Conclusion:There is an increased risk of venous thrombosis in patients with cancer. The risk is greatest in the first few months after diagnosis and in the presence of distal metastasis. Patients also with Factor V Leiden and prothrombin 20210A mutations have even higher risk.Summary: This is a report of the Multiple Environmental and Genetic Assessment (MEGA) of Risk Factors for Venous Thrombosis Study. MEGA is a case controlled population based study evaluating risk of venous thrombosis with various risk factors. This report details risk of venous thrombosis with cancer and the joint effects of cancer and selected genetic mutations predisposing to venous thrombosis. Patients were identified at 6 anticoagulation clinics in the Netherlands between March 1, 1999, and May 31, 2002. Patients included were those 18-70 years of age with a first time diagnosis of pulmonary embolism or lower extremity deep venous thrombosis. Control patients, (partners of the patients with venous thrombosis) were also utilized in the study. Both patients and controls received a questionnaire to evaluate acquired risk factors for venous thrombosis. Once anticoagulation therapy had been discontinued for three months, patients and controls were interviewed and blood taken for analysis of Factor V Leiden and prothrombin 20210A mutations.In patients with malignancy, the overall risk of venous thrombosis was increased 7 times (odds ratio [OR], 6.7; 95% CI, 5.2-8.6). The highest risk was present in patients with hematologic malignancies (OR 28.0, 95% CI, 4.0-199.7). Risk was also substantially increased in patient with gastrointestinal cancers (OR 18.9; 95% CI, 4.6-77.8), and patients with pulmonary malignancies (OR 24.8; 95% CI, 3.4-181.1). Risk was highest in the first several months following malignancy diagnosis (adjusted OR 53.5; 95% CI, 8.6-334.3). In patients with cancer the presence of distal metastatic disease further increased the risk of venous thromboembolism (VTE) compared to patients without metastatic disease (adjusted OR, 19.8; 95% CI, 2.6-149.1). The combination of cancer and Factor V Leiden mutation increased the risk of VTE 12 times compared to patients with Factor V Leiden mutation and no diagnosed malignancy. Results were similar for patients with and without cancer with respect to the prothrombin 20210A mutation.Comment: The data raises the question as to whether patients with cancer should be screened for Factor V Leiden and prothrombin 20210A mutation and treated with prophylactic anticoagulation therapy if a mutation is present. Also the question arises whether prophylactic anticoagulation is indicated in patients with malignancies associated with an especially high risk for VTE. The cost effectiveness of such strategies and the ultimate ability of such strategies to prolong life or improve quality of life are clear in patients with cancer who are undergoing surgery or active chemotherapy (ACTA Haematol 2001;106:73-80). There is currently no data to suggest routine prophylaxis for VTE in all cancer patients would be...

Clinical trials demonstrated intermittent preventive treatment in pregnancy with mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected higher risk of mother-to-child transmission (MTCT) of HIV among HIV-positive women receiving MQ has also been observed. To determine if interactions between antiretroviral drugs (ARVs) and MQ could contribute to the increased MTCT observed in women receiving MQ, we performed a retrospective cross-sectional analysis of ARV plasma concentrations in peripheral blood (maternal plasma) and cord blood (cord plasma) collected at delivery from 186 mothers participating in a randomized clinical trial of MQ (n = 102) compared with placebo (n = 84) in Kenya. Plasma zidovudine (AZT), lamivudine (3TC), and nevirapine (NVP) concentrations were measured by high-performance liquid chromatography–tandem mass spectrometry. Although only 4% (7/186) reported not using these ARVs, AZT, 3TC, and NVP were all below the limit of detection in 44% of maternal plasma and 42% of cord plasma samples, and proportions were similar between the two study arms. Median concentrations of AZT and 3TC were not significantly lower in the MQ arm compared with the placebo arm for maternal plasma and cord plasma (p > .05). However, median NVP concentrations were significantly lower in the MQ study arm compared with the placebo study arm in both maternal plasma (1,597 ng/mL vs. 2,353 ng/mL, Mann–Whitney Rank Sum, p = .023) and cord plasma (2,038 ng/mL vs. 2,434 ng/mL, p = .048). Reduced NVP concentrations in maternal and cord plasma of women receiving MQ suggest MQ may affect NVP metabolism for both mother and infant. These results highlight the need to evaluate potential drug–drug interactions between candidate antimalarials and ARVs for use in pregnant women.

BackgroundThe addition of a pharmacist during the validation, preparation and administration of cytostatics ensures the detection and resolution of drug-related problems.PurposeTo quantify and analyse the pharmacist’s contribution during the validation process, to ensure safety during all the stages of use of cytostatic drugs.Material and methodsA prospective observational study of 4 months. All pharmacist interventions (PIs) related to medication errors (MEs) were recorded, from the prescription to the administration of chemotherapy. All prescriptions associated with chemotherapy, biological treatments and supportive care drugs were considered. The MEs and their severity were classified according to the Updated Classification of Medication Errors, by the Ruiz-Jarabo group 2000. The variables recorded were: potential gravity, if it reached the patient, drugs involved and medical policy.ResultsDuring the study period 38 PIs were recorded (24 drugs involved). PIs were made more often during the prescription process (86.8%), followed by administration (7.9%) and preparation (5.3%). Of these, in 81.6% of cases a cytostatic and/or biological agent was involved, and 18.4% involved a supportive care drug. The severity of PIs was: 18.4% minor, 31.6% moderate, 42.1% severe and 7.9% very severe. They reached the patient in 10.5% of cases. The drugs involved more often were carboplatin (33.3%), aprepitant (20.8%), paclitaxel (16.67%), azacitidine (12.5%), irinotecan, oxaliplatin and vincristine (5.3% each). The main MEs were: omission of medicine needed (26.3%), dose higher than needed (15.8%), omission in transcription (13.2%), dose lower than needed (10.5%), administration error (7.9%) and preparation error (5.3%).ConclusionThe pharmacist’s contribution prevented 89.5% of MEs from reaching the patient. These results reveal the importance of incorporating the pharmacist as an essential part of a multidisciplinary team to contribute to the safety of patients. The pharmacist should have a more active role in the areas of medicines preparation and administration; an appropriate ratio of pharmacists vs. number of validated patients is needed.References and/or acknowledgementsRuiz-Jarabo 2000.No conflict of interest.

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