Qualitative assessment of the suitability of the Dysphagia Symptom Questionnaire to monitor dysphagia in children aged 7-10 years with eosinophilic esophagitis.

BACKGROUND: The Dysphagia Symptom Questionnaire (DSQ) is a patient-reported outcome measure that assesses the frequency and severity of dysphagia in patients with eosinophilic esophagitis (EoE); however, it has only been validated for use in patients with EoE aged 11-40 years. This study examined the content validity of the DSQ and its usability on an electronic handheld device in children aged 7-10 years with EoE. METHODS: In this qualitative, observational cohort study, participants were recruited to partake in two rounds of interviews. During visit 1, a cognitive interview examined EoE-associated concepts and the appropriateness of the DSQ for assessing dysphagia. Participants completed the DSQ daily for 2 weeks, and DSQ scores were calculated. After 2 weeks, a second interview assessed the usability of the DSQ on the electronic device and the burden associated with completing it daily. RESULTS: Overall, 16 participants were included (aged 7-8 years: n = 8; aged 9-10 years: n = 8); most were male (75%) and white (81%), and the mean (standard deviation [SD]) age was 8.4 (1.3) years. The most commonly reported EoE-associated concept was 'trouble with swallowing' (63% [10/16]). Most participants reported that the questions were 'easy to complete' and 'relevant to someone with EoE and dysphagia'. Overall, participants reported understanding the questions and associated responses; however, further probing demonstrated inconsistent comprehension. Key challenging concepts included 'solid food', 'trouble swallowing', 'vomit', and 'relief'; some participants also reported difficulty differentiating between pain levels (31% [4/13]). Most caregivers reported that their child had experienced dysphagia (94% [15/16]); however, mean (SD) DSQ scores over the study period were low (7.3 [7.4]), suggesting infrequent and mild dysphagia, or a lack of comprehension of the questions. Most participants reported that completing the DSQ on the electronic device was easy (93% [14/15]) and they would be willing to complete it for longer than 2 weeks (73% [11/15]). CONCLUSIONS: Difficulties with comprehension and comprehensiveness suggest that the DSQ may not be sufficiently comprehensive for use in all patients in this population, and wording/phrasing changes are required before use in a clinical trial setting.

Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE). METHODS: This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined. RESULTS: Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo. CONCLUSIONS: BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.

Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials.

BACKGROUND: Questions remain regarding the safety of swallowed topical corticosteroids in eosinophilic oesophagitis (EoE). AIM: To assess the safety of an investigational formulation of budesonide (budesonide oral suspension; BOS) from six trials. METHODS: Safety data were integrated from six trials (healthy adults: SHP621-101 [phase 1]; patients with EoE: MPI 101-01 and MPI 101-06 [phase 2]; SHP621-301, SHP621-302 and SHP621-303 [phase 3]) for participants who received ≥1 dose of study drug (BOS 2.0 mg twice daily [b.i.d.], BOS any dose [including BOS 2.0 mg b.i.d.] and placebo). Adverse events (AEs), laboratory testing, bone density and adrenal AEs were assessed. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs). RESULTS: Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n = 292; BOS any dose, n = 448; placebo, n = 168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totalled 93.7, 122.4 and 25.0 participant-years of exposure (PY), respectively. Proportions of treatment-emergent AEs (TEAEs) and AESIs (any) reported were higher for BOS than placebo; however, most were mild/moderate in severity. The most commonly reported AESIs (exposure-adjusted incidence rates [per 100 PY]) in the BOS 2.0 mg b.i.d., BOS any dose and placebo groups were infections (133.5, 154.4 and 136.2, respectively) and gastrointestinal AEs (84.3, 80.9 and 92.1, respectively). Adrenal AEs were more frequent with BOS 2.0 mg b.i.d. and BOS any dose than placebo (44.8, 34.3 and 24.0, respectively). TEAEs and AESIs related to study drug or leading to discontinuation were infrequent. CONCLUSIONS: BOS was well-tolerated; most TEAEs with BOS were mild/moderate in severity. GOV NUMBERS: SHP621-101 (no clinical trials registration number), MPI 101-01 (NCT00762073), MPI 101-06 (NCT01642212), SHP621-301 (NCT02605837), SHP621-302 (NCT02736409) and SHP621-303 (NCT03245840).

Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents With Eosinophilic Esophagitis.

The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE) (MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2-9 or 10-18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution, and bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post dose and the half-life of budesonide was 3.3-3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.

Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study.

Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis-associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open-label, Phase 2, international, long-term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies. Thirty-three patients, ranging from 12 months to 18 years of age, were enrolled. Eight had FIC1 deficiency and 25 had BSEP deficiency. Of the latter, 6 had biallelic, protein truncating mutations (t)-BSEP, and 19 had ≥ 1 nontruncating mutation (nt)-BSEP. Patients received maralixibat 266 µg/kg orally, once daily, from baseline to Week 72, with twice-daily dosing permitted from Week 72. Long-term efficacy was determined at Week 240. Serum bile acid (sBA) response (reduction in sBAs of > 75% from baseline or concentrations <102.0 µmol/L) was achieved in 7 patients with nt-BSEP, 6 during once-daily dosing, and 1 after switching to twice-daily dosing. sBA responders also demonstrated marked reductions in sBAs and pruritus, and increases in height, weight, and QoL. All sBA responders remained liver transplant-free after > 5 years. No patients with FIC1 deficiency or t-BSEP deficiency met the sBA responder criteria during the study. Maralixibat was generally well-tolerated throughout the study. Conclusion: Response to maralixibat was dependent on progressive familial intrahepatic cholestasis subtype, and 6 of 19 patients with nt-BSEP experienced rapid and sustained reductions in sBA levels. The 7 responders survived with native liver and experienced clinically significant reductions in pruritus and meaningful improvements in growth and QoL. Maralixibat may represent a well-tolerated alternative to surgical intervention.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension.

BACKGROUND & AIMS: We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study. METHODS: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes. RESULTS: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns. CONCLUSIONS: For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).

Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration. METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined. RESULTS: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity. CONCLUSIONS: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.

Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study.

BACKGROUND: Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation. We evaluated the safety and efficacy of maralixibat for children with cholestasis in Alagille syndrome. METHODS: ICONIC was a placebo-controlled, randomised withdrawal period (RWD), phase 2b study with open-label extension in children (aged 1-18 years) with Alagille syndrome (NCT02160782). Eligible participants had more than three times the normal serum bile acid (sBA) levels and intractable pruritus. After 18 weeks of maralixibat 380 µg/kg once per day, participants were randomly assigned (1:1) to continue maralixibat or receive placebo for 4 weeks. Subsequently, all participants received open-label maralixibat until week 48. During the long-term extension (204 weeks reported), doses were increased up to 380 µg/kg twice per day. The primary endpoint was the mean sBA change during the RWD in participants with at least 50% sBA reduction by week 18. Cholestastic pruritus was assessed using observer-rated, patient-rated, and clinician-rated 0-4 scales. The safety population was defined as all participants who had received at least one dose of maralixibat. This trial was registered with ClinicalTrials.gov, NCT02160782, and is closed to recruitment. FINDINGS: Between Oct 28, 2014, and Aug 14, 2015, 31 participants (mean age 5·4 years [SD 4·25]) were enrolled and 28 analysed at week 48. Of the 29 participants who entered the randomised drug withdrawal period, ten (34%) were female and 19 (66%) were male. In the RWD, participants switched to placebo had significant increases in sBA (94 µmol/L, 95% CI 23 to 164) and pruritus (1·7 points, 95% CI 1·2 to 2·2), whereas participants who continued maralixibat maintained treatment effect. This study met the primary endpoint (least square mean difference -117 µmol/L, 95% CI -232 to -2). From baseline to week 48, sBA (-96 µmol/L, -162 to -31) and pruritus (-1·6 pts, -2·1 to -1·1) improved. In participants who continued to week 204 (n=15) all improvements were maintained. Maralixibat was generally safe and well tolerated throughout. The most frequent adverse events were gastrointestinal related. Most adverse events were self-limiting in nature and mild-to-moderate in severity. INTERPRETATION: In children with Alagille syndrome, maralixibat is, to our knowledge, the first agent to show durable and clinically meaningful improvements in cholestasis. Maralixibat might represent a new treatment paradigm for chronic cholestasis in Alagille syndrome. FUNDING: Mirum Pharmaceuticals.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD. METHODS: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care. RESULTS: Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers. CONCLUSIONS: The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.

Hepatotoxicity of Statins as Determined by Serum Alanine Aminotransferase in a Pediatric Cohort With Dyslipidemia.

OBJECTIVE: The aim of the study was to evaluate the hepatotoxicity of statins, as determined by serum alanine aminotransferase (ALT), in children and adolescents with dyslipidemia in real-world clinical practice. STUDY DESIGN: Clinical and laboratory data were prospectively collected between September 2010 and March 2014. We compared ALT levels between patients prescribed versus not prescribed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), and then compared ALT before and after initiation of statins. RESULTS: Over the 3.5-year observation period, there were 2704 ALT measurements among 943 patients. The mean age was 14 years; 54% were boys, 47% obese, and 208 patients were treated with statins. Median follow-up after first ALT was 18 months. The mean (SD) ALT in statin and non-statin users was 23 (20) U/L and 28 (28) U/L, respectively. In models adjusted for age, sex, and race, ALT was 2.1 U/L (95% CI 0.1 to 4.4; P = 0.04) lower among statin users, which was attenuated after adjustment for weight category. Patients started on statins during the observation period did not demonstrate an increase in ALT over time (ALT 0.9 U/L [95% confidence interval -5.2 to 3.4] increase per year; P = 0.7). CONCLUSIONS: In our study population, we did not observe a higher burden of ALT elevations among pediatric patients on statins as compared to those with dyslipidemia who are not on statins, supporting the hepatic safety of statin use in childhood.

