Clinical Focus


  • Internal Medicine

Academic Appointments


Professional Education


  • Medical Education: UCLA David Geffen School Of Medicine Registrar (2000) CA
  • Fellowship: Stanford University Endocrinology Fellowship (2014) CA
  • Residency: Brigham and Women's Hospital Internal Medicine Residency (2004) MA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2004)

All Publications


  • Successful recruitment of monolingual Spanish speaking Latinos to university phase II and III outpatient COVID-19 clinical treatment trials in Northern California. Contemporary clinical trials Levy, V., Bengoa, R. Y., Romero, P. P., Bollyky, J., Singh, U. 2022: 106891

    Abstract

    Through a public County/University partnership, we employed a Spanish/English bilingual research coordinator to increase awareness of newly available treatments with FDA Emergency Use Authorization and clinical trial opportunities for Latino outpatients with mild to moderate COVID-19. Out of the 550 San Mateo County outpatients with COVID-19 referred to Stanford University between July 2020 and April 2022, 9.5% elected to receive monoclonal antibody EUA treatment. COVID-19 treatment trial enrollment of County patients, 5% of those recruited, was commensurate with non-County populations enrollment. Recruitment models such as ours have the potential to increase US Latino populations' recruitment in outpatient COVID-19 treatment trials and contribute to decreasing COVID-19 health disparities.

    View details for DOI 10.1016/j.cct.2022.106891

    View details for PubMedID 36002110

  • Validity of at-home rapid antigen lateral flow assay and artificial intelligence read to detect SARS-CoV-2. Diagnostic microbiology and infectious disease Richardson, S., Kohn, M. A., Bollyky, J., Parsonnet, J. 2022; 104 (3): 115763

    Abstract

    BACKGROUND: The gold standard for COVID-19 diagnosis-reverse-transcriptase polymerase chain reaction (RT-PCR)- is expensive and often slow to yield results whereas lateral flow tests can lack sensitivity.METHODS: We tested a rapid, lateral flow antigen (LFA) assay with artificial intelligence read (LFAIR) in subjects from COVID-19 treatment trials (N=37; daily tests for 5 days) and from a population-based study (N=88; single test). LFAIR was compared to RT-PCR from same-day samples.RESULTS: Using each participant's first sample, LFAIR showed 86.2% sensitivity (95% CI 73.6%-98.8) and 94.3% specificity (88.8%-99.7%) compared to RT-PCR. Adjusting for days since symptom onset and repeat testing, sensitivity was 97.8% (89.9%-99.5%) on the first symptomatic day and decreased with each additional day. Sensitivity improved with artificial intelligence (AI) read (86.2%) compared to the human eye (71.4%).CONCLUSION: LFAIR showed improved accuracy compared to LFA alone. particularly early in infection.

    View details for DOI 10.1016/j.diagmicrobio.2022.115763

    View details for PubMedID 36070629

  • Oral hymecromone decreases hyaluronan in human study participants. The Journal of clinical investigation Rosser, J. I., Nagy, N., Goel, R., Kaber, G., Demirdjian, S., Saxena, J., Bollyky, J. B., Frymoyer, A. R., Pacheco-Navarro, A. E., Burgener, E. B., Rajadas, J., Wang, Z., Arbach, O., Dunn, C. E., Kalinowski, A., Milla, C. E., Bollyky, P. L. 2022; 132 (9)

    Abstract

    BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT02780752.FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970.

