ABSTRACT
Essentials Clinical significance of cancer-related isolated distal deep vein thrombosis (iDDVT) is unknown. We studied patients with iDDVT, with and without cancer, and proximal DVT with cancer. Cancer-related iDDVT patients have a much poorer prognosis than iDDVT patients without cancer. Cancer-related iDDVT patients have a similar prognosis to cancer-related proximal DVT patients. SUMMARY: Background Isolated distal deep vein thrombosis (iDDVT) (infra-popliteal DVT without pulmonary embolism [PE]) is a frequent event and, in the absence of cancer, is usually considered to be a minor form of venous thromboembolism (VTE). However, the clinical significance of cancer-related iDDVT is unknown. Methods Using data from the observational, prospective multicenter OPTIMEV cohort, we compared, at 3 years, the incidences of death, VTE recurrence and major bleeding in patients with cancer-related iDDVT with those in cancer patients with isolated proximal DVT (matched 1:1 on age and sex) and patients with iDDVT without cancer (matched 1:2 on age and sex). Results As compared with patients with cancer-related isolated proximal DVT (n = 92), those with cancer-related iDDVT (n = 92) had a similar risk of death (40.8% per patient-year (PY) vs. 38.3% per PY; aHR = 1.0, 95% CI[0.7-1.4]) and of major bleeding (3.8% per PY vs. 3.6% per PY, aCHR = 0.9 [0.3-3.2]) and a higher risk of VTE recurrence (5.4% per PY vs. 11.5% per PY; aCHR = 1.8 [0.7-4.5]). As compared with patients with iDDVT without cancer (n = 184), those with cancer-related iDDVT had a nine times higher risk of death (3.5% per PY vs. 38.3% per PY; aHR = 9.3 [5.5-15.9]), a higher risk of major bleeding (1.8% per PY vs. 3.6% per PY; aCHR = 2.0 [0.6-6.1]) and a higher risk of VTE recurrence (5.0% per PY vs. 11.5% per PY; aCHR = 2.0 [1.0-3.7]). The results remained similar in the subgroup of patients without history of VTE. Conclusion Patients with cancer-related iDDVT seem to have a prognosis that is similar to that of patients with cancer-related isolated proximal DVT and a dramatically poorer prognosis than patients with iDDVT without cancer. This underlines the high clinical significance of cancer-related iDDVT and the need for additional studies.
Subject(s)
Neoplasms/epidemiology , Popliteal Vein , Venous Thromboembolism/epidemiology , Venous Thrombosis/epidemiology , Aged , Aged, 80 and over , Female , France/epidemiology , Hemorrhage/epidemiology , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasms/blood , Neoplasms/diagnosis , Neoplasms/mortality , Prognosis , Proportional Hazards Models , Prospective Studies , Recurrence , Risk Assessment , Risk Factors , Time Factors , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Venous Thromboembolism/mortality , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/mortalityABSTRACT
Four rates of rifampicin infusion ranging from 3.3 to 15 mg/min in 12 tuberculous patients were studied. Blood samples (n = 10) were drawn during infusion and 8 h later. Urine samples were collected in six fractions during a 24-h period. Rifampicin and desacetylrifampicin were measured by high-pressure liquid chromatography. Results show that the maximum plasma concentrations increase linearly for each dose with the rate of infusion, and that the amounts excreted in the urines are highly dependent on the administered dose. Simulation of plasma concentrations after different dosage regimens shows that a double rate of infusion--20 mg min-1 during 1 h and then 200 mg h-1--allows plasma concentrations to be quickly reached and maintained at a 20 mg L-1 level, far higher than the minimum inhibitory concentrations of most germs.
Subject(s)
Rifampin/analogs & derivatives , Rifampin/metabolism , Tuberculosis, Pulmonary/metabolism , Adult , Aged , Female , Half-Life , Humans , Infusions, Parenteral , Kinetics , Male , Middle Aged , Rifampin/administration & dosageABSTRACT
The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1.72 mg L-1 and 4.09 +/- 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmax value (1.93 +/- 0.53 mg L-1) and t 1/2 beta value (4.65 +/- 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 +/- 0.0036 L h-1) and the amounts of RMP (20.7 +/- 9.9 mg) and DA-RMP (13.3 +/- 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.
