ABSTRACT
Cystic fibrosis-related hepatobiliary involvement (CFHBI) is a term used to describe a spectrum of hepatobiliary involvement ranging from a transient elevation of transaminase levels to advanced cystic fibrosis-associated liver disease (aCFLD). While CFHBI is common among people with cystic fibrosis (PwCF), aCFLD is rare impacting only approximately 5%-10% of the CF population. After respiratory/cardiorespiratory issues and transplant-related complications, aCFLD is now the 4th leading cause of mortality among PwCF. Additionally, aCFLD is an independent predictor of all-cause mortality and is associated with significant morbidity. Despite this recognition, our ability to predict those patients at greatest risk for aCFLD, identify early aCFLD, and monitor the incremental progression of CFHBI is lacking. Here, we review the strengths and weaknesses of the common biomarkers and imaging modalities used in the evaluation and monitoring of CFHBI, as well as the current understanding of genetic modifiers related to aCFLD.
Subject(s)
Biomarkers , Cystic Fibrosis , Liver Diseases , Humans , Cystic Fibrosis/genetics , Cystic Fibrosis/complications , Cystic Fibrosis/diagnostic imaging , Biomarkers/blood , Liver Diseases/genetics , Liver Diseases/diagnostic imaging , Liver Diseases/etiology , Early DiagnosisABSTRACT
BACKGROUND: Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF). METHODS: Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID. RESULTS: The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively. CONCLUSION: This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF.
ABSTRACT
ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.
Subject(s)
Diabetes Mellitus , Pancreatitis, Chronic , Humans , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Pain , Pancreatitis, Chronic/therapy , Pancreatitis, Chronic/drug therapy , United StatesABSTRACT
BACKGROUND: Pediatric radiologists can identify a liver ultrasound (US) pattern predictive of progression to advanced liver disease. However, reliably discriminating these US patterns remains difficult. Quantitative magnetic resonance imaging (MRI) may provide an objective measure of liver disease in cystic fibrosis (CF). OBJECTIVE: The purpose of this study was to determine if quantitative MRI, including MR elastography, is feasible in children with CF and to determine how quantitative MRI-derived metrics compared to a research US. MATERIALS AND METHODS: A prospective, multi-institutional trial was performed evaluating CF participants who underwent a standardized MRI. At central review, liver stiffness, fat fraction, liver volume, and spleen volume were obtained. Participants whose MRI was performed within 1 year of US were classified by US pattern as normal, homogeneous hyperechoic, heterogeneous, or nodular. Each MRI measure was compared among US grade groups using the Kruskal-Wallis test. RESULTS: Ninety-three participants (51 females [54.8%]; mean 15.6 years [range 8.1-21.7 years]) underwent MRI. MR elastography was feasible in 87 participants (93.5%). Fifty-eight participants had an US within 1 year of MRI. In these participants, a nodular liver had significantly higher stiffness (P<0.01) than normal or homogeneous hyperechoic livers. Participants with a homogeneous hyperechoic liver had a higher fat fraction (P<0.005) than others. CONCLUSION: MR elastography is feasible in children with CF. Participants with a nodular pattern had higher liver stiffness supporting the US determination of advanced liver disease. Participants with a homogeneous hyperechoic pattern had higher fat fractions supporting the diagnosis of steatosis.
Subject(s)
Cystic Fibrosis , Elasticity Imaging Techniques , Liver Diseases , Child , Female , Humans , Cystic Fibrosis/diagnostic imaging , Cystic Fibrosis/pathology , Feasibility Studies , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/pathology , Liver Diseases/pathology , Magnetic Resonance Imaging/methods , Prospective StudiesABSTRACT
BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. CONCLUSIONS: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD. CLINICAL TRIAL REGISTRATION: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).
Subject(s)
Cystic Fibrosis , Liver Diseases , Humans , Child , Prospective Studies , Cohort Studies , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Platelet Count , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiologyABSTRACT
INTRODUCTION: The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study. METHODS: In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT. RESULTS: Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers). CONCLUSION: Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT.
Subject(s)
Cystic Fibrosis , Humans , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator/therapeutic use , Pancreas , Clinical Protocols , Surveys and QuestionnairesABSTRACT
BACKGROUND AND AIMS: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF). METHODS: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models. RESULTS: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47). CONCLUSION: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions. CLINICALTRIALS: GOV: NCT03801993.
