A Case Series of Potential Pediatric Cyanotoxin Exposures Associated with Harmful Algal Blooms in Northwest Ohio.

Cyanobacterial harmful algal blooms (CyanoHABs) are increasing in prevalence and severity in the Great Lakes region, as well as both globally and locally. CyanoHABs have the potential to cause adverse effects on human health due to the production of cyanotoxins from cyanobacteria. Common routes of exposure include recreational exposure (swimming, skiing, and boating), ingestion, and aerosolization of contaminated water sources. Cyanotoxins have been shown to adversely affect several major organ systems contributing to hepatotoxicity, gastrointestinal distress, and pulmonary inflammation. We present three pediatric case reports that coincided with CyanoHABs exposure with a focus on presentation of illness, diagnostic work-up, and treatment of CyanoHAB-related illnesses. Potential cyanotoxin exposure occurred while swimming in the Maumee River and Maumee Bay of Lake Erie in Ohio during the summer months with confirmed CyanoHAB activity. Primary symptoms included generalized macular rash, fever, vomiting, diarrhea, and severe respiratory distress. Significant labs included leukocytosis and elevated C-reactive protein. All patients ultimately recovered with supportive care. Symptoms following potential cyanotoxin exposure coincide with multiple disease states representing an urgent need to develop specific diagnostic tests of exposure.

New simulation software to predict postoperative corneal stiffness before laser vision correction.

PURPOSE: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kc mean ) after laser vision correction (LVC) surgery. SETTING: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy. DESIGN: Retrospective observational case series. METHODS: 529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kc mean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters. RESULTS: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kc mean were not statistically different ( P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups ( P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0. CONCLUSIONS: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required.

Development of an assessment technique for basic science retention using the NBME subject exam data.

INTRODUCTION: One of the challenges in medical education is effectively assessing basic science knowledge retention. National Board of Medical Examiners (NBME) clerkship subject exam performance is reflective of the basic science knowledge accrued during preclinical education. The aim of this study was to determine if students' retention of basic science knowledge during the clerkship years can be analyzed using a cognitive diagnostic assessment (CDA) of the NBME subject exam data. METHODS: We acquired a customized NBME item analysis report of our institution's pediatric clerkship subject exams for the period of 2017-2020 and developed a question-by-content Q-matrix by identifying skills necessary to master content. As a pilot study, students' content mastery in 12 major basic science content areas was analyzed using a CDA model called DINA (deterministic input, noisy "and" gate). RESULTS: The results allowed us to identify strong and weak basic science content areas for students in the pediatric clerkship. For example: "Reproductive systems" and "Skin and subcutaneous tissue" showed a student mastery of 83.8 ± 2.2% and 60.7 ± 3.2%, respectively. CONCLUSIONS: Our pilot study demonstrates how this new technique can be applicable in quantitatively measuring students' basic science knowledge retention during any clerkship. Combined data from all the clerkships will allow comparisons of specific content areas and identification of individual variations between different clerkships. In addition, the same technique can be used to analyze internal assessments thereby creating an opportunity for the longitudinal tracking of student performances. Detailed analyses like this can guide specific curricular changes and drive continuous quality improvement in the undergraduate medical school curriculum.

Dynamic modeling of hospitalized COVID-19 patients reveals disease state-dependent risk factors.

