Mesoscale structural gradients in human tooth enamel.

The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 µm (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 µm). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg2+ and CO32-/Na+) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. By revealing additional complexity at the rod/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.

Physician workload and practice management in pediatric gastroenterology.

OBJECTIVES: The pediatric gastroenterology workforce has grown in the last few decades. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force to understand current pediatric gastroenterology organizations' practice structures. METHODS: 19-item electronic survey was distributed to NASPGHAN members who were clinical or academic division directors. RESULTS: 30% responded to the survey, all directors of academic practices. The median number of clinical sessions per week was seven sessions, and the median individual work relative value unit (wRVU) target for practices was 4000-4500. Healthcare team ratios compared to provider clinical full-time equivalent were reported as the following: Nursing 0.80, medical assistant (MA) 0.29, dietitian 0.29, social worker 0.14, and psychologist 0.13. Regarding compensation, 68.0% were salaried with bonus based on billing or director decision, 28.0% were salaried with no incentive pay, and 4.0% were salaried with a portion at risk if the target was not met, and a bonus was given if the target was met. Most practices participated in a wellness activity with the most common strategies being didactic lectures about physician burnout (80%), annual burnout check-ins (68%), and/or after-hours social activities (60%). CONCLUSIONS: Pediatric gastroenterology practices vary regarding clinical sessions per week and annual wRVU targets with the median at seven sessions per week and an annual goal of 4000-4500 wRVUs, similar to reported national benchmark goals at the 50th percentile. Healthcare teams, including nursing, MAs, dietitians, social workers, and psychologists, had similar ratios of staff to providers for all sizes and types of practices. Most practices are engaging in wellness initiatives.

Physician Burnout in Pediatric Gastroenterology.

OBJECTIVES: Physicians are prone to burnout which can negatively affect the quality of patient care and lead to medical errors. Burnout can also affect physicians by impacting their personal relationships, their sense of career fulfillment, and job satisfaction. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a taskforce to investigate burnout among pediatric gastroenterologists. METHODS: A 35-item electronic survey was developed to collect demographic and practice information and characterize the well-being of pediatric gastroenterologists. Burnout was assessed employing 2 single-item measures adapted from the Maslach Burnout Inventory. The survey was distributed to NASPGHAN members 3 times from February 2020 to March 2020. Descriptive statistics, Chi-square, and Fisher exact tests were used. RESULTS: One thousand seven hundred ninety-one e-mails were successfully sent and 408 participants (22.7%) returned surveys. A total of 28.8% reported high risk for emotional exhaustion, 17.5% reported high risk for depersonalization, and 33% reported overall burnout. Participants 44 years of age or younger reported significantly more burnout than those 45 years and older ( P = 0.018). Contributors to high burnout identified included increased patient load/demands, insufficient nursing support, electronic health record (EHR) use, insufficient administrative staff, excessive on-call coverage, and more complex patients. Forty-four percent reported not having enough time for their personal life including family. A total of 16.2% of participants reported that they would not choose to be a pediatric gastroenterologist again. CONCLUSIONS: Pediatric gastroenterologists are at risk for emotional exhaustion, depersonalization, and overall burnout. Strategies to prevent physician burnout should be implemented as soon as feasibly possible to improve individual mental health and patient care.

Temporal Dynamics of Nasopharyngeal and Tracheal Severe Acute Respiratory Syndrome Coronavirus 2 Cycle Thresholds in Coronavirus Disease 2019 Patients With Tracheostomy.

In this study of 45 patients with COVID-19 undergoing tracheostomy, nasopharyngeal and tracheal cycle threshold (Ct) values were analyzed. Ct values rose to 37.9 by the time of tracheostomy and remained >35 postoperatively, demonstrating that persistent test positivity may not be associated with persistent transmissible virus in this population.

Percutaneous and Open Tracheostomy in Patients with COVID-19: Comparison and Outcomes of an Institutional Series in New York City.

