A Modified Delphi Study for Curricular Content of Simulation-Based Medical Education for Pediatric Residency Programs.

OBJECTIVE: We sought to establish core knowledge topics and skills that are important to teach pediatric residents using simulation-based medical education (SBME). METHODS: We conducted a modified Delphi process with experts in pediatric SBME. Content items were adapted from the American Board of Pediatrics certifying exam content and curricular components from pediatric entrustable professional activities (EPAs). In round 1, participants rated 158 items using a four-point Likert scale of importance to teach through simulation in pediatric residency. A priori, we defined consensus for item inclusion as ≥70% rated the item as extremely important and exclusion as ≥70% rated the item not important. Criteria for stopping the process included reaching consensus to include and/or exclude all items, with a maximum of three rounds. RESULTS: A total of 59 participants, representing 46 programs and 25 states participated in the study. Response rates for the three rounds were 92%, 86% and 90%, respectively. The final list includes 112 curricular content items deemed by our experts as important to teach through simulation in pediatric residency. Seventeen procedures were included. Nine of the seventeen EPAs had at least one content item that experts considered important to teach through simulation as compared to other modalities. CONCLUSIONS: Using consensus methodology, we identified the curricular items important to teach pediatric residents using SBME. Next steps are to design a simulation curriculum to encompass this content.

Haplotype-based analysis resolves missing heritability in oculocutaneous albinism type 1B.

Oculocutaneous albinism (OCA) is a rare disorder of pigment production. Affected individuals have variably decreased global pigmentation and visual-developmental changes that lead to low vision. OCA is notable for significant missing heritability, particularly among individuals with residual pigmentation. Tyrosinase (TYR) is the rate-limiting enzyme in melanin pigment biosynthesis and mutations that decrease enzyme function are one of the most common causes of OCA. We present the analysis of high-depth short-read TYR sequencing data for a cohort of 352 OCA probands, ∼50% of whom were previously sequenced without yielding a definitive diagnostic result. Our analysis identified 66 TYR single-nucleotide variants (SNVs) and small insertion/deletions (indels), 3 structural variants, and a rare haplotype comprised of two common frequency variants (p.Ser192Tyr and p.Arg402Gln) in cis-orientation, present in 149/352 OCA probands. We further describe a detailed analysis of the disease-causing haplotype, p.[Ser192Tyr; Arg402Gln] ("cis-YQ"). Haplotype analysis suggests that the cis-YQ allele arose by recombination and that multiple cis-YQ haplotypes are segregating in OCA-affected individuals and control populations. The cis-YQ allele is the most common disease-causing allele in our cohort, representing 19.1% (57/298) of TYR pathogenic alleles in individuals with type 1 (TYR-associated) OCA. Finally, among the 66 TYR variants, we found several additional alleles defined by a cis-oriented combination of minor, potentially hypomorph-producing alleles at common variant sites plus a second, rare pathogenic variant. Together, these results suggest that identification of phased variants for the full TYR locus are required for an exhaustive assessment for potentially disease-causing alleles.

Untrapped: bilateral hypoplasia of the trapezius muscle.

Agenesis or congenital hypoplasia of skeletal muscles occurs infrequently but may occur with specific conditions such as Poland syndrome. The trapezius muscle can vary in the extent of its bony attachments or may have additional slips, however congenital absence or hypoplasia is extremely rare. There are only a few reports of partial or complete absence of the trapezius muscle. Two cases of bilateral absence of the trapezius were both in males and were accompanied by the absence of additional muscle in the pectoral girdle. Herein, we describe a case of a 56-year-old male cadaver with bilateral hypoplasia of the trapezius. The muscle was largely represented by atrophied muscle fibers with an abundance of fibrotic or fatty connective tissue. This subject had very minor hypoplasia of the left pectoralis major muscle, but the remaining muscles of the pectoral girdle were normal. The spinal accessory nerve terminated in the sternocleidomastoid muscle on both sides, failing to reach the trapezius. We interpret these findings to be consistent with a minor variant of Poland syndrome.

