Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 16, 2015
The goal of targeted antiretroviral therapy (ART) initiation is to minimize disease progression ... more The goal of targeted antiretroviral therapy (ART) initiation is to minimize disease progression among patients with HIV while also minimizing the therapeutic burden on these patients. Here, we examine whether the effect of delaying ART initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care. We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for treatment initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients between 18 and 34, 35 and 45, and 45 to 65 years of age at study entry. In the observed data, 10-year mortality was 13% (165 deaths). 10-year mortality increased from 11% under ART initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: 0.56, 2.17), and 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying ART bec...
International journal of epidemiology, Jan 28, 2015
Epidemiologists often use the potential outcomes framework to cast causal inference as a missing ... more Epidemiologists often use the potential outcomes framework to cast causal inference as a missing data problem. Here, we demonstrate how bias due to measurement error can be described in terms of potential outcomes and considered in concert with bias from other sources. In addition, we illustrate how acknowledging the uncertainty that arises due to measurement error increases the amount of missing information in causal inference. We use a simple example to show that estimating the average treatment effect requires the investigator to perform a series of hidden imputations based on strong assumptions.
International journal of epidemiology, Jan 29, 2015
Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in... more Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in most cases. Antibiotics modify the gastrointestinal microbiota, which may have unanticipated effects on the risk of subsequent diarrhoea. In a prospective observational cohort study, we assessed the effect of caregiver-reported antibiotic treatment for diarrhoea on the timing of a child's next episode among 434 children followed from birth to 3 years of age in Vellore, India. We estimated median time differences and time ratios from inverse probability of exposure-weighted Kaplan-Meier curves for the time to next diarrhoea episode, comparing children who did and did not receive antibiotics for the previous episode. Study children had more than five diarrhoea episodes on average in the first 3 years of life, and more than a quarter of all episodes were treated with antibiotics. Children who received antibiotics for their first diarrhoea episode had their second episode on average 8 w...
Cohort studies are often enriched for a primary exposure of interest to improve cost-effectivenes... more Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z → X → Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enri...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2014
Early mortality in people initiating antiretroviral treatment (ART) remains high. Empirical anti-... more Early mortality in people initiating antiretroviral treatment (ART) remains high. Empirical anti-tuberculosis treatment strategies aim to reduce early mortality by initiating anti-tuberculosis treatment in individuals at high risk of death from undiagnosed TB. Using data from 16 913 individuals starting ART under program conditions, we simulated the impact of three empirical treatment strategies (two clinical trials and a pragmatic approach), assuming that 50% of early deaths and 100% of incident TB are averted in those eligible. Compared to starting anti-tuberculosis treatment on clinical or mycobacteriological grounds, 4.4-31.4% more individuals were eligible for anti-tuberculosis treatment, 5.5-25.4% of deaths were averted and 10.9-57.3% of incident TB cases were prevented under empirical anti-tuberculosis treatment strategies. The proportion receiving any anti-tuberculosis treatment during the first 6 months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% a...
Although the standard recommendation is to exclude person-time not at risk (ie, time during which... more Although the standard recommendation is to exclude person-time not at risk (ie, time during which the outcome could not have occurred) from the denominators of disease rates, there are scenarios where person-time not at risk should be included. In particular, we draw an analogy between including person-time not at risk and intention-to-treat (ITT) analyses of randomized trials, and excluding person-time not at risk and compliance-corrected analysis of these same trials. Excluding person-time not at risk is appropriate when addressing questions of the biologic or mechanistic effects of an exposure, whereas the ITT-type approach typically addresses questions regarding the effect of an exposure under observed compliance patterns. The choice of approach directly affects the causal question being addressed and subsequent inference, with potential implications for public health. When interested in estimating treatment effects that allow and account for potential noncompliance, or where th...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2008
Kinshasa, Democratic Republic of Congo. To evaluate the implementation of three models of provide... more Kinshasa, Democratic Republic of Congo. To evaluate the implementation of three models of provider-initiated HIV counseling and testing (CT) for tuberculosis (TB) patients. HIV CT was offered to all TB patients aged > or =18 months registered for treatment at three project clinics between August 2004 and June 2005. HIV CT was performed at the TB clinic, the health center or the freestanding voluntary counseling and testing (VCT) center. HIV-infected patients received cotrimoxazole prophylaxis. Uptake of HIV CT was high (95-98%) when performed at the TB clinic or primary health care center, but significantly lower (68.5%) among patients referred to a free-standing VCT center. The overall HIV prevalence among the 1088 patients tested for HIV was 18.8%. HIV was associated with female sex (aOR 1.91), recurrent TB (aOR 2.74), extra-pulmonary TB (aOR 1.97) and age. Implementation of provider-initiated routine HIV CT by the TB nurse or health care worker at the primary health care cente...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 12, 2015
Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparitie... more Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparities in health outcomes among persons infected with HIV. However, evidence supporting the persistence of disparities in survival following therapy initiation is mixed. Patients initiating therapy in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between January 1, 1998 and December 30, 2011. Patients (n=10,017) were followed from therapy initiation until death from any cause, administrative censoring at 10 years after therapy initiation or the end of follow up on December 31, 2011. The 10-year risk of all-cause mortality was calculated from standardized Kaplan-Meier survival curves. Patients were followed for a median of 4.7 years (interquartile range: 2.2, 8.2). During 51,121 person-years of follow up, 1,224 of the 10,017 patients died. The overall 10-year mortality risk was 20.2% (95% confidence interval (CI): 19.2%, 21.3%)...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 13, 2015
Antiretroviral therapy (ART) administered in clinical trial settings virtually eliminates the se... more Antiretroviral therapy (ART) administered in clinical trial settings virtually eliminates the sexual transmission of HIV in serodiscordant couples, but effectiveness of treatment as prevention in the community is debated. Conflicting results from previous analyses in a Chinese cohort underscore the importance of determining effectiveness of ART delivered in resource limited settings. All available years of data (2006-2012) from local disease control records of HIV patients and their seronegative spouses in Henan Province, China were analyzed using marginal structural Cox models to estimate the effect of ART in the initially infected partner his or her partner's HIV seroconversion risk. We observed 157 seroconversion events in 4916 serosdiscordant couples, for an incidence rate of 0.59 cases per 100 person years (PY) [95% confidence intervals (CI), 0.51-0.70]. Of these, 84 occurred after the index partner had initiated ART (0.43/100PY; 95% CI, 0.35-0.53) and 73 while index par...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2007
The PDF file you selected should load here, if your Web browser has a PDF reader plug-in installe... more The PDF file you selected should load here, if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). Alternatively, the PDF file will download to your computer, where it can also be opened using a PDF reader. If you ...
Infectious diseases in obstetrics and gynecology, 2014
HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV t... more HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10) rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months ...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 16, 2015
The goal of targeted antiretroviral therapy (ART) initiation is to minimize disease progression ... more The goal of targeted antiretroviral therapy (ART) initiation is to minimize disease progression among patients with HIV while also minimizing the therapeutic burden on these patients. Here, we examine whether the effect of delaying ART initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care. We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for treatment initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients between 18 and 34, 35 and 45, and 45 to 65 years of age at study entry. In the observed data, 10-year mortality was 13% (165 deaths). 10-year mortality increased from 11% under ART initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: 0.56, 2.17), and 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying ART bec...
International journal of epidemiology, Jan 28, 2015
Epidemiologists often use the potential outcomes framework to cast causal inference as a missing ... more Epidemiologists often use the potential outcomes framework to cast causal inference as a missing data problem. Here, we demonstrate how bias due to measurement error can be described in terms of potential outcomes and considered in concert with bias from other sources. In addition, we illustrate how acknowledging the uncertainty that arises due to measurement error increases the amount of missing information in causal inference. We use a simple example to show that estimating the average treatment effect requires the investigator to perform a series of hidden imputations based on strong assumptions.
International journal of epidemiology, Jan 29, 2015
Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in... more Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in most cases. Antibiotics modify the gastrointestinal microbiota, which may have unanticipated effects on the risk of subsequent diarrhoea. In a prospective observational cohort study, we assessed the effect of caregiver-reported antibiotic treatment for diarrhoea on the timing of a child's next episode among 434 children followed from birth to 3 years of age in Vellore, India. We estimated median time differences and time ratios from inverse probability of exposure-weighted Kaplan-Meier curves for the time to next diarrhoea episode, comparing children who did and did not receive antibiotics for the previous episode. Study children had more than five diarrhoea episodes on average in the first 3 years of life, and more than a quarter of all episodes were treated with antibiotics. Children who received antibiotics for their first diarrhoea episode had their second episode on average 8 w...
