bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a Bayesian Individualization of Cyclosporine Dosage Regimen for Children Undergoing Allogeneic Hematopoietic Cell Transplantation: A Cost-Effectiveness Analysis
Authors: Beyron C. , Ceraulo A. , Bertrand Y. , Bleyzac N. , Philippe M. 
Published: April 2021

Background:
Cyclosporine A (CsA) is the main drug used to prevent graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). CsA therapeutic drug monitoring (TDM) has been performed for ages, with studies revealing clinical benefits, but failing to examine its economic impact. In this article, the main objective was to evaluate the economic impact of the CsA TDM strategy, based on a Bayesian approach, by assessing costs related to its clinical impact. Furthermore, TDM effectiveness was analyzed for pharmacokinetics and clinical outcomes.

Methods:
A cost-effective, nonrandomized, retrospective, single-center study compared 2 CsA monitoring and dose adaptation strategies in pediatric patients undergoing HSCT. From 2014 to 2016, CsA TDM was performed using a population pharmacokinetics model-coupled Bayesian approach by a pharmacist [“pharmacist-assisted individualization” (PAI)]. From 2017 to 2018, CsA TDM was performed by the clinician without a Bayesian approach (non-PAI group). HSCT costs were evaluated from the French National Insurance perspective. Economic and clinical outcomes were assessed by measuring incremental cost-effectiveness ratios.

Results:
The study included 144 patients: 90 and 54 patients in PAI and non-PAI groups, respectively. Both groups were comparable for sociodemographic and clinical characteristics. The mean total cost per patient was significantly lower (P < 0.01) in the PAI group (€85,947) than in the non-PAI group (€100,435). Multivariate analysis revealed that TDM based on the Bayesian approach was a protective factor (odds ratio = 0.86) for severe acute graft-versus-host disease. We noted that pharmacist-based TDM was the dominant strategy. Bayesian method–based TDM allowed an increase in the percentage of target attainment at any period post-HSCT.

Conclusions:
CsA TDM with a Bayesian approach is a cost-effective procedure, and highlighted clinical benefits encourage the development of new TDM strategies for HSCT.
CAUSES AND CLINICAL MANIFESTATIONS OF MASQUERADE SYNDROMES IN INTRAOCULAR INFLAMMATORY DISEASES
Authors: Rothova Aniki , Groen Fahriye , ten Berge Josianne C. E. M. , Lubbers Susanne M. , Vingerling Johannes R. , Thiadens Alberta A. H. J. 
Published: April 2021

Objective:
To identify the clinical characteristics and prevalence of neoplastic and nonneoplastic inflammatory masquerade syndromes (IMSs) in a tertiary center and determine the useful diagnostic tests.

Methods:
A retrospective cohort study of consecutive 1906 patients diagnosed with intraocular inflammatory disease.

Results:
Of all patients initially diagnosed with intraocular inflammatory disease, we identified 116 (6%) patients with noninflammatory causes (neoplastic IMSs in 36/116; 31% and nonneoplastic IMSs in 52/116; 45%). In addition, 26 patients (22%, 1.4% of all) had drug-induced uveitis and 2 (2%, 0.1% of all) had paraneoplastic uveitis. The large B-cell lymphoma was the most common neoplastic IMS (78%), and the major clinical features were presence of cells and floaters in the vitreous (69%) and chorioretinal lesions (33%). The causes of nonneoplastic IMSs included retinal vascular disorders (38%), hereditary retinal diseases (31%), and degenerative ocular disorders (19%). The common clinical manifestations consisted of chorioretinal scars (27%), small white–yellow retinal lesions (17%), and leaking vessels on fluorescein angiography (14%).