    View details for DOI 10.1172/JCI157983

    View details for PubMedID 35499083

  • Incidence and prevalence of COVID-19 within a healthcare worker cohort during the first year of the SARS-CoV-2 pandemic. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Doernberg, S. B., Holubar, M., Jain, V., Weng, Y., Lu, D., Bollyky, J. B., Sample, H., Huang, B., Craik, C. S., Desai, M., Rutherford, G. W., Maldonado, Y., CHART Study Consortium 2022

    Abstract

    BACKGROUND: Preventing SARS-CoV2 infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of COVID-19 in a US HCW cohort and to identify risk factors associated with infection.METHODS: We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models.RESULTS: 2435 HCWs contributed 768 person years of follow-up time. We identified 21/2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% CI, 0.53% to 1.32%). We identified 70/2414 (2.9%) incident infections yielding a cumulative incidence rate of 9.11 cases per 100 person years (95% CI 7.11 to 11.52). Community contact with a known COVID-19 case most strongly correlated with increased hazard for infection (HR 8.1, 95% CI, 3.8, 17.5). High-risk work-related exposures (i.e., breach in protective measures) drove an association between work exposure and infection (HR 2.5, 95% CI, 1.3-4.8). More cases were identified in HCW when community case rates were high.CONCLUSION: We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections but contact at work was not unless accompanied by high-risk exposure.

    View details for DOI 10.1093/cid/ciac210

    View details for PubMedID 35279023

  • Race-ethnicity and COVID-19 Vaccination Beliefs and Intentions: A Cross-Sectional Study among the General Population in the San Francisco Bay Area. Vaccines Weng, Y., Lu, D., Bollyky, J., Jain, V., Desai, M., Lindan, C., Boothroyd, D., Judson, T., Doernberg, S. B., Holubar, M., Sample, H., Huang, B., Maldonado, Y., Rutherford, G. W., Grumbach, K., On Behalf Of The California Pandemic Consortium 1800; 9 (12)

    Abstract

    OBJECTIVE: The study was designed to compare intentions to receive COVID-19 vaccination by race-ethnicity, to identify beliefs that may mediate the association between race-ethnicity and intention to receive the vaccine and to identify the demographic factors and beliefs most strongly predictive of intention to receive a vaccine.DESIGN: Cross-sectional survey conducted from November 2020 to January 2021, nested within a longitudinal cohort study of the prevalence and incidence of SARS-CoV-2 among a general population-based sample of adults in six San Francisco Bay Area counties (called TrackCOVID). Study Cohort: In total, 3161 participants among the 3935 in the TrackCOVID parent cohort responded.RESULTS: Rates of high vaccine willingness were significantly lower among Black (41%), Latinx (55%), Asian (58%), Multi-racial (59%), and Other race (58%) respondents than among White respondents (72%). Black, Latinx, and Asian respondents were significantly more likely than White respondents to endorse lack of trust of government and health agencies as a reason not to get vaccinated. Participants' motivations and concerns about COVID-19 vaccination only partially explained racial-ethnic differences in vaccination willingness. Concerns about a rushed government vaccine approval process and potential bad reactions to the vaccine were the two most important factors predicting vaccination intention.CONCLUSIONS: Vaccine outreach campaigns must ensure that the disproportionate toll of COVID-19 on historically marginalized racial-ethnic communities is not compounded by inequities in vaccination. Efforts must emphasize messages that speak to the motivations and concerns of groups suffering most from health inequities to earn their trust to support informed decision making.

    View details for DOI 10.3390/vaccines9121406

    View details for PubMedID 34960152

  • High Completion of COVID-19 Vaccination Among Health Care Workers Despite Initial Self-Reported Vaccine Reluctance. Open forum infectious diseases Jain, V., Doernberg, S. B., Holubar, M., Huang, B., Bollyky, J., Sample, H., Weng, Y., Lu, D., Desai, M., Maldonado, Y., Rutherford, G. 2021; 8 (10): ofab446

    View details for DOI 10.1093/ofid/ofab446

    View details for PubMedID 34734101

  • Design of a population-based longitudinal cohort study of SARS-CoV-2 incidence and prevalence among adults in the San Francisco Bay Area. Annals of epidemiology Lindan, C. P., Desai, M., Boothroyd, D., Judson, T., Bollyky, J., Sample, H., Weng, Y., Cheng, Y., Dahlen, A., Hedlin, H., Grumbach, K., Henne, J., Garcia, S., Gonzales, R., Craik, C. S., Maldonado, Y., Rutherford, G. 2021