Comparative effectiveness of bariatric procedures among adolescents: the PCORnet bariatric study.

BACKGROUND: Bariatric surgery has been used for treatment of severe obesity in adolescents but most studies have been small and limited in follow-up. OBJECTIVES: We hypothesized that electronic health record data could be used to compare effectiveness of bariatric procedures in adolescents. SETTING: Data were obtained from clinical research networks using a common data model to extract data from each site. METHODS: Adolescents who underwent a primary bariatric procedure from 2005 through 2015 were identified. The percent change in body mass index (BMI) at 1, 3, and 5 years was estimated using random effects linear regression for patients undergoing all operations. Propensity score adjusted estimates and 95% confidence intervals were estimated for procedures with >25 patients at each time period. RESULTS: This cohort of 544 adolescents was predominantly female (79%) and White (66%), with mean (±standard deviation) age of 17.3 (±1.6) years and mean BMI of 49.8 (± 7.8) kg/m2. Procedures included Roux-en-Y gastric bypass (RYGB; n = 177), sleeve gastrectomy (SG; n = 306), and laparoscopic adjustable gastric banding (n = 61). For those undergoing RYGB, SG, and laparoscopic adjustable gastric banding, mean (95% confidence interval) BMI changes of -31% (-30% to -33%), -28% (-27% to -29%), and -10% (-8% to -12%), were estimated at 1 year. For RYGB and SG, BMI changes of -29% (-26% to -33%) and -25% (-22% to -28%) were estimated at 3 years. CONCLUSIONS: Adolescents undergoing SG and RYGB experienced greater declines in BMI at 1- and 3-year follow-up time points, while laparoscopic adjustable gastric banding was significantly less effective for BMI reduction.

Statin-Associated Myopathy in a Pediatric Preventive Cardiology Practice.

OBJECTIVES: To describe muscle-related statin adverse effects in real-world pediatric practice. STUDY DESIGN: Using prospectively collected quality improvement data from a pediatric preventive cardiology practice, we compared serum creatine kinase (CK) levels among patients prescribed and not prescribed statins, and pre-/poststatin initiation. Multivariable mixed-effect models were constructed accounting for repeated measures, examining the effect of statins on log-transformed CK (lnCK) levels adjusted for age, sex, weight, season, insurance type, and race/ethnicity. RESULTS: Among 1501 patients seen over 3.5 years, 474 patients (14?±?4 years, 47% female) had at least 1 serum CK measured. Median (IQR) CK levels of patients prescribed (n?=?188 patients, 768 CK measurements) and not prescribed statins (n?=?351 patients, 682 CK measurements) were 107 (83) IU/L and 113 (81) IU/L, respectively. In multivariable-adjusted models, lnCK levels did not differ based on statin use (??=?0.02 [SE 0.05], P?=?.7). Among patients started on statins (n?=?86, 130 prestatin and 292 poststatin CK measurements), median CK levels did not differ in adjusted models (? for statin use on lnCK?=?.08 [SE .07], P?=?.2). There was a clinically insignificant increase in CK over time (??=?.08 [SE .04], P?=?.04 per year). No muscle symptoms or rhabdomyolysis were reported among patients with high CK levels. CONCLUSIONS: In a real-world practice, pediatric patients using statins did not experience higher CK levels, nor was there a meaningful CK increase with statin initiation. These data suggest the limited utility to checking CK in the absence of symptoms, supporting current guidelines.

Correlates of Achieving Statin Therapy Goals in Children and Adolescents with Dyslipidemia.