Cohort studies are often enriched for a primary exposure of interest to improve cost-effectivenes... more Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z → X → Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enri...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2014
Early mortality in people initiating antiretroviral treatment (ART) remains high. Empirical anti-... more Early mortality in people initiating antiretroviral treatment (ART) remains high. Empirical anti-tuberculosis treatment strategies aim to reduce early mortality by initiating anti-tuberculosis treatment in individuals at high risk of death from undiagnosed TB. Using data from 16 913 individuals starting ART under program conditions, we simulated the impact of three empirical treatment strategies (two clinical trials and a pragmatic approach), assuming that 50% of early deaths and 100% of incident TB are averted in those eligible. Compared to starting anti-tuberculosis treatment on clinical or mycobacteriological grounds, 4.4-31.4% more individuals were eligible for anti-tuberculosis treatment, 5.5-25.4% of deaths were averted and 10.9-57.3% of incident TB cases were prevented under empirical anti-tuberculosis treatment strategies. The proportion receiving any anti-tuberculosis treatment during the first 6 months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% a...
Although the standard recommendation is to exclude person-time not at risk (ie, time during which... more Although the standard recommendation is to exclude person-time not at risk (ie, time during which the outcome could not have occurred) from the denominators of disease rates, there are scenarios where person-time not at risk should be included. In particular, we draw an analogy between including person-time not at risk and intention-to-treat (ITT) analyses of randomized trials, and excluding person-time not at risk and compliance-corrected analysis of these same trials. Excluding person-time not at risk is appropriate when addressing questions of the biologic or mechanistic effects of an exposure, whereas the ITT-type approach typically addresses questions regarding the effect of an exposure under observed compliance patterns. The choice of approach directly affects the causal question being addressed and subsequent inference, with potential implications for public health. When interested in estimating treatment effects that allow and account for potential noncompliance, or where th...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2008
Kinshasa, Democratic Republic of Congo. To evaluate the implementation of three models of provide... more Kinshasa, Democratic Republic of Congo. To evaluate the implementation of three models of provider-initiated HIV counseling and testing (CT) for tuberculosis (TB) patients. HIV CT was offered to all TB patients aged > or =18 months registered for treatment at three project clinics between August 2004 and June 2005. HIV CT was performed at the TB clinic, the health center or the freestanding voluntary counseling and testing (VCT) center. HIV-infected patients received cotrimoxazole prophylaxis. Uptake of HIV CT was high (95-98%) when performed at the TB clinic or primary health care center, but significantly lower (68.5%) among patients referred to a free-standing VCT center. The overall HIV prevalence among the 1088 patients tested for HIV was 18.8%. HIV was associated with female sex (aOR 1.91), recurrent TB (aOR 2.74), extra-pulmonary TB (aOR 1.97) and age. Implementation of provider-initiated routine HIV CT by the TB nurse or health care worker at the primary health care cente...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 12, 2015
Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparitie... more Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparities in health outcomes among persons infected with HIV. However, evidence supporting the persistence of disparities in survival following therapy initiation is mixed. Patients initiating therapy in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between January 1, 1998 and December 30, 2011. Patients (n=10,017) were followed from therapy initiation until death from any cause, administrative censoring at 10 years after therapy initiation or the end of follow up on December 31, 2011. The 10-year risk of all-cause mortality was calculated from standardized Kaplan-Meier survival curves. Patients were followed for a median of 4.7 years (interquartile range: 2.2, 8.2). During 51,121 person-years of follow up, 1,224 of the 10,017 patients died. The overall 10-year mortality risk was 20.2% (95% confidence interval (CI): 19.2%, 21.3%)...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 13, 2015
Antiretroviral therapy (ART) administered in clinical trial settings virtually eliminates the se... more Antiretroviral therapy (ART) administered in clinical trial settings virtually eliminates the sexual transmission of HIV in serodiscordant couples, but effectiveness of treatment as prevention in the community is debated. Conflicting results from previous analyses in a Chinese cohort underscore the importance of determining effectiveness of ART delivered in resource limited settings. All available years of data (2006-2012) from local disease control records of HIV patients and their seronegative spouses in Henan Province, China were analyzed using marginal structural Cox models to estimate the effect of ART in the initially infected partner his or her partner's HIV seroconversion risk. We observed 157 seroconversion events in 4916 serosdiscordant couples, for an incidence rate of 0.59 cases per 100 person years (PY) [95% confidence intervals (CI), 0.51-0.70]. Of these, 84 occurred after the index partner had initiated ART (0.43/100PY; 95% CI, 0.35-0.53) and 73 while index par...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2007
The PDF file you selected should load here, if your Web browser has a PDF reader plug-in installe... more The PDF file you selected should load here, if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). Alternatively, the PDF file will download to your computer, where it can also be opened using a PDF reader. If you ...
Infectious diseases in obstetrics and gynecology, 2014
HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV t... more HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10) rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months ...
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Papers by Daniel Westreich