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1.
Birth Defects Res ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31322328

RESUMO

OBJECTIVE: To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). RESULTS: Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). CONCLUSION: The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

2.
Am J Epidemiol ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063192

RESUMO

Effect estimates from randomized trials and observational studies may not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a three-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocol (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive to the human immunodeficiency virus from the START randomized trial and the observational HIV-CAUSAL Collaboration.

3.
Clin J Am Soc Nephrol ; 14(5): 728-737, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30988164

RESUMO

BACKGROUND AND OBJECTIVES: Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach (i.e., dose, frequency, and duration). Little is known about the safety of these protocols. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD aged ≥65 years who initiated and continued center-based hemodialysis for ≥90 days between 2009 and 2012, and initiated at least one of the five common intravenous iron administration strategies; ranked by intensity (the amount of iron given at moderate-to-high iron indices), the order of strategies was 3 (least intensive), 2 (less intensive), 1 (reference), 4 (more intensive), and 5 (most intensive). We estimated the effect of continuous exposure to these strategies on cumulative risks of mortality and infection-related events with dynamic Cox marginal structural models. RESULTS: Of 13,249 eligible patients, 1320 (10%) died and 1627 (12%) had one or more infection-related events during the 4-month follow-up. The most and least commonly initiated strategy was strategy 2 and 5, respectively. Compared with the reference strategy 1, more intensive strategies (4 and 5) demonstrated a higher risk of all-cause mortality (e.g., most intensive strategy 5: 60-day risk difference: 1.3%; 95% confidence interval [95% CI], 0.8% to 2.1%; 120-day risk difference: 3.1%; 95% CI, 1.0% to 5.6%). Similarly, higher risks were observed for infection-related morbidity and mortality among more intensive strategies (e.g., strategy 5: 60-day risk difference: 1.8%; 95% CI, 1.2% to 2.6%; 120-day risk difference: 4.3%; 95% CI, 2.2% to 6.8%). Less intensive strategies (2 and 3) demonstrated lower risks of all-cause mortality and infection-related events. CONCLUSIONS: Among dialysis patients surviving 90 days, subsequent intravenous iron administration strategies promoting more intensive iron treatment at moderate-to-high iron indices levels are associated with higher risks of mortality and infection-related events.

4.
AIDS ; 33(8): 1385-1390, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932953

RESUMO

OBJECTIVE: We aimed to investigate potential causes of higher risk of treatment interruptions within the multicountry Strategic Timing of AntiRetroviral Treatment (START) trial in 2015. METHODS: We defined baseline as the date of starting antiretroviral therapy (ART) and a treatment interruption as discontinuing ART for at least 2 weeks. Participants were stratified by randomization arm and followed from baseline to earliest end date of the initial phase of START, death, date of consent withdrawn or date of first treatment interruption. Cox regression was used to calculate hazard ratios and 95% confidence intervals for factors that may predict treatment interruptions in each arm. RESULTS: Of the 3438 participants who started ART, 2286 were in the immediate arm and 1152 in the deferred arm. 12.9% of people in the immediate arm and 10.5% of people in the deferred arm experienced at least one treatment interruption by 3 years after starting ART. In adjusted analyses, age [hazard ratio for 35-50 years: 0.75 (95% confidence interval: 0.59-0.97) and >50 years: 0.53 (0.33-0.80) vs. <35 years], education status [hazard ratio for postgraduate education vs. less than high-school education (0.23 (0.10-0.50))] and region [hazard ratio for United States vs. Europe/Israel (3.16 (2.09-4.77))] were significantly associated with treatment interruptions in the immediate arm. In the deferred arm, age and education status were significantly associated with treatment interruptions. CONCLUSION: Within START, we identified younger age and lower educational attainment as potential causes of ART interruption. There is a need to strengthen adherence advice and wider social support in younger people and those of lower education status.

