Systematic review and meta-analysis of the etiology of heavy menstrual bleeding in 2,770 adolescent females.

BACKGROUND: Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding. METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10-19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling. RESULTS: Seventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22-25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8-21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27-7.27%) with 45.9% (95% CredI 43.8-47.%9) of the cases of indeterminate origin. CONCLUSIONS: The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.

Pediatric Syncope: A Systematic Review.

OBJECTIVES: The aims of the study were to perform the first systematic review of pediatric syncope etiologies and to determine the most common diagnoses with credible intervals (CredIs). METHODS: Review was performed within Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and used Embase, Scopus, PubMed, and the Cochrane Controlled Trial databases. The following inclusion criteria for the articles were used: minimum of 10 patients, standard definition of syncope used, subjects who were 21 years or younger, and subjects who were either a consecutive retrospective group or a prospective group. No restrictions were made regarding language of the studies, but an English abstract was required. The following information was collected: purpose of the study, definition of syncope, number of patients, patient age range, inclusion/exclusion criteria, and etiologies of syncope. RESULTS: Of the 500 articles initially identified, 11 studies met the inclusion criteria and were the basis for this review. Three thousand seven hundred patients were included, ranging in age from 3 months to 21 years. The most common etiologies identified were vasovagal (52.2%; 95% CredI, 50.6-53.9), postural orthostatic tachycardia syndrome (13.1%; 95% CredI, 12.1-14.2), and cardiac causes (4.0%; 95% CredI, 3.39-4.65). A total of 18.3% (95% CredI, 17.0-19.5) of patients were found to have syncope of unknown cause. CONCLUSIONS: Syncope is a common pediatric complaint. Most cases seen are a result of benign causes, with only a small percentage because of serious medical conditions. In addition, most syncopal episodes in the pediatric population are diagnosed clinically or with minimally invasive testing, emphasizing the importance of a detailed history and physical examination.

The Differential Diagnosis of Vertigo in Children: A Systematic Review of 2726 Cases.

OBJECTIVES: Vertigo is a relatively common complaint in children with 5.3% of pediatric patients complaining of this symptom. Although the causes of vertigo have been well established in adults, the diagnoses in children have not been well described. The aims of this systematic review are to discover the current information regarding etiologies of vertigo in children and to determine the most common diagnoses that present with vertigo in pediatric patients. METHODS: PubMed, Scopus, and Embase were searched using the PRISMA guidelines. The inclusion and exclusion criteria were established a priori. All results were analyzed using a Bayesian methodology for point estimation and credible interval calculation. RESULTS: From the database searches, 1419 titles were reviewed. Twenty-two studies met inclusion criteria. From these studies, a total of 2726 children aged 2 months to 19 years were reported. The top 4 diagnoses associated with childhood vertigo include vestibular migraine (23.8%; credible interval, 22.3%-25.5%), benign paroxysmal vertigo of childhood (13.7%; credible interval, 12.4%-15%), idiopathic or no identified association (11.7%; credible interval, 10.5%-12.9%), and labyrinthitis/vestibular neuronitis (8.47%, credible interval, 7.46%-9.55%) accounting for approximately 57% of cases. Less common diagnoses included Meniere disease and central nervous system tumors. CONCLUSIONS: Although the most common causes of pediatric vertigo include vestibular migraine and benign paroxysmal vertigo of childhood, the etiologies are myriad. Rates and credible intervals are provided to permit a probabilistic diagnostic approach to these children.

Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial.

