Clostridioides difficile Infection in Hospitalized Pediatric Patients: Comparisons of Epidemiology, Testing, and Treatment from 2013 to 2019.

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019. STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment. RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P < .001). C difficile-specific testing also decreased during the study period (P < .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P < .01) and oral vancomycin use increased (P < .001). CONCLUSIONS: Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment.

Indirect Standardization as a Case Mix Adjustment Method to Improve Comparison of Children's Hospitals' Antimicrobial Use.

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z-scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552-679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93-1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19-0.64; P = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions.

Impact of institutional routine surveillance endomyocardial biopsy frequency in the first year on rejection and graft survival in pediatric heart transplantation.

BACKGROUND: Routine surveillance biopsy (RSB) is performed to detect asymptomatic acute rejection (AR) after heart transplantation (HT). Variation in pediatric RSB across institutions is high. We examined center-based variation in RSB and its relationship to graft loss, AR, coronary artery vasculopathy (CAV), and cost of care during the first year post-HT. METHODS: We linked the Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR, 2002-2016), including all primary-HT aged 0-21 years. We characterized centers by RSB frequency (defined as median biopsies performed among recipients aged ≥12 months without rejection in the first year). We adjusted for potential confounders and center effects with mixed-effects regression analysis. RESULTS: We analyzed 2867 patients at 29 centers. After adjusting for patient and center differences, increasing RSB frequency was associated with diagnosed AR (OR 1.15 p = 0.004), a trend toward treated AR (OR 1.09 p = 0.083), and higher hospital-based cost (US$390 315 vs. $313 248, p < 0.001) but no difference in graft survival (HR 1.00, p = 0.970) or CAV (SHR 1.04, p = 0.757) over median follow-up 3.9 years. Center RSB-frequency threshold of ≥2/year was associated with increased unadjusted rates of treated AR, but no association was found at thresholds greater than this. CONCLUSION: Center RSB frequency is positively associated with increased diagnosis of AR at 1 year post-HT. Graft survival and CAV appear similar at medium-term follow-up. We speculate that higher frequency RSB centers may have increased detection of clinically less important AR, though further study of the relationship between center RSB frequency and differences in treated AR is necessary.

The impact of psychiatric disorders on outcomes following heart transplantation in children.

Psychiatric disorders are common in pediatric HTx recipients. However, the impact of psychiatric comorbidities on patient outcomes is unknown. We aimed to assess the impact of disorders of adjustment, depression, and anxiety on HTx outcomes in children; hypothesizing that the presence of psychiatric disorders during or preceding HTx would negatively impact outcomes. All pediatric HTx recipients ≥8 years of age who survived to hospital discharge were identified from a novel linkage between the PHIS and SRTR databases (2002-2016). Psychiatric disorders were identified using ICD codes during or preceding the HTx admission. Post-transplant graft survival, freedom from readmission, and freedom from rejection were analyzed using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to adjust for covariates. A total of 1192 patients were included, of which 133 (11.2%) had depression, 197 (16.5%) had anxiety, and 218 (18.3%) had adjustment disorders. The presence of depression was independently associated with higher rates of readmission (60.9% vs 54.1% at 6 months) (AHR 1.63, 95% CI 1.22-2.18, P = .001) and inferior graft survival (70.2% vs 83.4% at 5 years) (AHR 1.62, 95% CI 1.14-2.3, P = .007). Anxiety was independently associated with higher rates of readmission (60.4% vs 53.9% at 6 months) (AHR 1.46, 95% CI 1.09-1.94, P = .01). Anxiety and depression in the pretransplant period are independently associated with outcomes following HTx in children. Evaluation and management of psychiatric comorbidities represents an important component of care in this vulnerable population.

Interhospital Variability in Perioperative Red Blood Cell Ordering Patterns in United States Pediatric Surgical Patients.