Conclusion:
Noninflammatory causes were determined in 6% of a large population with initial diagnosis of intraocular inflammatory disease. Although neoplastic IMS was commonly characterized by vitreous cells and opacities, most common definitive diagnoses in nonneoplastic IMS encompassed diverse retinal disorders.
Agreement of Anterior Segment Parameters Between Schiempflug Topography and Swept-Source Optic Coherence Based Optic Biometry in Keratoconus and Healthy Subjects
Authors: Güçlü Hande , Akaray İrfan , Kaya Sultan , Sattarpanah Samira , Çınar Abdülkadir Can , Sakallıoğlu Kürşad , Korkmaz Selçuk , Gürlü Vuslat 
Published: April 2021

Purpose:
The aim of this study is to compare anterior segment parameters, including corneal thickness (CCT), keratometry and anterior chamber depth (ACD), and white to white corneal diameter (WTW), obtained by Pentacam Schiempflug imaging and intraocular lens (IOL) Master 700 swept-source optic coherence tomography biometry in keratoconus patients and healthy subjects.

Methods:
This prospective cross-sectional instrument agreement analysis includes 88 eyes of 50 keratoconus patients and 87 eyes of 50 healthy subjects. Biometry was performed using IOL Master 700, and topography was performed using Pentacam. The keratometry values (Kf, Ks, Km, and Kmax), ACD, WTW, CCT, axial length (AL), anterior chamber angle (ACA), and lens thickness (LT) were evaluated. Levels of agreement between devices were evaluated by Bland–Altman plots with 95% limits of agreement.

Results:
Intraocular lens Master 700 showed higher WTW, ACD, pupil diameter, and CCT values than Pentacam in both the keratoconus and control groups. However, there were no statistically significant differences in flat keratometry (Kf) and steep keratometry (Ks) values between the groups.

Conclusion:
Pentacam and IOL Master 700 may be used interchangeably in normal eyes and keratoconus eyes for the measurement of keratometry values and axis; however, these two devices should not be considered interchangeable for WTW, ACD, pupil diameter, and CCT measurements in both keratoconus patients and healthy subjects.
Effects of Dose, Age, Sex, Body Weight, and Smoking on Plasma Concentrations of Olanzapine and N-desmethyl Olanzapine in Inpatients With Schizophrenia
Authors: An Huimei , Fan Hongzhen , Chen Song , Qi Siyuan , Ma Botao , Shi Jing , Wang Zhiren , Yang Fude 
Published: April 2021

Abstract

Purpose
This study aimed to investigate the combined effects of dose, age, sex, body weight, and smoking on plasma concentrations of olanzapine (OLA) and N-desmethyl olanzapine (DMO) in Chinese inpatients with schizophrenia.

Methods
A retrospective study including 185 inpatients was conducted. The steady-state plasma concentrations of OLA (COLA) and DMO (CDMO) were measured using high-performance liquid chromatography-tandem mass spectrometry. The combined effects of dose, age, sex, body weight, and smoking on COLA and CDMO were evaluated.

Findings
Multiple linear regression analyses revealed that dose, age, body weight, and smoking had significant effects on COLA and CDMO in inpatients with schizophrenia treated with OLA. The dose was the most important determinant of COLA and CDMO and was positively correlated with both. Furthermore, smokers exhibited a significantly lower COLA and COLA + DMO, whereas higher body weight led to the reduction of COLA, CDMO, and COLA + DMO. Advanced age was associated with lower CDMO.

Implications
These results suggest that dose, age, body weight, and smoking have a significant influence on the plasma concentration of OLA and its metabolite DMO. Clinicians should consider the combined effects when prescribing OLA to patients with schizophrenia.
Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome
Authors: Chen Chen X. , Carpenter Janet S. , Gao Xiang , Toh Evelyn , Dong Qunfeng , Nelson David E. , Mitchell Caroline , Fortenberry J. Dennis 
Published: April 2021

Background
Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms.

Objectives
The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses.

Methods
We conducted a prospective, longitudinal, pilot study of 20 women (aged 15–24 years) grouped into three dysmenorrhea symptom-based phenotypes: “mild localized pain,” “severe localized pain,” and “severe multiple pain and gastrointestinal symptoms.” Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa.