OBJECTIVE: The study sought to investigate the disease state-dependent risk profiles of patient demographics and medical comorbidities associated with adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. MATERIALS AND METHODS: A covariate-dependent, continuous-time hidden Markov model with 4 states (moderate, severe, discharged, and deceased) was used to model the dynamic progression of COVID-19 during the course of hospitalization. All model parameters were estimated using the electronic health records of 1362 patients from ProMedica Health System admitted between March 20, 2020 and December 29, 2020 with a positive nasopharyngeal PCR test for SARS-CoV-2. Demographic characteristics, comorbidities, vital signs, and laboratory test results were retrospectively evaluated to infer a patient's clinical progression. RESULTS: The association between patient-level covariates and risk of progression was found to be disease state dependent. Specifically, while being male, being Black or having a medical comorbidity were all associated with an increased risk of progressing from the moderate disease state to the severe disease state, these same factors were associated with a decreased risk of progressing from the severe disease state to the deceased state. DISCUSSION: Recent studies have not included analyses of the temporal progression of COVID-19, making the current study a unique modeling-based approach to understand the dynamics of COVID-19 in hospitalized patients. CONCLUSION: Dynamic risk stratification models have the potential to improve clinical outcomes not only in COVID-19, but also in a myriad of other acute and chronic diseases that, to date, have largely been assessed only by static modeling techniques.

Implications of Diagnostic Drops on Scheimpflug Tomography: The Proper Order for Clinical Testing.

PURPOSE: The purpose of this article was to study the impact of instillation of 1% fluorescein and mydriatics on measurements made by Scheimpflug imaging. METHODS: This was a cross-sectional study of patients who had measurements of corneal shape (maximum keratometry and best fit sphere of anterior and posterior corneal surfaces), pachymetry (at the pupil center, corneal apex, and thinnest location), and anterior chamber parameters (depth, volume, and angle of anterior chamber and corneal volume) using the Pentacam HR before and after the instillation of fluorescein and mydriatics. Group A had baseline measurements that were repeated 1.5 hours after the instillation of 1% fluorescein and 0.8% tropicamide+ 5% phenylephrine eye drops. Group B had baseline measurements that were repeated 10 minutes after the instillation of 1% fluorescein, and group C had baseline measurements that were repeated 1.5 hours after the instillation of mydriatics. RESULTS: Overall, 131 eyes of 131 patients were studied: 87 in group A, 28 in group B, and 16 in group C. Significant differences and wide variations were noted in corneal pachymetry and anterior chamber parameters in all 3 groups. The highest magnitude and range of difference was observed in pachymetry at the pupil center (17 ± 53.5 µm) and in anterior chamber volume (26.7 ± 69.8 mm 3 ). Corneal shape measurements of anterior and posterior corneal surfaces were not significantly affected by either fluorescein or mydriatics. Pupillary dilation also affected the ability of the Pentacam to accurately trace the pupil margin in 19.5% of cases. CONCLUSIONS: For consistent and accurate measurements, it is important that Scheimpflug imaging be performed before other tests which may need the instillation of fluorescein or mydriatics.

Budget constrained machine learning for early prediction of adverse outcomes for COVID-19 patients.

The combination of machine learning (ML) and electronic health records (EHR) data may be able to improve outcomes of hospitalized COVID-19 patients through improved risk stratification and patient outcome prediction. However, in resource constrained environments the clinical utility of such data-driven predictive tools may be limited by the cost or unavailability of certain laboratory tests. We leveraged EHR data to develop an ML-based tool for predicting adverse outcomes that optimizes clinical utility under a given cost structure. We further gained insights into the decision-making process of the ML models through an explainable AI tool. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Health System in northwest Ohio and southeastern Michigan. We tested the performance of various ML approaches for predicting either increasing ventilatory support or mortality. We performed post hoc analysis to obtain optimal feature sets under various budget constraints. We demonstrate that it is possible to achieve a significant reduction in cost at the expense of a small reduction in predictive performance. For example, when predicting ventilation, it is possible to achieve a 43% reduction in cost with only a 3% reduction in performance. Similarly, when predicting mortality, it is possible to achieve a 50% reduction in cost with only a 1% reduction in performance. This study presents a quick, accurate, and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.

A Study of the Use and Outcomes From Respiratory Viral Testing at a Mid-Sized Children's Hospital.

