Biomedical subjects

L Sheiner

Publications and source records attributed to L Sheiner.

7 recordsLinked to original sources

PubMed2000

Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population.

OBJECTIVE: To examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. DESIGN AND SETTING: A cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. PARTICIPANTS: Thirty-four HIV-infected people with a median of 12 months of PI therapy. MAIN OUTCOMES: Adherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. RESULTS: Median adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36-65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). CONCLUSION: A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

Adult↗

PubMed1999

Population modelling in drug development.

In this paper we discuss the vital role that population (hierarchical) modelling can play within the drug development process. Specifically, population pharmacokinetic/pharmacodynamic models can provide reliable predictions of an individualized dose-exposure-response relationship. A predictive model of this kind can be used to simulate and hence design clinical trials, find initial dosage regimens satisfying an optimality criterion on the population distribution of responses, and individualized regimens satisfying such a criterion conditional on individual features, such as sex, age, etc. Throughout we emphasize prediction and advocate mechanistic as opposed to empirical modelling, and argue that the Bayesian approach is particularly natural in this setting.

Bayes Theorem↗

PubMed1998

Demographics and medical care spending: standard and non-standard effects.

"In this paper, [the authors] examine the effects of likely demographic changes on medical spending for the elderly. Standard forecasts highlight the potential for greater life expectancy to increase costs: medical costs generally increase with age, and greater life expectancy means that more of the elderly will be in the older age groups. Two factors work in the other direction, however. First, increases in life expectancy mean that a smaller share of the elderly will be in the last year of life, when medical costs generally are very high.... Second, disability rates among the surviving population have been declining in recent years by 0.5 to 1.5 percent annually.... Thus, changes in disability and mortality should, on net, reduce average medical spending on the elderly. However, these effects are not as large as the projected increase in medical spending stemming from increases in overall medical costs."

Americas↗

PubMed1991

VentPlan: a ventilator-management advisor.

VentPlan assists physicians, nurses, and respiratory therapists in the management of artificial respiration for critically ill patients in the intensive-care unit (ICU). VentPlan interprets clinical observations, monitored data, and arterial-blood-gas analyses to make recommendations for setting the ventilator. The VentPlan interface allows users to examine the physiologic model, to inspect details of the data on which the model is based, and to exercise the model to try out different ventilator settings before they implement a new setting. We also report here a preliminary evaluation of VentPlan's ability to predict the arterial oxygen and carbon-dioxide tensions following adjustments to the ventilator. We conclude that VentPlan's physiologic models are acceptably accurate for predicting the effects of small adjustments of the ventilator.

Critical Care↗

PubMed1988

Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum.

Because of recent resurgence in its consumption, the effects and health consequences of smokeless tobacco are of considerable public health interest. We studied the extent and time course of absorption of nicotine and cardiovascular effects of smokeless tobacco (oral snuff and chewing tobacco) and compared it with smoking cigarettes and chewing nicotine gum in 10 healthy volunteers. Maximum levels of nicotine were similar but, because of prolonged absorption, overall nicotine exposure was twice as large after single exposures to smokeless tobacco compared with cigarette smoking. All tobacco use increased heart rate and blood pressure, with a tendency toward a greater overall cardiovascular effect despite evidence of development of some tolerance to effects of nicotine with use of smokeless tobacco. Relatively low levels of nicotine and lesser cardiovascular responses were observed with use of nicotine gum. Adverse health consequences of smoking that are nicotine related would be expected to present a similar hazard with the use of smokeless tobacco.

Adult↗

PubMed1985

Computer-assisted drug assay interpretation based on Bayesian estimation of individual pharmacokinetics: application to lidocaine.

A microcomputer program for individualized drug level prediction based on Bayesian forecasting is presented. It is written so that the clinician can integrate patient demographics and drug levels to design a new dosage regimen tailored to an individual patient. The program's great flexibility and robustness make it appropriate for realistic clinical settings. A validation with a data set of lidocaine concentrations measured in 18 patients revealed that the program can predict serum lidocaine levels accurately enough to enhance individual patient dosage adjustment within a few hours after a dosage regimen is started.

Bayes Theorem↗

PubMedDate not supplied

Improving drug dosing in hospitalized patients: automated modeling of pharmacokinetics for individualization of drug dosage regimens.

Many clinical useful drugs have a narrow range of blood concentrations which are both safe and efficacious. Inter-individual and intra-individual variations in drug disposition are important factors causing blood concentrations of drug to fall outside of the therapeutic range. Modeling of the pharmacokinetics of the individual offers an effective approach to the problem of variation in drug disposition. Previous approaches for the modeling of individual pharmacokinetics have required either extensive computations or access to computer software and hardware in the clinical environment, and special expertise to interpret the results. This paper describes a prototype computer program, PK Monitor, which can, when connected with an appropriate interface, automatically monitor drug dosing and recommend changes that may be required to obtain blood concentrations in the therapeutic range. The software can also detect the occurrence of change in drug disposition which will lead to concentrations outside of the therapeutic range, identify potentially erroneous blood concentration measurements, and assess the need for further blood concentration measurements. This program will be an integral part of the MENTOR therapeutic monitoring system of programs. PK Monitor awaits a complete evaluation with the rest of the MENTOR system, but preliminary simulations suggest reasonable sensitivity and specificity in monitoring for unexpected data and change.

Drug Administration Schedule↗