Results
The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the “mild localized pain” phenotype, participants in the “multiple severe symptoms” phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses.

Discussion
The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women’s quality of life.
Ocular Point-of-Care Ultrasound
Authors: Shah Rahul , Rychwalski Paul , Kurzweil Ami , Tory Heather , Chicaiza Henry 
Published: April 2021

Abstract
Ocular point-of-care ultrasound has been used to assess for intraocular pathology, including retinal and vitreous detachment. We describe a pediatric patient whose initial point-of-care ultrasound examination appeared to be consistent with bilateral posterior vitreous detachment but who was ultimately diagnosed with intermediate uveitis.
Development of a Parent-Reported Outcome Measure for Febrile Infants ≤60 Days Old
Authors: Aronson Paul L. , Fleischer Eduardo , Schaeffer Paula , Fraenkel Liana , Politi Mary C. , White Marney A. 
Published: April 2021

Objective
We aimed to develop a parent-reported outcome measure for febrile infants 60 days or younger evaluated in the emergency department.

Methods
We conducted a 3-part study: (1) individual, semistructured interviews with parents of febrile infants 60 days or younger to generate potential items for the measure; (2) expert review with pediatric emergency medicine physicians and member checking with parents, who rated each item's clarity and relevance using 4-point scales; and (3) cognitive interviews with a new sample of parents, who gave feedback and rated the measure's ease of use on a 4-point scale. The measure was iteratively revised during each part of the development process.

Results
In part 1, we interviewed 24 parents of 21 infants. Interviews revealed several themes: parents' experiences with medical care, communication, and decision making; parents' emotions, particularly worry, fear, and stress; the infant's outcomes valued by parents; and the impact of the infant's illness on the family. From these themes, we identified 22 potential items for inclusion in the measure. In part 2, 10 items were revised for clarity based on feedback from physicians and parents, primarily under the domains of parents' emotions and the infant's outcomes. In part 3, we further revised the measure for clarity and added an item. The final measure included 23 items and was rated as excellent in its ease of use.

Conclusions
The 23-item parent-reported outcome measure includes the experiences and outcomes important to parents. Further studies are needed to evaluate the measure's psychometric properties.
Agitation and Restraint in a Pediatric Psychiatric Emergency Program
Authors: Agraharkar Shilpa , Horwitz Sarah , Lewis Kristen , Goldstein Gabriella , Havens Jennifer , Gerson Ruth 
Published: April 2021

Objectives
Agitation and restraint among pediatric psychiatric patients are a frequent, yet little studied, source of morbidity and, rarely, mortality in the emergency department (ED). This study examined agitation and restraint among youth patients in a specialized pediatric psychiatric ED, considering clinical and sociodemographic characteristics of those who required restraint to determine the clinical correlates of agitation and restraint in this population.

Methods
This descriptive study was a 6-year retrospective chart review of all patients restrained for acute agitation. Demographics, clinical characteristics, diagnoses, and reasons for restraint were collected. Relationships between sociodemographic and clinical variables to types of restraints used were examined, along with change over the study period in rate of and mean time in restraint.

Results
The average restraint rate was 1.94%, which remained fairly consistent throughout study period, although average time in restraint decreased significantly. Restraints were more common in males. Adolescents were overrepresented in the ED population, and after controlling for this, restraint rates were similar in adolescents and younger children. Physical aggression was the most frequent precipitant, although among adolescents verbal aggression was also a precipitant (more so than in younger children). Disruptive behavior disorder diagnoses were most frequently associated with restraint.

