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1.
Int J Epidemiol ; 53(4)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-39002174

ABSTRACT

BACKGROUND: Observational studies are frequently used to estimate the comparative effectiveness of different colorectal cancer (CRC) screening methods due to the practical limitations and time needed to conduct large clinical trials. However, time-varying confounders, e.g. polyp detection in the last screening, can bias statistical results. Recently, generalized methods, or G-methods, have been used for the analysis of observational studies of CRC screening, given their ability to account for such time-varying confounders. Discretization, or the process of converting continuous functions into discrete counterparts, is required for G-methods when the treatment and outcomes are assessed at a continuous scale. DEVELOPMENT: This paper evaluates the interplay between time-varying confounding and discretization, which can induce bias in assessing screening effectiveness. We investigate this bias in evaluating the effect of different CRC screening methods that differ from each other in typical screening frequency. APPLICATION: First, using theory, we establish the direction of the bias. Then, we use simulations of hypothetical settings to study the bias magnitude for varying levels of discretization, frequency of screening and length of the study period. We develop a method to assess possible bias due to coarsening in simulated situations. CONCLUSIONS: The proposed method can inform future studies of screening effectiveness, especially for CRC, by determining the choice of interval lengths where data are discretized to minimize bias due to coarsening while balancing computational costs.


Subject(s)
Bias , Colorectal Neoplasms , Early Detection of Cancer , Humans , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Time Factors , Mass Screening/methods , Observational Studies as Topic/methods , Confounding Factors, Epidemiologic
2.
Ocul Immunol Inflamm ; 29(6): 1064-1071, 2021 Aug 18.
Article in English | MEDLINE | ID: mdl-31821051

ABSTRACT

Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.


Subject(s)
Uveitis/physiopathology , Visual Acuity/physiology , Adolescent , Adult , Aged , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Tertiary Healthcare , Time Factors , Uveitis/drug therapy , Young Adult
3.
Am J Ophthalmol ; 208: 68-75, 2019 12.
Article in English | MEDLINE | ID: mdl-31344346

ABSTRACT

PURPOSE: To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases. DESIGN: Retrospective analysis of cohort study data. METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days. RESULTS: The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups. CONCLUSIONS: Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.


Subject(s)
Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Mycophenolic Acid/therapeutic use , Scleritis/drug therapy , Uveitis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Glucocorticoids/therapeutic use , Humans , Infant , Inflammation/drug therapy , Male , Middle Aged , Prednisone/therapeutic use , Retrospective Studies , Scleritis/physiopathology , Uveitis/physiopathology , Visual Acuity/physiology
4.
Stat Methods Med Res ; 28(2): 613-625, 2019 02.
Article in English | MEDLINE | ID: mdl-28980502

ABSTRACT

Marginal structural models are a class of causal models useful for characterizing the effect of treatment in the presence of time-varying confounding. They are more widely used than structural nested models, partly because these models are easier to understand and to implement. We extend marginal structural models to situations with clustered observations with unit- and cluster-level treatment and introduce an appropriate inferential method. We consider how to formulate models with cluster-level and unit-level treatments. For unit-level treatments, we consider cases with and without interference. We also consider the use of unit-specific inverse probability weights and certain working correlation structures to improve the efficiency of estimators in some situations. We apply our method to different scenarios including 2 or 3 units per cluster and a mixture of larger clusters. Simulation examples and data from the treatment arm of a glaucoma clinical trial were used to illustrate our method.


Subject(s)
Antihypertensive Agents/therapeutic use , Glaucoma/prevention & control , Models, Statistical , Administration, Topical , Cluster Analysis , Humans , Intraocular Pressure , Multicenter Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical data
5.
Stat Med ; 36(26): 4167-4181, 2017 Nov 20.
Article in English | MEDLINE | ID: mdl-28791722

ABSTRACT

In patients with chronic kidney disease (CKD), clinical interest often centers on determining treatments and exposures that are causally related to renal progression. Analyses of longitudinal clinical data in this population are often complicated by clinical competing events, such as end-stage renal disease (ESRD) and death, and time-dependent confounding, where patient factors that are predictive of later exposures and outcomes are affected by past exposures. We developed multistate marginal structural models (MS-MSMs) to assess the effect of time-varying systolic blood pressure on disease progression in subjects with CKD. The multistate nature of the model allows us to jointly model disease progression characterized by changes in the estimated glomerular filtration rate (eGFR), the onset of ESRD, and death, and thereby avoid unnatural assumptions of death and ESRD as noninformative censoring events for subsequent changes in eGFR. We model the causal effect of systolic blood pressure on the probability of transitioning into 1 of 6 disease states given the current state. We use inverse probability weights with stabilization to account for potential time-varying confounders, including past eGFR, total protein, serum creatinine, and hemoglobin. We apply the model to data from the Chronic Renal Insufficiency Cohort Study, a multisite observational study of patients with CKD.


