Biomedical subjects

Michael A Martin

Publications and source records attributed to Michael A Martin.

8 recordsLinked to original sources

PubMed2025

Patterns of HIV-1 viral load suppression and drug resistance during the dolutegravir transition: a population-based longitudinal study.

BACKGROUND: Data on the population-scale impact of dolutegravir (DTG)-based HIV regimens in sub-Saharan Africa are extremely limited. We used data from a surveillance cohort in southern Uganda to assess viral suppression and antiretroviral (ART) resistance over 10-years alongside DTG scale-up. METHODS: Consenting participants in the population-based Rakai Community Cohort Study between August 2011 and March 2023 aged 15-59 completed questionnaires and provided samples for HIV testing, viral load quantification, and viral deep-sequencing. We collected data on DTG-utilization at HIV care clinics. We estimated the prevalence of HIV suppression (<1,000 copies/mL) and ART resistance using robust Poisson regression. Bayesian logistic regression quantified associations between resistance and individual-level suppression across surveys. FINDINGS: Among 20,383 people living with HIV (PLHIV), suppression increased from 57.1% (95% confidence interval [CI]: 55.4%-58.8%) to 90.3% (95%CI: 89.2%-91.4%) between 2014 and 2022. By 2020 84.4% (95%CI: 83.7%-85.2%) and 64.6% (95%CI: 63.9%-65.3%) of men and women were on DTG regimens. Among treatment-experienced viremic PLHIV, overall resistance decreased from 51.1% (95%CI: 40.7%-64.1%, 2014) to 27.9% (95%CI: 21.3%-36.5%, 2022). Only two participants harbored intermediate/high-level DTG resistance, attributable to inQ148R, inE138K, and inG140A. Low-level INSTI resistance (inS153Y) was observed in 23/207 (7.5%) of viremic individuals, with putative evidence of transmission. By 2022, suppression was unrelated to prior history of NNRTI/NRTI resistance (risk ratios: 1.14, 95%HPD: 0.96-1.32 and 1.12, 95%HPD: 0.88 - 1.35). INTERPRETATION: Viral suppression increased during the DTG-transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PLHIV underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued genomic surveillance of ART resistance. FUNDING: National Institutes of Health and the Gates Foundation.

Journal Article↗

PubMed2025

Quantifying prevalence and risk factors of HIV multiple infection in Uganda from population-based deep-sequence data.

People living with HIV can acquire secondary infections through a process called superinfection, giving rise to simultaneous infection with genetically distinct variants (multiple infection). Multiple infection provides the necessary conditions for the generation of novel recombinant forms of HIV and may worsen clinical outcomes and increase the rate of transmission to HIV seronegative sexual partners. To date, studies of HIV multiple infection have relied on insensitive bulk-sequencing, labor intensive single genome amplification protocols, or deep-sequencing of short genome regions. Here, we identified multiple infections in whole-genome or near whole-genome HIV RNA deep-sequence data generated from plasma samples of 2,029 people living with viremic HIV who participated in the population-based Rakai Community Cohort Study (RCCS). We estimated individual- and population-level probabilities of being multiply infected and assessed epidemiological risk factors using the novel Bayesian deep-phylogenetic multiple infection model (deep - phyloMI) which accounts for bias due to partial sequencing success and false-negative and false-positive detection rates. We estimated that between 2010 and 2020, 4.09% (95% highest posterior density interval (HPD) 2.95%-5.45%) of RCCS participants with viremic HIV multiple infection at time of sampling. Participants living in high-HIV prevalence communities along Lake Victoria were 2.33-fold (95% HPD 1.3-3.7) more likely to harbor a multiple infection compared to individuals in lower prevalence neighboring communities. This work introduces a high-throughput surveillance framework for identifying people with multiple HIV infections and quantifying population-level prevalence and risk factors of multiple infection for clinical and epidemiological investigations.

Humans↗

PubMed2007

Retracted: Factors affecting hospital readmission rates for breast cancer patients in Western Australia.

By this notice, the Editor and the Publisher of the Journal of Surgical Oncology retract from publication the following article: "Factors Affecting Hospital Readmission Rates for Breast Cancer Patients in Western Australia," Michael A. Martin, Ramona Meyricke, Terry O'Neill, and Steven Roberts, Journal of Surgical Oncology, Published online January 17, 2007, DOI: 10.1002/jso.20742. The article has been formally deemed a duplicate submission. The Editor and the Publisher of the Journal of Surgical Oncology regret the occurrence of this unfortunate incident.

breast cancer↗

PubMed2006

Breast-conserving surgery versus mastectomy for survival from breast cancer: the Western Australian experience.

BACKGROUND: The focus of this study was the relative survival rates of breast cancer patients whose treatment was breast-conserving surgery compared with that of mastectomy, adjusting for tumor size and nodal status because these factors may be intrinsically associated with mastectomy being the treatment of choice. Patient age was also accounted for in the model. By adjusting for these factors, we mitigate them as confounders of treatment choice in assessing effects on survival rates. METHODS: Data were sourced from linked administrative data from the Western Australian Department of Health Record Linkage Unit. The data consisted of linked records containing the diagnosis, subsequent hospital admission, and death records of about 3000 women diagnosed with cancer in Western Australia between 1 January 1995 and 31 December 1999. Cox proportional hazards regression was used to investigate survival outcomes of breast-conserving surgery compared with that of mastectomy, adjusting for tumor size, nodal status, and subject age. RESULTS: The hazard of death is reduced by a factor of about one half for subjects whose treatment was breast-conserving surgery over treatment by mastectomy. Furthermore, the hazard of death increases substantially for subjects with nodal involvement over subjects for whom there has been no identified spread to regional lymph nodes. Hazard of death increases as both age and tumor size increase. CONCLUSIONS: Western Australian breast cancer patients treated with breast-conserving surgery have improved survival outcomes over those treated with mastectomy, after allowing for tumor size, patient age, and lymph node involvement.

