Bio

Bio


I am interested in using statistical methods to understand and improve human health. I currently collaborate with investigators in the medical school in chronic disease prevention, pediatrics, and nutrition. I joined the Stanford Quantitative Sciences Unit in 2015 after completing my PhD in Biostatistics at the University of North Carolina at Chapel Hill. I am also interested in software development. At UNC, I wrote the R packages RI2by2 and interferenceCI to accompany papers from my dissertation, titled "Causal inference for binary data with interference". At Stanford, I helped translate the near-far matching method into an R package titled nearfar.

Education & Certifications


  • PhD, University of North Carolina, Chapel Hill, Biostatistics (2015)

Publications

All Publications


  • Measuring socioeconomic adversity in early life ACTA PAEDIATRICA Anand, K. S., Rigdon, J., Rovnaghi, C. R., Qin, F., Tembulkar, S., Bush, N., LeWinn, K., Tylavsky, F. A., Davis, R., Barr, D. A., Gotlib, I. H. 2019; 108 (7): 1267–77

    View details for DOI 10.1111/apa.14715

    View details for Web of Science ID 000471904300016

  • Response to letter to the Editor ACTA PAEDIATRICA Rovnaghi, C. R., Tembulkar, S., Rigdon, J., Anand, K. S. 2019; 108 (7): 1362

    View details for DOI 10.1111/apa.14768

    View details for Web of Science ID 000471904300030

  • Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival AMERICAN JOURNAL OF TRANSPLANTATION Sang, A. X., McPherson, M. C., Ivison, G. T., Qu, X., Rigdon, J., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2019; 19 (5): 1305–14

    View details for DOI 10.1111/ajt.15216

    View details for Web of Science ID 000471342300010

  • Performance of Matching Methods to Unmatched Ordinary Least Squares Regression Under Constant Effects. American journal of epidemiology Vable, A. M., Kiang, M. V., Glymour, M. M., Rigdon, J., Drabo, E. F., Basu, S. 2019

    Abstract

    Matching methods are assumed to reduce the likelihood of a biased inference compared to ordinary least squares regression. Using simulations, we compare inferences from propensity score matching, coarsened exact matching, and un-matched covariate-adjusted ordinary least squares regression (OLS) to identify which methods, in which scenarios, produced unbiased inferences at the expected type I error rate of 5%. We simulated multiple datasets and systematically varied common support, discontinuities in the exposure and / or outcome, exposure prevalence, and analytic model misspecification. Matching inferences were often biased compared to OLS, particularly when common support was poor; when analysis models were correctly specified and common support was poor, the type I error rate was 1.6% for propensity score matching (statistically inefficient), 18.2% for coarsened exact matching (high), and 4.8% for OLS (expected). Our results suggest when estimates from matching and OLS are similar (i.e. confidence intervals overlap), OLS inferences are unbiased more often than matching inferences, however, when estimates from matching and OLS are dissimilar (i.e. confidence intervals do not overlap), matching inferences are unbiased more often than OLS inferences. This empirical 'rule of thumb' may help applied researchers identify situations when OLS inferences may be unbiased compared to matching inferences.

    View details for PubMedID 30995301

  • Substantial Cardiovascular Morbidity in Adults With Lower-Complexity Congenital Heart Disease CIRCULATION Saha, P., Potiny, P., Rigdon, J., Morello, M., Tcheandjieu, C., Romfh, A., Fernandes, S. M., McElhinney, D. B., Bernstein, D., Lui, G. K., Shaw, G. M., Ingelsson, E., Priest, J. R. 2019; 139 (16): 1889–99
  • To Text or Not to Text: Electronic Message Intervention to Improve Treatment Adherence Versus Matched Historical Controls. JMIR mHealth and uHealth Oppezzo, M. A., Stanton, M. V., Garcia, A., Rigdon, J., Berman, J. R., Gardner, C. D. 2019; 7 (4): e11720

    Abstract

    BACKGROUND: Ensuring treatment adherence is important for the internal validity of clinical trials. In intervention studies where touch points decrease over time, there is even more of an adherence challenge. Trials with multiple cohorts offer an opportunity to innovate on ways to increase treatment adherence without compromising the integrity of the study design, and previous cohorts can serve as historical controls. Electronically delivered nudges offer low-cost opportunities to increase treatment adherence.OBJECTIVE: This study aimed to evaluate the effectiveness of electronic messages (e-messages) on treatment adherence to the last cohort of a parent weight loss intervention during the second half of a year-long trial, when intervention checkpoint frequency decreases. Treatment adherence is measured by intervention class attendance and adherence to the intervention diet.METHODS: All participants in the last cohort (cohort 5, n=128) of a large randomized weight loss study were offered an e-message intervention to improve participant adherence during the last 6 months of a 1-year weight loss program. Overall, 3 to 4 electronic weekly messages asked participants about intervention diet adherence. A propensity score model was estimated using 97 participants who opted to receive e-messages and 31 who declined in cohort 5 and used to pair match cohort 5 e-message participants to a historical control group from cohorts 1 to 4. Moreover, 88 participants had complete data, yielding 176 participants in the final analyses. After matching, intervention and matched control groups were compared on (1) proportion of class attendance between the 6 and 12 month study endpoints, (2) diet adherence, as measured by total carbohydrate grams for low-carbohydrate (LC) and total fat grams for low-fat (LF) diets at 12 months, and (3) weight change from 6 to 12 months. The dose-response relationship between the proportion of text messages responded to and the 3 outcomes was also investigated.RESULTS: Compared with matched controls, receiving e-messages had no effect on (1) treatment adherence; class attendance after 6 months +4.6% (95% CI -4.43 to 13.68, P=.31), (2) adherence; LC -2.5 g carbohydrate, 95% CI -29.9 to 24.8, P=.85; LF +6.2 g fat, 95% CI -4.1 to 17.0, P=.26); or on (3) the secondary outcome of weight change in the last 6 months; +0.3 kg (95% CI -1.0 to 1.5, P=.68). There was a positive significant response correlation between the percentage of messages to which participants responded and class attendance (r=.45, P<.001).CONCLUSIONS: Although this e-message intervention did not improve treatment adherence, future studies can learn from this pilot and may incorporate more variety in the prompts and more interaction to promote more effective user engagement. Uniquely, this study demonstrated the potential for innovating within a multicohort trial using propensity score-matched historical control subjects.TRIAL REGISTRATION: ClinicalTrials.gov NCT01826591;https://clinicaltrials.gov/ct2/show/NCT01826591.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2016.12.021.

