristics and antiplatelet therapies. Although serious bleeding was strongly associated with mortality within the first month of the bleeding event, this association was not significant beyond 40 days. [ABSTRACT FROM AUTHOR]

The article details a study which examined the determinants of four-year cardiovascular event rates in outpatients with or at risk of atherothrombosis. Patients considered for the study were those diagnosed with coronary artery disease, cerebrovascular disease or peripheral arterial disease and those with multiple risk factors for atherothrombosis. Of the total 45,227 study participants, 2,315 died of cardiovascular reasons, 1,228 developed myocardial infarction and 1,898 experienced stroke. Study authors concluded that clinical descriptors are relevant in identifying patients at high risk of cardiovascular events.

Background: Otamixaban is an intravenous direct factor Xa inhibitor. We aimed to assess its efficacy and safety in non-ST-elevation acute coronary syndromes and to identify the optimum dose range for further assessment in a phase 3 study.Methods: In this double-blind, phase 2 trial undertaken in 196 sites in 36 countries, 3241 patients with non-ST-elevation acute coronary syndromes were randomly assigned via a central, telephone-based interactive voice response system to one of five doses of otamixaban (0.08 mg/kg bolus followed by infusions of 0.035 [n=125], 0.070 [676], 0.105 [662], 0.140 [658], or 0.175 [671] mg/kg/h) or to a control of unfractionated heparin (60 IU/kg intravenous bolus followed by an infusion of 12 IU/kg/h) plus eptifibatide (180 microg/kg intravenous bolus followed by an infusion of 1.0-2.0 microg/kg/min [n=449]). Both investigators and patients were unaware of treatment allocation. Enrolment into the lowest dose group was stopped early at the recommendation of the Data Monitoring Committee. The primary efficacy endpoint was a composite of death, myocardial infarction, urgent revascularisation, or bailout glycoprotein IIb/IIIa inhibitor use up to 7 days. The primary safety endpoint was TIMI major or minor bleeding not related to coronary-artery bypass grafting. Efficacy analyses were by intention to treat; safety analyses were in treated patients. This study is registered with ClinicalTrials.gov, number NCT00317395.Findings: Rates of the primary efficacy endpoint in the five otamixaban doses were 7.2% (nine of 125) with 0.035 mg/kg/h, 4.6% (31/676) with 0.070 mg/kg/h, 3.8% (25/662) with 0.105 mg/kg/h, 3.6% (24/658) with 0.140 mg/kg/h, and 4.3% (29/671) with 0.175 mg/kg/h (p=0.34 for trend). In the control group, the rate was 6.2% (28/449), yielding relative risks for the five otamixaban doses of 1.16 (95% CI 0.56-2.38), 0.74 (0.45-1.21), 0.61 (0.36-1.02), 0.58 (0.34-1.00), and 0.69 (0.42-1.15), respectively. Rates of the primary safety endpoint in the five otamixaban doses were 1.6% (two of 122), 1.6% (11/669), 3.1% (20/651), 3.4% (22/651), and 5.4% (36/664), respectively (p=0.0001 for trend); the rate in the control group was 2.7% (12/448).Interpretation: In patients with non-ST-elevation acute coronary syndromes, otamixaban infusions of 0.100-0.140 mg/kg/h might reduce ischaemic events and have a safety profile similar to unfractionated heparin plus eptifibatide. Further testing in a phase 3 trial is warranted.Funding: Sanofi-Aventis. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the efficacy and safety of otamixaban in patients with non-ST-elevation acute coronary syndrome. The study included 3,241 patients diagnosed with non-ST-elevation acute coronary syndrome, who were randomly assigned to either receive otamixaban or unfractionated heparin plus eptifibatide. Myocardial infarction, death, urgent revascularization and bailout glycoprotein were measured in each patient. Study authors concluded that otamixaban infusions might reduce ischemic events in patients with non-ST-elevation acute coronary syndrome. They also noted that otamixaban has the same safety profile with heparin plus eptifibatide.

While there has been strong evidence for the ability of neuropsychological performance at resolution of posttraumatic amnesia to predict later productivity, there has been less conclusive evidence for the relationship of neuropsychological test scores to concurrent productivity status. The purpose of the current study was to evaluate the relationship of neuropsychological test performance at 1 year post-injury to productivity assessed at the same time point. Participants were 518 persons with medically documented TBI who were enrolled in the TBI Model Systems Research and Demonstration Project. Stepwise logistic regression was utilized to determine the contributions of neuropsychological test scores to productivity after accounting for demographic characteristics, injury severity, and pre-injury productivity. Missing neuropsychological test scores were accounted for in the model. Variables that remained in the model and accounted for a significant proportion of the variance included age, duration of impaired consciousness, pre-injury productivity, and scores on measures of GOAT, Logical Memory II, and Trail Making Test, part B. The results indicate that neuropsychological test performance provides important information regarding the ability of persons with injury to return to productive activities. The results also indicate that inability to complete neuropsychological tests at 1 year post-injury is associated with non-productive activity. [ABSTRACT FROM AUTHOR]

To investigate the frequency and risk factors of major depressive disorder(MDD) after mild to moderate traumatic brain injury (TBI), 69 TBI and 52 generaltrauma (GT) patients were prospectively recruited and studied at 3-monthspostinjury. There was a nonsignificant difference in the proportion of MDDpatients in the TBI and GT groups. Therefore, a composite MDD group (TBI andGT patients) was compared to patients who were nondepressed. Female genderwas related to MDD, but no other risk factors were identified. MDD was associatedwith disability (Glasgow Outcome Scale, Community Integration Questionnaire)and cognitive impairment. MDD was comorbid with posttraumatic stress disorder.Implications for postacute management of mild to moderate TBI are discussed. [ABSTRACT FROM AUTHOR]

Previous studies of postconcussional disorder (PCD) have utilized a dimensionalapproach (i.e., number and/or severity ratings of symptoms) to study postconcussionalsymptoms. This study used a syndromal approach (modified form of the DSM-IVcriteria) for investigating risk factors for developing PCD, 3-months postinjury.The head trauma requirement was waived in order to determine specificity ofsymptoms to traumatic brain injury. Preliminary results from this ongoingstudy indicated significant risk factors including female gender, poor socialsupport, and elevated self-reported depressive symptoms at 1-month postinjury.Comorbidities included concurrent diagnosis of major depressive disorder and/orposttraumatic stress disorder. Hispanics were significantly less likely todevelop PCD than other racial/ethnic groups. PCD resulted more frequentlyfrom motor vehicle accidents and assaults. Screening tests for PCD risk factors/comorbiditiesperformed shortly after injury (i.e., during routine follow-up clinic appointments)coupled with appropriate referrals for psychoeducational interventions andsupport groups may avoid prolonged loss of productivity and poor perceivedquality of life in these patients. [ABSTRACT FROM AUTHOR]