Background: Continuous glucose monitoring (CGM), which studies have shown is beneficial for adults with type 1 diabetes, has not been well-evaluated in those with type 2 diabetes receiving insulin. Objective: To determine the effectiveness of CGM in adults with type 2 diabetes receiving multiple daily injections of insulin. Design: Randomized clinical trial. (The protocol also included a type 1 diabetes cohort in a parallel trial and subsequent second trial.) (ClinicalTrials.gov: NCT02282397). Setting: 25 endocrinology practices in North America. Patients: 158 adults who had had type 2 diabetes for a median of 17 years (interquartile range, 11 to 23 years). Participants were aged 35 to 79 years (mean, 60 years [SD, 10]), were receiving multiple daily injections of insulin, and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9% (mean, 8.5%). Intervention: Random assignment to CGM (n = 79) or usual care (control group, n = 79). Measurements: The primary outcome was HbA1c reduction at 24 weeks. Results: Mean HbA1c levels decreased to 7.7% in the CGM group and 8.0% in the control group at 24 weeks (adjusted difference in mean change, -0.3% [95% CI, -0.5% to 0.0%]; P = 0.022). The groups did not differ meaningfully in CGM-measured hypoglycemia or quality-of-life outcomes. The CGM group averaged 6.7 days (SD, 0.9) of CGM use per week. Limitation: 6-month follow-up. Conclusion: A high percentage of adults who received multiple daily insulin injections for type 2 diabetes used CGM on a daily or near-daily basis for 24 weeks and had improved glycemic control. Because few insulin-treated patients with type 2 diabetes currently use CGM, these results support an additional management method that may benefit these patients. Primary Funding Source: Dexcom.

Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects.

BACKGROUND: The etiologies of conjugated hyperbilirubinemia in infancy are diverse. OBJECTIVE: Determine the prevalence rates of the specific etiologies of conjugated hyperbilirubinemia in infancy. DATA SOURCES: EMBASE and Pubmed were searched electronically and the bibliographies of selected studies were search manually. The search was conducted independently by two authors. STUDY SELECTION: (1) prospective or retrospective case series or cohort study with 10 or more subjects; (2) consecutive infants who presented with conjugated hyperbilirubinemia; (3) subjects underwent appropriate diagnostic work-up for conjugated hyperbilirubinemia; (4) no specific diagnoses were excluded in the studied cohort. DATA EXTRACTION: Patient number, age range, country of origin, and categorical and specific etiologies. RESULTS: From 237 studies identified, 17 studies encompassing 1692 infants were selected. Idiopathic neonatal hepatitis (INH) occurred in 26.0% of cases; the most common specific etiologies were extrahepatic biliary atresia (EHBA) (25.89%), infection (11.47%), TPN- associated cholestasis (6.44%), metabolic disease (4.37%), alpha-1 anti-trypsin deficiency (4.14%), and perinatal hypoxia/ischemia (3.66%). CMV was the most common infection identified (31.51%) and galactosemia (36.49%) was the most common metabolic disease identified. LIMITATIONS: Major limitations are: (1) inconsistencies in the diagnostic evaluations among the different studies and (2) variations among the sample populations. CONCLUSIONS: INH is the most common diagnosis for conjugated hyperbilirubinemia in infancy while EHBA and infection are the most commonly identified etiologies. The present review is intended to be a guide to the differential diagnosis and evaluation of the infant presenting with conjugated hyperbilirubinemia.

The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects.

BACKGROUND: While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood. METHODS: EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. STUDY SELECTION: (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. DATA EXTRACTION: Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology. RESULTS: From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified. CONCLUSIONS: The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.

Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients.

BACKGROUND: Serum procalcitonin (PCT) concentrations have been studied as a diagnostic test for serious bacterial infections (SBIs) in children. However, the utility of a single measurement in the evaluation of SBIs in febrile infants younger than 91 days is not clear. OBJECTIVE: Use a systematic review and meta-analysis to determine: 1) the ability of serum PCT concentrations to identify febrile infants < 91 days of age at high and low risk for SBIs, and 2) to compare its utility with available clinical prediction rules. METHODS: The literature search identified studies of febrile infants segregated into risk groups using serum PCT concentrations. Some authors were contacted to provide subgroups < 91 days of age or to provide data with 0.3 ng/mL PCT cutoff values. Data were combined and validated using standard methodologies. RESULTS: Seven studies encompassing 2317 patients were identified; five of seven studies used a PCT discriminating concentration of 0.3 ng/mL. No heterogeneity or publication bias was identified. The overall relative risk (RR) was 3.97 (95% confidence interval [CI] 3.41-4.62) and was consistent by sensitivity analysis. The RR from a systematic review of clinical prediction rules was 30.6 (95% CI 7.0-68.13) and 8.75 (95% CI 2.29-15.2) for infants untreated and treated with antibiotics, respectively. CONCLUSIONS: Alone, measurement of serum PCT concentrations, though able to identify a group of young infants at risk for SBIs, is inferior to the available clinical prediction rules for identifying young, febrile infants at risk for SBIs. Serum concentrations ≤ 0.3 ng/mL may be helpful as an add-on test to current rules for identifying low-risk, febrile infants.

