Association of volume of patient encounters with residents' in-training examination performance.

BACKGROUND: Patient care and medical knowledge are Accreditation Council for Graduate Medical Education (ACGME) core competencies. The correlation between amount of patient contact and knowledge acquisition is not known. OBJECTIVE: To determine if a correlation exists between the number of patient encounters and in-training exam (ITE) scores in internal medicine (IM) and pediatric residents at a large academic medical center. DESIGN: Retrospective cohort study PARTICIPANTS: Resident physicians at Mayo Clinic from July 2006 to June 2010 in IM (318 resident-years) and pediatrics (66 resident-years). METHODS: We tabulated patient encounters through review of clinical notes in an electronic medical record during post graduate year (PGY)-1 and PGY-2. Using linear regression models, we investigated associations between ITE score and number of notes during the previous PGY, adjusted for previous ITE score, gender, medical school origin, and conference attendance. KEY RESULTS: For IM, PGY-2 admission and consult encounters in the hospital and specialty clinics had a positive linear association with ITE-3 % score (ß = 0.02; p = 0.004). For IM, PGY-1 conference attendance is positively associated with PGY-2 ITE performance. We did not detect a correlation between PGY-1 patient encounters and subsequent ITE scores for IM or pediatric residents. No association was found between IM PGY-2 ITE score and inpatient, outpatient, or total encounters in the first year of training. Resident continuity clinic and total encounters were not associated with change in PGY-3 ITE score. CONCLUSIONS: We identified a positive association between hospital and subspecialty encounters during the second year of IM training and subsequent ITE score, such that each additional 50 encounters were associated with an increase of 1 % correct in PGY-3 ITE score after controlling for previous ITE performance and continuity clinic encounters. We did not find a correlation for volume of encounters and medical knowledge for IM PGY-1 residents or the pediatric cohort.

The first reported case of compound heterozygous IL1RN mutations causing deficiency of the interleukin-1 receptor antagonist.

Interleukin-1 receptor antagonist (IL-1Ra) deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. We report the case of a 2-week-old male who presented with a swollen, erythematous left index finger and elevated serum markers of inflammation. He later developed cyclical fevers, diffuse pustular skin lesions, and thrombus formation. After not responding to broad-spectrum antimicrobial therapy and achieving only moderate success with systemic steroid therapy, he was ultimately treated with recombinant IL-1Ra, anakinra, and experienced significant clinical improvement. Sequencing of his IL1RN gene revealed that the patient was compound heterozygous for a known mutation (E77X) associated with IL-1Ra deficiency and a novel mutation in exon 2 of the gene (c.140delC; p.T47TfsX4). His case highlights IL-1Ra deficiency as an autoinflammatory disease that is distinct from neonatal-onset multisystem inflammatory disease but that also responds well to anakinra. Our patient is the first reported compound heterozygote for E77X and the novel mutation in exon 2 of the gene, the latter of which adds to what will surely be a growing database of pathologic mutations in IL1RN.

Congenital Cytomegalovirus Screening in Massachusetts Birth Hospitals: A Statewide Survey.

This study sought to assess the current state of screening for congenital cytomegalovirus infection in newborns among birth hospitals and newborn nurseries in the state of Massachusetts. A survey assessing hospital protocols for cytomegalovirus testing in newborns was distributed to all birth hospitals and newborn nurseries in Massachusetts from November 2020 to February 2021. 73.3% of hospitals responded to at least one survey question. Of these, fewer than half (48.5%) had any established approach for neonatal cytomegalovirus screening. Salivary polymerase chain reaction was the most common testing modality. Most hospitals did not perform confirmatory testing for positive test results. Most respondents (87.9%) did not know or did not answer how results of cCMV screening were reported to families and who was responsible for coordinating care for cCMV-infected infants. We conclude that congenital cytomegalovirus screening protocols are absent or incomplete in most Massachusetts birth hospitals and newborn nurseries. A cohesive strategy involving standardized education and screening guidelines is needed to reduce the incidence and burden of congenital cytomegalovirus disease on children and their families.