    Abstract

    We describe the design of a longitudinal cohort study to determine SARS-CoV-2 incidence and prevalence among a population-based sample of adults living in six San Francisco Bay Area counties.Using an address-based sample, we stratified households by county and by census-tract risk. Risk strata were determined by using regression models to predict infections by geographic area using census-level sociodemographic and health characteristics. We disproportionately sampled high and medium risk strata, which had smaller population sizes, to improve precision of estimates, and calculated a desired sample size of 3400. Participants were primarily recruited by mail and were followed monthly with PCR testing of nasopharyngeal swabs, testing of venous blood samples for antibodies to SARS-CoV-2 spike and nucleocapsid antigens, and testing of the presence of neutralizing antibodies, with completion of questionnaires about socio-demographics and behavior. Estimates of incidence and prevalence will be weighted by county, risk strata and sociodemographic characteristics of non-responders, and will take into account laboratory test performance.We enrolled 3842 adults from August to December, 2020, and completed follow-up March 31, 2021. We reached target sample sizes within most strata.Our stratified random sampling design will allow us to recruit a robust general population cohort of adults to determine the incidence of SARS-CoV-2 infection. Identifying risk strata was unique to the design and will help ensure precise estimates, and high-performance testing for presence of virus and antibodies will enable accurate ascertainment of infections.

    View details for DOI 10.1016/j.annepidem.2021.11.001

    View details for PubMedID 34800659

  • Figure Correction: The Effect of a Cellular-Enabled Glucose Meter on Glucose Control for Patients With Diabetes: Prospective Pre-Post Study. JMIR diabetes Bollyky, J. B., Melton, S. T., Xu, T., Painter, S. L., Knox, B. 2020; 5 (3): e21993

    Abstract

    [This corrects the article DOI: 10.2196/14799.].

    View details for DOI 10.2196/21993

    View details for PubMedID 32721921

  • The Effect of a Cellular-Enabled Glucose Meter on Glucose Control for Patients With Diabetes: Prospective Pre-Post Study. JMIR diabetes Bollyky, J. B., Melton, S. T., Xu, T., Painter, S. L., Knox, B. 2019; 4 (4): e14799

    Abstract

    BACKGROUND: Diabetes is a global epidemic affecting approximately 30 million people in the United States. The World Health Organization recommends using technology and telecommunications to improve health care delivery and disease management. The Livongo for Diabetes Program offers a remote monitoring technology with Certified Diabetes Educator outreach.OBJECTIVE: The purpose of this study was to examine health outcomes measured by changes in HbA1c, in time in target blood glucose range, and in depression symptoms for patients enrolled in a remote digital diabetes management program in a Diabetes Center of Excellence setting.METHODS: The impact of the Livongo for Diabetes program on hemoglobin A1c (HbA1c), blood glucose ranges, and depression screening survey results (Patient Health Questionnaire-2 [PHQ-2]) were assessed over 12 months in a prospective cohort recruited from the University of South Florida Health Diabetes Home for Healthy Living. Any patient ≥18 years old with a diagnosis of diabetes was approached for voluntary inclusion into the program. The analysis was a pre-post design for those members enrolled in the study. Data was collected at outpatient clinic visits and remotely through the Livongo glucose meter.RESULTS: A total of 86 adults were enrolled into the Livongo for Diabetes program, with 49% (42/86) female, an average age of 50 (SD 15) years, 56% (48/86) with type 2 diabetes mellitus, and 69% (59/86) with insulin use. The mean HbA1c drop amongst the group was 0.66% (P=.17), with all participants showing a decline in HbA1c at 12 months. A 17% decrease of blood glucose checks <70 mg/dL occurred concurrently. Participants with type 2 diabetes not using insulin had blood glucose values within target range (70-180 mg/dL) 89% of the time. Participants with type 2 diabetes using insulin were in target range 68% of the time, and type 1 diabetes 58% of the time. Average PHQ-2 scores decreased by 0.56 points during the study period.CONCLUSIONS: Participants provided with a cellular-enabled blood glucose meter with real-time feedback and access to coaching from a certified diabetes educator in an outpatient clinical setting experienced improved mean glucose values and fewer episodes of hypoglycemia relative to the start of the program.