Strokes in children: a systematic review.

CONTEXT: Pediatric strokes lead to significant morbidity and mortality. To date, no systematic review has been available to guide the initial diagnostic approach to pediatric stroke. OBJECTIVE: The objective of this review was to elucidate the current data regarding etiologies of stroke in children and then develop an initial diagnostic evaluation for the pediatric patient presenting to the emergency department with a stroke. DATA SOURCE: Using the PubMed engine, the MEDLINE database was searched using the Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines. STUDY SELECTION: The inclusion and exclusion criteria were established a priori. Studies must have extractable data regarding first strokes in pediatric patients with clear diagnostic categories. DATA EXTRACTION: A standardized tool was developed to extract demographic data and stroke etiologies. RESULTS: Twelve studies were found that met the inclusion criteria. From these studies, a total of 1455 children aged between 21 days and 20 years were available to assess the etiologies of stroke. CONCLUSIONS: In pediatric patients, the etiologies of stroke are varied and differ for children with ischemic stroke versus hemorrhagic stroke. With the present systematic review, a guide to the initial evaluation of stroke is presented.

Knowing Your Patient Population: Techniques to Capture Infants at High Risk for Physical Abuse in a Trauma Registry.

BACKGROUND: Physical abuse is a major public health concern and a leading cause of morbidity and mortality in infants. Clinical decision tools derived from trauma registries can facilitate timely risk-stratification. The Trauma Quality Improvement Program (TQIP) database does not report age for children <1 year who are at highest risk for abuse. We report a method to capture these infants despite the missing age. METHODS: Patients ≤17 years were identified from TQIP (2017-2019). The primary outcomes included injuries resulting from confirmed or suspected child abuse captured by diagnosis codes or report/investigation of physical abuse, or different caregiver at discharge available in TQIP. We used two methods to select infants within TQIP. In the first, World Health Organization (WHO) growth standards for stature or length-for-age and weight-for-age were selected to capture children younger than 1 year. In the second, a K-means machine learning algorithm was used to cluster patients by weight and height. We compared outcome and injury data with and without patients <1 year. RESULTS: Using the WHO growth standard 19,916 children <1 year were identified. A total of 20,513 patients had a report of physical abuse filed, and 9393 were infants <1 year. Increased age-adjusted odds ratios [95% CI] were seen for fractures of the upper limb (1.28 [1.22-1.34]), vertebrae (1.89 [1.68-2.13]), ribs (5.2 [4.8-5.63]), and spinal cord (3.39 [2.85-4.02]) and head injuries (1.55 [1.5-1.6]) with infants included. CONCLUSIONS: In a nationwide trauma registry, WHO growth standards can be used to capture patients under one year who are more adversely impacted by maltreatment. TYPE OF STUDY: Retrospective, Cross-sectional. LEVEL OF EVIDENCE: Level III, Diagnostic.

Obesity is not associated with increased resource utilization or morbidity in patients undergoing appendectomy.

BACKGROUND: Obesity is a growing public health concern that places patients at risk of morbidity and mortality following surgery. We sought to determine whether obesity influences our resource utilization and postoperative outcomes for patients who present with appendicitis. METHODS: Charts were reviewed for patients age 1-18 years identified from a prospective registry who presented with a diagnosis of appendicitis from 2017 to 2020. Patients who underwent appendectomy were eligible. Charts were reviewed for demographics, imaging studies, laboratory studies, length of stay, operative times and thirty-day postoperative adverse events defined as return to the emergency room, re-admission, postoperative abscess or return to the operating room. A multivariate logistic regression analysis was performed to identify differences in resource utilization and outcome. RESULTS: A total of 451 patients were identified. There were 126 obese patients (27.9%). Obese patients were not more likely to present with perforated appendicitis and were not more likely to undergo computed tomography scans. All patients underwent laparoscopic appendectomy. Although intraoperative times were significantly longer for Black patients and older patients, BMI did not influence length of surgery. Length of stay was significantly higher for younger patients (p = 0.019). Adverse events were seen in 38 patients (8.4%). There was no association between BMI and adverse events. CONCLUSIONS: Within our standardized management pathway, obesity does not influence management or patient outcomes for the treatment of appendicitis. Furthermore, obese patients did not require additional resource utilization. LEVEL OF EVIDENCE: III.

