Forgotten Pediatrics: 8 Disturbing Windows on the Past.

The 75 years since Pediatrics was first published has witnessed an explosion of the scientific knowledge base informing child health. Yet, the path leading to the present has not been linear. We examine several articles that illustrate some of the unexpected twists and turns that have characterized our specialty's history. We hope that it will provide a reminder of the ever-changing nature of scientific knowledge and the need to continually re-evaluate how our own cultural assumptions shape medical practice.

History of Medicine in the Clerkships: A Novel Model for Integrating Medicine and History.

The history of medicine has only unevenly been integrated into medical education. Previous attempts to incorporate the subject have focused either on the first year, with its already over-subscribed curriculum, or the fourth year in the form of electives that reach a small minority of students. Duke University provides an alternative model for other universities to consider. At our institution we have overcome many of the curricular limitations by including history during the mandatory third year clerkships. Reaching 100% of the medical school class, these sessions align with clinical disciplines, providing students a longitudinal perspective on what they are seeing and doing on the hospital wards. They are taught in conjunction with a medical history librarian and rely heavily on the utilization and interpretation of physical artifacts and archival manuscripts. The surgery, obstetrics/gynecology, and pediatrics rotations now feature successful and popular history of medicine sessions. Describing our lesson plans and featuring a list of both physical and online resources, we provide a model others can implement to increase the use, the framing, and the accessibility of history in their medical schools.

Recommendation Reversals in Gastroenterology Clinical Practice Guidelines.

Background: Recommendations in clinical practice guidelines (CPGs) may be reversed when evidence emerges to show they are futile or unsafe. In this study, we identified and characterized recommendation reversals in gastroenterology CPGs. Methods: We searched CPGs published by 20 gastroenterology societies from January 1990 to December 2019. We included guidelines which had at least two iterations of the same topic. We defined reversals as when (a) the more recent iteration of a CPG recommends against a specific practice that was previously recommend in an earlier iteration of a CPG from the same body, and (b) the recommendation in the previous iteration of the CPG is not replaced by a new diagnostic or therapeutic recommendation in the more recent iteration of the CPG. The primary outcome was the number of recommendation reversals. Secondary outcomes included the strength of recommendations and quality of evidence cited for reversals. Results: Twenty societies published 1022 CPGs from 1990 to 2019. Our sample for analysis included 129 unique CPGs. There were 11 recommendation reversals from 10 guidelines. New evidence was presented for 10 recommendation reversals. Meta-analyses were cited for two reversals, and randomized controlled trials (RCTs) for seven reversals. Recommendations were stronger after the reversal for three cases, weaker in two cases, and of similar strength in three cases. We were unable to compare recommendation strengths for three reversals. Conclusion: Recommendation reversals in gastroenterology CPGs are uncommon but highlight low value or harmful practices.

Factors Associated with Poor Quality of Life in a Canadian Cohort of Patients with Inflammatory Bowel Disease: A Cross-sectional Study.

BACKGROUND: Health-related quality of life (QoL) is often adversely affected in patients with inflammatory bowel disease (IBD). We aimed to identify factors associated with poor QoL among Canadian patients with IBD in clinical remission. METHODS: We enrolled patients at a single academic tertiary care center with inactive IBD. All eligible patients completed a series of questionnaires that included questions on demographics, disease activity, anxiety, depression and the presence of irritable bowel syndrome (IBS) symptoms. Stool sample for fecal calprotectin (FC) was also collected to assess for subclinical inflammation. The primary outcome measure was QoL assessed by the short inflammatory bowel disease questionnaire (SIBDQ), with planned subgroup comparisons for fatigue, anxiety, depression and IBS symptoms. RESULTS: Ninety-three patients were eligible for inclusion in this study. The median SIBDQ scores were lower in patients with anxiety (P < 0.001), depression (P = 0.004), IBS symptoms (P < 0.001) and fatigue (P = 0.018). Elevated FC in patients in clinical remission did not impact QoL. These findings were consistent on multivariate linear regression. CONCLUSIONS: Anxiety, depression, fatigue and IBS symptoms are all independently associated with lower QoL in patients with inactive IBD. Clinicians are encouraged to screen for these important factors as they may detrimentally impact QoL in IBD patients even in clinical remission.

Digital Behavioral Phenotyping Detects Atypical Pattern of Facial Expression in Toddlers with Autism.