    View details for DOI 10.2196/14799

    View details for PubMedID 31593545

  • Reduced medical spending associated with increased use of a remote diabetes management program and lower mean blood glucose values. Journal of medical economics Whaley, C. M., Bollyky, J. B., Lu, W., Painter, S., Schneider, J., Zhao, Z., He, X., Johnson, J., Meadows, E. S. 2019: 1–9

    Abstract

    AIMS: Many new mobile technologies are available to assist people in managing chronic conditions, but data on the association between the use of these technologies and medical spending remains limited. As the available digital technology offerings to aid in diabetes management increase, it is important to understand their impact on medical spending. The aim of this study was to investigate the financial impact of a remote digital diabetes management program using medical claims and real-time blood glucose data.MATERIALS AND METHODS: A retrospective analysis of multivariate difference-in-difference and instrumental variables regression modeling was performed using data collected from a remote digital diabetes management program. All employees with diabetes were invited, in a phased introduction, to join the program. Data included blood glucose (BG) values captured remotely from members via connected BG meters and medical spending claims. Participants included members (those who accepted the invitation, n=2,261) and non-members (n=8,741) who received health insurance benefits from three self-insured employers. Medical spending was compared between people with well-controlled (BG ≤ 154mg/dL) and poorly controlled (BG > 154mg/dL) diabetes.RESULTS: Program access was associated with a 21.9% (p<0.01) decrease in medical spending, which translates into a $88 saving per member per month at 1 year. Compared to non-members, members experienced a 10.7% (p<0.01) reduction in diabetes-related medical spending and a 24.6% (p<0.01) reduction in spending on office-based services. Well-controlled BG values were associated with 21.4% (p=0.03) lower medical spending.LIMITATIONS AND CONCLUSIONS: Remote digital diabetes management is associated with decreased medical spending at 1 year. Reductions in spending increased with active utilization. It will be beneficial for future studies to analyze the long-term effects of the remote diabetes management program and assess impacts on patient health and well-being.

    View details for DOI 10.1080/13696998.2019.1609483

    View details for PubMedID 31012392

  • Remote Lifestyle Coaching Plus a Connected Glucose Meter with Certified Diabetes Educator Support Improves Glucose and Weight Loss for People with Type 2 Diabetes. Journal of diabetes research Bollyky, J. B., Bravata, D., Yang, J., Williamson, M., Schneider, J. 2018; 2018: 3961730

    Abstract

    Connected health devices with lifestyle coaching can provide real-time support for people with type 2 diabetes (T2D). However, the intensity of lifestyle coaching needed to achieve outcomes is unknown.Livongo provides connected, two-way messaging glucose meters, unlimited blood glucose (BG) test strips, and access to certified diabetes educators. We evaluated the incremental effects of adding lifestyle coaching on BG, estimated HbA1c, and weight. We randomized 330 eligible adults (T2D, HbA1c > 7.5%, BMI ≥ 25) to receive no further intervention (n = 75), a connected scale (n = 115), scale plus lightweight coaching (n = 73), or scale plus intense coaching (n = 67) for 12 weeks. We evaluated the change in outcomes using ANOVA.Livongo participation alone resulted in improved BG control (mean HbA1c declined: 8.5% to 7.5%, p = 0.01). Mean weight loss and additional BG decreases were higher in the intensive compared with the lightweight coaching and scale-only groups (weight change (lb): -6.4, -4.1, and -1.1, resp., p = 0.01; BG change (mg/dL): -19.4, -11.3, and -2.9, resp., p = 0.02). The estimated 12-week program costs were 5.5 times more for intensive than lightweight coaching.Livongo participation significantly improves BG control in people with T2D. Additional lifestyle coaching may be a cost-effective intervention to achieve further glucose control and weight loss.