Subject(s)
Cohort Studies , Disease Progression , Models, Statistical , Blood Pressure , Causality , Computer Simulation , Confounding Factors, Epidemiologic , Glomerular Filtration Rate , Humans , Markov Chains , Probability , Renal Insufficiency, Chronic , Risk Factors
6.
Clin J Am Soc Nephrol ; 11(9): 1546-1556, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27340285

ABSTRACT

BACKGROUND AND OBJECTIVES: CKD is a global public health problem with significant mortality and morbidity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-ß, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants. RESULTS: Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of ≥50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-α and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P<0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P<0.01), and TNF-α (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P<0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P<0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P<0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P<0.001), and TNF-α (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P<0.001) with outcome were attenuated but remained significant. CONCLUSIONS: Elevated plasma levels of fibrinogen and TNF-α and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.


Subject(s)
C-Reactive Protein/metabolism , Cytokines/blood , Fibrinogen/metabolism , Inflammation/complications , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Adult , Aged , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Inflammation/blood , Interleukin-1/blood , Interleukin-6/blood , Kidney Failure, Chronic/etiology , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Serum Albumin/metabolism , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/blood
7.
Int J Biostat ; 11(2): 203-22, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26115504

ABSTRACT

In assessing the efficacy of a time-varying treatment structural nested models (SNMs) are useful in dealing with confounding by variables affected by earlier treatments. These models often consider treatment allocation and repeated measures at the individual level. We extend SNMMs to clustered observations with time-varying confounding and treatments. We demonstrate how to formulate models with both cluster- and unit-level treatments and show how to derive semiparametric estimators of parameters in such models. For unit-level treatments, we consider interference, namely the effect of treatment on outcomes in other units of the same cluster. The properties of estimators are evaluated through simulations and compared with the conventional GEE regression method for clustered outcomes. To illustrate our method, we use data from the treatment arm of a glaucoma clinical trial to compare the effectiveness of two commonly used ocular hypertension medications.


Subject(s)
Computer Simulation , Glaucoma/diagnosis , Glaucoma/drug therapy , Models, Statistical , Vasodilator Agents/administration & dosage , Case-Control Studies , Cluster Analysis , Female , Humans , Male , Statistics as Topic
8.
Clin Trials ; 12(4): 309-16, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25948621

ABSTRACT

BACKGROUND: A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point, and one ultimate outcome of interest and discuss new issues arising when variables are time-varying. METHODS: Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this article, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. CONCLUSION: In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this article has provided some motivation for future work on estimation and inference in such settings.


Subject(s)
Biomarkers , Outcome Assessment, Health Care , Therapeutics , Clinical Trials as Topic , Humans , Mathematical Concepts , Regression Analysis , Time Factors
9.
PLoS One ; 10(4): e0124772, 2015.
Article in English | MEDLINE | ID: mdl-25909952

ABSTRACT

BACKGROUND: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. METHODS: Plasma levels of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. RESULTS: LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). CONCLUSION: In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.


Subject(s)
Inflammation Mediators/blood , Myocardium/pathology , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/pathology , Adult , Aged , Biomarkers/blood , Cohort Studies , Echocardiography , Female , Humans , Hypertrophy, Left Ventricular/complications , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Logistic Models , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/complications , Risk Factors
10.
Stat Probab Lett ; 97: 185-191, 2015 Feb 01.
Article in English | MEDLINE | ID: mdl-25554715

ABSTRACT

Efficient semiparametric estimation of longitudinal causal effects is often analytically or computationally intractable. We propose a novel restricted estimation approach for increasing efficiency, which can be used with other techniques, is straightforward to implement, and requires no additional modeling assumptions.

12.
Stat Med ; 33(26): 4577-89, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-25042626

ABSTRACT

Propensity scores are widely used to control for confounding when estimating the effect of a binary treatment in observational studies. They have been generalized to ordinal and continuous treatments in the recent literature. Following the definition of propensity function and its parameterizations (called the propensity parameter in this paper) proposed by Imai and van Dyk, we explore sufficient conditions for selecting propensity parameters to control for confounding for continuous treatments in the context of regression-based adjustment in linear models. Typically, investigators make parametric assumptions about the form of the dose-response function for a continuous treatment. Such assumptions often allow the analyst to use only a subset of the propensity parameters to control confounding. When the treatment is the only predictor in the structural, that is, causal model, it is sufficient to adjust only for the propensity parameters that characterize the expectation of the treatment variable or its functional form. When the structural model includes selected baseline covariates other than the treatment variable, those baseline covariates, in addition to the propensity parameters, must also be adjusted in the model. We demonstrate these points with an example estimating the dose-response relationship for the effect of erythropoietin on hematocrit level in patients with end-stage renal disease.