    View details for PubMedID 30964436

  • To Text or Not to Text: Electronic Message Intervention to Improve Treatment Adherence Versus Matched Historical Controls JMIR MHEALTH AND UHEALTH Oppezzo, M. A., Stanton, M., Garcia, A., Rigdon, J., Berman, J. R., Gardner, C. D. 2019; 7 (4)

    View details for DOI 10.2196/11720

    View details for Web of Science ID 000465340100001

  • Effects Of Alternative Food Voucher Delivery Strategies On Nutrition Among Low-Income Adults HEALTH AFFAIRS Basu, S., Gardner, C. D., White, J. S., Rigdon, J., Carroll, M. M., Akers, M., Seligman, H. K. 2019; 38 (4): 577–84
  • Effects Of Alternative Food Voucher Delivery Strategies On Nutrition Among Low-Income Adults. Health affairs (Project Hope) Basu, S., Gardner, C. D., White, J. S., Rigdon, J., Carroll, M. M., Akers, M., Seligman, H. K. 2019; 38 (4): 577–84

    Abstract

    Nutrition assistance programs are the subject of ongoing policy debates. Two proposals remain uninformed by existing evidence: whether restricting benefits to allow only fruit and vegetable purchases improves overall dietary intake, and whether more frequent distribution of benefits (weekly versus monthly) induces more fruit and vegetable consumption and less purchasing of calorie-dense foods. In a community-based trial, we randomly assigned participants to receive food vouchers that differed in what foods could be purchased (fruit and vegetables only or any foods) and in distribution schedule (in weekly or monthly installments, holding total monthly value constant). The use of vouchers for fruit and vegetables only did not yield significantly greater improvements than the unrestricted voucher did in terms of fruit and vegetable consumption or Healthy Eating Index (HEI) score. Weekly vouchers also failed to yield significantly greater improvements than monthly vouchers did. Proposed policies to make assistance more restricted or more frequent, while holding benefit value constant, might not improve nutrition among low-income Americans.

    View details for PubMedID 30933599

  • Association of triglyceride to HDL cholesterol ratio with cardiometabolic outcomes JOURNAL OF INVESTIGATIVE MEDICINE Yang, M., Rigdon, J., Tsai, S. A. 2019; 67 (3): 663–68
  • Using Machine Learning to Identify Heterogeneous Effects in Randomized Clinical Trials-Moving Beyond the Forest Plot and Into the Forest. JAMA network open Goldstein, B. A., Rigdon, J. 2019; 2 (3): e190004

    View details for PubMedID 30848801

  • Response to letter to the Editor. Acta paediatrica (Oslo, Norway : 1992) Rovnaghi, C. R., Tembulkar, S., Rigdon, J., Anand, K. J. 2019

    Abstract

    We agree with Dr. Meyer (1) that socioeconomic disparities are far from being solved and, in fact, US disparities have increased in the past decade. Most studies on socioeconomic status attempt to disentangle specific factors mediating the inequities linked with poor health outcomes. Because of complex interactions between individual factors, we proposed a socioeconomic adversity index (SAI) combining such factors in the US(2). This article is protected by copyright. All rights reserved.

    View details for PubMedID 30825246

  • Using Machine Learning to Identify Heterogeneous Effects in Randomized Clinical Trials-Moving Beyond the Forest Plot and Into the Forest JAMA NETWORK OPEN Goldstein, B. A., Rigdon, J. 2019; 2 (3)
  • Substantial Cardiovascular Morbidity in Adults with Lower-Complexity Congenital Heart Disease. Circulation Saha, P., Potiny, P., Rigdon, J., Morello, M., Tcheandjieu, C., Romfh, A., Fernandes, S. M., McElhinney, D. B., Bernstein, D., Lui, G. K., Shaw, G. M., Ingelsson, E., Priest, J. R. 2019

    Abstract

    BACKGROUND: Although lower-complexity cardiac malformations constitute the majority of adult congenital heart disease (ACHD), the long-term risks of adverse cardiovascular events and relationship with conventional risk factors in this population are poorly understood. We aimed to quantify the risk of adverse cardiovascular events associated with lower-complexity ACHD that is unmeasured by conventional risk factors.METHODS: A multi-tiered classification algorithm was used to select individuals with lower-complexity ACHD and individuals without ACHD for comparison amongst >500,000 British adults in the UK Biobank (UKB). ACHD diagnoses were sub-classified as "isolated aortic valve (AoV)" and "non-complex" defects. Time-to-event analyses were conducted for primary endpoints of fatal or non-fatal acute coronary syndrome (ACS), ischemic stroke, heart failure (HF), and atrial fibrillation, and a secondary combined endpoint for major adverse cardiovascular event (MACE). Maximum follow-up time for the study period was 22 years using retrospectively and prospectively collected data from the UKB.RESULTS: We identified 2,006 individuals with lower-complexity ACHD and 497,983 unexposed individuals in the UKB (median [IQR] age at enrollment 58 [51,63]). Of the ACHD-exposed group, 59% were male; 51% were current or former smokers; 30% were obese; 69%, 41%, and 7% were diagnosed or treated for hypertension, hyperlipidemia, and diabetes respectively. After adjustment for 12 measured cardiovascular risk factors, ACHD remained strongly associated with the primary endpoints, with hazard ratios (HR) ranging from 2.0 (95% confidence interval [CI] 1.5-2.8, p<0.001) for ACS to 13.0 (95% CI 9.4-18.1, p<0.001) for HF. ACHD-exposed individuals with ≤2 cardiovascular risk factors had a 29% age-adjusted incidence rate of MACE in contrast to 13% in non-ACHD individuals with ≥5 risk factors.CONCLUSIONS: Individuals with lower-complexity ACHD had higher burden of adverse cardiovascular events relative to the general population that was unaccounted for by conventional cardiovascular risk factors. These findings highlight the need for closer surveillance of patients with mild to moderate ACHD and further investigation into management and mechanisms of cardiovascular risk unique to this growing population of high-risk adults.

    View details for PubMedID 30813762

  • Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial AMERICAN JOURNAL OF CLINICAL NUTRITION Shih, C. W., Hauser, M. E., Aronica, L., Rigdon, J., Gardner, C. D. 2019; 109 (2): 433–41
  • Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial. The American journal of clinical nutrition Shih, C. W., Hauser, M. E., Aronica, L., Rigdon, J., Gardner, C. D. 2019

    Abstract

    Background: For low-carbohydrate diets, a public health approach has focused on the replacement of carbohydrates with unsaturated fats. However, little research exists on the impacts of saturated fat intake on the lipid profile in the context of whole-food-based low-carbohydrate weight-loss diets.Objectives: The primary aim of this secondary analysis of the DIETFITS weight loss trial was to evaluate the associations between changes in percentage of dietary saturated fatty acid intake (%SFA) and changes in low-density lipoproteins, high-density lipoproteins, and triglyceride concentrations for those following a healthy low-carbohydrate (HLC) diet. The secondary aim was to examine these associations specifically for HLC dieters who had the highest 12-month increases in %SFA.Methods: In the DIETFITS trial, 609 generally healthy adults, aged 18-50 years, with body mass indices of 28-40 kg/m2 were randomly assigned to a healthy low-fat (HLF) or HLC diet for 12 months. In this analysis, linear regression, both without and with adjustment for potential confounders, was used to measure the association between 12-month change in %SFA and blood lipids in 208 HLC participants with complete diet and blood lipid data.Results: Participants consumed an average of 12-18% of calories from SFA. An increase of %SFA, without significant changes in absolute saturated fat intake, over 12 months was associated with a statistically significant decrease in triglycerides in the context of a weight-loss study in which participants simultaneously decreased carbohydrate intake. The association between increase in %SFA and decrease in triglycerides was no longer significant when adjusting for 12-month change in carbohydrate intake, suggesting carbohydrate intake may be a mediator of this relationship.Conclusions: Those on a low-carbohydrate weight-loss diet who increase their percentage intake of dietary saturated fat may improve their overall lipid profile provided they focus on a high-quality diet and lower their intakes of both calories and refined carbohydrates. This trial was registered at clinicaltrials.gov as NCT01826591.