Commonly used screening tools for autism spectrum disorder (ASD) generally rely on subjective caregiver questionnaires. While behavioral observation is more objective, it is also expensive, time-consuming, and requires significant expertise to perform. As such, there remains a critical need to develop feasible, scalable, and reliable tools that can characterize ASD risk behaviors. This study assessed the utility of a tablet-based behavioral assessment for eliciting and detecting one type of risk behavior, namely, patterns of facial expression, in 104 toddlers (ASD N = 22) and evaluated whether such patterns differentiated toddlers with and without ASD. The assessment consisted of the child sitting on his/her caregiver's lap and watching brief movies shown on a smart tablet while the embedded camera recorded the child's facial expressions. Computer vision analysis (CVA) automatically detected and tracked facial landmarks, which were used to estimate head position and facial expressions (Positive, Neutral, All Other). Using CVA, specific points throughout the movies were identified that reliably differentiate between children with and without ASD based on their patterns of facial movement and expressions (area under the curves for individual movies ranging from 0.62 to 0.73). During these instances, children with ASD more frequently displayed Neutral expressions compared to children without ASD, who had more All Other expressions. The frequency of All Other expressions was driven by non-ASD children more often displaying raised eyebrows and an open mouth, characteristic of engagement/interest. Preliminary results suggest computational coding of facial movements and expressions via a tablet-based assessment can detect differences in affective expression, one of the early, core features of ASD. LAY SUMMARY: This study tested the use of a tablet in the behavioral assessment of young children with autism. Children watched a series of developmentally appropriate movies and their facial expressions were recorded using the camera embedded in the tablet. Results suggest that computational assessments of facial expressions may be useful in early detection of symptoms of autism.

Computer Vision Analysis for Quantification of Autism Risk Behaviors.

Observational behavior analysis plays a key role for the discovery and evaluation of risk markers for many neurodevelopmental disorders. Research on autism spectrum disorder (ASD) suggests that behavioral risk markers can be observed at 12 months of age or earlier, with diagnosis possible at 18 months. To date, these studies and evaluations involving observational analysis tend to rely heavily on clinical practitioners and specialists who have undergone intensive training to be able to reliably administer carefully designed behavioural-eliciting tasks, code the resulting behaviors, and interpret such behaviors. These methods are therefore extremely expensive, time-intensive, and are not easily scalable for large population or longitudinal observational analysis. We developed a self-contained, closed-loop, mobile application with movie stimuli designed to engage the child's attention and elicit specific behavioral and social responses, which are recorded with a mobile device camera and then analyzed via computer vision algorithms. Here, in addition to presenting this paradigm, we validate the system to measure engagement, name-call responses, and emotional responses of toddlers with and without ASD who were presented with the application. Additionally, we show examples of how the proposed framework can further risk marker research with fine-grained quantification of behaviors. The results suggest these objective and automatic methods can be considered to aid behavioral analysis, and can be suited for objective automatic analysis for future studies.

Impact of a digital Modified Checklist for Autism in Toddlers-Revised on likelihood and age of autism diagnosis and referral for developmental evaluation.

LAY ABSTRACT: This was a project in primary care for young children (1-2 years old). We tested a parent questionnaire on a tablet. This tablet questionnaire asked questions to see whether the child may have autism. We compared the paper and pencil version of the questionnaire to the tablet questionnaire. We read the medical charts for the children until they were 4 years old to see whether they ended up having autism. We found that doctors were more likely to recommend an autism evaluation when a parent used the tablet questionnaire. We think that the tablet's automatic scoring feature helped the doctors. We also think that the doctors benefited from the advice the tablet gave them.

Automatic emotion and attention analysis of young children at home: a ResearchKit autism feasibility study.

Current tools for objectively measuring young children's observed behaviors are expensive, time-consuming, and require extensive training and professional administration. The lack of scalable, reliable, and validated tools impacts access to evidence-based knowledge and limits our capacity to collect population-level data in non-clinical settings. To address this gap, we developed mobile technology to collect videos of young children while they watched movies designed to elicit autism-related behaviors and then used automatic behavioral coding of these videos to quantify children's emotions and behaviors. We present results from our iPhone study Autism & Beyond, built on ResearchKit's open-source platform. The entire study-from an e-Consent process to stimuli presentation and data collection-was conducted within an iPhone-based app available in the Apple Store. Over 1 year, 1756 families with children aged 12-72 months old participated in the study, completing 5618 caregiver-reported surveys and uploading 4441 videos recorded in the child's natural settings. Usable data were collected on 87.6% of the uploaded videos. Automatic coding identified significant differences in emotion and attention by age, sex, and autism risk status. This study demonstrates the acceptability of an app-based tool to caregivers, their willingness to upload videos of their children, the feasibility of caregiver-collected data in the home, and the application of automatic behavioral encoding to quantify emotions and attention variables that are clinically meaningful and may be refined to screen children for autism and developmental disorders outside of clinical settings. This technology has the potential to transform how we screen and monitor children's development.