Association of Adverse Childhood Experiences and Resilience With Obesity, High Blood Pressure, and Parental Report of Behavioral Health Symptoms in Children: A Cross Sectional Study.

The interplay between Adverse Childhood Experiences (ACEs) and resilience on health in children is not well understood. Parents completed 3 questionnaires: ACEs, Child and Youth Resilience Measure (CYRM), and the Pediatric Symptom Checklist-17(PSC-17). BMI and blood pressure were measured. 19.8% of children had 4 or more ACEs, resilience ranged from 25 to 51, 14.3% had a positive PSC-17 score, 25.6% were obese, 3.1% had systolic hypertension, and 1.2% had diastolic hypertension. Higher ACEs (ACE OR: 1.398, 95% CI = 1.044-1.893, P = .026) and lower resilience (Resilience OR: 0.740, 95% CI 0.668-0.812; P = 1.13 × 10-9) were predictive of increased reports of behavioral health symptoms, but not obesity or hypertension. The personal resilience subscale was a predictor of positive PSC-17 score (OR 0.646, 95% CI = 0.546-0.749, P = 3.18 × 10-8); relationship subscale was not. Cultivating resilience, especially personal aspects, may provide an effective intervention for behavioral health symptoms in children.

Derivation and Validation of a Machine Learning Algorithm for Predicting Venous Thromboembolism in Injured Children.

BACKGROUND: Venous thromboembolism (VTE) causes significant morbidity in pediatric trauma patients. We applied machine learning algorithms to the Trauma Quality Improvement Program (TQIP) database to develop and validate a risk prediction model for VTE in injured children. METHODS: Patients ≤18 years were identified from TQIP (2017-2019, n = 383,814). Those administered VTE prophylaxis ≤24 h and missing the outcome (VTE) were removed (n = 347,576). Feature selection identified 15 predictors: intubation, need for supplemental oxygen, spinal injury, pelvic fractures, multiple long bone fractures, major surgery (neurosurgery, thoracic, orthopedic, vascular), age, transfusion requirement, intracranial pressure monitor or external ventricular drain placement, and low Glasgow Coma Scale score. Data was split into training (n = 251,409) and testing (n = 118,175) subsets. Machine learning algorithms were trained, tested, and compared. RESULTS: Low-risk prediction: For the testing subset, all models outperformed the baseline rate of VTE (0.15%) with a predicted rate of 0.01-0.02% (p < 2.2e-16). 88.4-89.4% of patients were classified as low risk by the models. HIGH-RISK PREDICTION: All models outperformed baseline with a predicted rate of VTE ranging from 1.13 to 1.32% (p < 2.2e-16). The performance of the 3 models was not significantly different. CONCLUSION: We developed a predictive model that differentiates injured children for development of VTE with high discrimination and can guide prophylaxis use. LEVEL OF EVIDENCE: Prognostic, Level II. TYPE OF STUDY: Retrospective, Cross-sectional.

Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial.

BACKGROUND: Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve ß-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. METHODS: In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protégé study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0·5 U/kg per day and glycated haemoglobin A(1c) (HbA(1C)) of less than 6·5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. FINDINGS: 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19·8% (41/207) in the 14-day full-dose group; 13·7% (14/102) in the 14-day low-dose group; 20·8% (22/106) in the 6-day full-dose group; and 20·4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0·03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). INTERPRETATION: Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in ß-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children. FUNDING: MacroGenics, the Juvenile Diabetes Research Foundation, and Eli Lilly.

A 13-Year-Old Male With Left Eye Swelling.