Otoendoscopes to Enhance Telemedicine During the COVID-19 Pandemic.

OBJECTIVES: As telemedicine has become increasingly utilized during the COVID-19 pandemic, portable otoendoscopy offers a method to perform an ear examination at home. The objective of this pilot study was to assess the quality of otoendoscopic images obtained by non-medical individuals and to determine the effect of a simple training protocol on image quality. METHODS: Non-medical participants were recruited and asked to capture images of the tympanic membrane before and after completion of a training module, as well as complete a survey about their experience using the otoendoscope. Images were de-identified, randomized, and evaluated by 6 otolaryngologists who were blinded as to whether training had been performed prior to the image capture. Images were rated using a 5-point Likert scale. RESULTS: Completion of a training module resulted in a significantly higher percentage of tympanic membrane visible on otoendoscopic images, as well as increased physician confidence in identifying middle ear effusion/infection, cholesteatoma, and deferring an in-person otoscopy (P < .0001). However, even with improved image quality, in most cases, physicians reported that they would not feel comfortable using the images to for diagnosis or to defer an in-person examination. Most participants reported that the otoendoscope was simple to use and that they would feel comfortable paying for the device. CONCLUSIONS: At-home otoendoscopes can offer a sufficient view of the tympanic membrane in select cases. The use of a simple training tool can significantly improve image quality, though often not enough to replace an in-person otoscopic exam.

Hearing Aid Use in Children With Unilateral Hearing Loss: A Randomized Crossover Clinical Trial.

OBJECTIVES/HYPOTHESIS: In children with mild to moderately severe unilateral hearing loss (UHL), assess whether subject-reported quality of life (QOL) and teacher- and parent-reported perception of listening difficulty are affected by use of a hearing aid (HA) with baseline accommodations, compared to children receiving only baseline accommodations. STUDY DESIGN: Randomized crossover clinical trial. METHODS: Thirty-seven children 6-12 years of age with mild to moderately severe UHL and ≥80% word recognition scores in the poorer hearing ear were randomized into arm 1, using baseline accommodations (frequency-modulated system and strategic seating) for 12 weeks, followed by addition of a HA for 12 weeks. The other participants were randomized into the reverse methodology: arm 2, using a HA in addition to baseline accommodations for 12 weeks, followed by baseline accommodations alone. Surveys of QOL (Hearing Environments and Reflection on Quality of Life) and listening difficulties or challenges with hearing amplification (CHILD and LIFE-R questionnaires) were administered at 6-week intervals. Differences in mean survey scores, percent change, and improvement over time were computed between the two arms and inter-arm intervals. Per-protocol analysis was used. RESULTS: Of the 37 children enrolled, 34 children underwent the study interventions and were included in the analysis, (arm 1 = 20, arm 2 = 14) (mean [standard deviation] age = 8 [1.5] years; 21 boys [61.8%]). Survey scores averaged across both arms during the HA interval (77.79 [15.13]) were significantly higher than during the baseline-only interval (69.67 [14.69], P = .036). There was no significant difference between trial arms in mean scores between the two HA intervals (P = .450) and two baseline-only intervals (P = .539). CONCLUSIONS: Hearing-related QOL and listening ability improved in children who met eligibility criteria with mild to moderately severe UHL with HA use compared with baseline accommodations alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02269124. LEVEL OF EVIDENCE: 1 Laryngoscope, 132:881-888, 2022.

Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea.

