19 results on '"Saul, Bradley"'
Search Results
2. Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study
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Hyams, Jeffrey S, Davis, Sonia, Mack, David R, Boyle, Brendan, Griffiths, Anne M, LeLeiko, Neal S, Sauer, Cary G, Keljo, David J, Markowitz, James, Baker, Susan S, Rosh, Joel, Baldassano, Robert N, Patel, Ashish, Pfefferkorn, Marian, Otley, Anthony, Heyman, Melvin, Noe, Joshua, Oliva-Hemker, Maria, Rufo, Paul, Strople, Jennifer, Ziring, David, Guthery, Stephen L, Sudel, Boris, Benkov, Keith, Wali, Prateek, Moulton, Dedrick, Evans, Jonathan, Kappelman, Michael D, Marquis, Alison, Sylvester, Francisco A, Collins, Margaret H, Venkateswaran, Suresh, Dubinsky, Marla, Tangpricha, Vin, Spada, Krista L, Britt, Ashley, Saul, Bradley, Gotman, Nathan, Wang, Jessie, Serrano, Jose, Kugathasan, Subra, Walters, Thomas, and Denson, Lee A
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- 2017
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3. Is fasting safe? A chart review of adverse events during medically supervised, water-only fasting
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Finnell, John S., Saul, Bradley C., Goldhamer, Alan C., and Myers, Toshia R.
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- 2018
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4. Lipid Testing Trends in the US Before and After the Release of the 2013 Cholesterol Treatment Guidelines
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Levintow,Sara N, Reading,Stephanie R, Saul,Bradley C, Yu,Ying, Reams,Diane, McGrath,Leah J, Philip,Kiran, Dluzniewski,Paul J, and Brookhart,M Alan
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Clinical Epidemiology - Abstract
Sara N Levintow,1,2 Stephanie R Reading,3 Bradley C Saul,1 Ying Yu,1 Diane Reams,1 Leah J McGrath,1 Kiran Philip,3 Paul J Dluzniewski,3 M Alan Brookhart1,4 1NoviSci, Inc, Durham, NC, USA; 2Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; 3Center for Observational Research, Amgen, Thousand Oaks, CA, USA; 4Department of Population Health Sciences, Duke University, Durham, NC, USACorrespondence: Sara N LevintowNoviSci, Inc, PMB 218, 201 W Main St, Ste 200, Durham, NC 27701 Email slevintow@novisci.comBackground: The 2013 ACC/AHA cholesterol treatment guidelines removed the recommendation to treat adults at risk of cardiovascular disease to goal levels of low-density lipoprotein cholesterol (LDL-C). We anticipated that the frequency of LDL-C testing in clinical practice would decline as a result. To test this hypothesis, we evaluated the frequency of LDL-C testing before and after the guideline release.Methods: We used the MarketScan® Commercial and Medicare Supplemental claims data (1/1/2007– 12/31/2016) to identify four cohorts: 1) statin initiators (any intensity), 2) high-intensity statin initiators, 3) ezetimibe initiators, and 4) patients at very high cardiovascular risk (≥ 2 hospitalizations for myocardial infarction or ischemic stroke, with prevalent statin use). Rates of LDL-C testing by calendar year quarter were estimated for each cohort. To estimate rates in the absence of a guideline change, we fit a time-series model to the pre-guideline rates and extrapolated to the post-guideline period, adjusting for covariates, seasonality, and time trend.Results: Pre- and post-guideline rates (LDL-C tests per 1,000 persons per quarter) were 248 and 235, respectively, for 3.9 million statin initiators; 263 and 246 for 1.3 million high-intensity statin initiators; 277 and 261 for 323,544 ezetimibe initiators; and 180 and 158 for 42,108 very high-risk patients. For all cohorts, observed post-guideline rates were similar to model-predicted rates. On average, the difference between observed and predicted rates was 8.5 for patients initiating any statin; 2.6 for patients initiating a high-intensity statin; 11.4 for patients initiating ezetimibe, and − 0.5 for high-risk patients.Conclusion: We observed no discernible impact of the release of the 2013 ACC/AHA guidelines on LDL-C testing rates. Rather, there was a gradual decline in testing rates starting prior to the guideline change and continuing throughout the study period. Our findings suggest that the guidelines had little to no impact on use of LDL-C testing.Keywords: low-density lipoprotein cholesterol, statin, ezetimibe, cardiovascular disease, guideline adherence, database, epidemiology
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- 2020
5. Lessons Learned Using Real‐World Data to Emulate Randomized Trials: A Case Study of Treatment Effectiveness for Newly Diagnosed Immune Thrombocytopenia.