    View details for PubMedID 30649213

  • Measuring socioeconomic adversity in early life. Acta paediatrica (Oslo, Norway : 1992) Anand, K. J., Rigdon, J., Rovnaghi, C. R., Qin, F., Tembulkar, S., Bush, N., LeWinn, K., Tylavsky, F. A., Davis, R., Barr, D. A., Gotlib, I. H. 2019

    Abstract

    AIM: Early life adversity in leads to enduring effects on physical and mental health, school performance, and other outcomes. We sought to identify potentially modifiable factors leading to socioeconomic adversity in early life.METHODS: We enrolled 1,503 pregnant women aged 16-40 years, without pregnancy complications or pre-existing conditions from Shelby County, Tennessee. Social, familial, and economic variables were analyzed using principal components (PCs) analyses to generate the Socioeconomic Adversity Index (SAI). This was replicated using the National Survey of Children's Health (NSCH). Health and social outcomes were compared across the quintile groups defined by SAI values at the county, state, and national levels.RESULTS: Significant differences occurred across the SAI Quintile-1 to Quintile-5 groups in marital status, household structure, annual income, education, and health insurance. Significantly worse health and social outcomes occurred in the lower vs. higher SAI quintiles, including maternal depression, parental incarceration, child's birthweight, and potential for child abuse. Maternal age and race also differed significantly across the SAI quintiles.CONCLUSION: Modifiable factors contributing to socioeconomic adversity in early life included marital status, household structure, annual income, education, and health insurance. Those exposed to greater socioeconomic adversity as defined by SAI values had significantly worse maternal and child outcomes. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30614554

  • Dual blockade of the PI3K/Akt/mTOR pathway inhibits post-transplant Epstein-Barr virus B cell lymphomas and promotes allograft survival. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Sang, A. X., McPherson, M. C., Ivison, G. T., Qu, X., Rigdon, J., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2018

    Abstract

    Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation that often manifests as Epstein-Barr virus (EBV)-associated B cell lymphomas. Current treatments for PTLD have limited efficacy and can be associated with graft rejection or systemic toxicities. The mTOR inhibitor, rapamycin, suppresses tumor growth of EBV+ B cell lymphoma cells in vitro and in vivo; however, the efficacy is limited and clinical benefits of mTOR inhibitors for PTLD are variable. Here, we show constitutive activation of multiple nodes within the PI3K/Akt/mTOR pathway in EBV+ PTLD-derived cell lines. Inhibition of either PI3K or Akt, with specific inhibitors CAL-101 and MK-2206, respectively, diminished growth of EBV+ B cell lines from PTLD patients in a dose-dependent manner. Importantly, rapamycin combined with CAL-101 or MK-2206 had a synergistic effect in suppressing cell growth as determined by IC50 isobolographic analysis and Loewe indices. Moreover, these combinations were significantly more effective than rapamycin alone in inhibiting tumor xenograft growth in NOD-SCID mice. Finally, both CAL-101 and MK-2206 also prolonged survival of heterotopic cardiac allografts in C57BL/6 mice. Thus, combination therapy with rapamycin and a PI3K inhibitor, or an Akt inhibitor, can be an efficacious treatment for EBV-associated PTLD, while simultaneously promoting allograft survival. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30549430

  • Association of triglyceride to HDL cholesterol ratio with cardiometabolic outcomes. Journal of investigative medicine : the official publication of the American Federation for Clinical Research Yang, M., Rigdon, J., Tsai, S. A. 2018

    Abstract

    Electronic medical records (EMRs) offer a potential opportunity to identify patients at high risk for cardiometabolic disease, which encompasses type 2 diabetes and cardiovascular disease (CVD). The objective of this retrospective cohort study is to use information gathered from EMR to investigate the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and cardiometabolic outcomes in a general population of subjects over 50 years of age during a follow-up period of 8-9 years. TG/HDL-C was recorded for each of 1428 subjects in 2008, and diagnoses of type 2 diabetes and CVD were recorded through chart review until 2017. Cox proportional hazards models controlling for demographic characteristics and other risk factors demonstrated that high TG/HDL-C (>2.5 in women or >3.5 in men) was significantly associated with increased incidence of type 2 diabetes (HR 1.66; 95% CI 1.07 to 2.57; p=0.0230). There was also a suggested association between high TG/HDL-C and incidence of CVD (HR 1.51; 95% CI 0.98 to 2.35; p=0.0628). These findings suggest that using TG/HDL-C, which can be easily calculated from data in an EMR, should be another tool used in identifying patients at high cardiometabolic risk.

    View details for PubMedID 30530527

  • Breastfeeding Duration and the Risk of Coronary Artery Disease. Journal of women's health (2002) Rajaei, S., Rigdon, J., Crowe, S., Tremmel, J., Tsai, S., Assimes, T. L. 2018

    Abstract

    BACKGROUND: Previous studies have suggested that prolonged breastfeeding has beneficial effects on the health of the mother including the reduction of long-term risk of coronary artery disease (CAD). The mechanism of this association remains unclear.METHODS: We surveyed 643 women aged 40-65 years receiving outpatient care at Stanford University Hospital on their reproductive/lactation history, including 137 women (cases) with clinically confirmed CAD. Survey data were supplemented with traditional risk factor data for CAD obtained from the participant's medical record. We then conducted logistic regression analyses to assess the relationship between breastfeeding duration and case-control status for each of the two separate definitions of duration. The first was based on the participant's single longest duration of breastfeeding considering all live births reported and the second was based on a participant's total duration of breastfeeding summed over all live births. For each of these two definitions, we ran three sequential models each with a different reference group-(1) nulliparous women, (2) parous women that never breastfed, and (3) parous women with a short duration of breastfeeding-successively excluding women in the reference group of the previous model(s).RESULTS: Just over one-half (51.6%) of the women surveyed reported a history of breastfeeding. We found nominally significant associations (p=0.04-0.12) for our multivariate analyses that modeled maximum duration of breastfeeding. When compared with nulliparous women, parous women who either never breastfed or always breastfed for <5 months had approximately double the risk of CAD. Among parous women, women who breastfeed for ≥5 months at least once in their lifetime had a 30% decrease risk of CAD compared with those who did not initiate breastfeeding. Among parous women who breastfed ≥1 month, women who breastfed ≥5 months had 50% decreased risk of CAD. We found similar point estimates of effect for analogous analyses modeling maximum breastfeeding duration but p-values for these analyses were not significant. Unadjusted analyses demonstrated higher valued odds ratios and lower p-values suggesting the presence of some confounding by traditional risk factors.CONCLUSIONS: Parous women who breastfeed ≥5 months in at least one pregnancy seem to be at decreased risk of CAD later in their life, whereas parous women who either never breastfed or discontinued breastfeeding early seem to be at increased risk. More research is needed to more reliably quantify and determine the nature of the relationship between parity, breastfeeding duration, and risk of CAD.