Untrapped: bilateral hypoplasia of the trapezius muscle / 대한해부학회지

Agenesis or congenital hypoplasia of skeletal muscles occurs infrequently but may occur with specific conditions such as Poland syndrome. The trapezius muscle can vary in the extent of its bony attachments or may have additional slips, however congenital absence or hypoplasia is extremely rare. There are only a few reports of partial or complete absence of the trapezius muscle. Two cases of bilateral absence of the trapezius were both in males and were accompanied by the absence of additional muscle in the pectoral girdle. Herein, we describe a case of a 56-year-old male cadaver with bilateral hypoplasia of the trapezius. The muscle was largely represented by atrophied muscle fibers with an abundance of fibrotic or fatty connective tissue. This subject had very minor hypoplasia of the left pectoralis major muscle, but the remaining muscles of the pectoral girdle were normal. The spinal accessory nerve terminated in the sternocleidomastoid muscle on both sides, failing to reach the trapezius. We interpret these findings to be consistent with a minor variant of Poland syndrome.

Employment Opportunities for Pediatric Critical Care Fellowship Trained Physicians in the United States.

Pediatric Critical Care Medicine (PCCM) training programs and trained fellows in the United State increased steadily without a corresponding increase in population growth. PCCM trainees worry about limited employment prospects. This study aimed to quantify the demand for PCCM trained physicians in the United States by prospectively tracking full-time employment opportunities over 12 months. The number of advertised opportunities identified was low compared with number of fellows likely to be seeking jobs during same time period. If market demand remains stable, there is risk of excess supply if number of newly fellowship-trained PCCM physicians continues to rise.

Is Referral to Home Health Rehabilitation After Inpatient Rehabilitation Facility Associated With 90-Day Hospital Readmission for Adult Patients With Stroke?

OBJECTIVE: We examined the association between home health rehabilitation referral and 90-day risk-adjusted hospital readmission after discharge from inpatient rehabilitation facilities among adult patients recovering from stroke (N = 1219). DESIGN: A secondary data analysis of the 2005-2006 Stroke Recovery in Underserved Population database. A logistic regression model, multilevel model, and the propensity score inverse probability weighting model were used to evaluate the risk of 90-day rehospitalization between patients with stroke who received a referral for home health rehabilitation and those who did not receive a home health rehabilitation referral at inpatient rehabilitation facility discharge. RESULTS: The regression, multilevel, and propensity score inverse probability weighting models indicated that inpatient rehabilitation facility patients with stroke who received home health rehabilitation referral had substantially lower odds of 90-day rehospitalization after inpatient rehabilitation facility discharge compared with those who were not referred to home health (odds ratio = 0.325, 95% confidence interval = 0.138-0.764; odds ratio = 0.340, 95% confidence interval = 0.139-0.832; odds ratio = 0.407, 95% confidence interval = 0.183-0.906, respectively). CONCLUSIONS: Our findings suggest the importance of continuation of care (home health) after hospitalization and intense inpatient rehabilitation for stroke. Additional research is needed to establish appropriate use criteria and explore potential underuse of home health services as well as the benefits for follow-up outpatient services for those who do not qualify for home health at inpatient rehabilitation facility discharge.

Burnout in Pediatric Critical Care Medicine Fellows.