Use of a Digital Modified Checklist for Autism in Toddlers - Revised with Follow-up to Improve Quality of Screening for Autism.

OBJECTIVES: To assess changes in quality of care for children at risk for autism spectrum disorders (ASD) due to process improvement and implementation of a digital screening form. STUDY DESIGN: The process of screening for ASD was studied in an academic primary care pediatrics clinic before and after implementation of a digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up with automated risk assessment. Quality metrics included accuracy of documentation of screening results and appropriate action for positive screens (secondary screening or referral). Participating physicians completed pre- and postintervention surveys to measure changes in attitudes toward feasibility and value of screening for ASD. Evidence of change was evaluated with statistical process control charts and χ2 tests. RESULTS: Accurate documentation in the electronic health record of screening results increased from 54% to 92% (38% increase, 95% CI 14%-64%) and appropriate action for children screening positive increased from 25% to 85% (60% increase, 95% CI 35%-85%). A total of 90% of participating physicians agreed that the transition to a digital screening form improved their clinical assessment of autism risk. CONCLUSIONS: Implementation of a tablet-based digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up led to improved quality of care for children at risk for ASD and increased acceptability of screening for ASD. Continued efforts towards improving the process of screening for ASD could facilitate rapid, early diagnosis of ASD and advance the accuracy of studies of the impact of screening.

Effect of Standardised Scoring Conventions on Inter-rater Reliability in the Endoscopic Evaluation of Crohn's Disease.

BACKGROUND AND AIMS: The Crohn's Disease Endoscopic Index of Severity [CDEIS] and Simplified Endoscopic Score for Crohn's Disease [SES-CD] demonstrate consistent overall intra- and inter-rater reliability. However, the reliability of some index items is relatively poor. We evaluated scoring conventions to improve the reliability of these items. METHODS: Five gastroenterologists with no previous experience scoring the CDEIS or SES-CD were trained on their use. A total of 65 video recordings of colonoscopies were scored blindly by each gastroenterologist before and after additional training on index scoring conventions. Intra-class correlation coefficients [ICCs] assessed the effect of application of these conventions on the reliability of the CDEIS, SES-CD, and a Global Evaluation of Lesion Severity [GELS] score. RESULTS: Following training on scoring conventions, inter-rater ICCs (95% confidence interval [CI]) for the total SES-CD score increased from 0.78 [0.71, 0.85] to 0.85 [0.79, 0.89]. The ICCs for the total CDEIS and GELS scores were not affected: corresponding inter-rater ICCs were 0.74 [0.65, 0.81] and 0.49, [0.38, 0.61] before and 0.73 [0.65, 0.81] and 0.53 [0.42, 0.64] following application of scoring conventions. Estimations of ulcer depth, surface area, anatomical location, and stenosis were important sources of variability. CONCLUSIONS: Use of scoring conventions previously developed by expert central readers enhanced the reliability of the SES-CD but did not similarly affect the CDEIS or GELS. As the SES-CD is more likely to be reliable than the CDEIS and can be optimised with targeted training, it is the preferred instrument for use in clinical trials.

Generation of monoclonal antibodies to the AML1-ETO fusion protein: strategies for overcoming high homology.

The chromosomal translocation t(8;21) often found in acute myeloid leukemia generates an oncogenic fusion protein AML1-ETO. This chimeric oncoprotein disrupts wild-type AML1 function and dysregulates genes important for normal myelopoiesis. Monoclonal antibodies that can capture and detect the AML1-ETO fusion protein would help with early diagnosis and treatment prognosis of acute myeloid leukemia. We report the development of murine monoclonal antibodies (MAbs) that specifically bind epitopes encoded by either AML1 or ETO. Since alignment to the human ETO protein indicated almost 100% homology to the mouse ortholog, a strategy was needed to instruct humoral immunity in mice to focus and respond to self-epitopes. Our strategy to develop capture/detector reagents involved producing MAbs that would bind to epitopes within the non-fused myelopic protein (i.e., either AML1 or ETO). This included a process to select antibodies for their ability to also recognize the translocated chromosomal AML1-ETO fusion protein and to identify complementary capture/detector antibody pairs. Construction of a peptide hapten-carrier complex and use of a rapid immunization protocol resulted in IgM-IgG ETO specific MAbs. These MAbs bound specifically to a recombinant form of AML1-ETO fusion protein expressed in HEK and to an endogenous AML1-ETO form of the fusion protein expressed in Kasumi-1. We report the development of murine hybridoma MAbs derived from immunizations with a peptide "self-epitope." Our findings provide a potential strategy to instruct humoral immunity in mice to focus and respond to self-epitopes. This strategy has been validated with the oncogenic fusion protein AML1-ETO involved in acute myeloid leukemia.

