bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Male Athlete Triad—A Consensus Statement From the Female and Male Athlete Triad Coalition Part II: Diagnosis, Treatment, and Return-To-Play
Authors: Fredericson Michael , Kussman Andrea , Misra Madhusmita , Barrack Michelle T. , De Souza Mary Jane , Kraus Emily , Koltun Kristen J. , Williams Nancy I. , Joy Elizabeth , Nattiv Aurelia 
Published: June 2021

Abstract:
The Male Athlete Triad is a medical syndrome most common in adolescent and young adult male athletes in sports that emphasize a lean physique, especially endurance and weight-class athletes. The 3 interrelated conditions of the Male Athlete Triad occur on spectrums of energy deficiency/low energy availability (EA), suppression of the hypothalamic–pituitary–gonadal axis, and impaired bone health, ranging from optimal health to clinically relevant outcomes of energy deficiency/low EA with or without disordered eating or eating disorder, functional hypogonadotropic hypogonadism, and osteoporosis or low bone mineral density with or without bone stress injury (BSI). Because of the importance of bone mass acquisition and health concerns in adolescence, screening is recommended during this time period in the at-risk male athlete. Diagnosis of the Male Athlete Triad is best accomplished by a multidisciplinary medical team. Clearance and return-to-play guidelines are recommended to optimize prevention and treatment. Evidence-based risk assessment protocols for the male athlete at risk for the Male Athlete Triad have been shown to be predictive for BSI and impaired bone health and should be encouraged. Improving energetic status through optimal fueling is the mainstay of treatment. A Roundtable on the Male Athlete Triad was convened by the Female and Male Athlete Triad Coalition in conjunction with the 64th Annual Meeting of the American College of Sports Medicine in Denver, Colorado, in May of 2017. In this second article, the latest clinical research to support current models of screening, diagnosis, and management for at-risk male athlete is reviewed with evidence-based recommendations.
Improving Medication Tolerance
Authors: Ballou Sarah , Iturrino Johanna , Rangan Vikram , Cheng Vivian , Kelley John M. , Lembo Anthony , Kaptchuk Ted J. , Nee Judy 
Published: June 2021

Objectives:
Tricyclic antidepressants (TCAs) are commonly used to treat disorders of gut-brain interaction (DGBI). However, these medications are often associated with side effects that lead to early treatment discontinuation. Research in other chronic medical conditions suggests that many TCA side effects may be caused by nocebo (negative placebo) effects. The current study tests a brief, verbal intervention aimed at improving tolerance of TCAs in DGBI by providing education about nocebo effects.

Materials and Methods:
This pilot randomized controlled trial was performed in a tertiary care gastroenterology clinic. Participants with DGBI were randomized “standard information,” describing the benefits and risks of TCAs, or “augmented information,” which included an additional <30-second education about nocebo effects. Two weeks after their visit, participants were emailed a survey evaluating the number and bothersomeness of side effects, adequate relief, global improvement, and treatment satisfaction.

Results:
Thirty-one patients were randomized and 22 responded to the survey. The average age was 40% and 59% were women. Although not statistically significant, the augmented group attributed nominally fewer symptoms to TCAs than the standard group, with a medium effect size (1.5 vs. 4.2, effect size d=0.56, P=0.212) and reported being significantly less bothered by those symptoms (13.4 vs. 38.1, P=0.037). A nominally larger percentage of the augmented group reported adequate relief of symptoms after 2 weeks of treatment compared with the standard group (55% vs. 27%, respectively).

Conclusions:
This pilot study demonstrates that a brief (≈30 s) clinical intervention addressing nocebo effects may improve tolerance of TCAs. These findings provide support for future, fully powered studies to evaluate the impact of framing on clinical outcomes, especially in chronic conditions.
Dementia Diagnosis Disparities by Race and Ethnicity
Authors: Lin Pei-Jung , Daly Allan T. , Olchanski Natalia , Cohen Joshua T. , Neumann Peter J. , Faul Jessica D. , Fillit Howard M. , Freund Karen M. 
Published: June 2021

Background:
Dementia is often underdiagnosed and this problem is more common among some ethnoracial groups.

Objective:
The objective of this study was to examine racial and ethnic disparities in the timeliness of receiving a clinical diagnosis of dementia.

Research Design:
This was a prospective cohort study.

Subjects:
A total of 3966 participants age 70 years and above with probable dementia in the Health and Retirement Study, linked with their Medicare and Medicaid claims.

Measures:
We performed logistic regression to compare the likelihood of having a missed or delayed dementia diagnosis in claims by race/ethnicity. We analyzed dementia severity, measured by cognition and daily function, at the time of a dementia diagnosis documented in claims, and estimated average dementia diagnosis delay, by race/ethnicity.