Importance: Patients with Down syndrome have a high incidence of persistent obstructive sleep apnea (OSA) and limited treatment options. Upper airway hypoglossal stimulation has been shown to be effective for adults with OSA but has not yet been evaluated for pediatric populations. Objective: To evaluate the safety and effectiveness of upper airway stimulation for adolescent patients with Down syndrome and severe OSA. Design, Setting, and Participants: This prospective single-group multicenter cohort study with 1-year follow-up was conducted between April 1, 2015, and July 31, 2021, among a referred sample of 42 consecutive adolescent patients with Down syndrome and persistent severe OSA after adenotonsillectomy. Intervention: Upper airway stimulation. Main Outcomes and Measures: The prespecified primary outcomes were safety and the change in apnea-hypopnea index (AHI) from baseline to 12 months postoperatively. Polysomnographic and quality of life outcomes were assessed at 1, 2, 6, and 12 months postoperatively. Results: Among the 42 patients (28 male patients [66.7%]; mean [SD] age, 15.1 [3.0] years), there was a mean (SD) decrease in AHI of 12.9 (13.2) events/h (95% CI, -17.0 to -8.7 events/h). With the use of a therapy response definition of a 50% decrease in AHI, the 12-month response rate was 65.9% (27 of 41), and 73.2% of patients (30 of 41) had a 12-month AHI of less than 10 events/h. The most common complication was temporary tongue or oral discomfort, which occurred in 5 patients (11.9%). The reoperation rate was 4.8% (n = 2). The mean (SD) improvement in the OSA-18 total score was 34.8 (20.3) (95% CI, -42.1 to -27.5), and the mean (SD) improvement in the Epworth Sleepiness Scale score was 5.1 (6.9) (95% CI, -7.4 to -2.8). The mean (SD) duration of nightly therapy was 9.0 (1.8) hours, with 40 patients (95.2%) using the device at least 4 hours a night. Conclusions and Relevance: Upper airway stimulation was able to be safely performed for 42 adolescents who had Down syndrome and persistent severe OSA after adenotonsillectomy with positive airway pressure intolerance. There was an acceptable adverse event profile with high rates of therapy response and quality of life improvement. Trial Registration: ClinicalTrials.gov Identifier: NCT02344108.

Long-term stability of hypoglossal nerve stimulation for the treatment of obstructive sleep apnea in children with Down syndrome.

IMPORTANCE: Obstructive sleep apnea (OSA) occurs in 55-97% of people with Down syndrome (DS). Even after adenotonsillectomy, residual OSA often persists into adulthood due, in part, to tongue base collapse. Implantable hypoglossal nerve stimulators are being investigated in children and young adults with DS and persistent, moderate to severe OSA. However, the long-term necessity for such an intervention-especially as patients mature and voltage adjustment becomes warranted-has not been previously reported in the pediatric DS population. OBJECTIVE: To assess the long-term need for implantable hypoglossal nerve stimulators and the necessity for voltage adjustment in children and young adults with Down syndrome. DESIGN: This is a case series from an ongoing clinical trial assessing safety and efficacy of hypoglossal nerve stimulation among 42 children and young adults with DS and persistent OSA, despite adenotonsillectomy and trialed positive airway pressure (PAP) therapy. We focus here on the first 4 participants who have undergone implantation by age 13 and have completed at least 44 months of follow-up. PARTICIPANTS: 4 participants (2 male, 2 female; ages 10-13 years) with DS and persistent, severe OSA (AHI > 10 events/h) underwent hypoglossal nerve stimulator implantation and were followed for 44-58 months. SETTING: Participants completed in-lab sleep studies at baseline (before implantation), 1 year postoperatively, and 44-58 months postoperatively. During their most recent follow-up, 2 participants completed split-night sleep studies in which assessment was done with the device both on and off. INTERVENTIONS: Hypoglossal nerve stimulator implantation. MAIN OUTCOMES AND MEASURES: Stability in titrated and untitrated OSA as measured by the apnea-hypopnea index (AHI); growth measures including BMI; and quality of life as measured by the OSA-18 questionnaire. RESULTS: Compared to baseline, all 4 participants maintained reductions of at least 50% in AHI over the course of follow-up. At recent follow-up, two participants had persistent, moderate OSA despite stimulation therapy. The other two participants achieved 100% reductions in AHI with stimulation therapy; when they underwent split-night sleep studies, the severe OSA persisted with the device turned off. Improvement in OSA-18 quality of life scores was observed in three of the four participants. CONCLUSION: and Relevance: Hypoglossal nerve stimulation continues to effectively control OSA in children with DS as they mature, while their underlying untitrated OSA appears to persist into adulthood. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT2344108.