    View details for DOI 10.1155/2018/3961730

    View details for PubMedID 29888288

    View details for PubMedCentralID PMC5977036

  • Remote Lifestyle Coaching Plus a Connected Glucose Meter with Certified Diabetes Educator Support Improves Glucose and Weight Loss for People with Type 2 Diabetes JOURNAL OF DIABETES RESEARCH Bollyky, J. B., Bravata, D., Yang, J., Williamson, M., Schneider, J. 2018
  • Use of a Connected Glucose Meter and Certified Diabetes Educator Coaching to Decrease the Likelihood of Abnormal Blood Glucose Excursions: The Livongo for Diabetes Program JOURNAL OF MEDICAL INTERNET RESEARCH Downing, J., Bollyky, J., Schneider, J. 2017; 19 (7): e234

    Abstract

    The Livongo for Diabetes Program offers members (1) a cellular technology-enabled, two-way messaging device that measures blood glucose (BG), centrally stores the glucose data, and delivers messages back to the individual in real time; (2) unlimited BG test strips; and (3) access to a diabetes coaching team for questions, goal setting, and automated support for abnormal glucose excursions. The program is sponsored by at-risk self-insured employers, health plans and provider organizations where it is free to members with diabetes or it is available directly to the person with diabetes where they cover the cost.The objective of our study was to evaluate BG data from 4544 individuals with diabetes who were enrolled in the Livongo program from October 2014 through December 2015.Members used the Livongo glucose meter to measure their BG levels an average of 1.8 times per day. We estimated the probability of having a day with a BG reading outside of the normal range (70-180 mg/dL, or 3.9-10.0 mmol/L) in months 2 to 12 compared with month 1 of the program, using individual fixed effects to control for individual characteristics.Livongo members experienced an average 18.4% decrease in the likelihood of having a day with hypoglycemia (BG <70 mg/dL) and an average 16.4% decrease in hyperglycemia (BG >180 mg/dL) in months 2-12 compared with month 1 as the baseline. The biggest impact was seen on hyperglycemia for nonusers of insulin. We do not know all of the contributing factors such as medication or other treatment changes during the study period.These findings suggest that access to a connected glucose meter and certified diabetes educator coaching is associated with a decrease in the likelihood of abnormal glucose excursions, which can lead to diabetes-related health care savings.

    View details for PubMedID 28698167

  • Elimination diet and the development of multiple tree-nut allergies. Pediatric research Elizur, A., Bollyky, J. B., Block, W. M. 2017

    Abstract

    BackgroundDespite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nut allergies.MethodsPatients (n=60, aged 4-15 years), recruited for a multiple food (tree nuts, peanut, milk, egg, soy, sesame, and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFCs) to foods still eliminated.ResultsThere was significantly less evidence for eliminating tree nuts compared with other foods, as reflected by a lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20-40% for other foods, respectively P<0.001) or later in life (14.5% vs. 38-75%, respectively P=0.001), and a higher rate of negative skin prick test (SPT)/specific IgE (sIgE) at initial diagnosis (25% vs. <10%, P<0.001). SPT/sIgE increased significantly from past initial levels to present for tree nuts (P<0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive.ConclusionsTree nuts are often eliminated from the diet of multiple-food-allergic patients, despite their low probability for allergy. Sensitization and allergy to most tree nuts exist years later, suggesting that it developed during the period of elimination.Pediatric Research advance online publication, 14 June 2017; doi:10.1038/pr.2017.127.

