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Biomedical subjects

Maya L Petersen

Publications and source records attributed to Maya L Petersen.

6 recordsLinked to original sources

Assessing the effectiveness of antiretroviral adherence interventions. Using marginal structural models to replicate the findings of randomized controlled trials.

Randomized controlled trials of interventions to improve adherence to antiretroviral medications are not always feasible. Marginal structural models (MSM) are a statistical methodology that aims to replicate the findings of randomized controlled trials using observational data. Under the assumption of no unmeasured confounders, 3 MSM estimators are available to estimate the causal effect of an intervention. Two of these estimators, G-computation and inverse probability of treatment weighted (IPTW), can be implemented using standard software. G-computation relies on fitting a multivariable regression of adherence on the intervention and confounders. Thus, it is related to the standard multivariable regression approach to estimating causal effects. In contrast, IPTW relies on fitting a multivariable logistic regression of the intervention on confounders. This article reviews the implementation of these methods, the assumptions underlying them, and interpretation of results. Findings are illustrated with a theoretic data example in which MSM are used to estimate the effect of a behavioral intervention on adherence to antiretroviral therapy.

Anti-HIV Agents↗

Estimation of direct causal effects.

Many common problems in epidemiologic and clinical research involve estimating the effect of an exposure on an outcome while blocking the exposure's effect on an intermediate variable. Effects of this kind are termed direct effects. Estimation of direct effects is typically the goal of research aimed at understanding mechanistic pathways by which an exposure acts to cause or prevent disease, as well as in many other settings. Although multivariable regression is commonly used to estimate direct effects, this approach requires assumptions beyond those required for the estimation of total causal effects. In addition, when the exposure and intermediate variables interact to cause disease, multivariable regression estimates a particular type of direct effect-the effect of an exposure on an outcome when the intermediate is fixed at a specified level. Using the counterfactual framework, we distinguish this definition of a direct effect (controlled direct effect) from an alternative definition, in which the effect of the exposure on the intermediate is blocked, but the intermediate is otherwise allowed to vary as it would in the absence of exposure (natural direct effect). We illustrate the difference between controlled and natural direct effects using several examples. We present an estimation approach for natural direct effects that can be implemented using standard statistical software, and we review the assumptions underlying our approach (which are less restrictive than those proposed by previous authors).

Clinical Trials as Topic↗

Assessing HIV resistance in developing countries: Brazil as a case study.

Increased transmission of resistant HIV has been raised as a potential consequence of expanded access to antiretroviral therapy. We review how limitations in resources and health care infrastructure may impact the transmission of resistant HIV, and we examine data from Brazil as a case study. We introduce a biological and clinical framework to identify the major determinants of transmitted resistance and to discuss how these determinants may be affected by a lack of infrastructure. We then use our framework to examine HIV resistance data from Brazil. This country was chosen as a case study due to its extensive experience delivering antiretroviral drugs and because of the availability of data on the prevalence of resistant HIV there. The data from Brazil show that antiretroviral therapy can be delivered in a resource-limited setting without resulting in widespread transmission of resistant virus. While the Brazilian experience does not necessarily generalize to countries with less health care infrastructure, neither theory nor data support a foregone conclusion that resistance will necessarily dominate HIV epidemics in the developing world to a greater extent than it does in the developed world.

Anti-Retroviral Agents↗

Adherence to antiretroviral therapy: a qualitative study with physicians from Rio de Janeiro, Brazil.

Brazil provides free antiretroviral (ARV) therapy to some 150,000 individuals living with HIV/ AIDS). ARV regimens require optimal adherence to achieve undetectable viral loads and to avoid viral resistance. Physicians play a key role to foster ARV adherence, but until now little is known about the communication between physicians/ people living with HIV/AIDS in this setting. In-depth interviews were conducted with 40 physicians treating people living with HIV/AIDS at six public reference centers in Rio de Janeiro, Brazil. Interview topics included: experiences in the treatment of people living with HIV/AIDS, relationship and dialogue with patients, barriers/facilitators to adherence, and effectiveness of available services. Barriers to ARV adherence were mainly related to the low quality of patient-provider relationship. Other barriers were related to "chaotic" patients' lifestyles, and inadequate knowledge and/or negative beliefs about HIV/AIDS and ARV effectiveness. It is necessary to improve networking between services, establish agile referral systems, and improve health professionals' integration. These structural changes could contribute to improved adherence, resulting in improved quality of life for people living with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

Highly active antiretroviral therapy in Brazil: the challenge of universal access in a context of social inequality.

OBJECTIVE: To investigate trends in AIDS mortality and incidence in Brazil over the period of 1984 to 2000 and to assess the impact of the introduction of universal access to highly active antiretroviral therapy (HAART) in the country in 1996. METHODS: Data from the Brazilian disease notification system and the national mortality information system were used to calculate annual region-specific and sex-specific AIDS incidence and mortality rates. We also calculated sex- and region-specific ratios of the number of AIDS deaths in one year to the number of AIDS cases notified two years earlier. RESULTS: AIDS mortality rates for both men and women and in all five of the geographic regions of Brazil declined following introduction of HAART, despite continued growth in AIDS incidence. The ratio of the number of AIDS deaths in one year to the number of AIDS cases notified two years earlier for men equalized rapidly with the ratio for women following introduction of HAART. More recently, AIDS incidence declined for both sexes and in most of the regions of Brazil. CONCLUSIONS: Despite Brazil's resource limitations and disparities in wealth between men and women and among the country's regions, the introduction of universal access to HAART in Brazil has helped achieve impressive declines in AIDS mortality, and it may also be contributing to declines in AIDS incidence.

Acquired Immunodeficiency Syndrome↗

Divalproex sodium for the treatment of conduct disorder: a randomized controlled clinical trial.

BACKGROUND: New treatments for conduct disorder are sorely needed. We aimed to test the efficacy of divalproex sodium for the treatment of conduct disorder. METHOD: Seventy-one youths with conduct disorder according to DSM-IV criteria were enrolled in a randomized, controlled, 7-week clinical trial. Subjects were all adolescent males with at least 1 crime conviction. Subjects were randomized into high- and low-dose conditions and were openly managed by a clinical team. Subjects and independent outcome raters were blinded to condition. Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Improvement (CGI-I) ratings, Weinberger Adjustment Inventory ratings, and staff ratings of behavioral privilege were used to assess outcome. RESULTS: Intent-to-treat analyses showed significant associations between assignment to the high-dose condition and ratings on the CGI-S (p =.02) and CGI-I (p =.0008). Self-reported weekly impulse control was significantly better in the high-dose condition (p <.05), and association between improvement in self-restraint and treatment condition was of borderline statistical significance (p <.06). Parallel analyses comparing outcome by blood drug level achieved strengthened the results, as expected. CONCLUSION: This preliminary study in a most difficult population suggests a role for divalproex sodium in the treatment of conduct disorder. Divalproex sodium improved self-reported impulse control and self-restraint, variables shown to be predictive of criminal recidivism. Studies are needed of longer-term impact and side-effect profiles. This is one of few controlled psychopharmacologic studies of conduct disorder.

Adolescent↗