Subject(s)
Cystic Fibrosis , Gastrointestinal Diseases , Adult , Child , Humans , Male , Female , Infant , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Quality of Life , Prospective Studies , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Abdominal Pain/diagnosis , Abdominal Pain/epidemiology , Abdominal Pain/etiologyABSTRACT
BACKGROUND: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD. METHODS: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event. RESULTS: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×103/microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6-11.8) vs NL (5.3, 4.2-7, p < 0.0001). Over 6.3 years follow-up (1.3-10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events. CONCLUSIONS: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease.
Subject(s)
Cystic Fibrosis , Elasticity Imaging Techniques , Esophageal and Gastric Varices , Hypertension, Portal , Humans , Child , Follow-Up Studies , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Esophageal and Gastric Varices/pathology , Gastrointestinal Hemorrhage/pathology , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/etiologyABSTRACT
OBJECTIVES: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. METHODS: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. RESULTS: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. CONCLUSIONS: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
Subject(s)
Cystic Fibrosis , Liver Diseases , Humans , Child, Preschool , Quality of Life , Prospective Studies , Health Status , Cystic Fibrosis/complications , Cystic Fibrosis/diagnostic imaging , Surveys and Questionnaires , Liver Diseases/etiology , Liver Diseases/complicationsABSTRACT
BACKGROUND: Concerns related to stool consistency are common in the first year of life among children with cystic fibrosis (CF). However, normal stool patterns for infants with CF have not been described. METHODS: Secondary analysis was completed from the previously described BONUS cohort which followed 231 infants with CF through the first 12 months of life. Pain, stool category, stool frequency, feeding type, PERT dose, acid suppression medication, antibiotics usage, stool softener usage and fecal calprotectin were described at 3, 6, and 12 months. Repeated measure ANOVA was used to test the difference in mean stool number. Generalized linear mixed models were used to investigate the relationship between stool characteristics and various factors. RESULTS: The frequency of constipation was stable throughout the first year of life (10-13%) while watery stool significantly decreased from 21.3% at 3 months to 5.8% at 12 months (p=<0.001). The number of stools at months 6 (mean=2.40) and 12 (mean=2.50) are significantly lower than in month 3 (mean=2.83), p<0.025. Exclusive breast feeding was associated with an increased risk for constipation (OR=2.64 [1.60-4.37], p = 0.002) while exclusive formula feeding and acid suppression was associated with decreased risk for constipation (OR=0.40 [0.26-0.61], p=<0.0001 and OR=0.59 [0.39-0.89], p = 0.01 respectively). Pain was not significantly associated with stool consistency. CONCLUSION: Stool frequency and consistency evolves in infant with CF in a fashion similar to that reported in non-CF infants over the first year. Constipation was not associated with pain and was less common among infants receiving acid suppression or exclusively formula feeding.
Subject(s)
Cystic Fibrosis , Anti-Bacterial Agents , Breast Feeding , Child , Constipation/diagnosis , Constipation/epidemiology , Constipation/etiology , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Feces , Female , Humans , Infant , Leukocyte L1 Antigen ComplexABSTRACT
Pediatric pancreatitis describes a spectrum covering acute pancreatitis, acute recurrent pancreatitis, and chronic pancreatitis, each with varying clinical manifestations and risk factors requiring a tailored diagnostic approach. We emphasize management strategies based on age, risk factors, recurrence, and complications. A discussion of the role of therapeutic endoscopy is reviewed and highlights the growing role of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in children with pancreatitis. Particular diagnostic challenges in autoimmune pancreatitis are reviewed with an emphasis on differentiating this entity from alternate pancreaticobiliary pathologies. Finally, we explore a multidisciplinary approach to acute recurrent and chronic pancreatitis.
