Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial.

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD): A Cluster Randomized Clinical Trial.

Importance: Antimicrobials are extensively prescribed to nursing home residents with advanced dementia, often without evidence of infection or consideration of the goals of care. Objective: To test the effectiveness of a multicomponent intervention to improve the management of suspected urinary tract infections (UTIs) and lower respiratory infections (LRIs) for nursing home residents with advanced dementia. Design, Setting, and Participants: A cluster randomized clinical trial of 28 Boston-area nursing homes (14 per arm) and 426 residents with advanced dementia (intervention arm, 199 residents; control arm, 227 residents) was conducted from August 1, 2017, to April 30, 2020. Interventions: The intervention content integrated best practices from infectious diseases and palliative care for management of suspected UTIs and LRIs in residents with advanced dementia. Components targeting nursing home practitioners (physicians, physician assistants, nurse practitioners, and nurses) included an in-person seminar, an online course, management algorithms (posters, pocket cards), communication tips (pocket cards), and feedback reports on prescribing of antimicrobials. The residents' health care proxies received a booklet about infections in advanced dementia. Nursing homes in the control arm continued routine care. Main Outcomes and Measures: The primary outcome was antimicrobial treatment courses for suspected UTIs or LRIs per person-year. Outcomes were measured for as many as 12 months. Secondary outcomes were antimicrobial courses for suspected UTIs and LRIs when minimal criteria for treatment were absent per person-year and burdensome procedures used to manage these episodes (bladder catherization, chest radiography, venous blood sampling, or hospital transfer) per person-year. Results: The intervention arm had 199 residents (mean [SD] age, 87.7 [8.0] years; 163 [81.9%] women; 36 [18.1%] men), of which 163 (81.9%) were White and 27 (13.6%) were Black. The control arm had 227 residents (mean [SD] age, 85.3 [8.6] years; 190 [83.7%] women; 37 [16.3%] men), of which 200 (88.1%) were White and 22 (9.7%) were Black. There was a 33% (nonsignificant) reduction in antimicrobial treatment courses for suspected UTIs or LRIs per person-year in the intervention vs control arm (adjusted marginal rate difference, -0.27 [95% CI, -0.71 to 0.17]). This reduction was primarily attributable to reduced antimicrobial use for LRIs. The following secondary outcomes did not differ significantly between arms: antimicrobials initiated when minimal criteria were absent, bladder catheterizations, venous blood sampling, and hospital transfers. Chest radiography use was significantly lower in the intervention arm (adjusted marginal rate difference, -0.56 [95% CI, -1.10 to -0.03]). In-person or online training was completed by 88% of the targeted nursing home practitioners. Conclusions and Relevance: This cluster randomized clinical trial found that despite high adherence to the training, a multicomponent intervention promoting goal-directed care for suspected UTIs and LRIs did not significantly reduce antimicrobial use among nursing home residents with advanced dementia. Trial Registration: ClinicalTrials.gov Identifier: NCT03244917.

Assessing the Value to the Patient of New Technologies in Anatomic Total Shoulder Arthroplasty.

BACKGROUND: Publications regarding anatomic total shoulder arthroplasty (TSA) have consistently reported that they provide significant improvement for patients with glenohumeral arthritis. New TSA technologies that have been introduced with the goal of further improving these outcomes include preoperative computed tomography (CT) scans, 3-dimensional preoperative planning, patient-specific instrumentation, stemless and short-stemmed humeral components, as well as metal-backed, hybrid, and augmented glenoid components. The benefit of these new technologies in terms of patient-reported outcomes is unknown. METHODS: We reviewed 114 articles presenting preoperative and postoperative values for commonly used patient-reported metrics. The results were analyzed to determine whether patient outcomes have improved over the 20 years during which new technologies became available. RESULTS: The analysis did not identify evidence that the results of TSA were statistically or clinically improved over the 2 decades of study or that any of the individual technologies were associated with significant improvement in patient outcomes. CONCLUSIONS: Additional research is required to document the clinical value of these new technologies to patients with glenohumeral arthritis. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience.

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

The trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias: study protocol for a cluster randomized controlled trial.

