Browsing by Author "Randell, Rachel L."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria
    (Oxford University Press, 2021) Basiaga, Matthew L.; Stern, Sara M.; Mehta, Jay J.; Edens, Cuoghi; Randell, Rachel L.; Pomorska, Anna; Irga-Jaworska, Ninela; Ibarra, Maria F.; Bracaglia, Claudia; Nicolai, Rebecca; Susic, Gordana; Boneparth, Alexis; Srinivasalu, Hemalatha; Dizon, Brian; Kamdar, Ankur A.; Goldberg, Baruch; Knupp-Oliveira, Sheila; Antón, Jordi; Mosquera, Juan M.; Appenzeller, Simone; O'Neil, Kathleen M.; Protopapas, Stella A.; Saad-Magalhães, Claudia; Akikusa, Jonathan D.; Thatayatikom, Akaluck; Cha, Seunghee; Nieto-González, Juan Carlos; Lo, Mindy S.; Brennan Treemarcki, Erin; Yokogawa, Naoto; Lieberman, Scott M.; Childhood Arthritis and Rheumatology Research Alliance and the International Childhood Sjögren Syndrome Workgroup; Pediatrics, School of Medicine
    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.
  • Thumbnail Image
    Item
    Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole
    (American Society for Microbiology, 2024) Randell, Rachel L.; Balevic, Stephen J.; Greenberg, Rachel G.; Cohen-Wolkowiez, Michael; Thompson, Elizabeth J.; Venkatachalam, Saranya; Smith, Michael J.; Bendel, Catherine; Bliss, Joseph M.; Chaaban, Hala; Chhabra, Rakesh; Dammann, Christiane E. L.; Downey, L. Corbin; Hornik, Chi; Hussain, Naveed; Laughon, Matthew M.; Lavery, Adrian; Moya, Fernando; Saxonhouse, Matthew; Sokol, Gregory M.; Trembath, Andrea; Weitkamp, Joern-Hendrik; Hornik, Christoph P.; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee; Pediatrics, School of Medicine
    Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.