Bone marrow involvement in small cell lung cancer: Prognostic significance and correlation with hematological and biochemical parameters

The more metastatic sites and bone marrow metastasis in small cell lung cancer (SCLC), the worse the prognosis. Diagnosing the bone marrow invasion at the beginning of the therapy is important for determining of the prognosis and planning the treatment. Abnormalities of some blood parameters may help to estimate the extent of bone marrow invasion by cancer cells. In this retrospective review, the changes in routine laboratory tests that may indicate bone marrow invasion, the predictive values of these tests, and the prognostic importance of bone marrow invasion were evaluated in SCLC patients who were being followed up according to a protocol. One hundred and forty‐four patients with SCLC were enrolled in this study. Retrospectively, it was evaluated that 25 (17.4%) of the patients had bone marrow metastasis. According to univariate analysis, there was a significant difference between hemoglobin, white blood cell count, platelet count, lactate dehydrogenase, alkaline phosphatase and uric acid of the patients with and without bone marrow involvement. Among the biochemical parameters, the elevated LDH and AP had the highest sensitivity and specificity as indicators of bone marrow invasion (0.80–0.82 and 0.84–0.78, respectively). The median overall survival of extensive‐stage disease with and without bone marrow metastasis were 4.0 ± 1.0 months (95% CI 2.2–5.7) and 7.0 ± 1.2 months (95% CI 4.7–9.3), respectively (P = 0.03). Bone marrow metastasis was found to be an indicator of a bad prognosis. Bone marrow biopsy, that is an invasive procedure, can be performed on selected patients who have changes of routine laboratory tests suggesting bone marrow invasion.     

Inpatient costs, length of stay, and mortality for cerebrovascular events in community hospitals

BACKGROUND: Accurate estimates of inpatient cost, length of stay (LOS), and mortality are necessary for the development of economic models to estimate the cost-effectiveness of stroke-related treatments. Estimates based on data from academic institutions may not be generalizable to community hospitals. In this study, the authors estimated inpatient costs, LOS, and in-hospital mortality for patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic cerebral infarction (ICI), and TIA who were treated in community hospitals. METHODS: The authors selected patients using International Classification of Diseases-9-Clinical Modification primary diagnosis codes from the HBSI EXPLORE database. They analyzed patient-level data and inpatient costs, derived from detailed utilization data, for all patients admitted to 137 community hospitals in 1998. Multivariate statistical techniques were used to examine patient-, hospital-, and outcome-related factors associated with inpatient costs. RESULTS: Patients with SAH incurred the highest average cost ($23,777, n = 1,124), followed by patients with ICH ($10,241, n = 3,139), ICI ($5,837, n = 18,740), and TIA ($3,350, n = 7,861). Patient subgroups ranked in the same order for average LOS at 11.5 days for SAH, 7.5 days for ICH, 5.9 days for ICI, and 3.4 days for TIA. Almost one third of patients with SAH (29.0%) and ICH (33.1%) died during hospitalization, whereas 7.0% with ICI and 0.2% with TIA died. For each event, as patient age increased, average costs consistently decreased. Also, average costs were higher among patients treated in community teaching hospitals compared to community nonteaching hospitals for each cerebrovascular event (10 to 29%). CONCLUSIONS: Inpatient costs, LOS, and mortality for patients with cerebrovascular disease are dependent on patient and hospital characteristics.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Aminoglycoside serum assays restricted through a pharmacy program.

A pharmacy program designed to reduce the inappropriate use of aminoglycoside serum assays is described, and the results of an evaluation of the program are reported. If the clinical status of the patient for whom an assay is ordered does not correspond to the indications for the test, a pharmacist calculates predicted aminoglycoside serum levels based on renal function and discourages the physician from having the test performed. If the indications for a test are met, the pharmacist checks for potential interactions. He specifies the exact times serum samples are to be collected, and he prepares a pharmacokinetic report for the physician based on the test results. During the 18-month evaluation, 67 tests were ordered for 53 patients. Three tests were not performed based on pharmacist advice. Five tests could not be evaluated. Of the remaining 59 tests, 56 (95% were used appropriately; 54 of the appropriate decisions made (92%) were a result of the physician following the recommendations of the pharmacist. The program appears to prevent problems that occur when aminoglycoside serum assays are not restricted.     

Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers

Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor of CYP3A-mediated metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of cyclosporine and micafungin before and with concomitant administration. The pharmacokinetics of single-dose oral cyclosporine (5 mg/kg) were estimated on days 1, 9, and 15 (n = 27). Subjects received micafungin (100 mg/d over 1 hour) on days 7, 9, and 11 through 15. Micafungin pharmacokinetics were estimated on days 7, 9, and 15. Mean apparent oral cyclosporine clearances were estimated to be 645+/-236 mL/h/kg, 546+/-101 mL/h/kg (P = .01), and 540+/-104 mL/h/kg (P = .02) for days 1, 9, and 15, respectively. Micafungin appears to be a mild inhibitor of cyclosporine metabolism.     

Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum

Preexisting hypertension complicates 5% of all pregnancies. The objective of this study was to evaluate steady-state atenolol pharmacokinetics and pharmacodynamics (n = 17) during the second trimester (2nd T), third trimester (3rd T), and 3 months postpartum. Pregnancy as compared to 3 months postpartum (nonpregnant control) resulted in significant (P < .05) changes, including the following: 42% (2nd T) and 50% (3rd T) increase in creatinine clearance, 38% (2nd T) and 36% (3rd T) increase in atenolol renal clearance, 12% (2nd T) and 11% (3rd T) decrease in atenolol half-life, 20% (2nd T) and 28% (3rd T) increase in cardiac output, 15% (2nd T) and 23% (3rd T) increase in resting heart rate, and 22% (2nd T) and 21% (3rd T) decrease in total peripheral resistance in subjects on steady-state oral atenolol for treatment of hypertension in pregnancy. In conclusion, the renal clearance of atenolol along with creatinine clearance is increased during pregnancy. However, this does not translate into an increase in apparent oral clearance of atenolol, possibly related to the high variability in bioavailability. Atenolol administration did not appear to change the pattern of the increase in cardiac output and the decrease in total peripheral resistance, which normally occurs during pregnancy.