    View details for DOI 10.1038/pr.2017.127

    View details for PubMedID 28549059

  • Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children. journal of allergy and clinical immunology. In practice Andorf, S., Borres, M. P., Block, W., Tupa, D., Bollyky, J. B., Sampath, V., Elizur, A., Lidholm, J., Jones, J. E., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2017

    Abstract

    Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically.We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs).Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat.Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies.Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

    View details for DOI 10.1016/j.jaip.2017.01.016

    View details for PubMedID 28351786

  • The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice. Clinical and experimental immunology Kuipers, H. F., Nagy, N., Ruppert, S. M., Sunkari, V. G., Marshall, P. L., Gebe, J. A., Ishak, H. D., Keswani, S. G., Bollyky, J., Frymoyer, A. R., Wight, T. N., Steinman, L., Bollyky, P. L. 2016; 185 (3): 372-381

    Abstract

    Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan synthesis in mouse models of cancer, autoimmunity, and a variety of other inflammatory disorders where hyaluronan (HA) has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration, and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after one week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a one-week loading period on the drug is required for most protocols. At steady state, over 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulfated metabolite, 4-methylumbelliferyl sulfate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0.65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/cei.12815

    View details for PubMedID 27218304

  • Different Triggers for the Diagnosis of Individual Food Allergies in Multiple Food Allergic Patients Elizur, A., Bollyky, J. B., Block, W., Nadeau, K. C. MOSBY-ELSEVIER. 2016: AB156
  • Exploring Correlations Between Cross-Reactive Tree Nuts in Multiple Food Allergic Patients Chang, A., Block, W., Bollyky, J. B., Chinthrajah, R., Nadeau, K. C., Elizur, A. MOSBY-ELSEVIER. 2016: AB200
  • Opening clinical trial data: are the voluntary data-sharing portals enough? BMC MEDICINE Geifman, N., Bollyky, J., Bhattacharya, S., Butte, A. J. 2015; 13: 280

    Abstract

    Data generated by the numerous clinical trials conducted annually worldwide have the potential to be extremely beneficial to the scientific and patient communities. This potential is well recognized and efforts are being made to encourage the release of raw patient-level data from these trials to the public. The issue of sharing clinical trial data has recently gained attention, with many agreeing that this type of data should be made available for research in a timely manner. The availability of clinical trial data is most important for study reproducibility, meta-analyses, and improvement of study design. There is much discussion in the community over key data sharing issues, including the risks this practice holds. However, one aspect that remains to be adequately addressed is that of the accessibility, quality, and usability of the data being shared. Herein, experiences with the two current major platforms used to store and disseminate clinical trial data are described, discussing the issues encountered and suggesting possible solutions.

    View details for DOI 10.1186/s12916-015-0525-y

    View details for Web of Science ID 000365069700001

    View details for PubMedID 26560699

    View details for PubMedCentralID PMC4642633

  • Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective DIABETES-METABOLISM RESEARCH AND REVIEWS Bollyky, J. B., Xu, P., Butte, A. J., Wilson, D. M., Beam, C. A., Greenbaum, C. J. 2015; 31 (6): 588-594

    Abstract

    Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies.Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey.Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children.The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/dmrr.2643

    View details for PubMedID 25689602

  • Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases. Current allergy and asthma reports Sabounchi, S., Bollyky, J., Nadeau, K. 2015; 15 (6): 33-?

    Abstract

    There has been significant increase in the prevalence of atopy over the past decade that cannot be explained by genetic predisposition. Environmental factors including nutrition, the uterine environment, and lifestyle factors are known to play a role in gene expression through epigenetic modifications. In this article, we review the literature on the environmental impact on epigenetic modulation of atopic diseases including asthma, food allergy, eczema, and allergic rhinitis. Recent public release of epigenomic data for hundreds of human tissues provides a powerful resource for further investigation of the molecular basis of atopic diseases.

    View details for DOI 10.1007/s11882-015-0533-1

    View details for PubMedID 26141578

  • Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases CURRENT ALLERGY AND ASTHMA REPORTS Sabounchi, S., Bollyky, J., Nadeau, K. 2015; 15 (6)

    Abstract

    There has been significant increase in the prevalence of atopy over the past decade that cannot be explained by genetic predisposition. Environmental factors including nutrition, the uterine environment, and lifestyle factors are known to play a role in gene expression through epigenetic modifications. In this article, we review the literature on the environmental impact on epigenetic modulation of atopic diseases including asthma, food allergy, eczema, and allergic rhinitis. Recent public release of epigenomic data for hundreds of human tissues provides a powerful resource for further investigation of the molecular basis of atopic diseases.

