Identifying Region-Specific Allergy Sensitization Clusters to Optimize Diagnosis and Reduce Costs.

OBJECTIVE: To delineate quantitatively the allergen sensitization patterns in a large pediatric cohort and inform the selection of a region-specific panel of allergen tests for timely and cost-effective in vitro atopy screening. STUDY DESIGN: IgE levels for specific allergens from patients in the Texas Children's Health System were analyzed retrospectively. Statistical and network analyses were conducted to reveal sensitization patterns. RESULTS: Network analysis of 114 distinct allergens among 12 065 patients identified 2 main groups of allergens: environmental and food. Approximately 67.5% of patients were sensitized to environmental allergens, 47.2% to food allergens, and 7.3% to at least 1 allergen from both groups. We identified a novel panel of 13 allergens that could detect sensitization in 95% of patients, whereas panels of 7 allergens within each category effectively identified sensitization in 95% of patients with specific sensitivities. This data-driven approach is estimated to reduce overall testing costs by 52%. In agreement with literature, we observed correlations among allergens within specific categories, such as pollen, shellfish, nuts, and dairy allergens. CONCLUSIONS: This study provides insights into allergen sensitization patterns informing an algorithmic testing approach tailored for primary care settings. The use of a region and population-specific test panel can efficiently identify atopy, leading to more targeted testing. This strategy has the potential to refine laboratory testing, reduce costs, and improve the appropriateness of referrals to allergy specialists, ultimately enhancing diagnostic accuracy and resource allocation.

Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study.

INTRODUCTION: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret-He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort. METHODS: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret-He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret-He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret-He in ID, IDA, and anemia without ID groups. RESULTS: Ret-He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret-He was significantly lower in ID. A Ret-He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret-He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively. CONCLUSION: Our large pediatric tertiary care hospital study demonstrates that Ret-He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID.

Factors Associated With Severe Illness in Patients Aged <21 Years Hospitalized for COVID-19.

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

A Daily Operational Huddle and a Real-Time Communication Application Improve Efficiency of Laboratory Processes.

CONTEXT.­: Clinical laboratory processes that require cooperation among geographically distinct sections often face challenges. We describe these challenges as related to the Gram staining of cerebrospinal fluid, a key test in the management of patients with suspected central nervous system infections, and our attempts to improve quality outcomes. OBJECTIVE.­: To evaluate multiple tools and strategies for their effectiveness in optimizing the turnaround time of tests sharing a specimen or workflow. DESIGN.­: Over the course of 5 years, the turnaround time of cerebrospinal fluid Gram stain was studied at one of the largest children's health systems in the United States. Baseline data showed suboptimal compliance to targeted turnaround times. A conventional approach to process standardization and 2 innovative tools that facilitate horizontal integration were applied to the main campus laboratory as follows: a daily operational huddle and a novel electronic communication application that was interfaced with the laboratory information system. Turnaround time and its variation were assessed. Two other hospital laboratories within the health system that did not undergo these quality interventions served as controls. RESULTS.­: Standardization of processes reduced the variability of turnaround time but only minimally shortened it. In contrast, an interteam daily huddle that monitored key quality metrics together with the communication application improved turnaround time significantly and sustainably. CONCLUSIONS.­: Communication strategies involving a physical or virtual gathering of laboratory representatives encourage horizontal communication and improve turnaround times. These tools are generally applicable and could be used to improve other processes in healthcare, especially those where a workflow is shared between 2 geographically distinct areas of a health system.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Changes in Test Volumes During Coronavirus Disease 2019 (COVID-19): A Laboratory Stewardship Opportunity.

CONTEXT.­: Coronavirus disease 2019 (COVID-19) changed the dynamics of health care delivery, shifting patient priorities and deferring care perceived as less urgent. Delayed or eliminated care may place patients at risk for adverse outcomes. OBJECTIVE.­: To identify opportunities for laboratory test stewardship to close potential gaps in care created by the COVID-19 pandemic. DESIGN.­: The study was a retrospective time series design examining laboratory services received before and during the COVID-19 pandemic at a large metropolitan health system serving women and children. RESULTS.­: Laboratory test volumes displayed 3 distinct patterns: (1) a decrease during state lockdown, followed by near-complete or complete recovery; (2) no change; and (3) a persistent decrease. Tests that diagnose or monitor chronic illness recovered only partially. For example, hemoglobin A1c initially declined 80% (from 2232 for April 2019 to 452 for April 2020), and there was a sustained 16% drop (28-day daily average 117 at August 30, 2019, to 98 at August 30, 2020) 4 months later. Blood lead dropped 39% (from 2158 for April 2019 to 1314 for April 2020) and remained 23% lower after 4 months. CONCLUSIONS.­: The pandemic has taken a toll on patients, practitioners, and health systems. Laboratory professionals have access to data that can provide insight into clinical practice and identify pandemic-related gaps in care. During the pandemic, the biggest patient threat is underuse, particularly among tests to manage chronic diseases and for traditionally underserved communities and people of color. A laboratory stewardship program, focused on peri-pandemic care, positions pathologists and other laboratory professionals as health care leaders with a commitment to appropriate, equitable, and efficient care.

Revisiting sweat chloride test results based on recent guidelines for diagnosis of cystic fibrosis.