    View details for PubMedID 30523760

  • Birth Location of Infants with Critical Congenital Heart Disease in California. Pediatric cardiology Purkey, N. J., Axelrod, D. M., McElhinney, D. B., Rigdon, J., Qin, F., Desai, M., Shin, A. Y., Chock, V. Y., Lee, H. C. 2018

    Abstract

    The American Academy of Pediatrics classifies neonatal intensive care units (NICUs) from level I to IV based on the acuity of care each unit can provide. Birth in a higher level center is associated with lower morbidity and mortality in high-risk populations. Congenital heart disease accounts for 25-50% of infant mortality related to birth defects in the U.S., but recent data are lacking on where infants with critical congenital heart disease (CCHD) are born. We used a linked dataset from the Office of Statewide Health Planning and Development to access ICD-9 diagnosis codes for all infants born in California from 2008 to 2012. We compared infants with CCHD to the general population, identified where infants with CCHD were born based on NICU level of care, and predicted level IV birth among infants with CCHD using logistic regression techniques. From 2008 to 2012, 6325 infants with CCHD were born in California, with 23.7% of infants with CCHD born at a level IV NICU compared to 8.4% of the general population. Level IV birth for infants with CCHD was associated with lower gestational age, higher maternal age and education, the presence of other congenital anomalies, and the diagnosis of a single ventricle lesion. More infants with CCHD are born in a level IV NICU compared to the general population. Future studies are needed to determine if birth in a lower level of care center impacts outcomes for infants with CCHD.

    View details for PubMedID 30415381

  • Near-Far Matching in R: The nearfar Package JOURNAL OF STATISTICAL SOFTWARE Rigdon, J., Baiocchi, M., Basu, S. 2018; 86 (CN5): 1–21
  • Preventing false discovery of heterogeneous treatment effect subgroups in randomized trials. Trials Rigdon, J., Baiocchi, M., Basu, S. 2018; 19 (1): 382

    Abstract

    BACKGROUND: Heterogeneous treatment effects (HTEs), or systematic differences in treatment effectiveness among participants with different observable features, may be important when applying trial results to clinical practice. Current methods suffer from a potential for false detection of HTEs due to imbalances in covariates between candidate subgroups.METHODS: We introduce a new method, matching plus classification and regressiontrees (mCART), that yields balance in covariates in identified HTE subgroups. We compared mCART to a classical method (logistic regression [LR] with backwards covariate selection using the Akaike information criterion ) and two machine-learning approaches increasingly applied to HTE detection (random forest [RF] and gradient RF) in simulations with a binary outcome with known HTE subgroups. We considered an N=200 phase II oncology trial where there were either no HTEs (1A) or two HTE subgroups (1B) and an N=6000 phase III cardiovascular disease trial where there were either no HTEs (2A) or four HTE subgroups (2B). Additionally, we considered an N=6000 phase III cardiovascular disease trial where there was no average treatment effect but there were four HTE subgroups (2C).RESULTS: In simulations 1A and 2A (no HTEs), mCART did not identify any HTE subgroups, whereas LR found 2 and 448, RF 5 and 2, and gradient RF 5 and 24, respectively (all false positives). In simulation 1B, mCART failed to identify the two true HTE subgroups whereas LR found 4, RF 6, and gradient RF 10 (half or more of which were false positives). In simulations 2B and 2C, mCART captured the four true HTE subgroups, whereas the other methods found only false positives. All HTE subgroups identified by mCART had acceptabletreated vs.control covariate balance with absolute standardized differences less than 0.2, whereas the absolute standardized differences for the other methods typically exceeded 0.2. The imbalance in covariates in identified subgroups for LR, RF, and gradient RF indicates the false HTE detection may have been due to confounding.CONCLUSIONS: Covariate imbalances may be producing false positives in subgroup analyses. mCART could be a useful tool to help prevent the false discovery of HTE subgroups in secondary analyses of randomized trial data.

    View details for PubMedID 30012181

  • THE EFFECT OF A TEXT MESSAGE-BASED INTERVENTION ON ADHERENCE, WEIGHT LOSS, AND DIET QUALITY Stanton, M., Oppezzo, M., Garcia, A., Rigdon, J., Gardner, C. OXFORD UNIV PRESS INC. 2018: S645
  • Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion The DIETFITS Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Gardner, C. D., Trepanowski, J. F., Del Gobbo, L. C., Hauser, M. E., Rigdon, J., Ioannidis, J. A., Desai, M., King, A. C. 2018; 319 (7): 667–79

    Abstract

    Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.clinicaltrials.gov Identifier: NCT01826591.

    View details for PubMedID 29466592

  • Antioxidants from diet or supplements do not alter inflammatory markers in adults with cardiovascular disease risk. A pilot randomized controlled trial NUTRITION RESEARCH Dewell, A., Tsao, P., Rigdon, J., Gardner, C. D. 2018; 50: 63–72

    Abstract

    Antioxidants have been reported to have anti-inflammatory effects, but there is a lack of research comparing food to supplement antioxidant sources. The aim of this study was to determine if increases in intake of foods naturally rich in antioxidants would lower blood levels of inflammatory markers more than consuming antioxidant supplements among adults with cardiovascular disease risk factors. Eighty-eight generally healthy adults with ≥1 elevated risk factor for cardiovascular disease were randomized in a single-blind (diets)/double-blind (supplements), parallel-group study for 8 weeks. Participants consumed (1) usual diet and placebo pills (n = 29), (2) usual diet and antioxidant supplements (n = 29), or (3) antioxidant-rich foods closely matched to antioxidant content of supplements and placebo (n = 30). Usual diet combined with antioxidant supplements or increased antioxidant-rich food intake was designed to approximately double daily habitual antioxidant intake. Antioxidant pills included carotenoids, mixed tocopherols, vitamin C, and selenium. Fasting blood samples were analyzed for inflammatory marker concentrations of interleukin-6, monocyte chemotactic protein-1, and soluble intercellular adhesion molecule-1. Participants in the intervention groups successfully doubled most antioxidants as verified by diet records and elevated blood concentrations in treatment groups. Baseline levels of inflammatory markers for the entire study group were 110 ± 65 pg/mL for monocyte chemotactic protein-1, 0.9 ± 0.7 pg/mL for interleukin-6, and 217 ± 56 ng/mL for soluble intercellular adhesion molecule-1 (means ± standard deviation) and did not differ by treatment arm. After 8 weeks, there were no significant within-group changes or between-group 8-week change differences in inflammatory marker concentrations. In conclusion, no beneficial effects were detected on the inflammatory markers investigated in response to antioxidants from foods or supplements.

