RESUMEN
Warfarin-dosing algorithms combine clinical factors and dosing history with the current international normalized ratio (INR) to estimate the therapeutic warfarin dose. Unfortunately, these approaches can result in an overdose if the INR is spuriously low. Our goal was to develop an alert mechanism based on prior INRs in addition to the current INR. Using data from the Genetics InFormatics Trial (GIFT) of Warfarin to Prevent DVT, we analyzed warfarin dose estimates for days 3 through 11 that were ≥10 % higher than an average of the previous two dose estimates. We fit a stepwise mixed model to current and prior dose estimates, and subsequently compared the root-mean-square-error (RMSE) in predicting the final therapeutic dose using the GIFT algorithm versus the mixed model. From 861 dosing records (obtain from 556 patients), 646 dosing records (75 %) were randomly selected for the derivation cohort and 215 dosing records (25 %) for the validation cohort. Using one prior dose estimate improved the accuracy of the warfarin dose estimate. Compared to a dose estimate based on current INR (GIFT algorithm), the mixed model reduced the RMSE in the derivation cohort by 0.0015 mg/day (RMSE 0.2079 vs. 0.2094; p = 0.039). In the validation cohort, the RMSE reduction was not significant. A mixed model of dose estimates based on the current and most recent INRs shows potential to improve the safety of warfarin dosing. Clinicians should be cautious about aggressively escalating the warfarin dose after an INR that is lower than expected.
Asunto(s)
Algoritmos , Relación Normalizada Internacional/métodos , Modelos Cardiovasculares , Trombosis de la Vena/prevención & control , Warfarina/administración & dosificación , Warfarina/farmacocinética , Anciano , Femenino , Humanos , Masculino , Trombosis de la Vena/sangre , Warfarina/efectos adversosRESUMEN
The risk of venous thromboembolism (VTE) is higher after the total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The genetics-informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT) is a 2 × 2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) is a lower target international normalized ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR ≥ 4, and death.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Oxigenasas de Función Mixta/genética , Trombosis de la Vena/tratamiento farmacológico , Warfarina , Citocromo P-450 CYP2C9 , Relación Dosis-Respuesta a Droga , Genotipo , Humanos , Periodo Posoperatorio , Trombosis de la Vena/genética , Trombosis de la Vena/patología , Trombosis de la Vena/cirugía , Vitamina K Epóxido Reductasas , Warfarina/administración & dosificación , Warfarina/efectos adversos , Warfarina/farmacocinéticaRESUMEN
OBJECTIVE: To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. DESIGN: Meta-analysis of individual patient data. DATA SOURCES: Authors of 13 studies (n = 10,002) provided their datasets, and these individual patient data were merged into one dataset. ELIGIBILITY CRITERIA: Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. MAIN OUTCOME MEASURES: Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. RESULTS: Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤ 1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. CONCLUSION: Combined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.
Asunto(s)
Atención Primaria de Salud/métodos , Trombosis de la Vena/diagnóstico , Diagnóstico Diferencial , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Anamnesis , Valor Predictivo de las Pruebas , Probabilidad , Factores de Riesgo , Trombosis de la Vena/sangreRESUMEN
OBJECTIVE: To determine the level of intervention provided by primary care physicians to individuals who smoke. SETTING: 45 primary care clinics throughout the upper Midwest. PATIENTS: 6,086 men and women (M:F = 1:2), ages 50 to 68, who sought medical care at any one of the 45 primary care clinics and completed two questionnaires regarding preventive medical services received during the previous 3 years (1990-1993). RESULTS: Of patients who smoke, 92% reported that their clinician had asked about their smoking status. Additionally, 86% reported being informed at their clinic of the dangers of tobacco use. A smaller percentage of individuals (60.1%) reported being explicitly advised on how to quit, and fewer still (27.2%) reported being referred to a stop smoking program. CONCLUSIONS: While most clinicians inquire about their patients' smoking status and recommend they quit, there currently exists a deficiency in the translation of these recommendations into concise, explicit instructions on how to quit. By increasing the frequency of clinicians giving specific advice about how to quit, the overall success rate of the public health campaign against tobacco use will be greatly enhanced.