OBJECTIVE: The aim of this study was to report the safety, efficacy, and early results of tracheostomy in patients with COVID-19 and determine whether differences exist between percutaneous and open methods. SUMMARY BACKGROUND DATA: Prolonged respiratory failure is common in symptomatic patients with COVID-19, the disease process caused by infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tracheostomy, although posing potential risk to the operative team and other healthcare workers, may be beneficial for safe weaning of sedation and ventilator support. However, short- and long-term outcomes remain largely unknown. METHODS: A prospectively collected database of patients with COVID-19 undergoing tracheostomy at a major medical center in New York City between April 4 and April 30, 2020 was reviewed. The primary endpoint was need for continued mechanical ventilation. Secondary outcomes included complication rates, sedation weaning, and need for intensive care unit (ICU) level of care. Patient characteristics, perioperative conditions, and outcomes between percutaneous and open groups were analyzed. RESULTS: During the study period, 67 consecutive patients underwent tracheostomy, including 48 males and 19 females with a median age of 66 years [interquartile range (IQR) 52-72]. Two surgeons alternated techniques, with 35 tracheostomies performed percutaneously and 32 via an open approach. The median time from intubation to tracheostomy was 23 days (IQR 20-26). At a median follow-up of 26 days, 52 patients (78%) no longer required mechanical ventilation and 58 patients (87%) were off continuous sedation. Five patients (7.5%) died of systemic causes. There were 11 total complications (16%) in 10 patients, most of which involved minor bleeding. There were no significant differences in outcomes between percutaneous and open methods. CONCLUSIONS: Tracheostomy under apneic conditions by either percutaneous or open technique can be safely performed in patients with respiratory failure due to COVID-19. Tracheostomy facilitated weaning from continuous intravenous sedation and mechanical ventilation. Continued follow-up of these patients to ascertain long-term outcome data is ongoing.

Health and Financial Burdens Associated With Venous Thrombosis in Hospitalized Children With Inflammatory Bowel Disease.

ABSTRACT: Venous thromboembolism (VTE) is a known complication in children with inflammatory bowel disease (IBD). Despite awareness of the increased thrombosis risk in this population, prophylaxis is not standardly used and there is limited published guidance for thrombosis prevention. To better appreciate the impact of thrombosis in this population, we compared children with IBD who did or did not have a VTE, using the Pediatric Health Information System inpatient database from 2009 to 2017. In hospitalized children with IBD, VTE was associated with longer median hospital stays (11 vs 5 days), need for intensive care unit admission (30.2% vs 4.8%), higher median adjusted costs ($32.8k vs $12.3k) and hospital charges ($96.6k vs $36k), and in-hospital death (1.5% vs 0.2%) (P  < 0.001 in all comparisons). These findings highlight the need to determine and implement appropriate strategies to reduce VTE rates in children with IBD, given its association with high morbidity, mortality, and cost.

Assessment of provider practices regarding venous thromboembolism management and prevention in pediatric acute leukemia patients.

Despite the known occurrence of venous thromboembolism (VTE) in the pediatric oncology population, there are no leukemia-specific VTE treatment guidelines. The primary objective of this study was to assess current practices regarding the management and prevention of VTE in the pediatric acute lymphoblastic leukemia (ALL) population. We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology and the pediatric subcommittee of VENUS (VTE Network US of the Hemostasis and Thrombosis Research Society). Survey items included questions on demographics and clinical practice. Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Treatment duration, re-imaging timeline, and class of anticoagulants used were reported for catheter-associated deep vein thrombus, pulmonary embolism, and cerebral venous sinus thrombosis. While there are some common themes regarding VTE management, there is notable variation in the overall practice as well as with the decision to continue anticoagulation in the presence of thrombocytopenia. Given the variation seen, a multi-center, prospective clinical trial is urgently needed for developing consensus guidelines for the management of VTE in children with ALL.

Extrapolation of ACOSOG Z0011 trial results-A survey of breast cancer providers.