    View details for PubMedID 29540273

  • Inhibition of Multiple Nodes in the PI3K/Akt/mTOR Pathway Synergistically Suppresses Post-Transplant B Cell Lymphomas Sang, A., McPherson, M., Ivison, G., Qu, X., Rigdon, J., Esquivel, C., Krams, S., Martinez, O. WILEY. 2018: 20
  • Near-Far Matching in R: The nearfar Package. Journal of statistical software Rigdon, J., Baiocchi, M., Basu, S. 2018; 86 (CS-5)

    Abstract

    Estimating the causal treatment effect of an intervention using observational data is difficult due to unmeasured confounders. Many analysts use instrumental variables (IVs) to introduce a randomizing element to observational data analysis, potentially reducing bias created by unobserved confounders. Several persistent problems in the field have served as limitations to IV analyses, particularly the prevalence of "weak" IVs, or instrumental variables that do not effectively randomize individuals to the intervention or control group (leading to biased and unstable treatment effect estimates), as well as IV-based estimates being highly model dependent, requiring parametric adjustment for measured confounders, and often having high mean squared errors in the estimated causal effects. To overcome these problems, the study design method of "near-far matching" has been devised, which "filters" data from a cohort by simultaneously matching individuals within the cohort to be "near" (similar) on measured confounders and "far" (different) on levels of an IV. To facilitate the application of near-far matching to analytical problems, we introduce the R package nearfar and illustrate its application to both a classical example and a simulated dataset. We illustrate how the package can be used to "strengthen" a weak IV by adjusting the "near-ness" and "far-ness" of a match, reduce model dependency, enable nonparametric adjustment for measured confounders, and lower mean squared error in estimated causal effects. We additionally illustrate how to utilize the nearfar package when analyzing either continuous or binary treatments, how to prioritize variables in the match, and how to calculate F statistics of IV strength with or without adjustment for measured confounders.

    View details for PubMedID 30386186

  • Status of evolutionary medicine within the field of nutrition and dietetics A survey of professionals and students EVOLUTION MEDICINE AND PUBLIC HEALTH Basile, A. J., Schwartz, D. B., Rigdon, J., Stapell, H. 2018: 201–10

    Abstract

    Through an online survey of nutrition and dietetic professionals and students, we learned there is interest to incorporate evolutionary medicine into the nutrition and dietetics field and education programs.Evolutionary medicine is an emerging field that examines the evolutionary significance of modern disease to develop new preventative strategies or treatments. While many areas of interest in evolutionary medicine and public health involve diet, we currently lack an understanding of whether nutrition and dietetics professionals and students appreciate the potential of evolutionary medicine.Cross-sectional online survey to measure the level of appreciation, applicability and knowledge of evolutionary medicine among nutrition and dietetics professionals and students. We then examined the relationships between support of evolutionary medicine and (i) professionals and students, (ii) US region, (iii) religious belief and (iv) existing evolutionary knowledge.A total of 2039 people participated: students (n = 893) and professionals (n = 1146). The majority of the participants agree they are knowledgeable on the theory of evolution (59%), an understanding of evolution can aid the nutrition and dietetics field (58%), an evolutionary perspective would be beneficial in dietetics education (51%) and it is equally important to understand both the evolutionary and direct causes of disease (71%). Significant differences in responses between professionals and students suggest students are currently learning more about evolution and are also more supportive of using an evolutionary perspective. Whereas differences in responses by US region were minimal, differences by religious belief and prior evolutionary knowledge were significant; however, all responses were either neutral or supportive at varying strengths.There is interest among professionals and students to incorporate evolutionary medicine into the nutrition and dietetics field and education programs.

    View details for PubMedID 30254747

  • Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research Afghahi, A., Purington, N., Han, S. S., Desai, M., Pierson, E., Mathur, M. B., Seto, T., Thompson, C. A., Rigdon, J., Telli, M. L., Badve, S. S., Curtis, C., West, R. B., Horst, K., Gomez, S. L., Ford, J. M., Sledge, G. W., Kurian, A. W. 2018

    Abstract

    Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC.Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM and OM. For a subgroup with TILs data available, we explored the relationship between TILs and peripheral lymphocyte counts.1,463 Stage I-III TNBC patients were diagnosed from 2000-2014; 1113 (76%) received neoadjuvant/adjuvant chemotherapy within one year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.16-0.35) and BCM (HR: 0.19, CI: 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (N=70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.

    View details for PubMedID 29581131

  • Supplemental Nutrition Assistance Program (SNAP) Participation and Health Care Expenditures Among Low-Income Adults JAMA INTERNAL MEDICINE Berkowitz, S. A., Seligman, H. K., Rigdon, J., Meigs, J. B., Basu, S. 2017; 177 (11): 1642–49

    Abstract

    Food insecurity is associated with high health care expenditures, but the effectiveness of food insecurity interventions on health care costs is unknown.To determine whether the Supplemental Nutrition Assistance Program (SNAP), which addresses food insecurity, can reduce health care expenditures.This is a retrospective cohort study of 4447 noninstitutionalized adults with income below 200% of the federal poverty threshold who participated in the 2011 National Health Interview Survey (NHIS) and the 2012-2013 Medical Expenditure Panel Survey (MEPS).Self-reported SNAP participation in 2011.Total health care expenditures (all paid claims and out-of-pocket costs) in the 2012-2013 period. To test whether SNAP participation was associated with lower subsequent health care expenditures, we used generalized linear modeling (gamma distribution, log link, with survey design information), adjusting for demographics (age, gender, race/ethnicity), socioeconomic factors (income, education, Social Security Disability Insurance disability, urban/rural), census region, health insurance, and self-reported medical conditions. We also conducted sensitivity analyses as a robustness check for these modeling assumptions.A total of 4447 participants (2567 women and 1880 men) were enrolled in the study, mean (SE) age, 42.7 (0.5) years; 1889 were SNAP participants, and 2558 were not. Compared with other low-income adults, SNAP participants were younger (mean [SE] age, 40.3 [0.6] vs 44.1 [0.7] years), more likely to have public insurance or be uninsured (84.9% vs 67.7%), and more likely to be disabled (24.2% vs 10.6%) (P < .001 for all). In age- and gender-adjusted models, health care expenditures between those who did and did not participate in SNAP were similar (difference, $34; 95% CI, -$1097 to $1165). In fully adjusted models, SNAP was associated with lower estimated annual health care expenditures (-$1409; 95% CI, -$2694 to -$125). Sensitivity analyses were consistent with these results, also indicating that SNAP participation was associated with significantly lower estimated expenditures.SNAP enrollment is associated with reduced health care spending among low-income American adults, a finding consistent across several analytic approaches. Encouraging SNAP enrollment among eligible adults may help reduce health care costs in the United States.

