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Biomedical subjects

B A Craig

Publications and source records attributed to B A Craig.

11 recordsLinked to original sources
PubMed2000

Model selection for quantitative trait locus analysis in polyploids.

Over the years, substantial gains have been made in locating regions of agricultural genomes associated with characteristics, diseases, and agroeconomic traits. These gains have relied heavily on the ability to statistically estimate the association between DNA markers and regions of a genome (quantitative trait loci or QTL) related to a particular trait. The majority of these advances have focused on diploid species, even though many important agricultural crops are, in fact, polyploid. The purpose of our work is to initiate an algorithmic approach for model selection and QTL detection in polyploid species. This approach involves the construction of all possible chromosomal configurations (models) that may result in a gamete, model reduction based on estimation of marker dosage from progeny data, and lastly model selection. While simplified for initial explanation, our approach has demonstrated itself to be extendible to many breeding schemes and less restricted settings.

Agriculture↗
PubMed2000

Modeling approach to diameter breakpoint determination.

In determining zone diameter breakpoints, the error-rate bounded method focuses directly on the observed discrepancy percentages (very major, major, and minor). These percentages, however, are quite variable due to the number of isolates investigated, the drug-specific relationship between MIC and zone diameter, the location of the isolates relative to the MIC intermediate zone, and the inherent variability of each test. To overcome potential sampling problems, a hierarchical model is proposed which explicitly accounts for each of these factors and probabilities from this model are used to determine diameter breakpoints. A simulation study is performed to demonstrate the improved consistency of this model-based procedure. Application to three published scatterplots demonstrate its interpretability advantages.

Bayes Theorem↗
PubMed1999

Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. Swiss HIV Cohort Study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has become the most important strategy for treating HIV infection in developed countries; however, access to HAART might vary under different funding policies. The Swiss health care system provides unrestricted access to HAART for all patients who need these newer combination therapies. This study investigated the impact of this funding policy on the society and health care system. METHODS: A cost-effectiveness analysis with natural history data and productivity estimates was based on the Swiss HIV Cohort Study. A random sample of patient charts was used to estimate health care costs. In addition to a base-case scenario, a pessimistic and an optimistic scenario of natural disease history was developed. Costs were expressed in 1997 Swiss francs (100 CHF correspond to about US$67) and effects as projected years of life gained. RESULTS: In the analysis limited to health care costs, on the basis of projected survival in each scenario, the cost-effectiveness ratio was 33,000 CHF (base case), 14,000 CHF (optimistic), and 45,000 CHF (pessimistic) per year of life gained. When changes in productivity were included, cost savings occurred in the base-case and optimistic scenarios. The cost-effectiveness ratio was 11,000 CHF per year of life gained in the pessimistic scenario. CONCLUSIONS: HAART increases expected survival and health care costs. However, when productivity gains are included, society will probably save costs or pay a low price for substantial health benefits. The study provides strong arguments, from a societal perspective, to continue the current policy of providing unrestricted access to HAART in Switzerland. The presented results also suggest that this policy could be of interest for other developed countries. Decision makers in developed countries where access to HAART is limited should re-evaluate their policy for the benefit of the society at large.

Anti-HIV Agents↗
PubMed1999

A Bayesian approach to modelling the natural history of a chronic condition from observations with intervention.

To assess the costs and benefits of screening and treatment strategies, it is important to know what would have happened had there been no intervention. In today's ethical climate, however, it is almost impossible to observe this directly and therefore must be inferred from observations with intervention. In this paper, we illustrate a Bayesian approach to this situation when the observations are at separated and unequally spaced time points and the time of intervention is interval censored. We develop a discrete-time Markov model which combines a non-homogeneous Markov chain, used to model the natural progression, with mechanisms that describe the possibility of both treatment intervention and death. We apply this approach to a subpopulation of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based cohort study to investigate prevalence, incidence, and progression of diabetic retinopathy. In addition, posterior predictive distributions are discussed as a prognostic tool to assist researchers in evaluating costs and benefits of treatment protocols. While we focus this approach on diabetic retinopathy cohort data, we believe this methodology can have wide application.

Age of Onset↗
PubMed1999

Estimating AIDS-free survival in a severely immunosuppressed asymptomatic HIV-infected population in the era of antiretroviral triple combination therapy. Swiss HIV Cohort Study.