Results:
A higher proportion of non-Hispanic Blacks and Hispanics had a missed/delayed clinical dementia diagnosis compared with non-Hispanic Whites (46% and 54% vs. 41%, P<0.001). Fully adjusted logistic regression results suggested more frequent missed/delayed dementia diagnoses among non-Hispanic Blacks (odds ratio=1.12; 95% confidence interval: 0.91–1.38) and Hispanics (odds ratio=1.58; 95% confidence interval: 1.20–2.07). Non-Hispanic Blacks and Hispanics had a poorer cognitive function and more functional limitations than non-Hispanic Whites around the time of receiving a claims-based dementia diagnosis. The estimated mean diagnosis delay was 34.6 months for non-Hispanic Blacks and 43.8 months for Hispanics, compared with 31.2 months for non-Hispanic Whites.

Conclusions:
Non-Hispanic Blacks and Hispanics may experience a missed or delayed diagnosis of dementia more often and have longer diagnosis delays. When diagnosed, non-Hispanic Blacks and Hispanics may have more advanced dementia. Public health efforts should prioritize racial and ethnic underrepresented communities when promoting early diagnosis of dementia.
Alveolar bone grafting and gingivoperiosteoplasty in bilateral cleft lip and palate
Authors: Chhajlani Rahul , Chhajlani Prakash , Bonanthaya Krishnamurthy , Mahajan Ravi Kumar 
Published: June 2021

Purpose of review
Gingivoperiosteoplasty (GPP) and alveolar bone grafting (ABG) procedures have a vast history. There have been many publications regarding ABG and secondary ABG, with and without presurgical infant orthopedics (PSIO), in bilateral cleft lip and palate patients. There is little long-term data available describing results of both techniques.

Recent findings
The interdisciplinary approach to primary and secondary surgical procedures has proven to be beneficial for patients with bilateral cleft lip and palate. In the neonates, naso-alveolar molding (NAM) has been found to optimize the aesthetic outcome as well as re-approximating the arches to facilitate GPP. During the mixed dentition stage, arch preparation/expansion before the secondary ABG procedure improves arch morphology, restores the functional interarch relationship, and facilitates surgery.

Summary
This review aims to highlight the key points of both the procedures and why combining both procedures along with PSIO procedures such as NAM might be helpful for the patients in the long term.
Inadequate Bowel Preparation in Pediatric Colonoscopy—Prospective Study of Potential Causes
Authors: Kumar Sanjay , Bennett William E. , Bozic Molly A. , Croffie Joseph M. , Ferrell Emily , Hon Emily C. , Khan Hamza H. , McFerron Brian A. , Molleston Jean P. , Pfefferkorn Marian D. , Steiner Steven J. , Rao Girish S. , Vanderpool Charles P. , Waseem Shamaila , Watts Abhishek , Gupta Sandeep K. 
Published: June 2021

ABSTRACT

Objectives:
Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children.

Methods:
We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0–9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score—adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models.

Results:
A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2–18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy.

Conclusion:
Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20–40%).
Associations Between Subclass Profile of IgG Response to Gluten and the Gastrointestinal and Motor Symptoms in Children With Cerebral Palsy
Authors: Stenberg Reidun , Uhde Melanie , Ajamian Mary , Green Peter H. , Myleus Anna , Alaedini Armin 
Published: June 2021

ABSTRACT

Objective:
Gastrointestinal problems are often seen in children with cerebral palsy, although the etiology and underlying mechanisms are not fully understood. Recent data point to significantly elevated levels of IgG antibody to dietary gluten in cerebral palsy independent of celiac disease, a gluten-mediated autoimmune enteropathy. We aimed to further characterize this antibody response by examining its subclass distribution and target reactivity in the context of relevant patient symptom profile.

Methods:
Study participants included children with cerebral palsy (n = 70) and celiac disease (n = 85), as well as unaffected controls (n = 30). Serum IgG antibody to gluten was investigated for subclass distribution, pattern of reactivity towards target proteins, and relationship with gastrointestinal symptoms and motor function.

Results:
The anti-gluten IgG antibody response in the cerebral palsy cohort was constituted of all 4 subclasses. In comparison with celiac disease, however, IgG1, IgG2, and IgG3 subclasses were significantly lower, whereas the IgG4 response was significantly higher in cerebral palsy. Within the cohort of cerebral palsy patients, levels of anti-gluten IgG1, IgG3, and IgG4 were greater in those with gastrointestinal symptoms, and the IgG3 subclass antibody correlated inversely with gross motor function. The anti-gluten IgG antibodies targeted a broad range of gliadin and glutenin proteins.