A 13-year-old male presented with a 10-day history of left eye swelling and pain. These symptoms prompted presentation to the emergency department. He had no significant past medical history and no preceding fevers or chills. He was found on examination of the eyes and the orbit to have left supraorbital erythema, edema, and pain with upward and medial gaze. Examination of the globe, fundus, and visual fields were normal. His white blood cell count was 6.2 (x1000/mm3) with an erythrocyte sedimentation rate of 4 (mm/hr). Diagnostic endoscopic biopsy was performed. Here we present this case alongside clinical reasoning and diagnostic evaluation with relevant input from respective experts. This case discussion reviews the final diagnosis, as well as the corresponding evaluation and management. Diagnostic algorithms based on literature review and clinical experience are also included.

Effect of Feeding Strategies on the Development of Fulminant Necrotizing Enterocolitis.

INTRODUCTION: Necrotizing enterocolitis (NEC) causes significant neonatal morbidity. A subset of infants experience precipitous decline and death from fulminant-NEC (F-NEC). We sought to determine the effect of feeding practices on the development of this more virulent form of NEC. MATERIALS AND METHODS: Premature neonates developing Bell's stage II or III NEC between May 2011 and June 2017 were reviewed. Infants were stratified as having NEC or F-NEC, defined as NEC-totalis or NEC causing rapid decline and death within 72 hours. Risk factors extracted included demographics, gestational age, and weight at NEC diagnosis. Feeding data extracted included age at first feed, caloric density, type of feed (breast milk or formula), and whether full volume feeds were reached. Univariate analysis and multivariate analysis were performed. RESULTS: A total of 98 patients were identified, of which 80 were included. In total, 57 patients had NEC and 23 had F-NEC. Reaching full volume feeds was associated with F-NEC on both univariate and multivariate analysis (37.9 vs. 4.5%; odds ratio: 67, 95% confidence interval: 6.606-2041, p = 0.003). Infants developing F-NEC achieved full feeds earlier (22.5 vs. 19.8 days, p = 0.025) on univariate but not multivariate analysis. There was no difference in the rates of NEC and F-NEC among infants receiving breast milk (standard or fortified) or formula (standard or increased caloric density; p = 0.235). CONCLUSION: Among premature neonates with NEC, reaching full volume feedings was associated with a nearly 70-fold increased risk of F-NEC. Assuming it was possible to predict an infant's development of NEC, alternative feeding regimens might reduce the risk of F-NEC in this population.

The Association of Adverse Childhood Experiences and Resilience With Health Outcomes in Adolescents: An Observational Study.

The relationship between Adverse childhood experiences (ACEs), resilience, and health outcomes has not been as thoroughly studied in adolescents. Adolescents completed the ACEs Questionnaire and a validated resilience measure (Child Youth Resilience Measure, or CYRM). Poor health outcome was having 1 or more: obesity, hypertension, and/or depression. 34.5% of teens had a poor health outcome, 38.6% had ACE scores of 4 or more, and resilience ranged from 45 to 84 (mean = 74.6). By univariate and bivariate analysis, ACEs (OR = 1.11, 95% CI = 1.03-1.19, P = .0039; OR = 1.08, 95% CI = 1.0-1.16, P = .045) and resilience (OR = 0.95, 95% CI = 0.92-0.98, P = .0016; OR = 0.96, 95% CI = 0.93-0.99, P = .016) were significantly associated with poor health outcome. Resilience relationship subscale was significantly associated with reduced health risk (OR = 0.85, 95%CI = 0.75-0.95, P = .005). ACEs are associated with poor health outcomes in adolescents, resilience is inversely related, and the caregiver relationship may be the driving force.

A valuation of infusion therapy to preserve islet function in type 1 diabetes.