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McGrath, Leah J., Nielson, Carrie, Saul, Bradley, Breskin, Alexander, Yu, Ying, Nicolaisen, Sia K., Kilpatrick, Karynsa, Ghanima, Waleed, Christiansen, Christian F., Bahmanyar, Shahram, Linder, Marie, Eisen, Melissa, Wasser, Jeffrey, Altomare, Ivy, Kuter, David, Sørensen, Henrik T., Kelsh, Michael, and Brookhart, M. Alan
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IDIOPATHIC thrombocytopenic purpura ,DIAGNOSIS ,TREATMENT effectiveness ,PLATELET count ,MEDICAL registries ,SAMPLE size (Statistics) - Abstract
Regulatory agencies are increasingly considering real‐world evidence (RWE) to support label expansions of approved medicines. We conducted a comparative effectiveness study to emulate a proposed randomized trial of romiplostim vs. standard‐of‐care (SOC) therapy among patients with recently diagnosed (≤12 months) immune thrombocytopenia (ITP), that could support expansion of the romiplostim label. We discuss challenges that we encountered and solutions that were developed to address those challenges. Study size was a primary concern, particularly for romiplostim initiators, given the rarity of ITP and the stringent trial eligibility criteria. For this reason, we leveraged multiple data sources (Nordic Country Patient Registry for Romiplostim; chart review study of romiplostim initiators in Europe; Flatiron Health EMR linked with MarketScan claims). Additionally, unlike the strictly controlled clinical trial setting, platelet counts were not measured at regular intervals in the observational data sources, and therefore the end point of durable platelet response often used in trials could not be reliably measured. Instead, the median platelet count was chosen as the primary end point. Ultimately, while we observed a slightly higher median platelet count in the romiplostim group vs. SOC, precision was limited because of small study size (median difference was 11 × 109/L (95% CI: −59, 81)). We underscore the importance of conducting comprehensive feasibility assessments to identify fit‐for‐purpose data sources with sufficient sample size, data elements, and follow‐up. Beyond technical challenges, we also discuss approaches to increase the credibility of RWE, including systematic incorporation of clinical expertise into study design decisions, and separation between decision makers and the data. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Applications of and Tools for Causal Inference
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Saul, Bradley
- Abstract
Various topics related to causal inference with application to infectious disease and ecology are studied and software tools for such applications developed. The causal g-methods of Robins and colleagues – the parametric g-formula, marginal structural models, and structural nested models – are applied to a causal assessment of impaired water quality in North Carolina’s Cape Fear River. The application demonstrates how a potential outcomes’ causal analysis can be done with routine stream monitoring data. Under certain conditions, each of the g-methods can be cast in an estimating equation framework. Causal models often ‘stack’ estimating equations from multiple models, which can be a source of programming errors and bottlenecks. An R package for obtaining point and variance estimates from any arbitrary set of estimating equations is presented. The context of infectious diseases stimulated many advances in causal inference methods in the past 15 years. These methods and important contributions to the science of infectious diseases are reviewed.
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- 2017
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7. Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children.
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Mack, David R., Saul, Bradley, Boyle, Brendan, Griffiths, Anne, Sauer, Cary, Markowitz, James, LeLeiko, Neal, Keljo, David, Rosh, Joel R., Baker, Susan S., Steiner, Steve, Heyman, Melvin B., Patel, Ashish S., Baldassano, Robert, Noe, Joshua, Rufo, Paul, Kugathasan, Subra, Walters, Thomas, Marquis, Alison, and Thomas, Sonia M.
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- 2020
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8. Using negative control outcomes to assess the comparability of treatment groups among women with osteoporosis in the United States.