Conclusions:
These findings reveal an anti-gluten IgG subclass distribution in cerebral palsy that is significantly different from that in celiac disease. Furthermore, the observed association between IgG subclass and symptom profile is suggestive of a relationship between the immune response and disease pathophysiology that may indicate a role for defects in gut immune and barrier function in cerebral palsy.
Reduced Systemic Corticosteroid Use among Pediatric Patients With Inflammatory Bowel Disease in a Large Learning Health System
Authors: Kandavel Prashanthi , Eder Sally J. , Adler Jeremy 
Published: June 2021

ABSTRACT

Objectives:
Corticosteroids have long been used to treat inflammatory bowel disease. However, cumulative corticosteroid exposure is associated with adverse effects, particularly in growing children. Professional guidelines recommend steroid-sparing strategies. It remains unknown whether corticosteroid use has decreased in children with inflammatory bowel disease.

Methods:
We performed retrospective cohort study using data from 2007 to 2018 from the international multi-center ImproveCareNow Network, a pediatric inflammatory bowel disease quality improvement collaborative. Pediatric patients diagnosed with inflammatory bowel disease were included. Patients with missing diagnosis or corticosteroid use data were excluded. We performed serial cross-sectional analyses of period prevalence and used multivariate regression models.

Results:
27,321 patients were included (65% Crohn disease, 28% ulcerative colitis, 7% indeterminate colitis). Corticosteroids were used in 10,206 (37%). Corticosteroid use decreased from 28% (2007) to 12% (2018). Black patients received corticosteroids more commonly than white patients. This disparity improved as corticosteroid use decreased in both groups. Most corticosteroid use occurred <120 days after diagnosis. Corticosteroid or 5-aminosalicylate use <120 days after diagnosis predicted later corticosteroid use. Anti-tumor necrosis factor-alpha medication use <120 days after diagnosis was associated with a reduction in corticosteroid use. As corticosteroid use decreased, steroid-sparing therapy use increased and height and weight z scores improved, particularly among children with Crohn disease. Despite improvement across the network, variation in corticosteroid usage remains.

Conclusions:
Corticosteroid use among pediatric patients with inflammatory bowel disease in the ImproveCareNow Network has decreased over time. Racial disparities in corticosteroid use were found, but gradually improved.
Could Commercial Formulations Replace Individualized Prescription in Pediatric Home Parenteral Nutrition?
Authors: Ferreira Mariana , Guerra Paula , Ferreras Cristina , Espinheira Maria do Céu , Trindade Eunice , Dias Jorge Amil 
Published: June 2021

ABSTRACT

Objectives:
Standard parenteral nutrition (PN) solutions are safe and can meet the nutritional requirements of a significant number of pediatric patients. However, they may not always be adequate for those on long term PN. We aimed to compare the composition of individually tailored prescriptions in a pediatric population on home PN with that of available commercial PN formulations.

Methods:
Retrospective analysis of the individual prescriptions of metabolically stable pediatric patients on home PN over a 1-year period (March 2019 to March 2020). These were compared with commercially available solutions with electrolytes, and replacement was considered adequate if three successive criteria were met: non-protein calorie to volume ratio (maximum variation 15%); non-protein calorie to nitrogen ratio (NPC:N) (maximum variation either 20% for long term use or 35% for possible short term use); electrolyte concentration (maximum increase 20%).

Results:
Twenty-four patients were included (67% male; median age 7.5 years). The most common diagnosis was short bowel syndrome (58%). Replacement with a standard formulation was considered appropriate for possible short term use (maximum variation of 35% in NPC:N) in 16 (67%) patients and for long term use (maximum variation of 20% in NPC:N), the number of patients decreased to 10 (42%).

Conclusions:
Standard PN solutions can be adequate for a significant proportion of pediatric patients on home PN. Their use in the short term may also be appropriate in holiday periods or in settings of limited resources or restricted access to hospital facilities, such as those imposed by the COVID-19 pandemic.
Predictive Fat Mass Equations for Children With Inflammatory Bowel Disease
Authors: Penagini Francesca , Leone Alessandro , Borsani Barbara , Bosetti Alessandra , Dilillo Dario , Rendo Giulia , Calcaterra Valeria , Bertoli Simona , Mora Stefano , Battezzati Alberto , Bedogni Giorgio , Zuccotti Gian Vincenzo 
Published: June 2021

ABSTRACT

Objective:
Evaluate accuracy of skinfold thicknesses and body mass index (BMI) for the prediction of fat mass percentage (FM%) in paediatric inflammatory bowel disease (IBD) and to develop population-specific formulae based on anthropometry for estimation of FM%.

Methods:
IBD children (n = 30) and healthy controls (HCs, n = 144) underwent anthropometric evaluation and dual-energy X-ray absorptiometry (DEXA) scan, as the clinical reference for measurement of body composition. Body FM% estimated with skinfolds thickness was compared with FM% measured with DEXA. By means of 4 prediction models, population specific formulae for estimation of FM% were developed.