Feasibility and safety of adhesiolysis using transgastric NOTES approach: a pilot survival study in a porcine model.

OBJECTIVES: Although adhesions can be removed by adhesiolysis using laparotomy or laparoscopy, they typically recur sometimes with equal severity. It is suggested that minimizing the invasiveness of the operative technique by using natural orifice translumenal endoscopic surgery (NOTES) may reduce adhesion re-formation. The aim of the study was to evaluate the feasibility and safety of adhesiolysis by using a novel transgastric NOTES approach and collect pilot data on adhesion recurrence after transgastric NOTES adhesiolysis. METHODS: One nonsurvival and 5 survival female pigs were used in this experimental survival study. Interventions included (a) induction of adhesions by laparotomy, (b) 2 weeks survival, (c) transgastric NOTES adhesiolysis with endoscopic evaluation and scoring of adhesions before and immediately after adhesiolysis, (d) 2 weeks survival, and (e) necropsy with endoscopic and necroscopic evaluation and scoring of recurrent adhesions. Main outcome measures were (a) survival and complication rates and (b) assessment of adhesion formation and re-formation using the Hopkins Adhesion Formation Score. RESULTS: No mortality and no complications were observed. A total of 11 adhesions formed before the adhesiolysis in 5 survival study animals. All were successfully divided. The frequency of adhesions and median adhesion formation score decreased significantly immediately after adhesiolysis compared with that prior to the procedure (frequency, 11 vs 0, P = .011; the median score = 2.0 [range 1-3] vs 0.0 [range 0-0], P = .004). The treatment gains maintained at 2 weeks after the adhesiolysis. LIMITATIONS: The limitations of this study were the low number of study animals and short-term follow-up data. CONCLUSIONS: Adhesiolysis using NOTES transgastric approach is feasible, safe, and effective with minimal adhesion re-formation.

Video. "No scar" small bowel resection in a survival porcine model using transcolonic NOTES(®) and transabdominal approach.

BACKGROUND: Fundamental techniques and essential tools for performing "no scar" surgery still need to be developed. Our study was designed to evaluate the feasibility of performing small bowel resection by transcolonic NOTES(®) and transabdominal approach using rigid laparoscopic and flexible endoscopic instruments. METHODS: One non survival and four survival experiments were performed using a porcine model. The endoscope with an overtube was advanced into the peritoneal cavity through the colotomy. Mini-laparoscopic instruments were placed through the abdominal wall under the endoscopic observation. The endoscope was replaced with a rigid linear stapler. The small bowel was identified. The segment of the small bowel was resected by firing the endo stapler, and extracted through the colon. The two limbs of the small bowel were approximated with two stay-sutures. An enterotomy was then created on the antimesenteric sides of each line. A side-to-side anastomosis was performed with another application of the endo stapler. The stapler was withdrawn. The enterotomy was closed by suturing. The colotomy was closed with endoclips and the endoscope was withdrawn. The mini-laparoscopic instruments were removed. RESULTS: Small bowel resection was successfully performed in all animals. The surgery time was 70 minutes. There was no mortality or complications. The animals recovered uneventfully, and survived the 2 weeks postprocedure period. They remained healthy, and gained weight. Necropsy was performed 2 weeks after the surgery. On necropsy, evaluation of the abdominal skin revealed no scars. The peritoneal cavity was examined. No signs of infection, bleeding, perforations, and adhesions were noted. Endoscopic examination of the colotomy and anastomosis revealed complete healing that was confirmed by histopathology. CONCLUSIONS: The study has demonstrated the feasibility of small bowel resection using transcolonic NOTES(®) and transabdominal approach. Simultaneous use of flexible endoscopic and rigid laparoscopic instruments in NOTES(®) is not only feasible but has significant advantages and greatly facilitates the performance of the operation, yet leaves no scars.