Browsing by Author "Gariepy, Cheryl E."
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Item Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis(Wiley, 2022-11) Uc, Aliye; Cress, Gretchen A.; Wang, Fuchenchu; Abu-El-Haija, Maisam; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Gonska, Tanja; Lin, Tom K.; Liu, Quin Y.; Mehta, Megha; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Pediatrics, School of MedicineObjectives: To investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Results: Of 689 children, 365 had ARP (53%), 324 CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Conclusions: Children with family history of CP, constant pain or obstructive risk factors should raise suspicion for CP.Item Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis(Wiley, 2022) Uc, Aliye; Cress, Gretchen A.; Wang, Fuchenchu; Abu-El-Haija, Maisam; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Gonska, Tanja; Lin, Tom K.; Liu, Quin Y.; Mehta, Megha; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Pediatrics, School of MedicineObjectives: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Results: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Conclusions: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.Item Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors(Lippincott, Williams & Wilkins, 2020-04) Schwarzenberg, Sarah J.; Uc, Aliye; Zimmerman, Bridget; Wilschanski, Michael; Wilcox, C. Mel; Whitcomb, David C.; Werlin, Steven L.; Troendle, David; Tang, Gong; Slivka, Adam; Singh, Vikesh K.; Sherman, Stuart; Shah, Uzma; Sandhu, Bimaljit S.; Romagnuolo, Joseph; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Muniraj, Thiruvengadam; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Lewis, Michele; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Guda, Nalini; Gonska, Tanja; Giefer, Matthew J.; Gelrud, Andres; Gariepy, Cheryl E.; Gardner, Timothy B.; Freedman, Steven D.; Forsmark, Christopher E.; Fishman, Douglas S.; Cote, Gregory A.; Conwell, Darwin; Brand, Randall E.; Bellin, Melena; Barth, Bradley; Banks, Peter A.; Anderson, Michelle A.; Amann, Stephen T.; Alkaade, Samer; Abu-El-Haija, Maisam; Abberbock, Judah N.; Lowe, Mark E.; Yadav, Dhiraj; Medicine, School of MedicineObjectives: To investigate the natural history of chronic pancreatitis (CP), patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.Item Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study(Wolters Kluwer, 2020-07) Dike, Chinenye R.; Zimmerman, Bridget; Zheng, Yuhua; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Pohl, John; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Husain, Sohail Z.; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Fishman, Douglas S.; Bellin, Melena; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineObjective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Study design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.Item Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors(Wiley, 2022) Tham, See Wan; Wang, Fuchenchu; Gariepy, Cheryl E.; Cress, Gretchen A.; Abu-El-Haija, Maisam A.; Bellin, Melena D.; Ellery, Kate M.; Fishman, Douglas S.; Gonska, Tanja; Heyman, Melvin B.; Lin, Tom K.; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Nathan, Jaimie D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Uc, Aliye; Palermo, Tonya M.; INternational Study Group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) and Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC); Pediatrics, School of MedicineObjectives: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL. Methods: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment. Results: The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001). Conclusions: Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.Item Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis(Wolters Kluwer, 2018-09) Uc, Aliye; Zimmerman, M. Bridget; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Palermo, Joseph J.; Ooi, Chee Y.; Liu, Quin; Lin, Tom K.; Morinville, Veronique D.; McFerron, Brian A.; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Freedman, Steven D.; Fishman, Douglas S.; Bellin, Melena D.; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Pediatrics, School of MedicineOBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.Item INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort Study: Design and Rationale for INSPPIRE 2 From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer(Wolters Kluwer, 2018-11) Uc, Aliye; Perito, Emily R.; Pohl, John F.; Shah, Uzma; Abu-El-Haija, Maisam; Barth, Bradley; Bellin, Melena D.; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan W.; Husain, Sohail Z.; Maqbool, Asim; Mascarenhas, Maria R.; McFerron, Brian A.; Morinville, Veronique D.; Lin, Tom K.; Liu, Quin Y.; Nathan, Jaimie D.; Rhee, Sue J.; Ooi, Chee Y.; Sellers, Zachary M.; Schwarzenberg, Sarah Jane; Serrano, Jose; Troendle, David M.; Werlin, Steven L.