Conclusions
A lower rate of restraint is reported here than has been seen in programs where youths are treated in medical or adult psychiatric EDs. Hospitals without specialized pediatric psychiatric emergency programs should invest in staff training in deescalation techniques and in access to pediatric psychiatric treatment. The finding that, of youth restrained, a significant proportion were under 12 years old and/or carried diagnoses not typically associated with aggressive behavior, indicates that crisis prevention, management, and treatment should include younger populations and diverse diagnostic groups, rather than focusing narrowly on older patients with psychotic or substance use disorders.
Physician Risk Perception and Testing Behaviors for Children With Fever
Authors: Marchese Ashley L. , Fine Andrew M. , Levy Jason A. , Monuteaux Michael C. , Michelson Kenneth A. 
Published: April 2021

Objectives
Risk tolerance and risk perceptions may impact clinicians' decisions to obtain diagnostic tests. We sought to determine whether physician risk perception was associated with the decision to obtain blood or imaging tests among children who present to the emergency department with fever.

Methods
We conducted a retrospective, cross-sectional study in the Boston Children's Hospital emergency department. We included children aged 6 months to 18 years from May 1, 2014 to April 30, 2019, with fever. Our primary outcome was diagnostic testing: obtaining a blood and/or imaging test. We assessed risk perception using 3 scales: the Risk Tolerance Scale (RTS), Stress From Uncertainty Scale (SUS), and Malpractice Fear Scale (MFS). A z score was assigned to each physician for each scale. Mixed-effects logistic regression assessed the association between physician risk perception and blood or imaging testing. We also examined the relationship between each risk perception scale and several secondary outcomes: blood testing, urine testing, diagnostic imaging, specialist consultation, hospitalization, and revisit within 72 hours.

Results
The response rate was 55/56 (98%). We analyzed 12,527 encounters. Blood/imaging testing varied between physicians (median, 48%; interquartile range, 41%–53%; range, 30%–71%). Risk Tolerance Scale responses were not associated with blood/imaging testing (odds ratio [OR], 1.03 per SD of increased risk perception; 95% confidence interval [CI], 0.95–1.13). Stress From Uncertainty Scale responses were not associated with blood/imaging testing (OR, 1.04 per SD; 95% CI, 0.95–1.14). Malpractice Fear Scale responses were not associated with blood/imaging testing (OR, 1.00 per SD; 95% CI, 0.91–1.09). There was no significant association between RTS, MFS, or SUS and any secondary outcome, except that there was a weak association between SUS and specialist consultation (OR, 1.12; 95% CI, 1.00–1.24).

Conclusions
Across 55 pediatric emergency physicians with variable testing practices, there was no association between risk perception and blood/imaging testing in febrile children.
Point-of-Care Ultrasound on Management of Cellulitis Versus Local Angioedema in the Pediatric Emergency Department
Authors: Tay Ee Tein , Ngai Ka Ming , Tsung James W. , Sanders Jennifer E. 
Published: April 2021

Objectives
To evaluate whether ultrasound can differentiate between cellulitis and angioedema from insect bites in pediatric patients.

Methods
A prospective, pre-post study in an urban pediatric emergency department of patients younger than 21 years with soft tissue swelling from insect bites without abscesses were enrolled. Treating physician's pretest opinions regarding the diagnosis and need for antibiotics were determined. Ultrasound of the affected areas was performed, and effects on management were recorded. Further imaging, medications, and disposition were at the discretion of the enrolling physician. Phone call follow-ups were made within a week of presentation.

Results
Among 103 patients enrolled with soft tissue swelling secondary to insect bites, ultrasound changed the management in 27 (26%) patients (95% confidence interval [CI], 18–35%). Of the patients who were indeterminate or believed to require antibiotics, ultrasound changed management in 6 (23%) of 26 patients (95% CI, 6%–40%). In those patients who were believed not to require antibiotics, ultrasound changed management in 12 (16%) 77 patients (95% CI, 7%–24%). Patients with diagnosis of local angioedema achieved symptom resolution 1.4 days sooner than patients diagnosed with cellulitis (mean, −1.389; 95% CI, −2.087 to −0.690; P < 0.001). No patient who was initially diagnosed as local angioedema received antibiotics upon patient follow-up.

