Residency spiral concussion curriculum design.

BACKGROUND: Resident-focused concussion curricula that measure learner behaviours are currently unavailable. We sought to fill this gap by developing and iteratively implementing a Spiral Integrated Concussion Curriculum (SICC). APPROACH: Programme elements of the concussion curriculum include academic half-days (AHDs) and three half-day clinics for first- and second-year family medicine residents. Our SICC utilises social cognitive learning principles, the constructivism paradigm and utilisation-focused evaluation. EVALUATION: A mixed-method evaluation with a pre-/post-test design and interviews was utilised. Surveys and knowledge tests were used to measure knowledge and confidence pre-AHD and 6 months post-AHD. Interviews at 6 months explored programme perception and behaviour change. Of the 141 programme attendees, 114 (80%) participated in the pre-intervention knowledge test and 33 completed the pre- and post-AHD test. Immediate pre-/post-testing demonstrated statistically significant improvement in knowledge (p = 0.042). At 6 months post-AHD, residents in Cycle 1 (n = 5) had a knowledge decrease of 3.33% (p > 0.05). Residents in Cycle 2 (n = 7) had a knowledge increase of 11.6% (p > 0.05). Both cycles of residents had an increase in confidence (Cycle 1: 65.0% [p = 0.025]; Cycle 2: 62.8% [p = 0.0014]). Residents (5 out of 6) reported positive behavioural changes at 6 months. Valued programme elements included concussion diagnosis and management, the self-study guide resource and the organised structure. IMPLICATIONS: The SICC enriched these residents' learning and fostered sustained knowledge improvement and behavioural change at 6 months post-intervention. This approach may provide a workable design for future competency-based curriculum development.

Time-to-event modeling for achieving a stable warfarin dose using genetic and non-genetic covariates.

BACKGROUND: Time-to-event modeling is gaining importance in drug dosage determination, particularly using pharmacometrics approaches. OBJECTIVES: To evaluate the various time-to-event models for estimating the time to achieve a stable warfarin dose in the Bahraini population. MATERIAL AND METHODS: A cross-sectional study evaluating the non-genetic and genetic covariates (single nucleotide polymorphisms (SNPs) in CYP2C9, VKORC1 and CYP4F2 genotypes) was conducted in patients receiving warfarin for at least 6 months. Time to achieving a stable dose of warfarin was defined as the duration (in days) from the day of initiating warfarin until 2 consecutive prothrombin time-international normalized ratio (PT-INR) values were observed in the therapeutic range with a gap of at least 7 days. Exponential, Gompertz, log-logistics, and Weibull models were tested, and the model with the lowest objective function value (OFV) was chosen. The covariate selection was carried out using the Wald test and OFV. A hazard ratio (HR) with a 95% confidence interval (95% CI) was estimated. RESULTS: A total of 218 participants were included in the study. The Weibull model was observed to have the lowest OFV (1989.82). The expected time to reach a stable dose in the population was 21.35 days. The CYP2C9 genotypes were identified as the only significant covariate. The HR (95% CI) for achieving a stable warfarin dose within 6 months of initiation for individuals with CYP2C9 *1/*2 was 0.2 (0.09, 0.3), 0.2 (0.1, 0.5) for CYP2C9 *1/*3, 0.14 (0.04, 0.6) for CYP2C9 *2/*2, 0.2 (0.03, 0.9) for CYP2C9 *2/*3, and 0.8 (0.45, 0.9) for those with the C/T genotype for CYP4F2. CONCLUSION: We estimated the population time-to-event parameters for achieving a stable warfarin dose in our population and observed CYP2C9 genotypes to be the main predictor covariate followed by CYP4F2. The influence of these SNPs needs to be validated in a prospective study and an algorithm to predict a stable warfarin dose and the time to achieve it needs to be developed.

Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy.

PURPOSE: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death. EXPERIMENTAL DESIGN: Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter. RESULTS: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy. CONCLUSIONS: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.

Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.