This study was a retrospective analysis of inpatient and emergency department (ED) data on respiratory pathogen panel (RPP) testing between December 16, 2013, and December 15, 2015, at a mid-sized children's hospital. We assessed whether RPP decreases antibiotic days of therapy and length of hospital stay for pediatric patients with acute respiratory infections. In the inpatient population, patients testing positive with RPP were given fewer antibiotic days of therapy (2.99 vs 4.30 days; P = .032) and had shorter hospital stays (2.84 vs 3.80 days; P = .055) than patients testing negative. In the ED population, patients testing positive with RPP received fewer discharge prescriptions for antibiotics than patients not tested (8.8% vs 41.1%; P < .001). RPP use was more prevalent in admitted patients than in ED patients (78.9% vs 7.3%; P < .001). Our results suggest that RPP testing curbs antibiotic use and decreases length of hospital stay.

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.).

Comparison of pediatric and general emergency medicine practice patterns in infants with fever.

OBJECTIVES: To evaluate and compare the management approaches of pediatric and general emergency medicine physicians in infants presenting to the emergency department (ED) with complaint of fever. METHODS: Infants 90 days of age or younger with a chief complaint of fever were included for review. Vital signs, laboratory workup, disposition, and final diagnosis were collected. Compliance with guidelines was assessed and compared between EDs. RESULTS: Compliance with admission guidelines was not significantly different in any of the 3 age groups evaluated between the pediatric and general ED (PED and GED). Compliance with guideline recommendations for laboratory workup was not significantly different between the 2 EDs, nor was overall compliance with guideline recommendations. CONCLUSIONS: No significant variations in the management of febrile infants or compliance with published guidelines between PED and GED physicians were observed. Young infants can be safely treated for fever in the PED or GED.

Lactobacillus endocarditis with prosthetic material: a case report on non-surgical management with corresponding literature review.

Lactobacilli are rod shaped gram positive bacteria that naturally colonize the human gastrointestinal and genitourinary tracts and occasionally cause disease in humans. Lactobacillus infections are found in patients who are immunocompromized or have severe comorbidities. We report Lactobacillus endocarditis in a 17-year-old adolescent girl with cardiac prosthetic material following surgical correction for complex cyanotic congenital heart disease. Accurate identification of the organism can be delayed. Despite in vivo susceptibility to vancomycin, our patient clinically failed vancomycin therapy but ultimately responded to a six-week course of penicillin, in addition to a 4-week course of clindamycin and gentamicin. She recovered without the need for surgical intervention and has been symptom free for one year. Upon review of the literature, we found that Lactobacillus endocarditis has not been reported in a pediatric patient with complex cyanotic congenital heart disease.

Challenges in the management of infections due to carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) infections are increasing and are associated with considerable morbidity and mortality. Members of the Emerging Infections Network treating CRE encountered difficulties in obtaining laboratory results and struggled with limited treatment options. In addition, many treated patients experienced an alarming degree of drug toxicity from CRE therapies.

Higher incidence of perineal community acquired MRSA infections among toddlers.

BACKGROUND: A six-fold increase in pediatric MRSA infections, prompted us to examine the clinical profile of children with MRSA infections seen at Mercy Children's Hospital, Toledo, Ohio and to characterize the responsible strains. METHODS: Records were reviewed of pediatric patients who cultured positive for MRSA from June 1 to December 31, 2007. Strain typing by pulsed field gel electrophoresis (PFT) and DiversiLab, SCCmec typing, and PCR-based lukSF-PV gene (encodes Panton-Valentine leukocidin), arginine catabolic mobile element (ACME) and cap5 gene detection was performed. RESULTS: Chart review of 63 patients with MRSA infections revealed that 58(92%) were community acquired MRSA (CAMRSA). All CAMRSA were skin and soft tissue infections (SSTI). Twenty five (43%) patients were aged < 3 yrs, 19(33%) aged 4-12 and 14(24%) aged 13-18. Nineteen (76%) of those aged < 3 yrs had higher incidence of perineal infections compared to only 2(11%) of the 4-12 yrs and none of the 13-18 yrs of age. Infections in the extremities were more common in the older youth compared to the youngest children. Overall, there was a significant association between site of the infection and age group (Fisher's Exact p-value < 0.001). All CAMRSA were USA300 PFT, clindamycin susceptible, SCCmec type IVa and lukSF-PV gene positive. Nearly all contained ACME and about 80% were cap5 positive. Of the 58 USA300 strains by PFT, 55(95%) were also identified as USA300 via the automated repetitive sequence-based PCR method from DiversiLab. CONCLUSIONS: CAMRSA SSTI of the perineum was significantly more common among toddlers and that of the extremities in older children. The infecting strains were all USA300 PFT. Further studies are needed to identify the unique virulence and colonization characteristics of USA300 strains in these infections.