Subject(s)
Pancreatitis/diagnosis , Pancreatitis/therapy , Acute Disease/therapy , Adolescent , Age Factors , Autoimmune Pancreatitis/diagnosis , Autoimmune Pancreatitis/therapy , Child , Child, Preschool , Cholangiopancreatography, Endoscopic Retrograde/methods , Endoscopy/methods , Fluid Therapy/methods , Humans , Infant , Malnutrition/epidemiology , Nutrition Therapy/methods , Pain Management/methods , Pancreatitis/epidemiology , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/therapy , Recurrence , Risk FactorsABSTRACT
BACKGROUND: The Food and Drug Administration considers patient-reported outcome measures (PROMs) an essential part of clinical research studies for approval of new drugs and new indications for existing drugs. GALAXY evaluated the feasibility of electronic PROMs (ePROMS) to conduct a comprehensive evaluation of gastrointestinal (GI) symptoms in persons with cystic fibrosis (pwCF). METHODS: Three validated GI ePROMs (PAC-SYM, PAGI-SYM and PAC-QOL) were combined with a Stool-Specific questionnaire to make up the GALAXY ePROMs and administered prospectively across 26 CF centers in the United States. The ePROMs were completed at enrollment visit and then electronically at weeks 1, 2 and 4. PwCF at least 2 years and older were eligible for the study. Reminders were only provided by the mobile application during the study window. RESULTS: There were 402 participants enrolled in GALAXY. Of those, 169 (42%) were under 18 years old and 193 (48%) were female. The proportion of all follow-up weeks with at least 1 ePROM fully completed was 80%, slightly higher in those ≥18 years of age (82.5%) compared to those <18 years of age (76.5%). When assessing the completion for all 4 ePROMs, the percentage was 77.6%, also higher among those ≥18 year of age (81.5% versus 72.2% for < 18 years of age). CONCLUSION: Using ePROMs, our study demonstrated that GI symptoms can be feasibly collected with good reproducibility and with minimal involvement of research coordinator time. This mechanism of symptom collection may provide an efficient tool for future CF trials.
Subject(s)
Biomedical Research/methods , Cystic Fibrosis , Mobile Applications , Patient Reported Outcome Measures , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Prospective Studies , Young AdultABSTRACT
BACKGROUND: Definitive non-invasive detection of pediatric choledocholithiasis could allow more efficient identification of those patients who are most likely to benefit from therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for stone extraction. OBJECTIVE: To craft a pediatric choledocholithiasis prediction model using a combination of commonly available serum laboratory values and ultrasound results. METHODS: A retrospective review of laboratory and imaging results from 316 pediatric patients who underwent intraoperative cholangiogram or ERCP due to suspicion of choledocholithiasis were collected and compared to presence of common bile duct stones on cholangiography. Multivariate logistic regression with supervised machine learning was used to create a predictive scoring model. Monte-Carlo cross-validation was used to validate the scoring model and a score threshold that would provide at least 90% specificity for choledocholithiasis was determined in an effort to minimize non-therapeutic ERCP. RESULTS: Alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, and common bile duct diameter via ultrasound were found to be the key clinical variables to determine the likelihood of choledocholithiasis. The dictated specificity threshold of 90.3% yielded a sensitivity of 40.8% and overall accuracy of 71.5% in detecting choledocholithiasis. Positive predictive value was 71.4% and negative predictive value was 72.1%. CONCLUSION: Our novel pediatric choledocholithiasis predictive model is a highly specific tool to suggest ERCP in the setting of likely choledocholithiasis.
Subject(s)
Choledocholithiasis , Child , Cholangiography , Cholangiopancreatography, Endoscopic Retrograde , Choledocholithiasis/diagnostic imaging , Choledocholithiasis/surgery , Common Bile Duct , Humans , Retrospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND: The management of acute pancreatitis (AP) in children was historically derived from adult practice recommendations. Pediatric-specific recommendations for treatment of AP were recently developed by North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, but their impact on clinical outcomes has yet to be evaluated. We developed an AP order set on the basis of these recommendations to assess impact on clinical outcomes. METHODS: Patients admitted to a single center with 3 children's hospitals in 2017 and 2018 for isolated AP were included in a retrospective review. Patient demographic data, order set use, treatment variables (eg, fluid type, rate, type and timing of diet initiation, and narcotic use), and outcome variables (eg, length of stay [LOS], PICU admission, and 30-day readmission) were collected. Mixed-effects modeling was used to estimate the impact of order set use on clinical outcomes. RESULTS: There were 159 pancreatitis encounters and 137 unique patients who met inclusion criteria. In 2018, when using the log transform of LOS in a linear mixed-effects model for clustering by hospital, there was a 10% decrease in mean LOS, but this failed to reach statistical significance (P = .30). Among the 107 encounters who received at least 1 dose of narcotic, there were significantly fewer doses prescribed after implementation of the order set: mean (SD) of5.22 (2.86) vs 3.59 (2.47) (P < .001). Thirty-day readmission (P = .25) and PICU admission rates (P = .31) were not different between years. CONCLUSIONS: The implementation of a pancreatitis order set is associated with a significant decrease in narcotic use in pediatric patients with AP without increasing readmission rates or PICU admissions.