OBJECTIVES: Assess the overall level of burnout in pediatric critical care medicine fellows and examine factors that may contribute to or protect against its development. DESIGN: Cross-sectional observational study. SETTING: Accreditation Council for Graduate Medical Education-accredited pediatric critical care medicine fellowship programs across the United States. SUBJECTS: Pediatric critical care medicine fellows and program directors. INTERVENTIONS: Web-based survey that assessed burnout via the Maslach Burnout Inventory, as well as other measures that elicited demographics, sleepiness, social support, perceptions about prior training, relationships with colleagues, and environmental burnout. MEASUREMENTS AND MAIN RESULTS: One-hundred eighty-seven fellows and 47 program directors participated. Fellows from 30% of programs were excluded due to lack of program director participation. Average values on each burnout domain for fellows were higher than published values for other medical professionals. Personal accomplishment was greater (lower burnout) among fellows more satisfied with their career choice (ß 9.319; p ≤ 0.0001), spiritual fellows (ß 1.651; p = 0.0286), those with a stress outlet (ß 3.981; p = 0.0226), those comfortable discussing educational topics with faculty (ß 3.078; p = 0.0197), and those comfortable seeking support from their co-fellows (ß 3.762; p = 0.0006). Depersonalization was higher for second year fellows (ß 2.034; p = 0.0482), those with less educational debt (ß -2.920; p = 0.0115), those neutral/dissatisfied with their career choice (ß -6.995; p = 0.0031), those with nursing conflict (ß -3.527; p = 0.0067), those who perceived burnout among co-fellows (ß 1.803; p = 0.0352), and those from ICUs with an increased number of patient beds (ß 5.729; p ≤ 0.0001). Emotional exhaustion was higher among women (ß 2.933; p = 0.0237), those neutral/dissatisfied with their career choice (ß -7.986; p = 0.0353), and those who perceived burnout among co-fellows (ß 5.698; p ≤ 0.0001). Greater sleepiness correlated with higher burnout by means of lower personal accomplishment (r = -1.64; p = 0.0255) and higher emotional exhaustion (r = 0.246; p = 0.0007). Except for tangible support, all other forms of social support showed a small to moderate correlation with lower burnout. CONCLUSIONS: Pediatric critical care medicine fellows in the United States are experiencing high levels of burnout, which appears to be influenced by demographics, fellow perceptions of their work environment, and satisfaction with career choice. The exclusion of fellows at 30% of the programs may have over or underestimated the actual level of burnout in these trainees.

Expanding Faculty Development of Teaching Skills: A National Needs Assessment of Pediatric Critical Care Medicine Faculty.

OBJECTIVES: High-quality clinical teaching is an essential element in preparing trainees to become independently competent clinicians. In order to better understand the context-specific faculty development needs of teaching faculty in a specific community, we sought to determine the self-reported teaching skill deficits of pediatric critical care medicine faculty and their preferences and motivations regarding faculty development to enhance their teaching. DESIGN: Modified Delphi technique was used to create an online survey in which respondents rated their need for education on a variety of teaching skills, their preferred learning modalities, and factors that motivate their participation in faculty development. SETTING: Pediatric Critical Care Medicine divisions at the 64 sites in the United States with fellowship programs. SUBJECTS: Five-hundred forty-five Pediatric Critical Care Medicine faculty who teach fellows and other trainees. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Response rate was 40%. Respondents reported a median of 8.5 years (interquartile range, 4-16 yr) as teaching faculty. The median age of faculty was 44.6 years (interquartile range, 38-50 yr). Only 20% of respondents indicated that improving their teaching was a low priority. Thirty-six percent of respondents had not participated in any formal teaching skill development as faculty. The most frequently cited factors motivating engagement in faculty development were education being included as part of regularly attended conferences, resources readily available when needed, and participation promoted by a supervisor. Preferred learning modalities included a brief discussion with a colleague, a 10-minute video, and a regular conference series. CONCLUSIONS: Pediatric Critical Care Medicine faculty reported they experience challenges in teaching and would benefit from faculty development training aimed at improving their knowledge and skills about being an educator. Preferred learning methods and motivating factors highlight the importance of efficiency in content delivery and endorsement by faculty supervisors. Consideration of these needs and preferences may be useful in creating context-focused, community of practice-based faculty development programs.

Risk Factors for Red Blood Cell Transfusions in Children Undergoing Cardiac Catheterization.