Redefining Success by Focusing on Failures After Pediatric Hypoglossal Stimulation in Down Syndrome.

OBJECTIVES/HYPOTHESIS: Patients with Down syndrome have a high incidence of obstructive sleep apnea (OSA) and limited treatment options. Hypoglossal stimulation has shown efficacy but has not yet been approved for pediatric populations. Our objective is to characterize the therapy response of adolescent patients with down syndrome and severe OSA who underwent hypoglossal stimulation. STUDY DESIGN: Prospective longitudinal trial. METHODS: We are conducting a multicenter single-arm trial of hypoglossal stimulation for adolescent patients with Down syndrome and severe OSA. Interim analysis was performed to compare objective sleep and quality of life outcomes at 12 months postoperatively for the first 20 patients. RESULTS: The mean age was 15.5 and baseline AHI 24.2. Of the 20 patients, two patients (10.0%) had an AHI under 1.5 at 12 months; nine patients of 20 (45.0%) under five; and 15 patients of 20 (75.0%) under 10. The mean decrease in AHI was 15.1 (P < .001). Patients with postoperative AHI over five had an average baseline OSA-18 survey score of 3.5 with an average improvement of 1.7 (P = .002); in addition, six of these patients had a relative decrease of apneas compared to hypopneas and seven had an improvement in percentage of time with oxygen saturation below 90%. CONCLUSIONS: Patients with persistently elevated AHI 12 months after hypoglossal implantation experienced improvement in polysomnographic and quality of life outcomes. These results suggest the need for a closer look at physiologic markers for success beyond reporting AHI as the gold standard. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1663-1669, 2021.

Role of small bowel follow-through in diagnosing inflammation of the terminal ileum in pediatric patients.

BACKGROUND: The small bowel follow-through (SBFT) is a noninvasive imaging modality for evaluating terminal ileum (TI) inflammation. The accuracy of this modality in pediatric patients is not well established. PATIENTS AND METHODS: We retrospectively determined the sensitivity and specificity of SBFT for detecting TI inflammation diagnosed on histology in 93 pediatric patients studied in a single institution. RESULTS: The mean age at the first study was 12.9 years (range 1.1-20.9 years). Forty-five percent were girls. Twenty-five patients (27%) had abnormal TIs on SBFT. Seventeen patients (18%) had TI inflammation diagnosed by biopsy. The sensitivity of SBFT was 59% and the specificity was 80% for detecting TI inflammation diagnosed on histology. Sensitivity and specificity did not change by demographic factors, final diagnoses, presenting symptoms, or laboratory parameters, reflecting the presence of intestinal inflammation. CONCLUSIONS: The sensitivity and specificity of SBFT in pediatric patients were poor and did not vary with demographic factors, final diagnoses, presenting symptoms, or laboratory parameters. Prospective longitudinal studies comparing various imaging modalities (SBFT, magnetic resonance enterography, and capsule endoscopy) are required to determine which is the most effective tool for evaluating pediatric patients for TI inflammation.

The role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients.

Turner Syndrome patients have an absent second sex chromosome and a predisposition to autoimmune disease. We hypothesized that the autoimmune susceptibility in Turner Syndrome may be due to an alteration in the expression of the X-linked FOXP3 gene. FOXP3 is important in the development of regulatory T cells, and complete loss of FOXP3 expression has been shown to result in severe autoimmunity. To test this hypothesis, we characterized the regulatory T cells and performed immunophenotyping on the peripheral blood leukocytes of a cohort of Turner Syndrome patients. These patients retained regulatory T cell frequency and function despite an increased prevalence of autoimmunity. Immunophenotyping revealed a decrease in the ratio of CD4 to CD8 lymphocytes. These findings suggest that the autoimmune predisposition in Turner Syndrome is not due to alterations in regulatory T cells but may be associated with a change in the proportion of T cell subsets.

The enduring legacy of pioneering neuroscientist Dr. Jerzy Edwin Rose.