5.
BMC Pregnancy Childbirth ; 19(1): 81, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30813934

RESUMO

BACKGROUND: Each year, an estimated 15 million babies are born preterm, a global burden borne disproportionately by families in lower-income countries. Maternal HIV infection increases a woman's risk of delivering prematurely, and antiretroviral therapy (ART) may compound this risk. While prenatal progesterone prophylaxis prevents preterm birth among some high-risk women, it is unknown whether HIV-infected women could benefit from this therapy. We are studying the efficacy of progesterone supplementation to reduce the risk of preterm birth among pregnant women with HIV in Lusaka, Zambia. METHODS: The Improving Pregnancy Outcomes with Progesterone (IPOP) study is a Phase III double-masked, placebo-controlled, randomized trial of intramuscular 17-alpha hydroxprogesterone caproate (17P) to prevent preterm birth in HIV-infected women. A total of 800 women will be recruited prior to 24 weeks of gestation and randomly allocated to 17P or placebo administered by weekly intramuscular injection. The primary outcome will be a composite of live birth prior to 37 completed gestational weeks or stillbirth at any gestational age. Secondary outcomes will include very preterm birth (< 34 weeks), extreme preterm birth (< 28 weeks), small for gestational age (<10th centile), low birth weight (< 2500 g), and neonatal outcomes. In secondary analysis, we will assess whether specific HIV-related covariates, including the timing of maternal ART initiation relative to conception, is associated with progesterone's prophylactic efficacy, if any. DISCUSSION: We hypothesize that weekly prenatal 17P will reduce the risk of HIV-related preterm birth. An inexpensive intervention to prevent preterm birth among pregnant women with HIV could have substantial global public health impact. TRIAL REGISTRATION: NCT03297216 ; September 29, 2017.


Assuntos
Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Países em Desenvolvimento , Infecções por HIV/complicações , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Feminino , Idade Gestacional , Infecções por HIV/tratamento farmacológico , Humanos , Injeções Intramusculares , Nascimento Vivo , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Natimorto , Zâmbia
6.
Am J Epidemiol ; 188(7): 1355-1360, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30834430

RESUMO

In the absence of strong assumptions (e.g., exchangeability), only bounds for causal effects can be identified. Here we describe bounds for the risk difference for an effect of a binary exposure on a binary outcome in 4 common study settings: observational studies and randomized studies, each with and without simple random selection from the target population. Through these scenarios, we introduce randomizations for selection and treatment, and the widths of the bounds are narrowed from 2 (the width of the range of the risk difference) to 0 (point identification). We then assess the strength of the assumptions of exchangeability for internal and external validity by comparing their contributions to the widths of the bounds in the setting of an observational study without random selection from the target population. We find that when less than two-thirds of the target population is selected into the study, the assumption of exchangeability for external validity of the risk difference is stronger than that for internal validity. The relative strength of these assumptions should be considered when designing, analyzing, and interpreting observational studies and will aid in determining the best methods for estimating the causal effects of interest.

8.
Am J Epidemiol ; 188(5): 960-966, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726868

RESUMO

The disease risk score is a summary score that can be used to control for confounding with a potentially large set of covariates. While less widely used than the exposure propensity score, the disease risk score approach might be useful for novel or unusual exposures, when treatment indications or exposure patterns are rapidly changing, or when more is known about the nature of how covariates cause disease than is known about factors influencing propensity for the exposure of interest. Focusing on the simple case of a binary point exposure, we describe a marginal structural model for estimation of risk (or prevalence) ratios. The proposed model incorporates the disease risk score as an offset in a regression model, and it yields an estimate of a standardized risk ratio where the target population is the exposed group. Simulations are used to illustrate the approach, and an empirical example is provided. Confounder control based on the proposed method might be a useful alternative to approaches based on the exposure propensity score, or as a complement to them.

9.
Epidemiology ; 30(3): 358-364, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30640216

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) for determining efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) infection have not been conducted among US women because their lower HIV incidence requires impractically large studies. Results from higher-incidence settings, like Sub-Saharan Africa, may not apply to US women owing to differences in age, sexual behavior, coinfections, and adherence. METHODS: We propose a novel strategy for evaluating PrEP efficacy in the United States using data from both settings to obtain four parameters: (1) intention-to-treat (ITT) and (2) per-protocol effects in the higher-incidence setting, (3) per-protocol effect generalized to the lower-incidence setting, and (4) back-calculated ITT effect using adherence data from the lower-incidence setting. To illustrate, we simulated two RCTs comparing PrEP against placebo: one in 4000 African women and another in 500 US women. We estimated all parameters using g-computation and report risk ratios averaged over 2000 simulations, alongside the 2.5th and 97.5th percentiles of the simulation results. RESULTS: Twelve months after randomization, the African ITT and per-protocol risk ratios were 0.65 (0.47, 0.88) and 0.20 (0.08, 0.34), respectively. The US ITT and per-protocol risk ratios were 0.42 (0.20, 0.62) and 0.17 (0.03, 0.38), respectively. These results matched well the simulated true effects. CONCLUSIONS: Our simple demonstration informs the design of future studies seeking to estimate the effectiveness of a treatment (like PrEP) in lower-incidence settings where a traditional RCT would not be feasible. See video abstract at, http://links.lww.com/EDE/B506.