OBJECTIVES: Recent sweat chloride guidelines published by the Cystic Fibrosis Foundation changed the intermediate sweat chloride concentration range from 40-59 mmol/L to 30-59 mmol/L for age > 6 months. We wanted to know how this new guideline would impact detection of cystic fibrosis among patients who previously had sweat tests done at Texas Children's Hospital. METHODS: We revisited sweat chloride test results (n = 3012) in the last 5 years at Texas Children's Hospital based on the new guidelines on diagnosis of cystic fibrosis from the Cystic Fibrosis Foundation. RESULTS: We identified 125 patients that would be reclassified in the intermediate sweat chloride value with the new guidelines that were classified as "unlikely to have CF" in the previous guidelines. 8 (32%) patients with CFTR gene testing were positive for CFTR gene mutation(s). 4 (50%) of these patients were identified to have 2 CFTR mutations. One had variant combination that was reported to cause CF but all were diagnosed with CFTR-related metabolic syndrome. CONCLUSION: Our findings concur with the new CF diagnosis guidelines that changing the intermediate cut-off to 30-59 mmol/L sweat chloride concentration in combination with CFTR genetic analysis enhances the probability of identifying individuals that have risk of developing CF or have CF and enables for earlier therapeutic intervention.

Performance of a parallel diagnostic algorithm for HIV diagnosis in low risk pediatric and obstetric patient populations.

BACKGROUND: Little is known about the clinical performance of the 2010 APHL/CDC Western-blot independent HIV testing algorithm in low risk pediatric and obstetric patients. OBJECTIVE: To evaluate the performance of an alternate Western-blot independent algorithm and the individual algorithm components in diagnosing HIV infections in low risk pediatric and obstetric patients. STUDY DESIGN: 6242 specimens from pediatric and obstetric patients were tested by the Bio-Rad Multispot HIV-1/HIV-2 (MS) and VITROS Anti HIV 1+2 (VITROS) assays. 913 specimens were also tested by the ARCHITECT HIV Ag/Ab Combo assay (ARCHITECT). Discordant specimens were tested by the APTIMA HIV-1 RNA qualitative assay (RNA Qual). RESULTS: Twenty-eight specimens tested positive for HIV-1 by both MS and VITROS, 4 of these 28 specimens were also tested by and positive by ARCHITECT; all 28 positives identified by the algorithm were positive by viral load analysis. MS identified 164 preliminary positives, which were not confirmed as true positives, representing a specificity of 97.4%. This specificity varied between patient populations (96.1% in the pediatric population and 99.1% in the obstetric population). The specificities of VITROS and ARCHITECT were 99.2% and 99.4% for pediatric patients; 99.7% and 99.8% for obstetric patients, respectively. CONCLUSION: Our results highlight suboptimal specificity of MS in pediatric patients, and a lower specificity in both pediatric and obstetric patients relative to either VITROS or ARCHITECT. Additionally, parallel testing with both a third and fourth generation EIA in a low risk patient population provides a potential alternative to Western-blot dependent algorithms for confirmation.

Implementation of a quality improvement program to improve sweat test performance in a pediatric hospital.

CONTEXT: All positive screening of newborns for cystic fibrosis using the dried blood spot 2-tiered immunoreactive trypsinogen/DNA method requires subsequent sweat chloride testing for confirmation. Obtaining an adequate volume of sweat to measure chloride is a challenge for many cystic fibrosis centers across the nation. The standard for patients older than 3 months is less than 5% quantity not sufficient (QNS) and for patients 3 months or younger is less than 10% QNS. OBJECTIVE: To set up a quality improvement (QI) program for sweat testing to improve QNS rates using the Wescor Macroduct (Wescor, Inc, Logan, Utah) method at Texas Children's Hospital's laboratory, Houston, Texas. DESIGN: Single-center study. RESULTS: Quantity not sufficient rates were evaluated for 4 months before and 8 months after implementation of the QI program for patients aged 3 months or younger and those older than 3 months. The QI program included changes in technician training, service, site of collection, mode of collection, weekly review, and forms to screen patients for medications that may alter sweat production. A marked improvement was observed in the rates of QNS, which declined considerably from 16.7% to 8.5% (≤3 months old) and from 9.3% to 2.2% (>3 months old) after implementation of the QI initiative in both age categories. CONCLUSION: This report demonstrates the effectiveness of the QI program in significantly improving QNS rates in sweat chloride testing in a pediatric hospital.

Performance characteristics of urinalyses for the diagnosis of pediatric urinary tract infection.

PURPOSE: The purpose of this study is to determine whether point-of-care (POCT) urinalysis (UA) is as accurate as laboratory-performed UA in diagnosing urinary tract infections (UTIs) in the pediatric emergency department (PED). BASIC PROCEDURES: This was a retrospective series of children (0-18 years old) seen at a tertiary care PED from July 2008 to December 2012 in whom UA and urine culture were obtained. Urinalyses were considered positive if leukocyte esterase and/or nitrites were positive. Performance characteristics for the 2 types of UAs were calculated using urine culture as the reference standard. MAIN FINDINGS: A total of 43452 specimens were sent for laboratory-performed UA and culture, and 6492, for POCT UA and culture (in 2908 specimens, both UAs were performed). Sixty-four percent of specimens were from girls, 51% were catheterized, and 7.5% had UTIs. The sensitivity of POCT UAs and laboratory-performed UAs was 82.5% (confidence interval [CI], 79.4%-85.3%) and 89.1% (CI, 86.4%-88.8%), respectively. The superior performance of laboratory-performed UAs was driven by the sensitivity of microscopy. Laboratory-performed UAs were more sensitive than the POCT in girls (90.6% [CI, 89.4%-91.8%] vs 82.8% [79.4%-85.8%]). PRINCIPAL CONCLUSIONS: Although POCT UAs offer more rapid turnaround times, the sensitivity is greater for laboratory-performed UAs. Given the difficulty in following up PED patients after discharge as well as the potential morbidity from untreated UTIs, the rapidity of the POCT UA must be balanced against the lower sensitivity of this assay. The benefit of more accurate diagnosis may outweigh the potentially longer PED length of stay associated with a laboratory-performed UA.