The effect of the CYP2C19*2 heterozygote genotype on the pharmacokinetics of nelfinavir.
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Aryl Hydrocarbon Hydroxylases↗
Biomedical subjects
Mark Becker
Publications and source records attributed to Mark Becker.
Quality improvement implementation and hospital performance on quality indicators.
OBJECTIVE: To examine the association between the scope of quality improvement (QI) implementation in hospitals and hospital performance on selected indicators of clinical quality. DATA SOURCES: Secondary data from 1997 mailed survey of hospital QI practices, Medicare Inpatient Database, American Hospital Association's Annual Survey of Hospitals, the Bureau of Health Professions' Area Resource File, and two proprietary data sets compiled by Solucient Inc. containing data on managed care penetration and hospital financial performance. STUDY DESIGN: Cross-sectional study of 1,784 community hospitals to assess relationship between QI implementation approach and six hospital-level quality indicators. DATA COLLECTION/ABSTRACTION METHODS: Two-stage instrumental variables estimation in which predicted values (instruments) of four QI scope variables and control (exogenous) variables used to estimate hospital-level quality indicators. PRINCIPAL FINDINGS: Involvement by multiple hospital units in QI effort is associated with worse values on hospital-level quality indicators. Percentage of hospital staff and percentage of senior managers participating in formally organized QI teams are associated with better values on quality indicators. Percentage of physicians participating in QI teams is not associated with better values on the hospital-level quality indicators studied. CONCLUSIONS: Results supported the proposition that the scope of QI implementation in hospitals is significantly associated with hospital-level quality indicators. However, the direction of the association varied across different measures of QI implementation scope.
Cross-Sectional Studies↗
Pharmacokinetics of nelfinavir in subjects with hepatic impairment.
HIV-seronegative subjects with hepatic impairment (6 mild, 6 moderate) and 12 matched healthy controls received nelfinavir 1250 mg every 12 hours with food for 2 weeks. Mild impairment did not significantly change nelfinavir or major metabolite (M8) steady-state exposures compared with controls. In subjects with moderate impairment, steady-state area under the plasma concentration time-curve over the dosing interval and maximum observed plasma concentrations were 62% and 22% higher for nelfinavir than for controls, and for M8 were 46% and 35% of control values. With increasing degree of impairment, no trend toward increase in unbound nelfinavir was observed, but there was an increase in unbound M8 levels. Nelfinavir was safe and well tolerated. One subject with moderate impairment was discontinued because of transient leucopenia. Observed changes are unlikely to affect nelfinavir efficacy or markedly influence safety. Dose reduction of nelfinavir does not appear necessary for subjects with mild/moderate impairment. Further long-term evaluations of nelfinavir pharmacokinetics and safety in HIV-seropositive subjects with hepatic impairment may be useful.
Adult↗
Quality improvement implementation and hospital performance on patient safety indicators.
This study examines the association between scope of Quality Improvement (QI) implementation in hospitals and hospital performance on patient safety indicators. Secondary data sources included a 1997 survey of hospital QI practices, Medicare Inpatient Database, American Hospital Association's Annual Survey of Hospitals, the Bureau of Health Professions' Area Resource File, and two proprietary data sets. Using a sample of 1,784 community hospitals, the study employed two-stage instrumental variables estimation in which predicted values of four QI scope variables and control variables were used to estimate four patient safety indicators. Involvement by multiple hospital units in the QI effort is associated with worse values on all four patient safety indicators. Percentages of hospital staff and of senior managers participating in QI teams exhibited no statistically significant association with any patient safety indicator. Percentage of physicians participating in QI teams is associated with better values on two patient safety indicators.
Health Care Surveys↗
The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in HIV-infected patients.