OBJECTIVE: To identify risk factors associated with risk of red blood cell transfusions (RBCTs) following pediatric cardiac catheterizations. STUDY DESIGN: We performed a review of all pediatric cardiac catheterizations from 2012 to 2017. The primary endpoint was RBCT within 72 hours of pediatric cardiac catheterization. Patient and procedural factors were reviewed. Generalized linear modelling was performed to describe interactions among relevant risk factors. RESULTS: In total, 831 RBCTs occurred within 72 hours of 6028 pediatric cardiac catheterizations (13.8%). Univariate analysis revealed that the prevalence of RBCT was highest among infants (37.6% incidence of RBCT) and among those with higher estimated blood loss as a percent of blood volume (P = .03). Among infants, multivariate analysis revealed that weight (OR 0.72; 95% CI 0.63-0.81), complex 2-ventricle (OR 3.14, 95% CI 2.18-4.57), and single ventricle status (OR 5.21, 95% CI 3.42-8.01) were associated with risk of RBCT. Inpatient infants from intensive care (OR 4.74; 95% CI 3.49-6.49) or stepdown units (OR 2.33; 95% CI 1.58-3.46) were at higher risk. Length of procedure (OR 2.57; 95% CI 2.03-3.26) and oxygen saturation (OR 0.98; 95% CI 0.97-0.99; P < .01) were also associated with RBCTs. CONCLUSIONS: Hospitalized infants with single ventricle or complex 2-ventricle anatomy are at highest risk of RBCT. Length of procedure, blood loss, and oxygen saturations are additional risk factors associated with RBCT. Operators should consider these factors when planning pediatric cardiac catheterizations, particularly when exposure to RBCT is undesirable.

Achieving Self-Directed Integrated Cancer Aftercare (ASICA) in melanoma: protocol for a randomised patient-focused pilot trial of delivering the ASICA intervention as a means to earlier detection of recurrent and second primary melanoma.

BACKGROUND: Melanoma is common; 15,906 people in the UK were diagnosed with melanoma in 2015 and incidence has increased fivefold in 30 years. Melanoma affects old and young people, with poor prognosis once metastatic. UK guidelines recommend people treated for cutaneous melanoma receive extended outpatient, hospital follow up to detect recurrence or new primaries. Such follow up of the growing population of melanoma survivors is burdensome for both individuals and health services. Follow up is important since approximately 20% of patients with early-stage melanoma experience a recurrence and 4-8% develop a new primary; the risk of either is highest in the first 5 years. Achieving Self-directed Integrated Cancer Aftercare (ASICA) is a digital intervention to increase total-skin-self-examination (TSSE) by people treated for melanoma, with usual follow up. METHODS: We aim to recruit 240 adults with a previous first-stage 0-2C primary cutaneous melanoma, from secondary care in North-East Scotland and the East of England. Participants will be randomised to receive the ASICA intervention (a tablet-based digital intervention to prompt and support TSSE) or control group (treatment as usual). Patient-reported and clinical data will be collected at baseline, including the modified Melanoma Worry Scale (MWS), the Hospital Anxiety and Depression Scale (HADs), the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5 L), and questions about TSSE practice, intentions, self-efficacy and planning. Participants will be followed up by postal questionnaire at 3, 6 and 12 months following randomization, along with a 12-month review of clinical data. The primary timepoint for outcome analyses will be12 months after randomisation. DISCUSSION: If the ASICA intervention improves the practice of TSSE in those affected by melanoma, this may lead to improved psychological well-being and earlier detection of recurrent and new primary melanoma. This could impact both patients and National Health Service (NHS) resources. This study will determine if a full-scale randomised controlled trial can be undertaken in the UK NHS to provide the high-quality evidence needed to determine the effectiveness of the intervention. ASICA is a pilot study evaluating the effectiveness of the practice of digitally supported TSSE in those affected by melanoma. TRIAL REGISTRATION: Clinical Trials.gov, NCT03328247 . Registered on 1 November 2017.

Risk factors for acquiring functional and cognitive disabilities during admission to a PICU*.