BACKGROUND: Infections are common in nursing home (NH) residents with advanced dementia but are often managed inappropriately. Antimicrobials are extensively prescribed, but frequently with insufficient evidence to support a bacterial infection, promoting the emergence of multidrug-resistant organisms. Moreover, the benefits of antimicrobials remain unclear in these seriously ill residents for whom comfort is often the goal of care. Prior NH infection management interventions evaluated in randomized clinical trials (RCTs) did not consider patient preferences and lack evidence to support their effectiveness in 'real-world' practice. METHODS: This report presents the rationale and methodology of TRAIN-AD (Trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias), a parallel group, cluster RCT evaluating a multicomponent intervention to improve infection management for suspected urinary tract infections (UTIs) and lower respiratory tract infections (LRIs) among NH residents with advanced dementia. TRAIN-AD is being conducted in 28 facilities in the Boston, USA, area randomized in waves using minimization to achieve a balance on key characteristics (N = 14 facilities/arm). The involvement of the facilities includes a 3-month start-up period and a 24-month implementation/data collection phase. Residents are enrolled during the first 12 months of the 24-month implementation period and followed for up to 12 months. Individual consent is waived, thus almost all eligible residents are enrolled (target sample size, N = 410). The intervention integrates infectious disease and palliative care principles and includes provider training delivered through multiple modalities (in-person seminar, online course, management algorithms, and prescribing feedback) and an information booklet for families. Control facilities employ usual care. The primary outcome, abstracted from the residents' charts, is the number of antimicrobial courses prescribed for UTIs and LRIs per person-year alive. DISCUSSION: TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia. Its findings will provide an evidence base to support the benefit of a program addressing the critical clinical and public health problem of antimicrobial misuse in these seriously ill residents. Moreover, its hybrid efficacy-effectiveness design will inform the future conduct of cluster RCTs evaluating nonpharmacological interventions in the complex NH setting in a way that is both internally valid and adaptable to the 'real-world'. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03244917 . Registered on 10 August 2017.

Hepatic Venous Pressure Gradient Measurements in Children: Correlation With Hepatic Histology and Clinical Indicators of Portal Hypertension.

OBJECTIVES: In adults, elevated hepatic venous pressure gradients (HVPGs) are correlated with the degree of liver fibrosis on histopathology and predict worse outcomes including variceal bleeding and death. We aimed to examine the association between HVPG measurements, histopathologic findings, and clinical indicators of portal hypertension in children. METHODS: Utilizing retrospective data from 2 pediatric centers between 2006 and 2015, we identified children who underwent simultaneous HVPG measurement and transjugular liver biopsy. Medical charts were reviewed for histopathology, imaging, endoscopic, and clinical data. RESULTS: Forty-one children (median age 11 years) were included in the analysis with diagnoses of acute hepatitis (n = 15), chronic liver disease (n = 12), hepatic noncirrhotic portal hypertension (n = 4), acute liver failure (n = 3), and nonhepatic causes of portal hypertension (n = 7). Elevated mean HVPG measurements were found in children with acute liver failure (10 mmHg, range 4-12) and chronic liver disease (7 mmHg, range 1-12). HVPG measurements did not correlate with the histological severity of fibrosis (ρ = 0.23, P = 0.14) or portal inflammation (ρ = 0.24, P = 0.29), and no difference was found in HVPG when comparing children with and without a history of variceal bleeding (P = 0.43). CONCLUSIONS: HVPG measurements do not correlate significantly with the degree of hepatic fibrosis on biopsy. Furthermore, HVPG measurements are not associated with the presence of varices or history of variceal bleeding, suggesting the possibility of intrahepatic shunting in children with advanced liver disease. Therefore, unlike in adults, HVPG measurements may not accurately predict children who are at risk of complications from portal hypertension.

Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis.