We surveyed breast providers from a national oncology cooperative group to evaluate axillary management recommendations for patients with 1-2 positive sentinel lymph nodes (+SLNs) with scenarios not explicitly included in the Z0011 trial. These scenarios included patients underrepresented (premenopausal, HER2+/triple-negative tumors, and invasive lobular carcinoma) or excluded (treated with mastectomy or neo-adjuvant chemotherapy [NAC]) from the ACOSOG Z0011 trial. Survey response rate was 94/149 (64%). For patients in underrepresented groups, 45-63% of providers recommended no further axillary treatment. For mastectomy patients, 45-55% recommended multi-disciplinary discussion. 83% felt more data are needed to change practice, but 41% believed there would be significant accrual challenges to a clinical trial. For patients treated with NAC, recommendations varied widely. 85% felt more data are needed to change practice, but 26% felt there would be significant accrual challenges. For all scenarios, 86-100% of radiation oncologists recommended axillary radiation, while surgeons more often recommended no further axillary treatment. Traditional randomized trials are likely not feasible to provide answers to these critical management questions, so more pragmatic or big data studies may be needed.

Analysis of Gastrointestinal and Hepatic Manifestations of SARS-CoV-2 Infection in 892 Patients in Queens, NY.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19).1,2 The virus enters cells via the angiotensin-converting enzyme 2 receptor, which is present in enterocytes in the ileum and colon.3 Gastrointestinal (GI) manifestations include diarrhea, nausea, vomiting, and abdominal pain, and the prevalence of GI symptoms varies greatly, with a range between 2% and 57%.4 In addition, abnormal liver chemistries are reported commonly.4 As a medical center at the forefront of the early epidemic in the United States, we seek to contribute to the growing body of literature that outlines the gastrointestinal and hepatic manifestations of COVID-19.

An Instrument for Measuring Critical Appraisal Self-Efficacy in Rheumatology Trainees.

OBJECTIVE: Self-efficacy, the internal belief that one can perform a specific task successfully, influences behavior. To promote critical appraisal of medical literature, rheumatology training programs should foster both competence and self-efficacy for critical appraisal. This study aimed to investigate whether select items from the Clinical Research Appraisal Inventory (CRAI), an instrument measuring clinical research self-efficacy, could be used to measure critical appraisal self-efficacy (CASE). METHODS: One hundred twenty-five trainees from 33 rheumatology programs were sent a questionnaire that included two sections of the CRAI. Six CRAI items relevant to CASE were identified a priori; responses generated a CASE score (total score range 0-10; higher = greater confidence in one's ability to perform a specific task successfully). CASE scores' internal structure and relation to domain-concordant variables were analyzed. RESULTS: Questionnaires were completed by 112 of 125 (89.6%) trainees. CASE scores ranged from 0.5 to 8.2. The six CRAI items contributing to the CASE score demonstrated high internal consistency (Cronbach's α = 0.95) and unidimensionality. Criterion validity was supported by the findings that participants with higher CASE scores rated their epidemiology and biostatistics understanding higher than that of peers (P < 0.0001) and were more likely to report referring to studies to answer clinical questions (odds ratio 2.47, 95% confidence interval 1.41-4.33; P = 0.002). The correlation of CASE scores with percentage of questions answered correctly was only moderate, supporting discriminant validity. CONCLUSION: The six-item CASE instrument demonstrated content validity, internal consistency, discriminative capability, and criterion validity, including correlation with self-reported behavior, supporting its potential as a useful measure of critical appraisal self-efficacy.

A Suite of Mouse Reagents for Studying Amelogenesis.

Amelogenesis, the formation of dental enamel, is driven by specialized epithelial cells called ameloblasts, which undergo successive stages of differentiation. Ameloblasts secrete enamel matrix proteins (EMPs), proteases, calcium, and phosphate ions in a stage-specific manner to form mature tooth enamel. Developmental defects in tooth enamel are common in humans, and they can greatly impact the well-being of affected individuals. Our understanding of amelogenesis and developmental pathologies is rooted in past studies using epithelial Cre driver and knockout alleles. However, the available mouse models are limited, as most do not allow targeting different ameloblast sub-populations, and constitutive loss of EMPs often results in severe phenotype in the mineral, making it difficult to interpret defect mechanisms. Herein, we report on the design and verification of a toolkit of twelve mouse alleles that include ameloblast-stage specific Cre recombinases, fluorescent reporter alleles, and conditional flox alleles for the major EMPs. We show how these models may be used for applications such as sorting of live stage specific ameloblasts, whole mount imaging, and experiments with incisor explants. The full list of new alleles is available at https://dev.facebase.org/enamelatlas/mouse-models/ .

Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral.

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.

Improving Antibiotic Stewardship for Inpatients with Reported Beta-Lactam Allergies and Limited Access to Penicillin Skin Testing.

BACKGROUND: Penicillin allergy is commonly reported, but true allergy is rare. Inpatients with reported beta-lactam allergy are often treated with alternative antibiotics. Penicillin skin testing (PST) is not universally available for inpatients. METHODS: We designed a four-phase quality improvement project aimed to increase the percentage of inpatients on medical services with reported beta-lactam allergy who safely receive beta-lactam antibiotics at two hospitals with limited access to PST. First, we updated our hospital guideline to allow for cephalosporin graded challenge without antecedent PST. Second, we educated physicians, physician assistants, and nurses about the new guideline and beta-lactam allergy classification and management. Third, we designed a pocket card to reinforce the education. Last, we used antimicrobial stewardship software to screen our daily census to identify opportunities to improve management of patients with reported beta-lactam allergies. RESULTS: We observed a 29.2% increase in the percentage of patients who received beta-lactam antibiotics (excluding carbapenems) among those with reported beta-lactam allergy, from 42.2% (470/1,115) at baseline to 54.5% (379/696), p < 0.001, during the project period. There was a decrease in the use of alternative antibiotics, no change in hospital-onset Clostridioides difficile cases, and no increase in the number of infectious disease or allergy consults. The number of graded challenges increased during the project period, without any anaphylaxis events. CONCLUSION: A multiphase quality improvement project aimed to improve management of beta-lactam allergies and access to graded challenges led to an increase in beta-lactam utilization without an increase in anaphylaxis, even with limited access to PST.

Social determinants of health influence disease activity and functional disability in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND: Social determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functional disability over the first year of treatment in pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. METHODS: In this cohort study, unadjusted and adjusted generalized linear mixed effects models analyzed the effect of community poverty and other SDH on disease activity, using the clinical Juvenile Arthritis Disease Activity Score-10, and disability, using the Child Health Assessment Questionnaire, measured at baseline, 6, and 12 months. RESULTS: One thousand six hundred eighty-four patients were identified. High community poverty (≥20% living below the federal poverty level) was associated with increased odds of functional disability (OR 1.82, 95% CI 1.28-2.60) but was not statistically significant after adjustment (aOR 1.23, 95% CI 0.81-1.86) and was not associated with increased disease activity. Non-white race/ethnicity was associated with higher disease activity (aOR 2.48, 95% CI: 1.41-4.36). Lower self-reported household income was associated with higher disease activity and persistent functional disability. Public insurance (aOR 1.56, 95% CI 1.06-2.29) and low family education (aOR 1.89, 95% CI 1.14-3.12) was associated with persistent functional disability. CONCLUSION: High community poverty level was associated with persistent functional disability in unadjusted analysis but not with persistent moderate to high disease activity. Race/ethnicity and other SDH were associated with persistent disease activity and functional disability.

Comparison of Dermatologist Ratings on Health Care-Specific and General Consumer Websites.

Many patients utilize online physician-rating websites to find new providers, review their experiences, and schedule appointments. However, many physicians express distrust of the reviews on these sites. This study sought to compare the reviews of randomly selected dermatologists on health care-specific sites (eg, Healthgrades, Zocdoc, Vitals, WebMD) vs general consumer sites (eg, Google, Yelp) to determine which type of sites more accurately reflected overall patient sentiment. Our data suggest that health care-specific websites more consistently reflect overall patient sentiment than general consumer sites. Therefore, reviews from health care-specific sites may be more beneficial than general consumer sites for physicians seeking to understand patient sentiment and improve patient experiences.