BACKGROUND: Antiretroviral triple combination therapies have been evaluated in randomized controlled trials and cohort studies. Little is known about their impact on asymptomatic, severely immunosuppressed, HIV-infected individuals in a real world population. OBJECTIVES: To describe disease progression in a broad asymptomatic population of HIV-infected individuals with a CD4 count <100 cells/mm3 before and after the introduction of combination triple therapy. DESIGN: Six-month homogenous Markov chain consisting of four recurrent AIDS-free states and one absorbing AIDS state: (1) CD4 count > or =100 cells/mm3, (2) CD4 count 75 to 99 cells/mm3, (3) CD4 count 50 to 74 cells/mm3, (4) CD4 count 0 to 49 cells/mm3, and AIDS. SETTING: Swiss HIV Cohort Study database. PATIENTS: A total of 1027 patients contributed to 2634 pairs of 6-month observations from 1993 to 1995, and 681 patients contributed to 2077 pairs of 6-month observations from 1996 to 1997. MEASUREMENT: AIDS-free survival probabilities and the expected AIDS-free survival time. RESULTS: The expected number of AIDS-free months in a 3-year period was 17 (95% confidence interval [CI], 16-19) for patients starting in state 4 prior to 1996 versus 26 months (95% CI, 24-28) for patients starting in state 4 after 1996. For these two time periods, the corresponding expected numbers of AIDS-free months were 21 (95% CI, 20-22) versus 30 (95% CI, 28-32) for state 3 and 23 (95% CI, 21-24) versus 33 (95% CI, 32-34) for state 2. CONCLUSION: Expected 3-year AIDS-free survival in severely immunosuppressed individuals with CD4 counts <100 cells/mm3 improved significantly between 1993 to 1995 and 1996 to 1997.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Systematic validation of disease models for pharmacoeconomic evaluations. Swiss HIV Cohort Study.

Pharmacoeconomic evaluations are often based on computer models which simulate the course of disease with and without medical interventions. The purpose of this study is to propose and illustrate a rigorous approach for validating such disease models. For illustrative purposes, we applied this approach to a computer-based model we developed to mimic the history of HIV-infected subjects at the greatest risk for Mycobacterium avium complex (MAC) infection in Switzerland. The drugs included as a prophylactic intervention against MAC infection were azithromycin and clarithromycin. We used a homogenous Markov chain to describe the progression of an HIV-infected patient through six MAC-free states, one MAC state, and death. Probability estimates were extracted from the Swiss HIV Cohort Study database (1993-95) and randomized controlled trials. The model was validated testing for (1) technical validity (2) predictive validity (3) face validity and (4) modelling process validity. Sensitivity analysis and independent model implementation in DATA (PPS) and self-written Fortran 90 code (BAC) assured technical validity. Agreement between modelled and observed MAC incidence confirmed predictive validity. Modelled MAC prophylaxis at different starting conditions affirmed face validity. Published articles by other authors supported modelling process validity. The proposed validation procedure is a useful approach to improve the validity of the model.

AIDS-Related Opportunistic Infections↗
PubMed1999

Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy. The Swiss HIV Cohort Study.

We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers. The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials. The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved. In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months. In patients with AIDS, HAART durability had a major impact on expected survival and costs. Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect. The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved. The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS. In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially. Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1997

Analysis of aerial survey data on Florida manatee using Markov chain Monte Carlo.

We assess population trends of the Atlantic coast population of Florida manatee, Trichechus manatus latirostris, by reanalyzing aerial survey data collected between 1982 and 1992. To do so, we develop an explicit biological model that accounts for the method by which the manatees are counted, the mammals' movement between surveys, and the behavior of the population total over time. Bayesian inference, enabled by Markov chain Monte Carlo, is used to combine the survey data with the biological model. We compute marginal posterior distributions for all model parameters and predictive distributions for future counts. Several conclusions, such as a decreasing population growth rate and low sighting probabilities, are consistent across different prior specifications.

Animals↗
PubMed1992

Comparison of alternative diphasic lactation curve models under bovine somatotropin administration.

The multiphasic logistic function has recently been proposed as a model for lactation curves in dairy cattle. The applicability of several forms of this function was examined under three levels of recombinant bST administration beginning 100 d postpartum. Lactation curve models were fit to mean daily yields for each of the treatment groups and a control group. The traditional diphasic function was unable to model adequately the steep ascent and early peak in daily milk yield occurring immediately after calving in both treatment and control groups. The early portion of the lactation was more appropriately modeled using a diphasic function with a power transformation of time in the first phase, such that this phase became asymmetric. This modified diphasic function also resulted in smaller residuals and less autocorrelation than the triphasic function, which was used as a reference model, when both models were applied to the control group data. The increase in daily milk yield because of bST administration was modeled by the addition of a term consisting of a rising exponential function. Such a model may be useful for examining dosage effects in long-term bST studies in which injections begin in midlactation or later. Time series procedures reduced autocorrelation among residuals in both the control and treatment groups, and such models could be useful for removing autocorrelation in lactation curve applications that involve daily or weekly yield observations.

Animals↗