OBJECTIVE: To describe the risk factors for acquiring functional or cognitive disabilities during admission to a PICU. DESIGN: Retrospective analysis of a multicenter PICU database. SETTING: Twenty-four PICUs in the Virtual PICU Performance System network from January 1, 2009, through December 31, 2010. PATIENTS: Consecutive patients, who are 1 month to 18 years old, who survived to discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were acquired global functional disability and cognitive disability during admission to a PICU, measured by change in Pediatric Overall Performance Category or in Pediatric Cerebral Performance Category scores, respectively. The primary analysis cohort consisted of 29,352 admissions to the 24 Virtual PICU Performance System sites which collected the main outcome variables. Respectively, 10.3% and 3.4% of the cohort acquired global functional or cognitive disability. Trauma diagnosis (odds ratio, 4.50; 95% CI, 3.83-5.29; odds ratio, 3.91; 95% CI, 3.07-4.98), unscheduled admission to the PICU (odds ratio, 2.67; 95% CI, 2.27-3.12; odds ratio, 1.52; 95% CI, 1.16-2.00), highest risk of mortality category (odds ratio, 1.19; 95% CI, 1.02-1.39; odds ratio, 2.70; 95% CI, 2.15-3.40), oncologic primary diagnoses (odds ratio, 5.61; 95% CI, 4.56-6.91; odds ratio, 4.30; 95% CI, 2.97-6.24), and neurologic primary diagnoses (odds ratio, 2.04, 95% CI, 1.70-2.44; odds ratio, 4.29, 95% CI, 3.18-5.78) were independently associated with acquiring both functional and cognitive disability. Intervention risk factors for acquiring both functional and cognitive disability included invasive mechanical ventilation (odds ratio, 1.79; 95% CI, 1.60-2.00; odds ratio, 2.83; 95% CI, 2.36-3.39), renal replacement therapy (odds ratio, 2.43; 95% CI, 1.73-3.42; odds ratio, 1.76, 95% CI, 1.08-2.85), cardiopulmonary resuscitation (odds ratio, 1.91; 95% CI, 1.24-2.95; odds ratio, 1.81; 95% CI, 1.02-3.23), and extracorporeal membrane oxygenation (odds ratio, 7.40, 95% CI, 4.10-13.36; odds ratio, 14.04, 95% CI, 7.51-26.26). CONCLUSIONS: We identified a subset of patients whose potential for acquiring global functional and cognitive disability during admission to the PICU is high. This population may benefit from interventions that could mitigate this risk and from focused follow-up after discharge from the PICU.

Resonant coherence in photosynthetic electronic energy transfer by site-dependent pigment-protein interactions.

We have numerically examined the effect of site-dependent reorganization on the dynamics of coherent electronic excitation energy transfer in a donor and acceptor pair of photosynthetic pigment-protein complex. Using the quasi-adiabatic propagator path integral method (QUAPI), we have found that a specific proportionality between the site-energy mismatch ϵ and the site-reorganization energy mismatch λ simultaneously increases the length and robustness of the quantum coherence. This behavior is associated with a Rabi type resonance that is manifested in the amplitude and frequency in the coherent portion of the population dynamics. Impact of the resonance on robustness of the coherence under static disorder is also discussed.

Vitiligo: an evidence-based update. Report of the 13th Evidence Based Update Meeting, 23 May 2013, Loughborough, U.K.

The Evidence Based Update (EBU) meetings are annual one-day meetings held by the Centre of Evidence Based Dermatology at the University of Nottingham. The aim of the meeting is to discuss high-quality evidence, mainly in the form of systematic reviews and randomized controlled trials, on a different topic each year. The meetings are designed to be interactive with a panel discussion between international experts and delegates forming a key part of the meeting. The 13th EBU meeting was on vitiligo and took place on 23 May 2013 in Loughborough, U.K. The most recent research including new and unpublished studies was presented on the classification of vitiligo, the evidence behind different treatment options and current guidelines for vitiligo.

A mitochondria-targeted macrocyclic Mn(II) superoxide dismutase mimetic.

Superoxide (O(2)(·-)) is the proximal mitochondrial reactive oxygen species underlying pathology and redox signaling. This central role prioritizes development of a mitochondria-targeted reagent selective for controlling O(2)(·-). We have conjugated a mitochondria-targeting triphenylphosphonium (TPP) cation to a O(2)(·-)-selective pentaaza macrocyclic Mn(II) superoxide dismutase (SOD) mimetic to make MitoSOD, a mitochondria-targeted SOD mimetic. MitoSOD showed rapid and extensive membrane potential-dependent uptake into mitochondria without loss of Mn and retained SOD activity. Pulse radiolysis measurements confirmed that MitoSOD was a very effective catalytic SOD mimetic. MitoSOD also catalyzes the ascorbate-dependent reduction of O(2)(·-). The combination of mitochondrial uptake and O(2)(·-) scavenging by MitoSOD decreased inactivation of the matrix enzyme aconitase caused by O(2)(·-). MitoSOD is an effective mitochondria-targeted macrocyclic SOD mimetic that selectively protects mitochondria from O(2)(·-) damage.