    View details for PubMedID 28973507

    View details for PubMedCentralID PMC5710268

  • Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials PLOS MEDICINE Basu, S., Sussman, J. B., Rigdon, J., Steimle, L., Denton, B. T., Hayward, R. A. 2017; 14 (10): e1002410

    Abstract

    Intensive blood pressure (BP) treatment can avert cardiovascular disease (CVD) events but can cause some serious adverse events. We sought to develop and validate risk models for predicting absolute risk difference (increased risk or decreased risk) for CVD events and serious adverse events from intensive BP therapy. A secondary aim was to test if the statistical method of elastic net regularization would improve the estimation of risk models for predicting absolute risk difference, as compared to a traditional backwards variable selection approach.Cox models were derived from SPRINT trial data and validated on ACCORD-BP trial data to estimate risk of CVD events and serious adverse events; the models included terms for intensive BP treatment and heterogeneous response to intensive treatment. The Cox models were then used to estimate the absolute reduction in probability of CVD events (benefit) and absolute increase in probability of serious adverse events (harm) for each individual from intensive treatment. We compared the method of elastic net regularization, which uses repeated internal cross-validation to select variables and estimate coefficients in the presence of collinearity, to a traditional backwards variable selection approach. Data from 9,069 SPRINT participants with complete data on covariates were utilized for model development, and data from 4,498 ACCORD-BP participants with complete data were utilized for model validation. Participants were exposed to intensive (goal systolic pressure < 120 mm Hg) versus standard (<140 mm Hg) treatment. Two composite primary outcome measures were evaluated: (i) CVD events/deaths (myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or CVD death), and (ii) serious adverse events (hypotension, syncope, electrolyte abnormalities, bradycardia, or acute kidney injury/failure). The model for CVD chosen through elastic net regularization included interaction terms suggesting that older age, black race, higher diastolic BP, and higher lipids were associated with greater CVD risk reduction benefits from intensive treatment, while current smoking was associated with fewer benefits. The model for serious adverse events chosen through elastic net regularization suggested that male sex, current smoking, statin use, elevated creatinine, and higher lipids were associated with greater risk of serious adverse events from intensive treatment. SPRINT participants in the highest predicted benefit subgroup had a number needed to treat (NNT) of 24 to prevent 1 CVD event/death over 5 years (absolute risk reduction [ARR] = 0.042, 95% CI: 0.018, 0.066; P = 0.001), those in the middle predicted benefit subgroup had a NNT of 76 (ARR = 0.013, 95% CI: -0.0001, 0.026; P = 0.053), and those in the lowest subgroup had no significant risk reduction (ARR = 0.006, 95% CI: -0.007, 0.018; P = 0.71). Those in the highest predicted harm subgroup had a number needed to harm (NNH) of 27 to induce 1 serious adverse event (absolute risk increase [ARI] = 0.038, 95% CI: 0.014, 0.061; P = 0.002), those in the middle predicted harm subgroup had a NNH of 41 (ARI = 0.025, 95% CI: 0.012, 0.038; P < 0.001), and those in the lowest subgroup had no significant risk increase (ARI = -0.007, 95% CI: -0.043, 0.030; P = 0.72). In ACCORD-BP, participants in the highest subgroup of predicted benefit had significant absolute CVD risk reduction, but the overall ACCORD-BP participant sample was skewed towards participants with less predicted benefit and more predicted risk than in SPRINT. The models chosen through traditional backwards selection had similar ability to identify absolute risk difference for CVD as the elastic net models, but poorer ability to correctly identify absolute risk difference for serious adverse events. A key limitation of the analysis is the limited sample size of the ACCORD-BP trial, which expanded confidence intervals for ARI among persons with type 2 diabetes. Additionally, it is not possible to mechanistically explain the physiological relationships explaining the heterogeneous treatment effects captured by the models, since the study was an observational secondary data analysis.We found that predictive models could help identify subgroups of participants in both SPRINT and ACCORD-BP who had lower versus higher ARRs in CVD events/deaths with intensive BP treatment, and participants who had lower versus higher ARIs in serious adverse events.

    View details for PubMedID 29040268

  • Network analysis: a novel method for mapping neonatal acute transport patterns in California. Journal of perinatology Kunz, S. N., Zupancic, J. A., Rigdon, J., Phibbs, C. S., Lee, H. C., Gould, J. B., Leskovec, J., Profit, J. 2017; 37 (6): 702-708

    Abstract

    The objectives of this study are to use network analysis to describe the pattern of neonatal transfers in California, to compare empirical sub-networks with established referral regions and to determine factors associated with transport outside the originating sub-network.This cross-sectional database study included 6546 infants <28 days old transported within California in 2012. After generating a graph representing acute transfers between hospitals (n=6696), we used community detection techniques to identify more tightly connected sub-networks. These empirically derived sub-networks were compared with state-defined regional referral networks. Reasons for transfer between empirical sub-networks were assessed using logistic regression.Empirical sub-networks showed significant overlap with regulatory regions (P<0.001). Transfer outside the empirical sub-network was associated with major congenital anomalies (P<0.001), need for surgery (P=0.01) and insurance as the reason for transfer (P<0.001).Network analysis accurately reflected empirical neonatal transfer patterns, potentially facilitating quantitative, rather than qualitative, analysis of regionalized health care delivery systems.Journal of Perinatology advance online publication, 23 March 2017; doi:10.1038/jp.2017.20.

    View details for DOI 10.1038/jp.2017.20

    View details for PubMedID 28333155

  • Factors Associated With Provider Burnout in the NICU PEDIATRICS Tawfik, D. S., Phibbs, C. S., Sexton, J. B., Kan, P., Sharek, P. J., Nisbet, C. C., Rigdon, J., Trockel, M., Profit, J. 2017; 139 (5)

    Abstract

    NICUs vary greatly in patient acuity and volume and represent a wide array of organizational structures, but the effect of these differences on NICU providers is unknown. This study sought to test the relation between provider burnout prevalence and organizational factors in California NICUs.Provider perceptions of burnout were obtained from 1934 nurse practitioners, physicians, registered nurses, and respiratory therapists in 41 California NICUs via a validated 4-item questionnaire based on the Maslach Burnout Inventory. The relations between burnout and organizational factors of each NICU were evaluated via t-test comparison of quartiles, univariable regression, and multivariable regression.Overall burnout prevalence was 26.7% ± 9.8%. Highest burnout prevalence was found among NICUs with higher average daily admissions (32.1% ± 6.4% vs 17.2% ± 6.7%, P < .001), higher average occupancy (28.1% ± 8.1% vs 19.9% ± 8.4%, P = .02), and those with electronic health records (28% ± 11% vs 18% ± 7%, P = .03). In sensitivity analysis, nursing burnout was more sensitive to organizational differences than physician burnout in multivariable modeling, significantly associated with average daily admissions, late transfer proportion, nursing hours per patient day, and mortality per 1000 infants. Burnout prevalence showed no association with proportion of high-risk patients, teaching hospital distinction, or in-house attending presence.Burnout is most prevalent in NICUs with high patient volume and electronic health records and may affect nurses disproportionately. Interventions to reduce burnout prevalence may be of greater importance in NICUs with ≥10 weekly admissions.