Aged↗

PubMed2006

The question of nonlinearity in the dose-response relation between particulate matter air pollution and mortality: can Akaike's Information Criterion be trusted to take the right turn?

The shape of the dose-response relation between particulate matter air pollution and mortality is crucial for public health assessment, and departures of this relation from linearity could have important regulatory consequences. A number of investigators have studied the shape of the particulate matter-mortality dose-response relation and concluded that the relation could be adequately described by a linear model. Some of these researchers examined the hypothesis of linearity by comparing Akaike's Information Criterion (AIC) values obtained under linear, piecewise linear, and spline alternative models. However, at the current time, the efficacy of the AIC in this context has not been assessed. The authors investigated AIC as a means of comparing competing dose-response models, using data from Cook County, Illinois, for the period 1987-2000. They found that if nonlinearities exist, the AIC is not always successful in detecting them. In a number of the scenarios considered, AIC was equivocal, picking the correct simulated dose-response model about half of the time. These findings suggest that further research into the shape of the dose-response relation using alternative model selection criteria may be warranted.

Aged↗

PubMed2006

Mastectomy or breast conserving surgery? Factors affecting type of surgical treatment for breast cancer--a classification tree approach.

BACKGROUND: A critical choice facing breast cancer patients is which surgical treatment--mastectomy or breast conserving surgery (BCS)--is most appropriate. Several studies have investigated factors that impact the type of surgery chosen, identifying features such as place of residence, age at diagnosis, tumor size, socio-economic and racial/ethnic elements as relevant. Such assessment of "propensity" is important in understanding issues such as a reported under-utilisation of BCS among women for whom such treatment was not contraindicated. Using Western Australian (WA) data, we further examine the factors associated with the type of surgical treatment for breast cancer using a classification tree approach. This approach deals naturally with complicated interactions between factors, and so allows flexible and interpretable models for treatment choice to be built that add to the current understanding of this complex decision process. METHODS: Data was extracted from the WA Cancer Registry on women diagnosed with breast cancer in WA from 1990 to 2000. Subjects' treatment preferences were predicted from covariates using both classification trees and logistic regression. RESULTS: Tumor size was the primary determinant of patient choice, subjects with tumors smaller than 20 mm in diameter preferring BCS. For subjects with tumors greater than 20 mm in diameter factors such as patient age, nodal status, and tumor histology become relevant as predictors of patient choice. CONCLUSION: Classification trees perform as well as logistic regression for predicting patient choice, but are much easier to interpret for clinical use. The selected tree can inform clinicians' advice to patients.

Adult↗

PubMed2006

Bootstrap model averaging in time series studies of particulate matter air pollution and mortality.

The consensus from time series studies that have investigated the mortality effects of particulate matter air pollution (PM) is that increases in PM are associated with increases in daily mortality. However, recently concerns have been raised that the observed positive association between PM and mortality may be an artefact of model selection due to multiple hypothesis testing. This problem arises when a number of models are investigated, but only the "best" model is reported and all subsequent inference is based on this model, ignoring the model selection process. In this paper, we introduce the use of the bootstrap as a means of addressing the problems of model selection in PM mortality time series studies. Using the bootstrap to perform inference about the effect of PM on mortality is a process based on a set of models rather than on a single model. It is shown that using the bootstrap to overcome the problems of model selection is competitive with the existing methodology of Bayesian model averaging.

Air Pollutants↗

PubMed2006

Using supervised principal components analysis to assess multiple pollutant effects.

BACKGROUND: Many investigations of the adverse health effects of multiple air pollutants analyze the time series involved by simultaneously entering the multiple pollutants into a Poisson log-linear model. This method can yield unstable parameter estimates when the pollutants involved suffer high intercorrelation; therefore, traditional approaches to dealing with multicollinearity, such as principal component analysis (PCA), have been promoted in this context. OBJECTIVES: A characteristic of PCA is that its construction does not consider the relationship between the covariates and the adverse health outcomes. A refined version of PCA, supervised principal components analysis (SPCA), is proposed that specifically addresses this issue. METHODS: Models controlling for longterm trends and weather effects were used in conjunction with each SPCA and PCA to estimate the association between multiple air pollutants and mortality for U.S. cities. The methods were compared further via a simulation study. RESULTS: Simulation studies demonstrated that SPCA, unlike PCA, was successful in identifying the correct subset of multiple pollutants associated with mortality. Because of this property, SPCA and PCA returned different estimates for the relationship between air pollution and mortality. CONCLUSIONS: Although a number of methods for assessing the effects of multiple pollutants have been proposed, such methods can falter in the presence of high correlation among pollutants. Both PCA and SPCA address this issue. By allowing the exclusion of pollutants that are not associated with the adverse health outcomes from the mixture of pollutants selected, SPCA offers a critical improvement over PCA.

Air Pollutants↗