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McGrath, Leah J., Spangler, Leslie, Curtis, Jeffrey R., Ehrenstein, Vera, Sørensen, Henrik T., Saul, Bradley, Levintow, Sara N., Reams, Diane, Bradbury, Brian D., and Brookhart, M. Alan
- Abstract
Purpose In contrast to randomized clinical trials, comparative safety and effectiveness assessments of osteoporosis medications in clinical practice may be subject to confounding by indication. We used negative control outcomes to detect residual confounding when comparing osteoporosis medications. Methods: Using MarketScan Commercial and Supplemental claims, we identified women aged ≥55 years who initiated an oral bisphosphonate (BP) (risedronate, alendronate, or ibandronate), denosumab (an injected biologic), or intravenous zoledronic acid (ZA) from October 1, 2010 to September 30, 2015. Women with Paget's disease or cancer were excluded. We compared individual oral BPs to each other, denosumab to ZA, denosumab to oral BPs, and ZA to oral BPs, with respect to 11 negative control outcomes identified by subject matter experts. We estimated the 12‐month cumulative risk difference (RD) using inverse probability of treatment and censoring weights. Results: Among 148 587 women, most initiated alendronate (57%), followed by ibandronate (12%), ZA (11%), risedronate (10%), and denosumab (10%). Compared with denosumab, patients initiating ZA had similar risks of all negative control outcomes. Compared with oral BPs, patients initiating denosumab had a higher risk of a wellness visit (RD = 1.2%, 95% CI: 0.4, 1.9) and a lower risk of receiving herpes zoster vaccine (RD = −0.6%, 95% CI: −1.1, −0.2). Comparing ZA with oral BP initiators resulted in two outcomes with positive associations. Conclusions: Caution is warranted when comparing injectable vs oral osteoporosis medications, given the potential for unmeasured confounding. Evaluating negative control outcomes could be a standard validity check prior to conducting comparative studies. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Downstream Effects of Upstream Causes.
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Saul, Bradley C., Hudgens, Michael G., and Mallin, Michael A.
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CHLOROPHYLL in water , *STATISTICAL models , *WATER quality monitoring , *WATER pollution , *ENVIRONMENTAL protection - Abstract
The United States Environmental Protection Agency considers nutrient pollution in stream ecosystems one of the United States' most pressing environmental challenges. But limited independent replicates, lack of experimental randomization, and space- and time-varying confounding handicap causal inference on effects of nutrient pollution. In this article, the causal g-methods are extended to allow for exposures to vary in time and space in order to assess the effects of nutrient pollution on chlorophyll a—a proxy for algal production. Publicly available data from North Carolina's Cape Fear River and a simulation study are used to show how causal effects of upstream nutrient concentrations on downstream chlorophyll a levels may be estimated from typical water quality monitoring data. Estimates obtained from the parametric g-formula, a marginal structural model, and a structural nested model indicate that chlorophyll a concentrations at Lock and Dam 1 were influenced by nitrate concentrations measured 86 to 109 km upstream, an area where four major industrial and municipal point sources discharge wastewater. for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Doubly robust estimation in observational studies with partial interference.
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Lan Liu, Hudgens, Michael G., Saul, Bradley, Clemens, John D., Ali, Mohammad, and Emch, Michael E.
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CHOLERA vaccines ,SCIENTIFIC observation ,REGRESSION analysis ,THERAPEUTICS ,DIMENSION reduction (Statistics) - Abstract
Interference occurs when the treatment (or exposure) of one individual affects the outcomes of others. In some settings, it may be reasonable to assume that individuals can be partitioned into clusters such that there is no interference between individuals in different clusters, that is, there is partial interference. In observational studies with partial interference, inverse probability weighted (IPW) estimators have been something else different possible treatment effects. However, the validity of IPW estimators depends on the propensity score being known or correctly modelled. Alternatively, one can estimate the treatment effect using an outcome regression model. In this paper, we propose doubly robust (DR) estimators that utilize both models and are consistent and asymptotically normal if either model, but not necessarily both, is correctly specified. Empirical results are presented to demonstrate the DR property of the proposed estimators and the efficiency gain of DR over IPW estimators when both models are correctly specified. The different estimators are illustrated using data from a study examining the effects of cholera vaccination in Bangladesh. [ABSTRACT FROM AUTHOR]
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- 2019
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11. Effects of 7 days on an ad libitum low-fat vegan diet: the McDougall Program cohort.
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McDougall, John, Thomas, Laurie E., McDougall, Craig, Moloney, Gavin, Saul, Bradley, Finnell, John S., Richardson, Kelly, and Petersen, Katelin Mae
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Background: Epidemiologic evidence, reinforced by clinical and laboratory studies, shows that the rich Western diet is the major underlying cause of death and disability (e.g, from cardiovascular disease and type 2 diabetes) in Western industrialized societies. The objective of this study is to document the effects that eating a low-fat (≤10% of calories), high-carbohydrate (~80% of calories), moderate-sodium, purely plant-based diet ad libitum for 7 days can have on the biomarkers of cardiovascular disease and type 2 diabetes. Methods: Retrospective analysis of measurements of weight, blood pressure, blood sugar, and blood lipids and estimation of cardiovascular disease risk at baseline and day 7 from 1615 participants in a 10-day residential dietary intervention program from 2002 to 2011. Wilcoxon’s signed-rank test was used for testing the significance of changes from baseline. Results: The median (interquartile range, IQR) weight loss was 1.4 (1.8) kg (p < .001). The median (IQR) decrease in total cholesterol was 22 (29) mg/dL (p < .001). Even though most antihypertensive and antihyperglycemic medications were reduced or discontinued at baseline, systolic blood pressure decreased by a median (IQR) of 8 (18) mm Hg (p < .001), diastolic blood pressure by a median (IQR) of 4 (10) mm Hg (p < .001), and blood glucose by a median (IQR) of 3 (11) mg/dL (p < .001). For patients whose risk of a cardiovascular event within 10 years was >7.5% at baseline, the risk dropped to 5.5% (>27%) at day 7 (p < .001). Conclusions: A low-fat, starch-based, vegan diet eaten ad libitum for 7 days results in significant favorable changes in commonly tested biomarkers that are used to predict future risks for cardiovascular disease and metabolic diseases. [ABSTRACT FROM AUTHOR]
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- 2014
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12. Erratum to: Effects of 7 days on an ad libitum low-fat vegan diet: the McDougall Program cohort.