10.
Clin Infect Dis ; 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30615096

RESUMO

Background: The cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non-evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with HIV/HCVco-infection who are at high risk for liver disease progression. The goal of this work was to estimate the effects of DAA access policies on 10-year all-cause mortality among people with HIV. Methods: The study population included 3,056 adults with HIV in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study from October 1, 1994 through September 30, 2015. We used the parametric g-formula to estimate 10-year all-cause mortality under DAA access policies that included treating: 1) all people with HCV; 2) only people with suppressed HIV; 3) only people with severe fibrosis; and 4) only people with HIV suppression and severe fibrosis. Results: The 10-year risk difference (RD) of treating all co-infected persons with DAAs compared with no treatment was -3.7% (95% CI: -9.1%, 0.6%). Treating only those with suppressed HIV and severe fibrosis yielded a RD of -1.1% (95% CI: -2.8%, 0.6%), with 51% (95% CI: 38%, 59%) of co-infected persons receiving DAAs. Treating a random selection of 51% of co-infected persons at baseline decreased the risk by 1.9% (95% CI: -4.7%, 0.3%). Conclusions: Restrictive DAA access policies may decrease survival compared to treating similar proportions of people with HIV/HCV coinfection with DAAs at random. These findings suggest that lives could be saved by thoughtfully revising access policies.

11.
Am J Epidemiol ; 188(4): 632-636, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698633

RESUMO

Nonparametric bounds for the risk difference are straightforward to calculate and make no untestable assumptions about unmeasured confounding or selection bias due to missing data (e.g., dropout). These bounds are often wide and communicate uncertainty due to possible systemic errors. An illustrative example is provided.

12.
Am J Public Health ; 109(3): 451-453, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30676799

RESUMO

OBJECTIVES: To use dynamic visualizations of mortality risk functions over both calendar year and age as a way to estimate and visualize patterns in US life spans. METHODS: We built 49 synthetic cohorts, 1 per year 1968 to 2016, using National Center for Health Statistics (NCHS) mortality and population data. Within each cohort, we estimated age-specific probabilities of dying from any cause (all-cause analysis) or from a particular cause (cause-specific analysis). We then used Kaplan-Meier (all-cause) or Aalen-Johansen (cause-specific) estimators to obtain risk functions. We illustrated risk functions using time-lapse animations. RESULTS: Median age at death increased from 75 years in 1970 to 83 years in 2015. Risk by age 100 years of cardiovascular mortality decreased (from a risk of 55% in 1970 to 32% in 2015), whereas risk attributable to other (i.e., nonrespiratory and noncardiovascular) causes increased in compensation. CONCLUSIONS: Our findings were consistent with the trends published in the NCHS 2015 mortality report, and our dynamic animations added an efficient, interpretable tool for visualizing US mortality trends over age and calendar time.

13.
J Clin Endocrinol Metab ; 104(6): 1989-1998, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608562

RESUMO

CONTEXT: Hemoglobin A1C (HbA1C) is an important predictor of severe hypoglycemia. OBJECTIVE: To determine the association of proximal HbA1C level with first hypoglycemia hospitalization (HH) in adults with incident type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was designed using linked data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England in 1997 to 2014. The first hypoglycemia event as primary diagnosis for hospitalization after T2D diagnosis was identified. Proximal HbA1C was measured within 90 days before the first HH. MAIN OUTCOME MEASURE: OR for developing HH. RESULTS: The association of proximal HbA1C level with first HH was similar between HbA1C levels of 6.0% (OR, 1.54; 95% CI, 1.12 to 2.11) and 9.0% [1.48 (1.01 to 2.17)] compared with the reference HbA1C level of 7.0%. For proximal HbA1C level of 4.0% to 6.5%, every additional 0.5% increase in HbA1C was associated with lower first HH risk, with ORs (95% CI) ranging between 0.37 (0.20 to 0.67) and 0.86 (0.76 to 0.98). For proximal HbA1C level of 8.0% to 11.5%, every additional 0.5% increase in HbA1C was associated with higher first HH risk, with ORs (95% CI) ranging between 1.16 (1.04 to 1.29) and 1.34 (1.18 to 1.52). The U-shaped association between proximal HbA1C level and first HH did not exist among current sulfonylurea users but persisted among current insulin users (Pinteraction = 0.002). Among current noninsulin nonsulfonylurea users who had a first HH, 78% took insulin or sulfonylureas before the HH. CONCLUSIONS: Having either poor or near-normal HbA1C was associated with a higher risk of first HH within 3 months in T2D.