Subject(s)
Confounding Factors, Epidemiologic , Models, Statistical , Observational Studies as Topic/methods , Propensity Score , Aged , Computer Simulation , Dose-Response Relationship, Drug , Erythropoietin/therapeutic use , Hematocrit , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Renal Dialysis
13.
Pediatrics ; 134(1): 37-44, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24935993

ABSTRACT

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20-1.96) for clinical remission and 1.74 (95% CI, 1.33-2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4-11.1) for clinical remission and 5.0 (95% CI, 3.4-10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.


Subject(s)
Crohn Disease/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Biomedical Research , Controlled Clinical Trials as Topic , Feasibility Studies , Female , Humans , Male , Pediatrics
14.
Nephrol Dial Transplant ; 29(4): 864-72, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24516231

ABSTRACT

BACKGROUND: Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). METHODS: We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. RESULTS: The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. CONCLUSIONS: Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.


Subject(s)
DNA Methylation/genetics , Epigenesis, Genetic , Glomerular Filtration Rate , Renal Insufficiency, Chronic/genetics , Adult , Aged , Disease Progression , Epithelial-Mesenchymal Transition , Female , Humans , Male , Middle Aged , Prognosis , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/physiopathology , Young Adult
15.
Obesity (Silver Spring) ; 22(5): 1359-66, 2014 May.
Article in English | MEDLINE | ID: mdl-24415732

ABSTRACT

OBJECTIVE: The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined. METHODS: Plasma concentration of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-α, TGF-ß, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM). RESULTS: Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-α increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1ß, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] = 0.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively (P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans. CONCLUSIONS: BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans.


Subject(s)
Adiposity , Black or African American , Inflammation/ethnology , Kidney Failure, Chronic/ethnology , White People , Adult , Aged , Biomarkers/blood , Body Mass Index , C-Reactive Protein/metabolism , Cohort Studies , Cross-Sectional Studies , Electric Impedance , Fibrinogen/metabolism , Humans , Inflammation/blood , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-10/blood , Interleukin-1beta/blood , Interleukin-6/blood , Kidney Failure, Chronic/blood , Linear Models , Middle Aged , Multivariate Analysis , Serum Albumin , Socioeconomic Factors , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/blood
16.
Am J Kidney Dis ; 63(2): 236-43, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24182662

ABSTRACT

BACKGROUND: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. PREDICTORS: Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. OUTCOMES: Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage. RESULTS: Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. LIMITATIONS: Participants may not be representative of the entire CKD population. CONCLUSIONS: Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.


Subject(s)
Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Treatment Outcome , Young Adult
17.
Stat Med ; 33(20): 3421-33, 2014 Sep 10.
Article in English | MEDLINE | ID: mdl-23255088

ABSTRACT

Tom Ten Have made many contributions to causal inference and biostatistics before his untimely death. This paper reviews Tom's contributions and discusses potential related future research directions. We focus on Tom's contributions to longitudinal/repeated measures categorical data analysis and particularly his contributions to causal inference. Tom's work on causal inference was primarily in the areas of estimating the effect of receiving treatment in randomized trials with nonadherence and mediation analysis. A related area to mediation analysis he was working on at the time of his death was posttreatment effect modification with applications to designing adaptive treatment strategies.


Subject(s)
Biostatistics/methods , Causality , Randomized Controlled Trials as Topic/methods , Humans , Longitudinal Studies , Patient Compliance , Regression Analysis , Research
18.
Biometrics ; 69(3): 572-5, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24073863
19.
J Rheumatol ; 40(8): 1394-403, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23818712

ABSTRACT

OBJECTIVE: To evaluate the outcome of tumor necrosis factor-α inhibition (anti-TNF) for pediatric uveitis. METHODS: We retrospectively assessed children (age ≤ 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥ 2 consecutive ophthalmological examinations ≥ 28 days apart while taking no oral and ≤ 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. RESULTS: Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%-87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%-76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%-80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%-31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%-43%). CONCLUSION: Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Immunoglobulin G/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Uveitis, Anterior/drug therapy , Uveitis/drug therapy , Adalimumab , Adolescent , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/epidemiology , Child , Child, Preschool , Cohort Studies , Comorbidity , Etanercept , Female , Humans , Infant , Infliximab , Kaplan-Meier Estimate , Male , Retrospective Studies , Time Factors , Treatment Outcome , Uveitis/epidemiology , Uveitis, Anterior/epidemiology
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