Results:
No significant difference in terms of FM% measured by DEXA was found between IBD population and HCs (FM% 29.6% vs 32.2%, P = 0.108). Triceps skinfold thickness (TSF, Model 2) was better than BMI (Model 1) at predicting FM% (82% vs 68% of variance). The sum of 2 skinfolds (biceps + triceps; SF2, Model 3) showed an improvement in the prediction of FM% as compared with TSF, Model 2 (86% vs 82% of variance). The sum of 4 skinfolds (biceps + triceps + suprailiac + subscapular; Model 4) showed further improvement in the prediction of FM% as compared with SF2 (88% vs 86% of variance).

Conclusions:
The sum of 4 skinfolds is the most accurate in predicting FM% in paediatric IBD. The sum of 2 skinfolds is less accurate but more feasible and less prone to error. The newly developed population-specific formulae could be a valid tool for estimation of body composition in IBD population and an alternative to DEXA measurement.
Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease
Authors: Moore Hillary , Dubes Lucie , Fusillo Steven , Baldassano Robert , Stein Ronen 
Published: June 2021

ABSTRACT

Objectives:
Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD.

Methods:
This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks.

Results:
Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest.

Conclusions:
There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.
A Collaborative Effort to Advance Drug Development in Pediatric Constipation and Irritable Bowel Syndrome
Authors: Saps Miguel , Nurko Samuel , Benninga M.A. , Di Lorenzo Carlo , Garza Jose M. , Thapar Nikhil , Richards Kelly , Lee Jessica J. , Altepeter Tara 
Published: June 2021

ABSTRACTPediatric functional gastrointestinal disorders including irritable bowel syndrome with constipation and functional constipation are common conditions in childhood, but no drugs are U.S. Food and Drug Administration (FDA) approved for chronic use in pediatric patients with these disorders. Despite efforts to better standardize the diagnosis of these conditions in children (including recent modifications to the Rome criteria), conducting pediatric clinical trials to support drug approval remains a challenge. In March 2018, FDA, in collaboration with the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, American Gastroenterological Association, and American College of Gastroenterology, convened a public workshop to discuss the challenges and opportunities in conducting pediatric clinical trials in functional gastrointestinal conditions. The workshop assembled gastroenterologists, psychologists, patients, patient advocates, regulators, and industry representatives to discuss trial design and conduct including alternative designs, eligibility criteria, instruments for patient‐ and observer‐reported outcomes, and optimal primary endpoints to support regulatory approval. This report summarizes the workshop, key challenges and knowledge gaps identified, and outlines areas where further research efforts are needed to overcome barriers to developing drugs to treat these conditions.
Survival Benefits Following Liver Transplantation: A Matched-pair Analysis in Pediatric Patients With Cystic Fibrosis
Authors: Flemming Gunter , Baumann Ulrich , Richter Nicolas , Vondran Florian , Tümmler Burkhard , Dittrich Anna-Maria , Müller Carsten , Vogel Mandy , Pfister Eva-Doreen 
Published: June 2021

ABSTRACT

Objectives:
Cystic fibrosis-related liver disease (CFLD) with consecutive cirrhosis is the third most common cause of death in CF patients. The aim of this study was to identify the potential long-term benefits of liver transplantation (LTx) in a match-control comparison.

Methods:
Retrospective single-center data analysis of all pediatric LTx for CFLD between 1998 and 2014. A control group was selected from the local CF patient registry. Data were collected from case report forms and included clinical and laboratory data, lung function tests, the indication for LTx, and details of surgical procedures.

Results:
At our institution, 23 patients with severe CFLD median age 13.8 years (range 8.7–17.4; 16 boys) underwent LTx between 1998 and 2014. In all patients, normalization of hepatic CF manifestations were achieved after LTx. But obviously there was no significant positive influence on nutritional status. Signs of posttransplant liver steatosis were documented by ultrasound in 17 patients. Liver biopsies after LTx were performed in 19 patients, in 42% (n = 8) of these biopsies a fatty degeneration was observed. Five patients died after LTx, none because of primary hepatic dysfunction (1 because of posttransplant proliferative disorder, 4 because of infection). Analysis of matched control pairs revealed that liver function, anthropometry, pulmonary function, and life expectancy of CFLD patients with LTx are comparable with matched CF peers without CFLD.

Conclusions:
Isolated LTx normalizes the hepatic manifestation of CF disease. LTx enables children and adolescents with severe CFLD to have a comparable prognosis in terms of growth, life expectancy, and lung function as CF patients without advanced liver involvement. Our data clarifies the long-term perspectives of affected patients.