Publications by authors named "Rachel L Randell"

9 Publications

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Delivering clinical trials at home: protocol, design and implementation of a direct-to-family paediatric lupus trial.

Lupus Sci Med 2021 May;8(1)

Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA

Introduction: Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.

Methods: Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.

Discussion And Dissemination: Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.

Trial Registration Number: ClinicalTrials.gov Registry (NCT04358302).
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http://dx.doi.org/10.1136/lupus-2021-000494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108689PMC
May 2021

Painful, reappearing eruption in a medically complex 4-year-old.

BMJ Case Rep 2021 Feb 18;14(2). Epub 2021 Feb 18.

Pediatric Hospitalist Medicine, Department of Pediatrics, Duke University, Durham, North Carolina, USA.

A 4-year-old boy with atypical, complete DiGeorge and CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities and ear abnormalities) syndromes presented with frequent episodes of a painful, markedly erythematous eruption associated with swelling. Evaluation revealed non-specific findings on skin biopsy at the time of eruption and no pathogenic mutation in the SCN9A gene. The patient was diagnosed with secondary erythromelalgia based on clinical presentation. Erythromelalgia is a rare disorder characterised by recurrent episodes of pain and erythema typically affecting the distal extremities. This case represents the first case of erythromelalgia in the setting of DiGeorge and CHARGE syndromes.
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http://dx.doi.org/10.1136/bcr-2020-239310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896574PMC
February 2021

Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria.

Rheumatology (Oxford) 2020 Dec 6. Epub 2020 Dec 6.

Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan.

Objective: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population.

Methods: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria.

Results: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age.

Conclusion: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.
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http://dx.doi.org/10.1093/rheumatology/keaa757DOI Listing
December 2020

Tocilizumab in Refractory Autoimmune Encephalitis: A Series of Pediatric Cases.

Pediatr Neurol 2018 09 3;86:66-68. Epub 2018 Aug 3.

Division of Pediatric Rheumatology, Department of Pediatrics, Duke University, Durham, North Carolina.

Background: Autoimmune encephalitis can result in significant neurological and psychiatric morbidity and mortality in patients of all ages and often does not respond to standard therapies. Recent reports suggest efficacy of tocilizumab, a monoclonal antibody against interleukin 6, in refractory autoimmune encephalitis.

Results: We describe three children with refractory autoimmune encephalitis who experienced a robust, immediate clinical response following treatment with tocilizumab.

Conclusion: These findings support the efficacy and short-term safety of tocilizumab as a third-line treatment for refractory autoimmune encephalitis in children.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.07.016DOI Listing
September 2018

Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.

Clin Epidemiol 2018 28;10:215-222. Epub 2018 Feb 28.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.

Subjects And Methods: Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs).

Results: A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls.

Conclusion: This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.
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http://dx.doi.org/10.2147/CLEP.S143322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836686PMC
February 2018

Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study.

JMIR Res Protoc 2016 Jan 5;5(1):e3. Epub 2016 Jan 5.

Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, NC, United States.

Background: The Internet has successfully been used for patient-oriented survey research. Internet-based translational research may also be possible.

Objective: Our aim was to study the feasibility of collecting biospecimens from CCFA Partners, an Internet-based inflammatory bowel disease (IBD) cohort.

Methods: From August 20, 2013, to January 4, 2014, we randomly sampled 412 participants, plus 179 from a prior validation study, and invited them to contribute a biospecimen. Participants were randomized to type (blood, saliva), incentive (none, US $20, or US $50), and collection method for blood. The first 82 contributors were also invited to contribute stool. We used descriptive statistics and t tests for comparisons.

Results: Of the 591 participants, 239 (40.4%) indicated interest and 171 (28.9%) contributed a biospecimen. Validation study participants were more likely to contribute than randomly selected participants (44% versus 23%, P<.001). The return rate for saliva was higher than blood collected by mobile phlebotomist and at doctors' offices (38%, 31%, and 17% respectively, P<.001). For saliva, incentives were associated with higher return rates (43-44% versus 26%, P=.04); 61% contributed stool. Fourteen IBD-associated single nucleotide polymorphisms were genotyped, and risk allele frequencies were comparable to other large IBD populations. Bacterial DNA was successfully extracted from stool samples and was of sufficient quality to permit quantitative polymerase chain reaction for total bacteria.

Conclusions: Participants are willing to contribute and it is feasible to collect biospecimens from an Internet-based IBD cohort. Home saliva kits yielded the highest return rate, though mobile phlebotomy was also effective. All samples were sufficient for genetic testing. These data support the feasibility of developing a centralized collection of biospecimens from this cohort to facilitate IBD translational studies.
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http://dx.doi.org/10.2196/resprot.5171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719077PMC
January 2016

Validation of an internet-based cohort of inflammatory bowel disease (CCFA partners).

Inflamm Bowel Dis 2014 Mar;20(3):541-4

*University of North Carolina School of Medicine, Chapel Hill, North Carolina; †Center for Gastrointestinal Biology and Disease, and ‡Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; §Worldwide Epidemiology GlaxoSmithKline, Research Triangle Park, North Carolina; ‖Section of Biostatistics and Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and ¶Division of Gastroenterology and Hepatology, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.