    View details for DOI 10.1007/s11882-015-0533-1

    View details for Web of Science ID 000357428700004

    View details for PubMedID 26141578

  • 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Frontiers in immunology Nagy, N., Kuipers, H. F., Frymoyer, A. R., Ishak, H. D., Bollyky, J. B., Wight, T. N., Bollyky, P. L. 2015; 6: 123-?

    Abstract

    Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called "hymecromone" where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.

    View details for DOI 10.3389/fimmu.2015.00123

    View details for PubMedID 25852691

  • Big data approach towards the characterization of normal peripheral immune cells with data from ImmPort Andorf, S., Bollyky, J., Bhattacharya, S., Shankar, R., Dunn, P., Thomson, E., Wiser, J., Butte, A. AMER ASSOC IMMUNOLOGISTS. 2014
  • Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial LANCET Wherrett, D. K., Bundy, B., Becker, D. J., Dimeglio, L. A., Gitelman, S. E., Goland, R., Gottlieb, P. A., Greenbaum, C. J., Herold, K. C., Marks, J. B., Monzavi, R., Moran, A., Orban, T., Palmer, J. P., Raskin, P., Rodriguez, H., Schatz, D., Wilson, D. M., Krischer, J. P., Skyler, J. S. 2011; 378 (9788): 319-327

    Abstract

    Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity. We aimed to assess whether immunisation with GAD formulated with aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset type 1 diabetes.Patients aged 3-45 years who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 μg GAD-alum, two injections of 20 μg GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks later, and 8 weeks after the second injection. The randomisation sequence was computer generated at the TrialNet coordinating centre. Patients and study personnel were masked to treatment assignment. The primary outcome was the baseline-adjusted geometric mean area under the curve (AUC) of serum C-peptide during the first 2 h of a 4-h mixed meal tolerance test at 1 year. Secondary outcomes included changes in glycated haemoglobin A(1c) (HbA(1c)) and insulin dose, and safety. Analysis included all randomised patients with known measurements. This trial is registered with ClinicalTrials.gov, number NCT00529399.145 patients were enrolled and treated with GAD-alum (n=48), GAD-alum plus alum (n=49), or alum (n=48). At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0·412 nmol/L (95% CI 0·349-0·478) in the GAD-alum group, 0·382 nmol/L (0·322-0·446) in the GAD-alum plus alum group, and 0·413 nmol/L (0·351-0·477) in the alum group. The ratio of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was 0·998 (95% CI 0·779-1·22; p=0·98) for GAD-alum versus alum, and 0·926 (0·720-1·13; p=0·50) for GAD-alum plus alum versus alum. HbA(1c), insulin use, and the occurrence and severity of adverse events did not differ between groups.Antigen-based immunotherapy therapy with two or three doses of subcutaneous GAD-alum across 4-12 weeks does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge.US National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(11)60895-7

    View details for Web of Science ID 000293615800029

    View details for PubMedID 21714999

  • Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial LANCET Orban, T., Bundy, B., Becker, D. J., Dimeglio, L. A., Gitelman, S. E., Goland, R., Gottlieb, P. A., Greenbaum, C. J., Marks, J. B., Monzavi, R., Moran, A., Raskin, P., Rodriguez, H., Russell, W. E., Schatz, D., Wherrett, D., Wilson, D. M., Krischer, J. P., Skyler, J. S. 2011; 378 (9789): 412-419

    Abstract

    The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes.In this multicentre, double-blind, randomised controlled trial, patients aged 6-45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer-generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375.112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6·1-112) higher at 2 years with abatacept (n=73, 0·378 nmol/L) than with placebo (n=30, 0·238 nmol/L; p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months' delay (95% CI 3·47-15·6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]).Co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions.US National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(11)60886-6

    View details for Web of Science ID 000293615900032

    View details for PubMedID 21719096