14.
Eur J Gastroenterol Hepatol ; 31(5): 563-569, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30672827

RESUMO

BACKGROUND: The international guidelines for surveillance following the finding of a small tubular adenoma vary between no surveillance or colonoscopy at 5 or 10 years, whereas surveillance after an advanced adenoma is 3 years. Optimization of surveillance reduces the risk of colorectal cancer (CRC) with efficient use of colonoscopy resources. We assessed the risks of advanced colorectal neoplasia following a baseline finding of a small adenoma compared with advanced adenoma. PATIENTS AND METHODS: A retrospective audit was undertaken of patients enrolled in a CRC surveillance program, wherein regular colonoscopies and screening with faecal immunochemical test (FIT) were provided. Patients diagnosed with either small or advanced adenoma followed by at least one surveillance colonoscopy were included. Advanced adenoma included adenomas with features of villous change, size of at least 10 mm, high-grade dysplasia, three or more small tubular adenomas and traditional and sessile serrated adenomas. Subdistribution hazard ratios were calculated for advanced neoplasia (CRC or advanced adenoma). RESULTS: Overall, 378 patients (62.6±11.2 years, 57.9% male) were included, with 44.2% diagnosed with small adenoma and 55.5% with advanced adenoma at baseline. The crude cumulative incidence of advanced neoplasia at first surveillance was 13.2 and 18.5% after small and advanced adenoma (P=0.16) (at 45.9 and 35.6 months, respectively), which became significant for advanced adenoma after adjustment (subdistribution hazard ratio=2.55, 95% confidence interval=1.49-4.35, P<001). A positive FIT was the only independent predictor of advanced neoplasia after a small adenoma at baseline colonoscopy (odds ratio=5.05, 95% confidence interval=1.27-20.02, P=0.02). CONCLUSIONS: The risk of advanced neoplasia following a small adenoma was lower than that following an advanced adenoma, but was strongly predicted by a positive FIT. Reducing frequency of colonoscopy while providing regular FIT might be a more efficient use of resources for this population.


Assuntos
Pólipos Adenomatosos/patologia , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Detecção Precoce de Câncer/métodos , Pólipos Adenomatosos/epidemiologia , Idoso , Austrália/epidemiologia , Neoplasias do Colo/epidemiologia , Pólipos do Colo/epidemiologia , Progressão da Doença , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Carga Tumoral
16.
Int J Gynaecol Obstet ; 144(1): 9-15, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30267538

RESUMO

OBJECTIVE: To quantify differences in assessing preterm delivery when calculating gestational age from last menstrual period (LMP) versus ultrasonography biometry. METHODS: The Zambian Preterm Birth Prevention Study is an ongoing prospective cohort study that commenced enrolment in August 2015 at Women and Newborn Hospital of University Teaching Hospital in Lusaka, Zambia. Women at less than 20 weeks of pregnancy who were enrolled between August 17, 2015, and August 31, 2017, and underwent ultrasonography examination were included in the present analysis. The primary outcome was the difference between ultrasonography- and LMP-based estimated gestational age. Associations between baseline predictors and outcomes were assessed using simple regression. The proportion of preterm deliveries using LMP- and ultrasonography-derived gestational dating was calculated using Kaplan-Meier analysis. RESULTS: The analysis included 942 women. The discrepancy between estimating gestational age using ultrasonography and LMP increased with greater gestational age at presentation and among patients with no history of preterm delivery. In a Kaplan-Meier analysis of 692 deliveries, 140 (20.2%, 95% confidence interval [CI] 17.7-23.0) and 79 (11.4%, 95% CI 9.6-13.6) deliveries were classified as preterm by LMP and ultrasonography estimates, respectively. CONCLUSION: Taking ultrasonography as a standard, a bias was observed in LMP-based gestational age estimates, which increased with advancing gestation at presentation. This resulted in misclassification of term deliveries as preterm.