Conclusions
Point-of-care ultrasound changed physician management in 1 of 4 patients in the pediatric emergency department with soft tissue swelling secondary to insect bites. Ultrasound may guide the management in these patients and lead to improved antibiotic stewardship in conjunction with history and physical examination.
Maternal Confidence and Emergency Department Utilization Among Infants
Authors: Giusto Jina , Anton Megan , Gaiazov Sabrina , Huddleston Kathi , Levy Shira , Fuller Alma , Hourigan Suchitra , Niederhuber John , Hwang Vivian 
Published: April 2021

Objectives
To determine if maternal confidence affects emergency department (ED) utilization in the first year of life.

Methods
This retrospective cohort study examined the Maternal Confidence Questionnaire responses from a longitudinal birth cohort study and ED visits for these subjects across all Inova hospitals from January 2012 to July 2017 for full-term children 12 months or younger at the time of visit. Using logistic regression, maternal confidence, maternal race/ethnicity, age, education, parity, and insurance were evaluated against Emergency Severity Index acuity levels and ED visit frequency.

Results
Of 2429 participants in the longitudinal study, 316 subjects visited the ED and met inclusion criteria. Medicaid status was the main factor associated with any ED visit. Low maternal confidence did not correlate with more frequent or nonurgent ED visits. Higher maternal confidence scores were seen in Hispanic or Latino mothers and mothers with parity greater than 1. Hispanic or Latino mothers were more likely to have Medicaid and more likely to bring their child to the ED. Mothers with college education had lower maternal confidence scores, were less likely to visit the ED, but had higher acuity level visits.

Conclusions
Low maternal confidence did not correlate with frequent ED visits or nonurgent visits. Medicaid status was the main factor associated with any ED visit. Hispanic or Latino mothers had higher maternal confidence scores, were more likely to have Medicaid and more likely to bring their child to the ED.
Growth Faltering and Developmental Delay in HIV-Exposed Uninfected Ugandan Infants: A Prospective Cohort Study
Authors: Sirajee Reshma , Conroy Andrea L. , Namasopo Sophie , Opoka Robert O. , Lavoie Stephanie , Forgie Sarah , Salami Bukola O. , Hawkes Michael T. 
Published: April 2021

Background:HIV-exposed but uninfected (HEU) infants are at increased risk of impaired early linear growth and cognitive development. We examined associations between prenatal and postnatal growth and subsequent neurodevelopment in Ugandan HEU infants, hypothesizing that early insults may explain alterations in both somatic growth and brain development.Methods:We prospectively followed a cohort of HEU infants from birth to 18 months of age, and measured length/height, weight, head, and arm circumference longitudinally. The Malawi Development Assessment Tool (MDAT, 12 and 18 months) and the Color Object Association Test (18 months) were used for developmental assessments.Results:Among 170 HEU infants, the prevalence of low-birth weight and failure to thrive was 7.6% and 37%, respectively. HEU infants had MDAT scores that were similar to the reference population. The mean (SD) score on the Color Object Association Test was 5.5 (3.1) compared with 6.9 (5.3) in developmentally normal children. Developmental ability at age 18 months showed strong cross-sectional correlation with weight-for-age (ρ = 0.36,P< 0.0001), length/height-for-age (ρ = 0.41,P< 0.0001), head circumference-for-age (ρ = 0.26,P= 0.0011), and mid-upper arm circumference-for-age (ρ = 0.34,P= 0.0014). There was a statistically significant correlation between birth weight and MDAT z-score at 18 months (ρ = 0.20,P= 0.010). Failure to thrive was associated with lower MDAT z-score [median −0.13 (IQR −0.75 to +0.14) versus +0.14 (IQR −0.44 to +0.63),P= 0.042].Conclusion:Growth faltering in HEU infants was associated with lower attainment of developmental milestones at age 18 months. Our findings point to a simple screening method for identifying HEU infants at risk for developmental intervention.