The human nervous system maintains dominion over everything experienced in life, consolidating a constant barrage of stimuli and chemical fluctuation into memory, sense, emotion, and even character. Despite decades of productive investigation, comprehension of the nervous system's function and structure remain shrouded in mystery. Historically, the burden of elucidating these mysteries has fallen to neuroscientists bold enough to seek answers to this most nebulous vista. The legacy of one such neuroscientist, Jerzy Edwin Rose, endures today as a pillar of neuroscientific discovery. In the nascence of his career, Rose explored volumetric comparisons of human brain structure to that of other mammals, leading to the development of novel methods in neurophysiologic measurement and explanation. Rose would later segue mid-career into studies on the cooperation between the auditory cortex and thalamus, resulting in increased understanding of its functioning, structure, and anatomy. During the final saga of his long, fruitful career, Rose explored the electrophysiology of the auditory system, leading to novel methods using modern technology. Ultimately, the vast breadth of Rose's contributions to neuroscience has diminished the field's mystery, setting forth momentous groundwork for future discovery, and the inspiration to carry on in the spirit of his bold curiosity.

The impact of accelerometer use in exercise-associated hypoglycemia prevention in type 1 diabetes.

Exercise-associated hypoglycemia is a common adverse event in people with type 1 diabetes. Previous in silico testing by our group demonstrated superior exercise-associated hypoglycemia mitigation when a predictive low glucose suspend (PLGS) algorithm was augmented to incorporate activity data. The current study investigates the effectiveness of an accelerometer-augmented PLGS algorithm in an outpatient exercise protocol. Subjects with type 1 diabetes on insulin pump therapy participated in two structured soccer sessions, one utilizing the algorithm and the other using the subject's regular basal insulin rate. Each subject wore their own insulin pump and a Dexcom G4™ Platinum continuous glucose monitor (CGM); subjects on-algorithm also wore a Zephyr BioHarness™ 3 accelerometer. The algorithm utilized a Kalman filter with a 30-minute prediction horizon. Activity and CGM readings were manually entered into a spreadsheet and at five-minute intervals, the algorithm indicated whether the basal insulin infusion should be on or suspended; any changes were then implemented by study staff. The rate of hypoglycemia during and after exercise (until the following morning) was compared between groups. Eighteen subjects (mean age 13.4 ± 3.7 years) participated in two separate sessions 7-22 days apart. The difference in meter blood glucose levels between groups at each rest period did not achieve statistical significance at any time point. Hypoglycemia during the session was recorded in three on-algorithm subjects, compared to six off-algorithm subjects. In the postexercise monitoring period, hypoglycemia occurred in two subjects who were on-algorithm during the session and four subjects who were off-algorithm. The accelerometer-augmented algorithm failed to prevent exercise-associated hypoglycemia compared to subjects on their usual basal rates. A larger sample size may have achieved statistical significance. Further research involving an automated system, a larger sample size, and an algorithm design that favors longer periods of pump suspension is necessary.

The Impact of Accelerometer and Heart Rate Data on Hypoglycemia Mitigation in Type 1 Diabetes.

Aerobic exercise can lower blood glucose levels and alter insulin sensitivity both during and several hours after exercise, creating challenges for a closed-loop artificial pancreas. Predictive low glucose suspend (PLGS) algorithms are a first step toward an artificial pancreas, but few of these have been successfully applied to exercise. This study incorporates physical activity measurements from a combined accelerometer/heart rate monitor (HRM) to improve the performance of an existing PLGS algorithm at mitigating exercise-associated hypoglycemia in participants with type 1 diabetes. In all, 22 subjects with type 1 diabetes on insulin pump therapy were provided a combined accelerometer/HRM and (if not already using one) a continuous glucose monitor (CGM), then instructed to go about their everyday lives while wearing the devices. After the monitoring period, each subject's insulin pump, CGM, and accelerometer/HRM were downloaded and the data were used to augment an existing PLGS algorithm to incorporate activity. Using a computer simulator, the accelerometer-augmented algorithm was compared to the HRM-augmented algorithm to determine which was most effective at mitigating hypoglycemia. Mean length of monitoring was 4.9 days. Across all subjects, 11 061 CGM readings were recorded during the monitoring period. In the simulator analysis, the PLGS algorithm reduced hypoglycemia by 62%, compared to 71% and 74% reductions for the HRM-augmented and accelerometer-augmented algorithms, respectively; combined accelerometer and HRM augmentation provided a 76% reduction. In a simulated setting, the accelerometer-augmented pump suspension algorithm decreases the incidence of exercise-related hypoglycemia by a meaningful amount compared to the PLGS algorithm alone. Results also failed to justify the additional user burden of a HRM.