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Pediatrics, School of MedicineWe created the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE 2) cohort to study the risk factors, natural history, and outcomes of pediatric acute recurrent pancreatitis and chronic pancreatitis (CP). Patient and physician questionnaires collect information on demographics, clinical history, family and social history, and disease outcomes. Health-related quality of life, depression, and anxiety are measured using validated questionnaires. Information entered on paper questionnaires is transferred into a database managed by Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer's Coordinating and Data Management Center. Biosamples are collected for DNA isolation and analysis of most common pancreatitis-associated genes.Twenty-two sites (18 in the United States, 2 in Canada, and 1 each in Israel and Australia) are participating in the INSPPIRE 2 study. These sites have enrolled 211 subjects into the INSPPIRE 2 database toward our goal to recruit more than 800 patients in 2 years. The INSPPIRE 2 cohort study is an extension of the INSPPIRE cohort study with a larger and more diverse patient population. Our goals have expanded to include evaluating risk factors for CP, its sequelae, and psychosocial factors associated with pediatric acute recurrent pancreatitis and CP.Item Interobserver Agreement for CT and MRI Findings of Chronic Pancreatitis in Children: A Multicenter Ancillary Study Under the INSPPIRE Consortium(American Roentgen Ray Society, 2022) Trout, Andrew T.; Abu-El-Haija, Maisam; Anupindi, Sudha A.; Marine, Megan B.; Murati, Michael; Phelps, Andrew S.; Rees, Mitchell A.; Squires, Judy H.; Ellery, Kate M.; Gariepy, Cheryl E.; Maqbool, Asim; McFerron, Brian A.; Perito, Emily R.; Schwarzenberg, Sarah J.; Zhang, Bin; Andersen, Dana K.; Lowe, Mark E.; Uc, Aliye; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC); Radiology and Imaging Sciences, School of MedicineBackground: Imaging findings represent key criteria for diagnosing chronic pancreatitis in children. Understanding radiologists’ agreement for imaging findings is critical to standardizing and optimizing diagnostic criteria. Objective: To evaluate the interobserver agreement among experienced pediatric radiologists for subjective, quantitative, and semi-quantitative imaging findings of chronic pancreatitis in children. Methods: In this retrospective study, CT or MRI examinations performed in children with chronic pancreatitis were submitted by six sites participating in the INSPPIRE consortium. One pediatric radiologist from each of the six sites reviewed examinations; three of the radiologists independently reviewed all CT examinations, and the other three radiologists independently reviewed all MRI examinations. Reviewers recorded 13 categorical imaging findings of chronic pancreatitis and measured pancreas thickness and duct diameter. Agreement was assessed using kappa coefficients for the categorical variables and intraclass correlation coefficients (ICC) for the continuous measures. Results: A total of 76 CT and 80 MRI examinations performed in 110 children (mean age, 11.3±4.6 years; 65 girls, 45 boys) were reviewed. For CT, kappa coefficients for categorical findings ranged from −0.01 to 0.81, with relatively high kappa coefficients for parenchymal calcification (κ=0.81), main pancreatic duct dilation (κ=0.63), and atrophy (κ=0.52). ICCs for parenchymal thickness measurements ranged from 0.57 in the pancreas head to 0.80 in the body and tail. ICC for duct diameter was 0.85. For MRI, kappa coefficients for categorical findings ranged from −0.01 to 0.74, with relatively high kappa coefficients for main duct irregularity (κ=0.74), side branch dilation (κ=0.70), number of dilated side branches (κ=0.65), and main duct dilation (κ=0.64); kappa coefficient for atrophy was 0.52. ICCs for parenchymal thickness measurements ranged from 0.59 in the pancreas head to 0.68 in the tail. ICC for duct diameter was 0.77. Conclusion: Interobserver agreement was fair to moderate for most CT and MRI findings of chronic pancreatitis in children. Clinical Impact: This study highlights challenges for the imaging diagnosis of pediatric chronic pancreatitis. Standardized and/or objective criteria are needed given the importance of imaging in diagnosis.Item Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE(Wolters Kluwer, 2019-07-01) Lin, Tom K.; Abu-El-Haija, Maisam; Nathan, Jaimie D.; Palermo, Joseph P.; Barth, Bradley; Bellin, Melena; Fishman, Douglas S.; Freedman, Steven D.; Gariepy, Cheryl E.; Giefer, Matthew J.; Gonska, Tanja; Heyman, Melvin B.; Himes, Ryan; Husain, Sohail Z.; Liu, Quin; Maqbool, Asim; Mascarenhas, Maria; McFerron, Brian; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily; Pohl, John F.; Rhee, Sue; Schwarzenberg, Sarah Jane; Shah, Uzma; Troendle, David; Werlin, Steven L.; Wilschanski, Michael; Zimmerman, M. Bridget; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineThe significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact. Patients and Methods: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ2 or Fisher exact test for categorical variables. Results: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). Conclusions: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.Item Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE(Wiley, 2023) Morinville, Veronique D.; Husain, Sohail Z.; Wang, Fuchenchu; Cress, Gretchen A.; Abu-El-Haija, Maisam; Chugh, Ankur; Downs, Elissa; Ellery, Kate; Fishman, Douglas S.; Freeman, Alvin Jay; Gariepy, Cheryl E.; Giefer, Matthew; Gonska, Tanja; Liu, Quin; Maqbool, Asim; Mark, Jacob; Mcferron, Brian Arthur; Mehta, Megha; Nathan, Jaimie D.; Ng, Ken; Ooi, Chee Y.; Perito, Emily; Ruan, Wenly; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark; Uc, Aliye; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC); Pediatrics, School of MedicineObjectives: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. Methods: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. Results: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. Conclusions: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.