BACKGROUND: The nucleotide analogue, tenofovir, has been shown to lower plasma atazanavir levels in pharmacokinetic trials, an interaction that may be partly reversed by the addition of ritonavir, whereas plasma tenofovir levels are themselves raised when the drug is combined with lopinavir/ritonavir. OBJECTIVE: To investigate the effect of tenofovir coadministration on the steady-state pharmacokinetics of nelfinavir in HIV-infected patients. METHODS: Eighteen patients received nelfinavir 1250 mg twice daily plus prescribed nucleoside reverse transcriptase inhibitors for at least 14 days, with pharmacokinetic measurements performed on day 15. Treatment with nelfinavir was continued for another 7 days with the addition of 300 mg tenofovir once daily. Pharmacokinetic measurements were repeated on day 22. Plasma samples were analysed by liquid chromatography-tandem mass spectrometry for nelfinavir, its primary metabolite, M8, and tenofovir. The parameters AUC0-12, C0, Cmax and Tmax were compared for nelfinavir with and without tenofovir by calculating geometric mean ratios (GMRs) of the pharmacokinetic parameters with associated 95% confidence intervals (95% CIs). Safety was assessed throughout the study. RESULTS: The addition of tenofovir to the nelfinavir-based regimen had no effect on the pharmacokinetics of nelfinavir. The GMR of the nelfinavir AUC0-12 values was 0.97 (95% CI: 0.80-1.17). There was a slight decrease in M8 metabolite (AUC0-12 ratio, 0.87; 95% CI: 0.68-1.11) but this was not significant. No serious adverse events occurred through the study period. CONCLUSION: Nelfinavir does not require dose adjustment when coadministered with tenofovir and appears to be well-tolerated by HIV-infected patients.
Adenine↗
The effects of the World Trade Center event on birth outcomes among term deliveries at three lower Manhattan hospitals.
The effects of prenatal exposure to pollutants from the World Trade Center (WTC) disaster on fetal growth and subsequent health and development of exposed children remain a source of concern. We assessed the impact of gestational timing of the disaster and distance from the WTC in the 4 weeks after 11 September on the birth outcomes of 300 nonsmoking women who were pregnant at the time of the event. They were recruited at delivery between December 2001 and June 2002 from three hospitals close to the WTC site. Residential and work addresses of all participants for each of the 4 weeks after 11 September 2001 were geocoded for classification by place and timing of exposure. Average daily hours spent at each location were based on the women's reports for each week. Biomedical pregnancy and delivery data extracted from the medical records of each mother and newborn included medical complications, type of delivery, length of gestation, birth weight, birth length, and head circumference. Term infants born to women who were pregnant on 11 September 2001 and who were living within a 2-mile radius of the WTC during the month after the event showed significant decrements in term birth weight (-149 g) and birth length (-0.82 cm), compared with infants born to the other pregnant women studied, after controlling for sociodemographic and biomedical risk factors. The decrements remained significant with adjustment for gestational duration (-122 g and -0.74 cm, respectively). Women in the first trimester of pregnancy at the time of the WTC event delivered infants with significantly shorter gestation (-3.6 days) and a smaller head circumference (-0.48 cm), compared with women at later stages of pregnancy, regardless of the distance of their residence or work sites from the WTC. The observed adverse effects suggest an impact of pollutants and/or stress related to the WTC disaster and have implications for the health and development of exposed children.
Adolescent↗
Effects of nelfinavir and its M8 metabolite on lymphocyte P-glycoprotein activity during antiretroviral therapy.
The efflux pump P-glycoprotein decreases drug penetration into cells and tissues. To determine whether nelfinavir or its metabolites inhibit P-glycoprotein in lymphocytes from a healthy volunteer, whole blood cells from human immunodeficiency virus-negative donors were incubated either in human plasma to which nelfinavir or its M8 metabolite were added ex vivo or in plasma from human immunodeficiency virus-positive patients receiving nelfinavir. The 50% P-glycoprotein inhibitory concentrations of purified nelfinavir and M8 were 10.9 micromol/L and 29.5 micromol/L, respectively, for CD4(+) T cells and 19.3 micromol/L and >48 micromol/L, respectively, for CD8(+) T cells. Significant inhibitory activity was present in plasma from 27 of 46 patients (59%) receiving nelfinavir. Plasma nelfinavir concentrations correlated with percent inhibition on CD4(+) (rho = 0.85, P <.0001) and CD8(+) (rho = 0.83, P <.0001) T cells. The M8 concentrations correlated weakly with both inhibition and nelfinavir concentrations. On the basis of our findings in lymphocytes from a healthy volunteer exposed to plasma from human immunodeficiency virus-positive patients, we believe it is likely that CD4(+) and CD8(+) lymphocytes in patients receiving nelfinavir as therapy for human immunodeficiency virus may have P-glycoprotein inhibited by plasma concentrations of nelfinavir.
ATP Binding Cassette Transporter, Subfamily B, Mem↗