Assuntos
Idade Gestacional , Ciclo Menstrual , Adulto , Feminino , Humanos , Recém-Nascido , Variações Dependentes do Observador , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Estudos Prospectivos , Ultrassonografia Pré-Natal , Adulto Jovem , Zâmbia/epidemiologia
17.
PLoS One ; 13(12): e0208795, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30533053

RESUMO

BACKGROUND: Randomized controlled trials are often used to inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population-an assumption that may not hold in practice. METHODS: The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods' assumptions and provide detailed implementation instructions. ILLUSTRATION: We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. CONCLUSION: These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects.


Assuntos
Modelos Teóricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Humanos , Avaliação de Resultados (Cuidados de Saúde)
18.
BMC Med Res Methodol ; 18(1): 142, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30453971

RESUMO

BACKGROUND: When conducting a survival analysis, researchers might consider two broad classes of models: nonparametric models and parametric models. While nonparametric models are more flexible because they make few assumptions regarding the shape of the data distribution, parametric models are more efficient. Here we sought to make concrete the difference in efficiency between these two model types using effective sample size. METHODS: We compared cumulative risk of AIDS or death estimated using four survival models - nonparametric, generalized gamma, Weibull, and exponential - and data from 1164 HIV patients who were alive and AIDS-free in 1995. We added pseudo-observations to the sample until the spread of the 95% confidence limits for the nonparametric model became less than that for the parametric models. RESULTS: We found the 3-parameter generalized gamma to be a good fit to the nonparametric risk curve, but the 1-parameter exponential both underestimated and overestimated the risk at different times. Using two year-risk as an example, we had to add 354, 593, and 3960 observations for the nonparametric model to be as efficient as the generalized gamma, Weibull, and exponential models, respectively. CONCLUSIONS: These added observations represent the hidden observations underlying the efficiency gained through parametric model form assumptions. If the model is correctly specified, the efficiency gain may be justified, as appeared to be the case for the generalized gamma model. Otherwise, precision will be improved, but at the cost of specification bias, as was the case for the exponential model.

19.
Am J Epidemiol ; 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30312378

RESUMO

Our study explored the application of methods to generalize randomized controlled trial results to a target population without individual-level data. We compared four methods using aggregate data for the target population to generalize the JUPITER trial results to a target population of trial-eligible patients in Clinical Practice Research Datalink (CPRD). The gold-standard method used individual data from both the trial and CPRD to predict probabilities of being sampled in the trial and reweight trial participants to reflect CPRD patient characteristics. Methods 1 and 2 used weighting methods based on simulated individual data or the method of moments, respectively. Method 3 weighted the trial subgroup-specific treatment effects to match the distribution of an effect modifier in CPRD. Method 4 calculated the expected absolute benefits in CPRD assuming homogeneous relative treatment effect. Methods based on aggregate data for the target population generally yielded results between the trial and gold-standard estimates. Methods 1 and 2 yielded estimates closest to the gold-standard when continuous effect modifiers were represented as categorical variables. Although individual data or data on joint distributions remains the best approach to generalize the trial results, these methods using aggregate data may be useful tools for timely assessment of randomized trial generalizability.

20.
Clin Infect Dis ; 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30321289

RESUMO

Background: Persons living with human immunodeficiency virus (HIV; PLwH) are commonly co-infected with hepatitis C virus (HCV). Most co-infected individuals can achieve a sustained HCV virologic response after treatment with direct-acting antivirals (DAA). However, the effect of HCV co-infection and DAA treatment on mortality after initiating antiretroviral therapy (ART) is unknown for PLwH. Methods: We analyzed data from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Participants included those who had prevalent HIV or seroconverted during follow-up; all were antiretroviral-naive and acquired immunodeficiency syndrome (AIDS)-free prior to their first visit after 1 October 1994. The follow-up lasted 10 years or until 30 September 2015. We used parametric g-computation to estimate the effects of HCV infection and DAA treatment on mortality had participants initiated ART at study entry. Results: Of the 3056 eligible participants, 58% were female and 18% had HCV. The estimated 10-year all-cause mortality risk in the scenario in which no PLwH had HCV was 10.4% (95% confidence interval [CI] 6.0-18.0%). The 10-year mortality risk difference for HCV infection was 4.3% (95% CI 0.4-8.9%) and the risk ratio was 1.4 (95% CI 1.0-1.9). The risk difference for DAA treatment was -3.8% (95% CI -9.2-0.9%) and the risk ratio was 0.8 (95% CI 0.6-1.1). Conclusions: HCV co-infection remains an important risk factor for mortality among PLwH after initiating ART according to modern guidelines, and DAAs are effective at reducing mortality in this population. HCV prevention and treatment interventions should be prioritized to reduce mortality among PLwH.

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