Background: As traditional methods have become increasingly difficult, the Internet offers a mechanism for conducting survey research quickly and efficiently. However, the validity of this research depends on the ability of respondents to accurately report health status. We used a large Internet-based inflammatory bowel disease (IBD) cohort to validate self-reported IBD against physician reports.

Methods: Between June 22, 2012, and April 01, 2013, all participants of CCFA Partners (n = 6681) were invited to participate, and 450 were selected by random stratified sampling. We sent physicians a survey to confirm IBD diagnosis and characteristics. We used descriptive statistics to compare data.

Results: A total of 4423 participants (66%) indicated interest. Of 450 selected, 261 (58%) consented, and physician reports were obtained for 184 (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of confirmed). The matching between patient and physician reports for Crohn's disease (CD) was 82% for disease location, 89% for the presence of perianal disease, and 46% for disease behavior. For ulcerative colitis (UC), disease location matched 54% of the time. Physician reports confirmed the status of ever having bowel surgery for 97% of CD and 94% for UC and confirmed current pouch or ostomy in 84% of CD and 81% of UC.

Conclusions: Self-reported IBD in CCFA Partners is highly accurate, and participants are willing to release medical records for research. Self-reported phenotypic characteristics were less valid. The validity of IBD diagnoses among the participants of CCFA Partners supports the use of this cohort for patient-centered outcome research.
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http://dx.doi.org/10.1097/01.MIB.0000441348.32570.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112538PMC
March 2014

Patient perception of chronic illness care in a large inflammatory bowel disease cohort.

Inflamm Bowel Dis 2013 Jun;19(7):1428-33

School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7080, USA.

Background: Improvements in care for inflammatory bowel diseases could use the Chronic Care Model, an evidence-based approach that has improved patient outcomes and reduced costs in other illnesses. Specific aims include (1) to explore patient perception of chronic illness care in a large inflammatory bowel disease cohort and (2) to determine whether demographic factors, medication adherence, quality of life, disease type, and activity were associated with perception of chronic illness care.

Methods: We randomly selected 1000 participants from the Crohn's and Colitis Foundation of America Partners Internet cohort to receive the validated Patient Assessment of Chronic Illness Care (PACIC) instrument, which measures patient experience with specific aspects of care congruent with the Chronic Care Model on a scale of 1 to 5, with 5 being highest perception of care. We used descriptive and bivariate statistics to assess relationships.

Results: Nine hundred and forty-five participants completed the PACIC (576 Crohn's disease, 339 ulcerative colitis, and 30 indeterminate or other; 74% female, mean age 45 [SD = 15.1], mean PACIC 2.4 [SD = 0.93]). Recent gastroenterologist visit, hospitalization, surgery, and current pouch/ostomy were all associated with significantly higher PACIC (P < 0.05). PACIC correlated positively with quality of life (Pearson's correlation = 0.12, P = 0.003) but not medication adherence or disease activity.

Conclusions: Reports of chronic illness care in this inflammatory bowel disease cohort are in the same range as other illnesses. PACIC is positively associated with quality of life, so efforts to align care with the Chronic Care Model may benefit this population. Subjects who had more subspecialty interactions reported an increased perception of care, indicating the important role of direct patient contact.
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http://dx.doi.org/10.1097/MIB.0b013e3182813434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600129PMC
June 2013

4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells.

J Biol Chem 2011 Dec 8;286(52):45083-92. Epub 2011 Nov 8.

Division of Pulmonary Medicine and Cystic Fibrosis Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

Sodium 4-phenylbutyrate (4PBA) corrects trafficking of ΔF508-CFTR in Cystic Fibrosis (CF) epithelia, which is hypothesized to, at least in part, result from increased expression of Hsp70 (stress-induced 70 kDa heat shock protein). To identify other 4PBA-regulated proteins that may promote correction of ΔF508 trafficking, we performed differential display RT-PCR on mRNA from IB3-1 CF bronchiolar epithelial cells treated for 0-24 h with 1 mM 4PBA. In this screen, a STAT-3 (signal transducer and activator of transcription-3)-interacting protein, StIP-1 that regulates STAT-3 activation had transiently increased expression. StIP-1 is identical to Elongator protein 2 (Elp2), a component of the Elongator complex that regulates RNA polymerase II. Previous studies have suggested that Elongator regulates Hsp70 mRNA transcription, and that the Hsp70 promoter contains functional STAT-3-binding sites. We therefore tested the hypothesis that 4PBA increases Hsp70 expression by an Elongator- and STAT-3-dependent mechanism. 4PBA treatment of IB3-1 CF bronchiolar epithelial cells caused transiently increased expression of Hsp70 protein, as well as Elp2 protein and mRNA. Elp2 depletion by transfection of small interfering RNAs, reduced both Elp2 and Hsp70 protein expression. 4PBA also caused transient activation of STAT-3, and increased abundance of nuclear proteins that bind to the STAT-3-responsive element of the Hsp70 promoter. Luciferase reporter assays demonstrated that both Elp2 overexpression and 4PBA increase Hsp70 promoter activity, while Elp2 depletion blocked the ability of 4PBA to stimulate Hsp70 promoter activity. Together, these data suggest that Elp2 and STAT-3 mediate, at least in part, the stimulation of Hsp70 expression by 4PBA.
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http://dx.doi.org/10.1074/jbc.M111.293282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247989PMC
December 2011