OBJECTIVE: To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis. STUDY DESIGN: All existing randomized controlled trials testing the efficacy of the prophylaxis of early adrenal insufficiency using low-dose hydrocortisone on survival without BPD were considered for inclusion when data were available. The primary outcome was the binary variable survival without BPD at 36 weeks of postmenstrual age. RESULTS: Among 5 eligible studies, 4 randomized controlled trials had individual patient data available (96% of participants identified; n = 982). Early low-dose hydrocortisone treatment for 10-15 days was associated with a significant increase in survival without BPD (OR, 1.45; 95% CI, 1.11-1.90; P = .007; I2 = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I2 = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I2 = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I2 = 31.9%) when hydrocortisone was given in association with indomethacin exposure. The incidence of late-onset sepsis was increased in infants exposed to hydrocortisone (OR, 1.34; 95% CI, 1.02-1.75; P = .04; I2 = 0%), but no adverse effects were reported for either death or 2-year neurodevelopmental outcomes as assessed in an aggregate meta-analysis. CONCLUSIONS: This individual patient data meta-analysis showed that early low-dose hydrocortisone therapy is beneficial for survival without BPD in very preterm infants.

Association of Prognostic Estimates With Burdensome Interventions in Nursing Home Residents With Advanced Dementia.

Importance: Prognostication in advanced dementia is challenging but may influence care. Objectives: To determine the accuracy of proxies' prognostic estimates for nursing home residents with advanced dementia, identify factors associated with those estimates, and examine the association between their estimates and use of burdensome interventions. Design, Setting, and Participants: Data were combined from 2 studies that prospectively followed 764 residents with advanced dementia and their proxies in Boston-area nursing homes for 12 months: (1) the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia, conducted from September 2009 to November 2012 (362 resident/proxy dyads; 35 facilities); and (2) the Educational Video to Improve nursing home Care in End-Stage Dementia, conducted from March 2013 to July 2017 (402 resident/proxy dyads; 62 facilities). Proxies were the residents' formally or informally designated medical decision makers. Main Outcomes and Measures: During quarterly telephone interviews, proxies stated whether they believed the resident would live less than 1 month, 1 to 6 months, 7 to 12 months, or more than 12 months. Prognostic estimates were compared with resident survival. Resident and proxy characteristics associated with proxy prognostic estimates were determined. The association between prognostic estimates and whether residents experienced any of the following was determined: hospital transfers, parenteral therapy, tube feeding, venipunctures, and bladder catheterizations. Results: The residents' mean (SD) age was 86.6 (7.3) years; 631 (82.6%) were women and 133 (17.4%) were men. Of the 764 residents, 310 (40.6%) died later than 12 months. Proxies estimated survival with moderate accuracy (C statistic, 0.67). When proxies perceived the resident would die within 6 months, they were more likely to report being asked (183 [7.2%] of 2526) vs not being asked (126 [5.0%] of 2526) about goals of care by nursing home clinicians (adjusted odds ratio [AOR], 1.94; 95% CI, 1.50-2.52). Residents were less likely to experience burdensome interventions when the proxy prognostic estimate was less than 6 months (89 [4.4%] of 2031) vs greater than 6 months (1008 [49.6%] of 2031) (AOR, 0.46; 95% CI, 0.34-0.62). Conclusions and Relevance: Proxies estimated the prognosis of nursing home residents with advanced dementia with moderate accuracy. Having been asked about their opinion about the goal of care was associated with the proxies' perception that the resident had less than 6 months to live and that perception was associated with a lower likelihood the resident experienced burdensome interventions.

Human Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results. Case reports, reviews, articles focusing on inherited chromosomally integrated HHV-6, poster presentations, and articles not published in English were excluded. The remaining 467 articles were reviewed for the following requirements: a statistical analysis of HHV-6B reactivation and aGVHD was described, HHV-6B reactivation was defined by PCR, and blood (plasma, serum, or peripheral blood mononuclear cells) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n = 33). Publications were assigned to 1 of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n = 14), (2) aGVHD was analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n = 1), and (3) analysis without temporal specification (n = 18). A statistically significant association (P < .05) between HHV-6B reactivation and aGVHD was observed in 10 of 14 studies (71%) in group 1, 0 of 1 study (0%) in Group 2, and 8 of 18 studies (44.4%) in Group 3. Of the 14 studies that analyzed HHV-6B as a risk factor for subsequent aGVHD, 11 performed a multivariate analysis and reported a hazard ratio, which reached statistical significance in 9 of these studies. Meta-analysis of these 11 studies demonstrated a statistically significant association between HHV-6B and subsequent grades II to IV aGVHD (hazard ratio, 2.65; 95% confidence interval, 1.89 to 3.72; P < .001). HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.

Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial.

RATIONALE: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. METHODS: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. MEASUREMENTS AND MAIN RESULTS: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (ß-carotene, coenzyme Q10, γ-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. CONCLUSIONS: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease.

GOAL: To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD). BACKGROUND: IBD is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Diet is a potential therapeutic option for IBD based on the hypothesis that changing the fecal dysbiosis could decrease intestinal inflammation. STUDY: Pediatric patients with mild to moderate IBD defined by pediatric Crohn's disease activity index (PCDAI 10-45) or pediatric ulcerative colitis activity index (PUCAI 10-65) were enrolled into a prospective study of the SCD. Patients started SCD with follow-up evaluations at 2, 4, 8, and 12 weeks. PCDAI/PUCAI, laboratory studies were assessed. RESULTS: Twelve patients, ages 10 to 17 years, were enrolled. Mean PCDAI decreased from 28.1±8.8 to 4.6±10.3 at 12 weeks. Mean PUCAI decreased from 28.3±23.1 to 6.7±11.6 at 12 weeks. Dietary therapy was ineffective for 2 patients while 2 individuals were unable to maintain the diet. Mean C-reactive protein decreased from 24.1±22.3 to 7.1±0.4 mg/L at 12 weeks in Seattle Cohort (nL<8.0 mg/L) and decreased from 20.7±10.9 to 4.8±4.5 mg/L at 12 weeks in Atlanta Cohort (nL<4.9 mg/L). Stool microbiome analysis showed a distinctive dysbiosis for each individual in most prediet microbiomes with significant changes in microbial composition after dietary change. CONCLUSIONS: SCD therapy in IBD is associated with clinical and laboratory improvements as well as concomitant changes in the fecal microbiome. Further prospective studies are required to fully assess the safety and efficacy of dietary therapy in patients with IBD.

Hope, distress, and later quality of life among adolescent and young adults with cancer.

We aimed to explore the predictive value of screening for distress alone, hope alone, or a combination of both. In a multicenter prospective study, 37 English-speaking adolescents and young adults with cancer and 40 parents completed validated instruments at diagnosis ("baseline") and 3-6 months later ("follow-up"). Correlated regression models described associations. Within each instrument, baseline and follow-up scores were associated. However, only a composite hope/distress score predicted all three patient-centered outcomes. Multidimensional screens incorporating positive and negative psychosocial constructs may predict patient-centered outcomes better than isolated, single-construct instruments.

Level of Care Preferences Among Nursing Home Residents With Advanced Dementia.

CONTEXT: Delivering goal-directed care is a hallmark of high-quality palliative care, but requires an understanding of preferences. OBJECTIVES: To describe and identify factors associated with level of care preferences among proxies of nursing home (NH) residents with advanced dementia. METHODS: NH residents with advanced dementia and their proxies (N = 402 dyads) were recruited from 62 Boston-area facilities as part of an ongoing randomized clinical trial. At baseline, all proxies were asked to select which level of care they felt the resident should receive: intensive, basic, or comfort care. Multivariable logistic regression identified resident and proxy factors associated with a preference for comfort care (vs. basic or intensive medical care). RESULTS: Proxy level of care preferences were: comfort, 62.2%; basic, 31.1%; and intensive medical care, 6.5%. In multivariable analyses, proxy perception that the resident had less than six months to live was most strongly associated with a preference for comfort-focused care (adjusted odds ratio 12.25, 95% CI 4.04-37.08). Additional factors significantly associated with a preference for comfort care included older resident age, worse resident cognitive impairment, and the proxy having been asked about goals of care preferences by a NH health care provider (adjusted odds ratio 1.71, 95% CI 1.07, 2.74). CONCLUSION: Most proxies select comfort as the preferred level of care for NH residents with advanced dementia. Discussions regarding prognosis, as well as inquiry about goals of care, are modifiable factors that may promote a preference for comfort care in this population.