Reconstitution of CHIP E3 ubiquitin ligase activity.

CHIP, the carboxyl-terminus of Hsp70 interacting protein, is both an E3 ubiquitin ligase and an Hsp70 co-chaperone and is implicated in the degradation of cytosolic quality control and numerous disease substrates. CHIP has been shown to monitor the folding status of the CFTR protein, and we have successfully reconstituted this activity using a recombinant CFTR fragment consisting of the cytosolic NBD1 and R domains. We have found that efficient ubiquitination of substrates requires chaperone activity to either deliver the substrate to CHIP or to maintain the substrate in a ubiquitination-competent conformation. This chaperone activity can be provided by the Hsp70/Hsp40 molecular chaperone system as seen in the NBD1-R ubiquitination assay. Alternatively, heat treatment of CHIP can activate its own innate substrate-binding activity and allow for efficient ubiquitination of model substrates, such as denatured luciferase. Here, we describe methods for purifying the recombinant proteins necessary for in vitro reconstitution of CHIP ubiquitin ligase activity, as well as two methods used to monitor CHIP ligase activity. One method allows for the measurement of the Hsp70- and Hsp40-dependent CHIP activity while the other measures the Hsp40- and Hsp70-independent activity of heat-activated CHIP.

Analysis of CFTR folding and degradation in transiently transfected cells.

Misfolding and premature degradation of F508del-CFTR is the major cause of cystic fibrosis. Components of the ubiquitin-proteasome system function on the surface of the endoplasmic reticulum to select misfolded proteins for degradation. The folding status of F508del-CFTR is monitored by at least two ER quality control checkpoints. The ER-associated Derlin-1/RMA1 E3 complex appears to recognize folding defects in CFTR that involve misassembly of NBD1 into a complex with the R-domain. In contrast, the cytosolic Hsp70/CHIP E3 complex appears to sense folding defects that occur after synthesis of NBD2. Herein we describe methods that allow for the study of how modulation of these ER quality control factors by siRNA impacts CFTR folding and degradation. The experimental system described employs transiently transfected HEK293 cells and is utilized to monitor the biogenesis of CFTR by both Western blot and pulse chase studies. Methods to detect complexes formed between CFTR folding intermediates and ER quality control factors will also be described.

Measurement of recent exposure to Phlebotomus argentipes, the vector of Indian visceral Leishmaniasis, by using human antibody responses to sand fly saliva.

Antibody (IgG) responses to the saliva of Phlebotomus argentipes were investigated using serum samples from regions of India endemic and non-endemic for visceral leishmaniasis (VL). By pre-adsorbing the sera against the saliva of the competing human-biting but non-VL vector P. papatasi, we significantly improved the specificity of a P. argentipes saliva enzyme-linked immunosorbent assay. Using this method, we observed a statistically significant correlation between antibodies to P. argenitpes saliva and the average indoor density of female sand flies. Additionally, the method was able to detect recent changes in vector exposure when sera from VL patients were assayed before, during, and after hospitalization and protected from sand fly bites under untreated bed nets. Collectively, these results highlight the utility of antibodies to P. argentipes saliva as an important tool to evaluate VL vector control programs.

Epiphyte loads on seagrasses and microphytobenthos abundance are not reliable indicators of nutrient availability in oligotrophic coastal ecosystems.

Despite marked gradients in nutrient availability that control the abundance and species composition of seagrasses in south Florida, and the importance of nutrient availability in controlling abundance and composition of epiphytes on seagrasses in other locations, we did not find that epiphyte load on the dominant seagrass, Thalassia testudinum, or that the relative contribution of algal epiphytes to the epiphyte community, was positively correlated with nutrient availability in the water column or the sediment in oligotrophic seagrass beds. Further, the abundance of microphytobenthos, as indicated by Chlorophyll-a concentration in the sediments, was not directly correlated with concentrations of nutrients in the sediments. Our results suggest that epiphyte and microphytobenthos abundance are not unambiguous indicators of nutrient availability in relatively pristine seagrass environments, and therefore would make poor candidates for indicators of the status and trends of seagrass ecosystems in relatively low-nutrient environments like the Florida Keys.