Bilateral basal ganglia infarctions in a neonate born during maternal diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) during pregnancy carries significant risk of intrauterine fetal demise, but little is known about its postnatal sequelae in surviving neonates. We report here the case of an infant who was born to a mother with White's class C diabetes mellitus during an episode of DKA. Throughout pregnancy her glucose control was suboptimal, as evidenced by a predelivery glycosylated hemoglobin level of 8.1%. At 33 weeks' gestation, the mother presented with nausea and vomiting, a serum glucose concentration of 575 mg/dL, and other metabolic derangements consistent with DKA. Despite rehydration and insulin therapy, fetal distress necessitated cesarean delivery. At birth the infant required intubation, but her clinical status quickly improved and she was extubated within the first day of life. However, on day-of-life 4 she exhibited seizure-like activity, and subsequent brain MRI revealed bilateral basal ganglia infarctions. Previous research has revealed that the keto acid ß-hydroxybutyrate (ß-OHB) can cross the placenta into the fetal circulation and thereafter accumulate in the fetal brain, which leads to severe metabolic derangements. Furthermore, ß-OHB accumulates rapidly in the basal ganglia of older children during episodes of DKA, wherein its presence is associated with neuronal injury. We suspect that transplacental transfer of maternal ß-OHB led to an acquired ketoacidosis in the fetus and that accumulation of ß-OHB contributed to neuronal injury and subsequent infarction of the basal ganglia. Further research is necessary to better characterize neonatal complications of maternal DKA, as well as the possible inclusion of ß-OHB levels in the goal-directed treatment of this disease.

A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1.

UNLABELLED: High titer antibodies to type 1 interferons have been recently reported as being highly specific for patients with autoimmune polyglandular syndrome type 1 (APS1) in Finnish and Norwegian patients with mutations in the AIRE gene. Those studies employed a complex neutralization assay to define the type 1 interferon autoantibodies. Here we have established a competitive europium time resolved fluorescence assay for IFN-alpha autoantibodies and measured sera from subjects with APS1, first degree relatives of APS1 patients, patients with Addison's disease or Type 1 diabetes. The europium-based immunoassay utilizes plate bound human IFN-alpha incubated with sera with or without competition with fluid phase IFN-alpha, followed by anti-IgG biotinylated antibody and detection with streptavidin-europium. The index of IFN-alpha Ab was calculated as (CPS (Counts per second) without competition-CPS with competition)/(CPS positive standard sera without competition-CPS positive standard sera with competition). RESULTS are reported for raw CPS and indices and are compared across the different subjects. RESULTS: For normal controls (n=100) CPS without competition were 31,237+/-17,328 CPS while after subtracting the competition value, the results were -6563+/-10,303 CPS. The initial APS1 patient (used to create the index as 1.0) gave 394,063 CPS without competition and a delta of 363,662+/-31,587 CPS with competition. Scatchard plot analysis of this patient sample revealed a high avidity for IFN-alpha (K(d) of 0.5 nM). The CPS, delta, and index for 6/7 APS1 patients were strongly positive and 3 standard deviations or more above that of the normal controls. Using a cut-off of 2 standard deviations above normal controls, relatives of APS1 patients were negative for type I interferon autoantibodies as were 71 patients with Addison's disease (non-APS1) and 141 Type 1 diabetes patients. This simple high throughput competitive europium time resolved fluorescence assay had a sensitivity of > or =86% or greater and a specificity of >99.5%.