OBJECTIVES: Recent advances in monoclonal antibody therapies offer the prospect of the prevention or amelioration of type 1 diabetes mellitus (T1DM). The present study was designed to capture UK (English and Scottish) preference weights for the process of undergoing infusion therapy and the likely outcomes of treatment for children (8-12 years), adolescents (13-17 years), and adults. METHODS: Vignette descriptions of T1DM health states (describing infusion therapy and reduced insulin need) were constructed based on qualitative interviews with people with type 1 diabetes, clinicians and findings from a literature review. Utilities were elicited for each health state using the standard gamble interview from the general public, adults with diabetes, and parents of children with diabetes. Participants also completed other outcome measures-EQ-5D, Pediatric Quality-of-Life Inventory, and Hyperglycemic Fear Survey. Mixed model analyses were used to estimate the influence on utility of different participant characteristics. RESULTS: Self-report questionnaires indicated the nature and degree of impact of T1DM on adults', adolescents', and children's quality of life, with adolescents reporting the lowest health-related quality-of-life profile of all groups. The mixed model analysis indicated that each health state was a significant predictor of utility and the T1DM participants gave significantly higher utilities compared with the general public (P = 0.02). CONCLUSION: The general public and people with diabetes (or parents of children with diabetes) all place significant value on reducing the need for insulin injections; also, all recognize the disutility of undergoing infusion cycles. These values are suitable for supporting estimates of cost-effectiveness of infusion therapies in T1DM.

Integrating evidence based medicine into undergraduate medical education: combining online instruction with clinical clerkships.

BACKGROUND: Incorporation of evidence based medicine into the undergraduate curriculum varies from school to school. The purpose of this study was to determine if an online course in evidence based medicine run concurrently with the clinical clerkships in the 3rd year of undergraduate medical education provided effective instruction in evidence based medicine (EBM). DESCRIPTION: During the first 18 weeks of the 3rd year, students completed 6 online, didactic modules. Over the next 24 weeks, students developed questions independently from patients seen during clerkships and then retrieved and appraised relevant evidence. Online, faculty mentors reviewed student assignments submitted throughout the course to monitor progress. Mastery of the skills of EBM was assessed prior to and at the conclusion of the course using the Fresno test of competency. EVALUATION: Paired data were available from 139 students. Postcourse test scores (M= 77.7; 95% CI = 59-96.4) were significantly higher than precourse scores (M= 66.6; 95% CI = 46.5-86.7), p< .001. Paired evaluations demonstrated an average improvement of 11.1 +/- 20.0 points. All of the students submitted 4 independently derived questions and successfully retrieved and appraised evidence. CONCLUSIONS: Medical students successfully acquired and independently applied EBM skills following extended, online, faculty mentored instruction. This method of instruction provided uniform instruction across geographic sites and medical specialties and permitted efficient use of faculty time.

The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review.

BACKGROUND: The clinical manifestations and natural history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome in children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C. METHODS: Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search, and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion. RESULTS: MEDLINE and EMBASE searches produced 129 articles, and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty-two children (14.7%) had negative results for SARS-CoV-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), cheilitis/ "strawberry tongue" (55.7%), or extremity edema/erythema (47.5%). Median serum C-reactive protein, ferritin, fibrinogen, and D-dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone (57.6%) were the most common therapeutic interventions; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%), but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died. CONCLUSIONS: MIS-C following SARS-CoV-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, cheilitis, and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.

Derivation and Validation of a Simplified Clinical Prediction Rule for Identifying Children at Increased Risk for Clinically Important Traumatic Brain Injuries Following Minor Blunt Head Trauma.

Objective: To develop a simplified clinical prediction tool for identifying children with clinically important traumatic brain injuries (ciTBIs) after minor blunt head trauma by applying machine learning to the previously reported Pediatric Emergency Care Applied Research Network dataset. Study design: The deidentified dataset consisted of 43 399 patients <18 years old who presented with blunt head trauma to 1 of 25 pediatric emergency departments between June 2004 and September 2006. We divided the dataset into derivation (training) and validation (testing) subsets; 4 machine learning algorithms were optimized using the training set. Fitted models used the test set to predict ciTBI and these predictions were compared statistically with the a priori (no information) rate. Results: None of the 4 machine learning models was superior to the no information rate. Children without clinical evidence of a skull fracture and with Glasgow Coma Scale scores of 15 were at the lowest risk for ciTBIs (0.48%; 95% CI 0.42%-0.55%). Conclusions: Machine learning algorithms were unable to produce a more accurate prediction tool for ciTBI among children with minor blunt head trauma beyond the absence of clinical evidence of skull fractures and having Glasgow Coma Scale scores of 15.