OBJECTIVE: To determine the real-world effectiveness of statins and impact of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction among children and adolescents. STUDY DESIGN: We analyzed data prospectively collected from a quality improvement initiative in the Boston Children's Hospital Preventive Cardiology Program. We included patients ≤21 years of age initiated on statins between September 2010 and March 2014. The primary outcome was first achieving goal LDL-C, defined as <130 mg/dL, or <100 mg/dL with high-level risk factors (eg, diabetes, etc). Cox proportional hazards models were used to assess the impact of baseline clinical and lifestyle factors. RESULTS: Among the 1521 pediatric patients evaluated in 3813 clinical encounters over 3.5 years, 97 patients (6.3%) were started on statin therapy and had follow-up data (median age 14 [IQR 7] years, 54% were female, and 24% obese, 62% with at least one lifestyle risk factor). The median baseline LDL-C was 215 (IQR 78) mg/dL, and median follow-up after starting statin was 1 (IQR 1.3) year. The cumulative probability of achieving LDL-C goal within 1 year was 60% (95% CI 47-69). A lower probability of achieving LDL-C goals was associated with male sex (HR 0.5 [95% CI 0.3-0.8]) and higher baseline LDL-C (HR 0.92 [95% CI 0.87-0.98] per 10 mg/dL), but not age, body mass index percentile, lifestyle factors, or family history. CONCLUSIONS: The majority of pediatric patients started on statins reached LDL-C treatment goals within 1 year. Male patients and those with greater baseline LDL-C were less likely to be successful and may require increased support.

Update on Adolescent Bariatric Surgery.

Childhood obesity remains a significant public health issue. Approximately 8% of adolescent girls and 7% of adolescent boys have severe (≥class 2) obesity. Adolescent severe obesity is associated with numerous comorbidities, and persists into adulthood. Bariatric surgery is the most effective treatment available, resulting in major weight loss and resolution of important comorbid conditions. Clinical practice guidelines for pediatric obesity treatment recommend consideration of surgery after failure of behavioral approaches. Careful screening and postoperative management of patients by a multidisciplinary team is required. Long-term studies are needed to assess the impact of adolescent bariatric surgery.

Severe hypercholesterolemia and liver disease in a 3-year old.

Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. He was diagnosed with primary sclerosing cholangitis which was confirmed by liver biopsy. Our patient was treated with steroids and immunomodulator therapy which was associated with significant reduction in cholestasis and LDL-C levels. Lipoprotein-X has several properties that make it anti-atherogenic, which raises the question if treatment for hypercholesterolemia should be initiated.

Open repair of large abdominal wall hernias with and without components separation; an analysis from the ACS-NSQIP database.

BACKGROUND: Components separation technique emerged several years ago as a novel procedure to improve durability of repair for ventral abdominal hernias. Almost twenty-five years since its initial description, little comprehensive risk adjusted data exists on the morbidity of this procedure. This study is the largest analysis to date of short-term outcomes for these cases. METHODS: The ACS-NSQIP database identified open ventral or incisional hernia repairs with components separation from 2005 to 2012. A data set of cohorts without this technique, matched for preoperative risk factors and operative characteristics, was developed for comparison. A comprehensive risk-adjusted analysis of outcomes and morbidity was performed. RESULTS: A total of 68,439 patients underwent open ventral hernia repair during the study period (2245 with components separation performed (3.3%) and 66,194 without). In comparison with risk-adjusted controls, use of components separation increased operative duration (additional 83 min), length of stay (6.4 days vs. 3.8 days, p < 0.001), return to the OR rate (5.9% vs. 3.6%, p < 0.001), and 30-day morbidity (10.1% vs. 7.6%, p < 0.001) with no increase in mortality (0.0% in each group). CONCLUSIONS: Components separation technique for large incisional hernias significantly increases length of stay and postoperative morbidity. Novel strategies to improve short-term outcomes are needed with continued use of this technique.

Comparison of Controlled Attenuation Parameter and Liver Biopsy to Assess Hepatic Steatosis in Pediatric Patients.

OBJECTIVE: To assess whether the degree of steatosis as determined by controlled attenuation parameter (CAP) measurements correlates with that observed on liver biopsies in a single-center pediatric and young adult cohort. STUDY DESIGN: This cross-sectional study included patients undergoing liver biopsy as part of standard clinical care between January 25, 2012, and April 1, 2015, at Boston Children's Hospital. Eligible patients, with a variety of liver diseases, had CAP measurements within 1 year of biopsy. CAP values were compared across histologic steatosis grades using ANOVA. RESULTS: Sixty-nine patients (mean age, 16.0 ± 2.9 years; 62% male) were studied. CAP measurements were obtained at a median of 1.3 months (IQR, 0.5-3.2) after biopsy. Of the 69 subjects, 23 had steatosis on biopsy. Mean CAP value (dB/m) for subjects with no steatosis was 198 ± 37 vs 290 ± 47 for subjects with steatosis (P < .0001). There were statistically significant differences between CAP values in individuals with no steatosis vs mild/moderate steatosis (P < .0001), no steatosis vs marked steatosis (P < .0001), and mild/moderate vs marked steatosis (P = .004). CONCLUSION: This study demonstrated a difference in CAP between no steatosis and steatosis, and between grades of steatosis. CAP may be a useful noninvasive tool to detect hepatic steatosis in children.