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McDougall, John, Thomas, Laurie E, McDougall, Craig, Moloney, Gavin, Saul, Bradley, Finnell, John S, Richardson, Kelly, and Petersen, Katelin Mae
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VEGANISM ,LOW-fat diet - Abstract
A correction to the article "Effects of 7 days on an ad libitum low-fat vegan diet: the McDougall Program cohort" by John McDougall and colleagues is presented.
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- 2017
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13. Su1195 Simple Blood Testing Defines Severe New Onset Ulcerative Colitis in Children: The PROTECT Study.
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Mack, David R., Saul, Bradley, Davis, Sonia, Marquis, Alison, Boyle, Brendan, Griffiths, Anne M., Sauer, Cary, Markowitz, James, Leleiko, Neal S., Rosh, Joel R., Keljo, David J., Baker, Susan S., Pfefferkorn, Marian D., Heyman, Melvin B., Patel, Ashish S., Oliva-Hemker, Maria, Baldassano, Robert, Noe, Joshua D., Rufo, Paul A., and Otley, Anthony R.
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- 2015
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14. A LITTLE HEAT, A LITTLE HISTORY, A LITTLE DUATHLON LOVE IN RICHMOND.
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Saul, Bradley
- Abstract
A personal narrative is presented which explores the author's experience in participating in the duathlon competition.
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- 2009
15. Potential Effects of Prolonged Water-Only Fasting Followed by a Whole-Plant-Food Diet on Salty and Sweet Taste Sensitivity and Perceived Intensity, Food Liking, and Dietary Intake.
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Myers TR, Saul B, Karlsen M, Beauchesne A, Glavas Z, Ncube M, Bradley R, and Goldhamer AC
- Abstract
The overconsumption of calorie-dense foods high in added salt, sugar, and fat is a major contributor to current rates of obesity, and methods to reduce consumption are needed. Prolonged water-only fasting followed by an exclusively whole-plant-food diet free of added salt, oil, and sugar may reduce the consumption of these hyper-palatable foods, but such effects have not been quantified. Therefore, we conducted a preliminary study to estimate the effects of this intervention on salty and sweet taste detection and recognition thresholds and perceived taste intensity after at least five days of fasting and at refeed day three. We also assessed the effects on sweet, salty, and fatty food preference and overall dietary consumption 30 days after the day three refeed visit. Based on this data, we estimated that 10 days after the start of the fasting, salty taste recognition, sweet taste detection, and sweet taste recognition thresholds decreased significantly, salty taste intensity ratings increased significantly, and sweet taste intensity ratings decreased significantly. We also have preliminary data that prolonged water-only fasting followed by refeeding on an exclusively whole-food-plant diet may reduce salty/fatty and sweet/fatty food liking, reduce sugar intake, and increase vegetable intake. These results support further research into the effects of fasting and diet on taste function and food likability and consumption., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Myers et al.)
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- 2022
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16. The Calculus of M-Estimation in R with geex.
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Saul BC and Hudgens MG
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M-estimation, or estimating equation, methods are widely applicable for point estimation and asymptotic inference. In this paper, we present an R package that can find roots and compute the empirical sandwich variance estimator for any set of user-specified, unbiased estimating equations. Examples from the M-estimation primer by Stefanski and Boos (2002) demonstrate use of the software. The package also includes a framework for finite sample, heteroscedastic, and autocorrelation variance corrections, and a website with an extensive collection of tutorials.
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- 2020
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17. Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study.