Subject(s)
Pancreatitis , Acute Disease , Adult , Child , Humans , Length of Stay , Pancreatitis/diagnosis , Pancreatitis/epidemiology , Pancreatitis/therapy , Patient Readmission , Retrospective StudiesABSTRACT
OBJECTIVES: To identify factors that increase the risk of gastrointestinal-related (GI-related) hospitalization of infants with cystic fibrosis (CF) during the first year of life. METHODS: The Baby Observational and Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post-hoc assessment of the frequency and indications for GI-related admissions during the first year of life. RESULTS: Sixty-five participants had at least one admission in the first 12âmonths of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000âlipase units/kg per meal; hazard ratio [HR]â=â14.75, Pâ=â0.0005) and use of acid suppressive medications (HRâ=â4.94, Pâ=â0.01) during the study period were positively associated with subsequent GI-related admissions. High levels of fecal calprotectin (fCP) (>200âµg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI-related admissions (HRâ=â2.64, Pâ=â0.033 and HRâ=â4.49, Pâ=â0.002, respectively). During the first 12âmonths of life, participants with any admission had lower weight-for-length z scores (WLZ) (Pâ=â0.01). The impact of admission on WLZ was particularly evident in participants with a GI-related admission (Pâ<â0.0001). CONCLUSIONS: Factors associated with a higher risk for GI-related admission during the first 12âmonths include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI-related hospitalization had lower WLZ at 12âmonths of age than those not admitted as well as those admitted for non-GI-related indications.
Subject(s)
Cystic Fibrosis , Cohort Studies , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Enzyme Replacement Therapy , Hospitalization , Humans , Infant , Infant, Newborn , Neonatal ScreeningABSTRACT
BACKGROUND: Gastrointestinal (GI) involvement among persons with cystic fibrosis (CF) is highly prevalent, representing a significant source of morbidity. Persons with CF have identified GI concerns as a top research priority, yet universal clinical outcome measures capturing many of the GI symptoms experienced in CF are lacking. The GALAXY study was envisioned to address this unmet need. METHODS: The GALAXY study team partnered with Community Voice, a community of patients with CF and their caregivers, to identify the patient reported outcome measures that most accurately reflected their experience with GI symptoms in CF. We also surveyed CF care teams to identify the comfort level of various team members (providers, nurses and dieticians) in managing a variety of GI conditions. RESULTS: Members of Community Voice identified the combination of PAC-SYM, PAGI-SYM, PAC-QOL and the Bristol Stool scale with three additional symptom-specific questions as patient-reported outcome measures that comprehensively captured the CF experience with GI disease. CF care team providers reported a high level of comfort in treating GI conditions including constipation (92%), GERD (93%), and gassiness (77%), however comfort level was limited to only first-line interventions. CONCLUSION: By partnering with persons with CF as well as their caregivers and medical providers, the GALAXY study is designed to uniquely capture the prevalence and severity of GI involvement among persons with CF in a manner that reflects the CF patient experience. The results of GALAXY will inform the development of future interventional trials and serve as a reproducible and objective study endpoint.
Subject(s)
Cystic Fibrosis/diagnosis , Gastrointestinal Diseases/diagnosis , Cystic Fibrosis/complications , Gastrointestinal Diseases/etiology , Humans , Longitudinal Studies , Patient Reported Outcome Measures , Prospective Studies , Symptom AssessmentABSTRACT
ABSTRACT: The reported incidence of pediatric pancreatitis is increasing. Noninvasive imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), play important roles in the diagnosis, staging, follow-up, and management of pancreatitis in children. In this position paper, generated by members of the Pancreas Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Abdominal Imaging Committee of The Society for Pediatric Radiology (SPR), we review the roles of noninvasive imaging in pediatric acute, acute recurrent, and chronic pancreatitis. We discuss available evidence related to noninvasive imaging, highlighting evidence specific to pediatric populations, and we make joint recommendations for use of noninvasive imaging. Further, we highlight the need for research to define the performance and role of noninvasive imaging in pediatric pancreatitis.