    View details for DOI 10.1542/peds.2016-4134

    View details for Web of Science ID 000400371500040

    View details for PubMedID 28557756

  • Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA internal medicine Trepanowski, J. F., Kroeger, C. M., Barnosky, A., Klempel, M. C., Bhutani, S., Hoddy, K. K., Gabel, K., Freels, S., Rigdon, J., Rood, J., Ravussin, E., Varady, K. A. 2017

    Abstract

    Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease.A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease.Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.clinicaltrials.gov Identifier: NCT00960505.

    View details for DOI 10.1001/jamainternmed.2017.0936

    View details for PubMedID 28459931

  • Teamwork in the NICU Setting and Its Association with Health Care-Associated Infections in Very Low-Birth-Weight Infants. American journal of perinatology Profit, J., Sharek, P. J., Kan, P., Rigdon, J., Desai, M., Nisbet, C. C., Tawfik, D. S., Thomas, E. J., Lee, H. C., Sexton, J. B. 2017

    Abstract

    Background and Objective Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale-level and item-level associations with health care-associated infection (HAI) rates in very low-birth-weight (VLBW) infants. Methods Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6,663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2,073 of 3,294 eligible NICU health professionals (response rate 63%). The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (odds ratio, 0.82; 95% confidence interval, 0.73-0.92, p = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion Improving teamwork may be an important element in infection control efforts.

    View details for DOI 10.1055/s-0037-1601563

    View details for PubMedID 28395366

  • Burnout in the neonatal intensive care unit and its relation to healthcare-associated infections. Journal of perinatology Tawfik, D. S., Sexton, J. B., Kan, P., Sharek, P. J., Nisbet, C. C., Rigdon, J., Lee, H. C., Profit, J. 2017; 37 (3): 315-320

    Abstract

    To examine burnout prevalence among California neonatal intensive care units (NICUs) and to test the relation between burnout and healthcare-associated infection (HAI) rates in very low birth weight (VLBW) neonates.Retrospective observational study of provider perceptions of burnout from 2073 nurse practitioners, physicians, registered nurses and respiratory therapists, using a validated four-item questionnaire based on the Maslach Burnout Inventory. The relation between burnout and HAI rates among VLBW (<1500 g) neonates from each NICU was evaluated using multi-level logistic regression analysis with patient-level factors as fixed effects.We found variable prevalence of burnout across the NICUs surveyed (mean 25.2±10.1%). Healthcare-associated infection rates were 8.3±5.1% during the study period. Highest burnout prevalence was found among nurses, nurse practitioners and respiratory therapists (non-physicians, 28±11% vs 17±19% physicians), day shift workers (30±3% vs 25±4% night shift) and workers with 5 or more years of service (29±2% vs 16±6% in fewer than 3 years group). Overall burnout rates showed no correlation with risk-adjusted rates of HAIs (r=-0.133). Item-level analysis showed positive association between HAIs and perceptions of working too hard (odds ratio 1.15, 95% confidence interval 1.04-1.28). Sensitivity analysis of high-volume NICUs suggested a moderate correlation between burnout prevalence and HAIs (r=0.34).Burnout is most prevalent among non-physicians, daytime workers and experienced workers. Perceptions of working too hard associate with increased HAIs in this cohort of VLBW infants, but overall burnout prevalence is not predictive.Journal of Perinatology advance online publication, 17 November 2016; doi:10.1038/jp.2016.211.

    View details for DOI 10.1038/jp.2016.211

    View details for PubMedID 27853320

  • DIETFITS study (diet intervention examining the factors interacting with treatment success) - Study design and methods. Contemporary clinical trials Stanton, M. V., Robinson, J. L., Kirkpatrick, S. M., Farzinkhou, S., Avery, E. C., Rigdon, J., Offringa, L. C., Trepanowski, J. F., Hauser, M. E., Hartle, J. C., Cherin, R. J., King, A. C., Ioannidis, J. P., Desai, M., Gardner, C. D. 2017; 53: 151-161

    Abstract

    Numerous studies have attempted to identify successful dietary strategies for weight loss, and many have focused on Low-Fat vs. Low-Carbohydrate comparisons. Despite relatively small between-group differences in weight loss found in most previous studies, researchers have consistently observed relatively large between-subject differences in weight loss within any given diet group (e.g., ~25kg weight loss to ~5kg weight gain). The primary objective of this study was to identify predisposing individual factors at baseline that help explain differential weight loss achieved by individuals assigned to the same diet, particularly a pre-determined multi-locus genotype pattern and insulin resistance status. Secondary objectives included discovery strategies for further identifying potential genetic risk scores. Exploratory objectives included investigation of an extensive set of physiological, psychosocial, dietary, and behavioral variables as moderating and/or mediating variables and/or secondary outcomes. The target population was generally healthy, free-living adults with BMI 28-40kg/m(2) (n=600). The intervention consisted of a 12-month protocol of 22 one-hour evening instructional sessions led by registered dietitians, with ~15-20 participants/class. Key objectives of dietary instruction included focusing on maximizing the dietary quality of both Low-Fat and Low-Carbohydrate diets (i.e., Healthy Low-Fat vs. Healthy Low-Carbohydrate), and maximally differentiating the two diets from one another. Rather than seeking to determine if one dietary approach was better than the other for the general population, this study sought to examine whether greater overall weight loss success could be achieved by matching different people to different diets. Here we present the design and methods of the study.

    View details for DOI 10.1016/j.cct.2016.12.021

    View details for PubMedID 28027950

  • Re-evaluating associations between the Supplemental Nutrition Assistance Program participation and body mass index in the context of unmeasured confounders. Social science & medicine (1982) Rigdon, J., Berkowitz, S. A., Seligman, H. K., Basu, S. 2017; 192: 112–24

    Abstract

    To evaluate the association between participation in the Supplemental Nutrition Assistance Program (SNAP) and body mass index (BMI) in the presence of unmeasured confounding.We applied new matching methods to determine whether previous reports of associations between SNAP participation and BMI were robust to unmeasured confounders. We applied near-far matching, which strengthens standard matching by combining it with instrumental variables analysis, to the nationally-representative National Household Food Acquisition and Purchasing Survey (FoodAPS, N = 10,360, years 2012-13).In ordinary least squares regressions controlling for individual demographic and socioeconomic characteristics, SNAP was associated with increased BMI (+1.23 kg/m2, 95% CI: 0.84, 1.63). While propensity-score-based analysis replicated this finding, using instrumental variables analysis and particularly near-far matching to strengthen the instruments' discriminatory power revealed the association between SNAP and BMI was likely confounded by unmeasured covariates (+0.21 kg/m2, 95% CI: -3.88, 4.29).Previous reports of an association between SNAP and obesity should be viewed with caution, and use of near-far matching may assist similar assessments of health effects of social programs.