Nutritional Adequacy of the Specific Carbohydrate Diet in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: The specific carbohydrate diet (SCD) is an exclusion diet used as a therapy in inflammatory bowel disease. The aim of this study was to evaluate the nutritional adequacy of the SCD. METHODS: Prospective dietary data for 12 weeks were analyzed for pediatric patients on the SCD. Intake of 20 key nutrients was compared to dietary recommended intake levels and nutrient intake data from similarly aged children from The National Health and Nutrition Examination Survey National Youth Fitness Survey in 2012. RESULTS: Nine patients enrolled, with 8 patients completing the study. Six of 8 individuals completing the study had gained weight, 1 individual had weight loss, and 1 had no change in weight. Energy intake was significantly greater than 100% of the recommended daily allowance (RDA)/adequate intake for 64% of daily intakes completed for this study. The majority of participants' daily intakes met or exceeded the RDA for vitamins B2, B3, B5, B6, B7, B12, C, A, and E. One hundred percent of participants' intakes were below the RDA for vitamin D. Seventy-five percent of daily intakes were less than the RDA for calcium. The upper limit was met or exceeded for magnesium in 42% of daily intakes. Average vitamin A intake was significantly greater than the upper limit (P = 0.01). CONCLUSIONS: Nutrient intake of pediatric inflammatory bowel disease patients on the SCD was adequate when compared with a healthy peer reference population, but adequacy was variable when compared with the dietary recommended intakes. Close monitoring with a multidisciplinary team for patients using the SCD as an alternative or adjunct therapy is recommend to ensure positive outcomes for overall patient health.

Screening for Psychosocial and Family Risk in Pediatric Gastrointestinal Disorders.

OBJECTIVES: Screening for psychosocial comorbidity is recommended for pediatric patients presenting at an initial gastroenterology (GI) outpatient consultation. We developed and evaluated the psychometric properties of the GI Screener to address the need for a screening tool specific to pediatric GI patients. METHODS: 128 patients (8-18 years old, 63% female) and 126 parents completed age-specific versions of the GI Screener and 3 validated psychosocial comparison instruments (The Behavioral Assessment System for Children, The Functional Disability Inventory, The General Functioning scale of the Family Assessment Device) at their initial GI consultation. (30%) of families repeated the measures 2 weeks later. We identified GI Screener content domains and retained items using exploratory factor analysis. We evaluated internal consistency, construct validity, cross-informant reliability, and test-retest reliability of the trimmed measures. RESULTS: Exploratory factor analysis identified 2 factors in both the parent and child scales: Symptom Impact and Emotional Functioning. Internal consistency estimates for the trimmed scales were good (Cronbach's alpha >0.75) for both Child and Parent scales. We found that the GI Screener for both patient and parents had good construct validity. Cross-informant reliability between Parent and Child scales at baseline had an estimated correlation of 0.56, while intra class correlation coefficients between baseline and 2-week scores showed high test-retest reliability (>0.7). CONCLUSIONS: The GI Screener is a brief, valid and reliable measure that can aid in identifying families who are at high risk for psychosocial comorbidity facilitating the targeted delivery of psychosocial intervention and efficient use of health care resources.

Precolectomy Therapy Does Not Alter Histologic Findings Distribution in Resected Colon in Pediatric Ulcerative Colitis.

OBJECTIVES: Medically intractable pediatric ulcerative colitis can lead to colectomy after which patients commonly receive an ileoanal pouch. Postoperative complications are more common in patients with Crohn disease, a diagnosis that may be rendered after the colectomy specimen is examined. Because most children are likely to be exposed to medications before colectomy, we sought to examine whether such exposure influences the distribution of the inflammation within the resected colon and therefore potentially raise questions about the diagnosis accuracy. METHODS: We conducted a retrospective cohort study of 32 pediatric ulcerative colitis cases undergoing colectomy from 2007 to 2014 for clinical data and precolectomy treatment history. The resected colon histology was reviewed independently by 2 blinded pathologists. The acute/active inflammation was scored using the modified Riley score for 3 colonic segments (proximal, transverse, and distal colon) for each patient. Linear mixed-effects models were used to evaluate possible association between acute/active inflammation scores at various sites and medication use. RESULTS: Twelve cases (38%) showed decreasing acute inflammation score distally to proximally, 8 (25%) had increasing scores, and 12 cases showed no change. Patients were most commonly exposed to corticosteroids, followed by anti-tumor necrosis factor antibodies. There was no statistically or clinically significant change in the histologic scores across the colonic segments of the resected colon in association with exposure to any specific medication or combination of medications, sex, age at diagnosis and surgery, or duration of disease. CONCLUSIONS: Precolectomy therapy does not seem to influence the distribution of inflammation within the resected colon.

Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center.

OBJECTIVE: Despite dietary factors being implicated in the pathogenesis of inflammatory bowel disease (IBD), nutritional therapy, outside of exclusive enteral nutrition (EEN), has not had a defined role within the treatment paradigm of pediatric IBD within IBD centers. Based on emerging data, Seattle Children's Hospital IBD Center has developed an integrated dietary program incorporating the specific carbohydrate diet (SCD) into its treatment paradigm. This treatment paradigm uses the SCD as primary therapy as well as adjunctive therapy for the treatment of IBD. The aim of this study was to evaluate the potential effects of the SCD on clinical outcomes and laboratory studies of pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: In this retrospective study, we reviewed the medical records of patients with IBD on SCD. RESULTS: We analyzed 26 children on the SCD: 20 with CD and 6 with UC. Duration of the dietary therapy ranged from 3 to 48 mo. In patients with active CD (Pediatric Crohn's Disease activity index [PCDAI] >10), PCDAI dropped from 32.8 ± 13.2 at baseline to 20.8 ± 16.6 by 4 ± 2 wk, and to 8.8 ± 8.5 by 6 mo. The mean Pediatric Ulcerative Colitis Activity Index for patients with active UC decreased from a baseline of 28.3 ± 10.3 to 20.0 ± 17.3 at 4 ± 2 wk, to 18.3 ± 31.7 at 6 mo. CONCLUSION: This retrospective review provides evidence that the SCD can be integrated into a tertiary care center and may improve clinical and laboratory parameters for pediatric patients with nonstructuring, nonpenetrating CD as well as UC. Further prospective studies are needed to fully assess the safety and efficacy of the SCD in pediatric patients with IBD.

Adolescent and Young Adult Patient Engagement and Participation in Survey-Based Research: A Report From the "Resilience in Adolescents and Young Adults With Cancer" Study.

Conducting patient-reported outcomes research with adolescents and young adults (AYAs) is difficult due to low participation rates and high attrition. Forty-seven AYAs with newly diagnosed cancer at two large hospitals were prospectively surveyed at the time of diagnosis and 3-6 and 12-18 months later. A subset participated in 1:1 semistructured interviews. Attrition prompted early study closure at one site. The majority of patients preferred paper-pencil to online surveys. Interview participants were more likely to complete surveys (e.g., 93% vs. 58% completion of 3-6 month surveys, P = 0.02). Engaging patients through qualitative methodologies and using patient-preferred instruments may optimize future research success.

Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity.

OBJECTIVE: Excessive weight gain frequently occurs in patients with hypothalamic tumors and lesions leading to hypothalamic obesity (HO). METHODS: Digital brain magnetic resonance imaging (MRI) and clinical outcomes were studied retrospectively in a single center, including 45 children with postoperative lesions in the sellar region (41 craniopharyngiomas, 4 with Rathke's cleft cysts), ∼5 years post-surgery, mean age 13.9 years. Four standard sections covering hypothalamic areas critical to energy homeostasis were used to assess lesions and calculate a hypothalamic lesion score (HLS); the association with HO was examined. RESULTS: Compared to subjects who did not develop HO (n = 23), subjects with HO (n = 22) showed more frequently lesions affecting the third ventricular floor, mammillary bodies, and anterior, medial (all P < 0.05), and most importantly posterior hypothalamus (P < 0.01). The HLS correlated significantly with BMI z-score changes 12 and 30 months post-surgery, even after adjusting for potential confounders of gender, age at surgery, surgery date, surgery BMI z-score, hydrocephalus, and residual hypothalamic tumor (r = 0.34, P = 0.03; r = 0.40, P = 0.02, respectively). Diabetes insipidus was found to be an endocrine marker for HO risk. CONCLUSIONS: The extent of damage following surgery in the sellar region can be assessed by MRI using a novel scoring system for early HO risk assessment.

Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. METHODS: Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohn's Disease Activity Index (PCDAI of 10-29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. RESULTS: All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. CONCLUSIONS: This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.