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Hyams JS, Davis Thomas S, Gotman N, Haberman Y, Karns R, Schirmer M, Mo A, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo PA, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis MA, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Saul B, Wang J, Serrano J, Hommel K, Marigorta UM, Gibson G, Xavier RJ, Kugathasan S, Walters T, and Denson LA
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- Adolescent, Biomarkers metabolism, Child, Child, Preschool, Cohort Studies, Female, Hospitalization statistics & numerical data, Humans, Male, Treatment Outcome, Adrenal Cortex Hormones therapeutic use, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Colitis, Ulcerative drug therapy, Mesalamine therapeutic use
- Abstract
Background: Lack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course., Methods: In this inception cohort study, we recruited paediatric patients aged 4-17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada. Patients initially received standardised mesalazine or corticosteroids, with pre-established criteria for escalation to immunomodulators (ie, thiopurines) or anti-tumor necrosis factor-α (TNFα) therapy. We used RNA sequencing to define rectal gene expression before treatment, and 16S sequencing to characterise rectal and faecal microbiota. The primary outcome was week 52 corticosteroid-free remission with no therapy beyond mesalazine. We assessed factors associated with the primary outcome using logistic regression models of the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01536535., Findings: Between July 10, 2012, and April 21, 2015, of 467 patients recruited, 428 started medical therapy, of whom 400 (93%) were evaluable at 52 weeks and 386 (90%) completed the study period with no protocol violations. 150 (38%) of 400 participants achieved week 52 corticosteroid-free remission, of whom 147 (98%) were taking mesalazine and three (2%) were taking no medication. 74 (19%) of 400 were escalated to immunomodulators alone, 123 (31%) anti-TNFα therapy, and 25 (6%) colectomy. Low baseline clinical severity, high baseline haemoglobin, and week 4 clinical remission were associated with achieving week 52 corticosteroid-free remission (n=386, logistic model area under the curve [AUC] 0·70, 95% CI 0·65-0·75; specificity 77%, 95% CI 71-82). Baseline severity and remission by week 4 were validated in an independent cohort of 274 paediatric patients with newly diagnosed ulcerative colitis. After adjusting for clinical predictors, an antimicrobial peptide gene signature (odds ratio [OR] 0·57, 95% CI 0·39-0·81; p=0·002) and abundance of Ruminococcaceae (OR 1·43, 1·02-2·00; p=0·04), and Sutterella (OR 0·81, 0·65-1·00; p=0·05) were independently associated with week 52 corticosteroid-free remission., Interpretation: Our findings support the utility of initial clinical activity and treatment response by 4 weeks to predict week 52 corticosteroid-free remission with mesalazine alone in children who are newly diagnosed with ulcerative colitis. The development of personalised clinical and biological signatures holds the promise of informing ulcerative colitis therapeutic decisions., Funding: US National Institutes of Health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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18. Doubly Robust Estimation in Observational Studies with Partial Interference.
- Author
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Liu L, Hudgens MG, Saul B, Clemens JD, Ali M, and Emch ME
- Abstract
Interference occurs when the treatment (or exposure) of one individual affects the outcomes of others. In some settings it may be reasonable to assume individuals can be partitioned into clusters such that there is no interference between individuals in different clusters, i.e., there is partial interference. In observational studies with partial interference, inverse probability weighted (IPW) estimators have been proposed of different possible treatment effects. However, the validity of IPW estimators depends on the propensity score being known or correctly modeled. Alternatively, one can estimate the treatment effect using an outcome regression model. In this paper, we propose doubly robust (DR) estimators which utilize both models and are consistent and asymptotically normal if either model, but not necessarily both, is correctly specified. Empirical results are presented to demonstrate the DR property of the proposed estimators, as well as the efficiency gain of DR over IPW estimators when both models are correctly specified. The different estimators are illustrated using data from a study examining the effects of cholera vaccination in Bangladesh.
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- 2019
- Full Text
- View/download PDF
19. A Recipe for inferference: Start with Causal Inference. Add Interference. Mix Well with R.
- Author
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Saul BC and Hudgens MG
- Abstract
In causal inference, interference occurs when the treatment of one subject affects the outcome of other subjects. Interference can distort research conclusions about causal effects when not accounted for properly. In the absence of interference, inverse probability weighted (IPW) estimators are commonly used to estimate causal effects from observational data. Recently, IPW estimators have been extended to handle interference. Tchetgen Tchetgen and VanderWeele (2012) proposed IPW methods to estimate direct and indirect (or spillover) effects that allow for interference between individuals within groups. In this paper, we present inferference , an R package that computes these IPW causal effect estimates when interference may be present within groups. We illustrate use of the package with examples from political science and infectious disease.
- Published
- 2017
- Full Text
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