    View details for PubMedID 28965002

    View details for PubMedCentralID PMC5815398

  • Response to comment on 'Randomization inference for treatment effects on a binary outcome'. Statistics in medicine Rigdon, J., Loh, W. W., Hudgens, M. G. 2017; 36 (5): 876–80

    View details for PubMedID 28093845

    View details for PubMedCentralID PMC5358813

  • SLDAssay: A software package and web tool for analyzing limiting dilution assays. Journal of immunological methods Trumble, I. M., Allmon, A. G., Archin, N. M., Rigdon, J., Francis, O., Baldoni, P. L., Hudgens, M. G. 2017; 450: 10–16

    Abstract

    Serial limiting dilution (SLD) assays are used in many areas of infectious disease related research. This paper presents SLDAssay, a free and publicly available R software package and web tool for analyzing data from SLD assays. SLDAssay computes the maximum likelihood estimate (MLE) for the concentration of target cells, with corresponding exact and asymptotic confidence intervals. Exact and asymptotic goodness of fit p-values, and a bias-corrected (BC) MLE are also provided. No other publicly available software currently implements the BC MLE or the exact methods. For validation of SLDAssay, results from Myers et al. (1994) are replicated. Simulations demonstrate the BC MLE is less biased than the MLE. Additionally, simulations demonstrate that exact methods tend to give better confidence interval coverage and goodness-of-fit tests with lower type I error than the asymptotic methods. Additional advantages of using exact methods are also discussed.

    View details for PubMedID 28733216

    View details for PubMedCentralID PMC5595663

  • Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR). Radiotherapy and oncology Chaudhuri, A. A., Binkley, M. S., Rigdon, J., Carter, J. N., Aggarwal, S., Dudley, S. A., Qian, Y., Kumar, K. A., Hara, W. Y., Gensheimer, M., Nair, V. S., Maxim, P. G., Shultz, D. B., Bush, K., Trakul, N., Le, Q., Diehn, M., Loo, B. W., Guo, H. H. 2016; 119 (3): 454-460

    Abstract

    To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR).We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ⩾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake.Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001).Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

    View details for DOI 10.1016/j.radonc.2016.05.007

    View details for PubMedID 27267049

  • Use of Gene Expression Profiling and Chemotherapy in Early-Stage Breast Cancer: A Study of Linked Electronic Medical Records, Cancer Registry Data, and Genomic Data Across Two Health Care Systems. Journal of oncology practice / American Society of Clinical Oncology Afghahi, A., Mathur, M., Thompson, C. A., Mitani, A., Rigdon, J., Desai, M., Yu, P. P., de Bruin, M. A., Seto, T., Olson, C., Kenkare, P., Gomez, S. L., Das, A. K., Luft, H. S., Sledge, G. W., Sing, A. P., Kurian, A. W. 2016; 12 (6): e697-709

    Abstract

    The 21-gene recurrence score (RS) identifies patients with breast cancer who derive little benefit from chemotherapy; it may reduce unwarranted variability in the use of chemotherapy. We tested whether the use of RS seems to guide chemotherapy receipt across different cancer care settings.We developed a retrospective cohort of patients with breast cancer by using electronic medical record data from Stanford University (hereafter University) and Palo Alto Medical Foundation (hereafter Community) linked with demographic and staging data from the California Cancer Registry and RS results from the testing laboratory (Genomic Health Inc., Redwood City, CA). Multivariable analysis was performed to identify predictors of RS and chemotherapy use.In all, 10,125 patients with breast cancer were diagnosed in the University or Community systems from 2005 to 2011; 2,418 (23.9%) met RS guidelines criteria, of whom 15.6% received RS. RS was less often used for patients with involved lymph nodes, higher tumor grade, and age < 40 or ≥ 65 years. Among RS recipients, chemotherapy receipt was associated with a higher score (intermediate v low: odds ratio, 3.66; 95% CI, 1.94 to 6.91). A total of 293 patients (10.6%) received care in both health care systems (hereafter dual use); although receipt of RS was associated with dual use (v University: odds ratio, 1.73; 95% CI, 1.18 to 2.55), there was no difference in use of chemotherapy after RS by health care setting.Although there was greater use of RS for patients who sought care in more than one health care setting, use of chemotherapy followed RS guidance in University and Community health care systems. These results suggest that precision medicine may help optimize cancer treatment across health care settings.

    View details for DOI 10.1200/JOP.2015.009803

    View details for PubMedID 27221993

    View details for PubMedCentralID PMC4957259

  • Exact confidence intervals in the presence of interference STATISTICS & PROBABILITY LETTERS Rigdon, J., Hudgens, M. G. 2015; 105: 130-135
  • Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer BREAST CANCER RESEARCH Afghahi, A., Forgo, E., Mitani, A. A., Desai, M., Varma, S., Seto, T., Rigdon, J., Jensen, K. C., Troxell, M. L., Gomez, S. L., Das, A. K., Beck, A. H., Kurian, A. W., West, R. B. 2015; 17

    Abstract

    Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment.We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS.We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013).CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross-sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS.

    View details for DOI 10.1186/s13058-015-0623-y

    View details for Web of Science ID 000359348400001

    View details for PubMedID 26265211

    View details for PubMedCentralID PMC4534146

  • Exact Confidence Intervals in the Presence of Interference. Statistics & probability letters Rigdon, J., Hudgens, M. G. 2015; 105: 130–35

    Abstract

    For two-stage randomized experiments assuming partial interference, exact confidence intervals are proposed for treatment effects on a binary outcome. Empirical studies demonstrate the new intervals have narrower width than previously proposed exact intervals based on the Hoeffding inequality.

    View details for PubMedID 26190877

    View details for PubMedCentralID PMC4504023

  • Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer. Breast cancer research Afghahi, A., Forgó, E., Mitani, A. A., Desai, M., Varma, S., Seto, T., Rigdon, J., Jensen, K. C., Troxell, M. L., Gomez, S. L., Das, A. K., Beck, A. H., Kurian, A. W., West, R. B. 2015; 17: 108-?

    Abstract

    Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment.We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS.We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013).CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross-sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS.

    View details for DOI 10.1186/s13058-015-0623-y

    View details for PubMedID 26265211