Current understanding of fever and host immunity.

PURPOSE OF REVIEW: Inherited and acquired immune system dysfunctions associated with fever are reviewed. Recent evidence of best practices in the diagnosis and treatment of fever caused by infections in children are also discussed. RECENT FINDINGS: Descriptive studies on clinical presentation of periodic fever and outcomes associated with and without interventions are discussed. Diagnostic evaluation and therapy of fever and neutropenia in cancer patients and challenges associated with the diagnosis of Kawasaki disease are also included. New evidence on the treatment of urinary tract infection in the neonate, and clinical evaluation tools for febrile infants, are reviewed. SUMMARY: Immune-dysfunction as a cause of fever is not well understood. In order to target therapy appropriately, more studies are needed to understand the pathogenesis of fever in this population. Better diagnostic methods are available for detection of viruses, especially in patients with fever and neutropenia, but further investigation is required for the interpretation of those results.

2009 pandemic influenza: a review.

PURPOSE OF REVIEW: A review of influenza is particularly relevant this year due to the ongoing novel H1N1 influenza pandemic. RECENT FINDINGS: Surveillance and clinical data including risk factors for infection and complications due to the current H1N1 pandemic are reviewed. New evidence on the safety of antiviral agents in children and studies on interventions to reduce community transmission of influenza are included. Influenza vaccine efficacy and improving immunization coverage have also been addressed by recent studies. SUMMARY: These studies from the early phase of the pandemic identify the population that are at high risk for complications, and affirm that active surveillance and prevention are important aspects of a public health response. Appropriate use of antiviral agents and improving influenza immunization coverage for all ages continue to be a challenge. Further studies are underway to improve the public health response, and the pandemic H1N1 strain is being incorporated into the 2010 seasonal influenza vaccine.

Fever.

PURPOSE OF REVIEW: The present review presents novel infections and better evidence on current practices related to fever in children. RECENT FINDINGS: Studies using more accurate diagnostic methods have provided evidence for prevalence of certain diseases, their clinical presentation and anticipated complications. Answers to certain clinical dilemmas related to febrile children in a pediatric office practice have been addressed recently. Some studies have explored current issues like immunization of pregnant women with influenza vaccine and the outbreak investigation of the swine H1N1 influenza. SUMMARY: Fever still remains the most common reason for visits to the pediatrician or emergency room. Better diagnostic methods; appropriate therapeutic or preventive strategies; and continued surveillance for novel infections have improved outcomes from both an individual and public health perspective.

Fever.

PURPOSE OF REVIEW: A comprehensive review of the current advances in the field of fever in children is presented. RECENT FINDINGS: Clinical and diagnostic predictors of serious disease in a child with fever are still being explored for early diagnosis so that therapy could be appropriately targeted. Host susceptibility and immune response are making strides in the understanding of disease pathogenesis and in identifying the causes of fever. Measurement of fever as a screening tool, a review of the efficacy of antipyretics alone or in combination, and finally a global perspective of fever have been discussed through a review of some of the publications in the past 18 months. SUMMARY: Better markers are required to predict serious bacterial infection in a child with fever. Clinical application of the host immune response in the diagnosis and management of fever is the direction of the future.