OBJECTIVE: To evaluate perioperative red blood cell (RBC) ordering and interhospital variability patterns in pediatric patients undergoing surgical interventions at US children's hospitals. STUDY DESIGN: This is a multicenter cross-sectional study of children aged <19 years admitted to 38 pediatric tertiary care hospitals participating in the Pediatric Health Information System in 2009-2014. Only cases performed at all represented hospitals were included in the study, to limit case mix variability. Orders for blood type and crossmatch were included when done on the day before or the day of the surgical procedure. The RBC transfusions included were those given on the day of or the day after surgery. The type and crossmatch-to-transfusion ratio (TCTR) was calculated for each surgical procedure. An adjusted model for interhospital variability was created to account for variation in patient population by age, sex, race/ethnicity, payer type, and presence/number of complex chronic conditions (CCCs) per patient. RESULTS: A total of 357 007 surgical interventions were identified across all participating hospitals. Blood type and crossmatch was performed 55 632 times, and 13 736 transfusions were provided, for a TCTR of 4:1. There was an association between increasing age and TCTR (R(2) = 0.43). Patients with multiple CCCs had lower TCTRs, with a stronger relationship (R(2) = 0.77). There was broad variability in adjusted TCTRs among hospitals (range, 2.5-25). CONCLUSIONS: The average TCTR in US children's hospitals was double that of adult surgical data, and was associated with wide interhospital variability. Age and the presence of CCCs markedly influenced this ratio. Studies to evaluate optimal preoperative RBC ordering and standardization of practices could potentially decrease unnecessary costs and wasted blood.

Assessing Structural Quality Elements of Pediatric Emergency Care.

BACKGROUND AND OBJECTIVE: Emergency departments must have appropriate resources and equipment available to meet the unique needs of children. We assessed the availability of stakeholder-endorsed quality structure performance measures for pediatric emergency department patients. METHODS: A survey of Child Health Corporation of America member hospitals was conducted. Six broad equipment groups were queried: general, monitoring, respiratory, vascular access, fracture-management, and specialized pediatric trays. Equipment availability was determined at the level of the individual item, 6 broad groups, and 44 equipment subgroups. The survey queried the availability of 8 protocol/procedure elements: method to identify age-based abnormal vital signs, patient-centered care advisory council, bronchiolitis evidence-based guideline, pediatric radiation dosing standards, suspected child abuse protocols, use of validated pediatric triage tool, and presence of nurse and physician pediatric coordinators. RESULTS: Fifty-two percent (22/42) of sites completed the survey. Forty-one percent reported availability of all 113 recommended equipment items. Every hospital reported complete availability of equipment in 77% of the subgroups. The most common missing items were adult-sized lumbar puncture needles, hypothermia thermometers, and various sizes of laryngeal mask airways. Regarding the protocol/procedure elements, a method to identify age-based abnormal vital signs, pediatric radiation dosing standard, and nurse and physician pediatric coordinators were present in 100%. Ninety-five percent used a validated triage tool and had suspected child abuse protocols. CONCLUSIONS: Presence of necessary pediatric emergency equipment is better in the surveyed hospitals than in prior reports. Most responding hospitals have important protocol/procedures in place. These data may provide benchmarks for optimal care.

Respiratory virus testing and clinical outcomes among children hospitalized with pneumonia.

BACKGROUND: Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain. OBJECTIVE: To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019. MAIN OUTCOMES AND MEASURES: Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing. RESULTS: There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p < .001). Molecular testing increased (27.2% to 40.0%, p < .001) and antigen testing decreased (33.2% to 7.8%, p < .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing. CONCLUSIONS: Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

The Resource Use Inflection Point for Safe NICU Discharge.

OBJECTIVES: (1) To identify a resource use inflection point (RU-IP) beyond which patients in the NICU no longer received NICU-level care, (2) to quantify variability between hospitals in patient-days beyond the RU-IP, and (3) to describe risk factors associated with reaching an RU-IP. METHODS: We evaluated infants admitted to any of the 43 NICUs over 6 years. We determined the day that each patient's total daily standardized cost was <10% of the mean first-day NICU room cost and remained within this range through discharge (RU-IP). We compared days beyond an RU-IP, the total standardized cost of hospital days beyond the RU-IP, and the percentage of patients by hospital beyond the RU-IP. RESULTS: Among 80 821 neonates, 80.6% reached an RU-IP. In total, there were 234 478 days after the RU-IP, representing 24.3% of the total NICU days and $483 281 268 in costs. Variability in the proportion of patients reaching an RU-IP was 33.1% to 98.7%. Extremely preterm and very preterm neonates, patients discharged with home health care services, or patients receiving mechanical ventilation, extracorporeal membrane oxygenation, or feeding support exhibited fewer days beyond the RU-IP. Conversely, receiving methadone was associated with increased days beyond the RU-IP. CONCLUSIONS: Identification of an RU-IP may allow health care systems to identify readiness for discharge from the NICU earlier and thereby save significant NICU days and health care dollars. These data reveal the need to identify best practices in NICUs that consistently discharge infants more efficiently. Once these best practices are known, they can be disseminated to offer guidance in creating quality improvement projects to provide safer and more predictable care across hospitals for patients of all socioeconomic statuses.

Variation in Early Inflammatory Marker Testing for Infection-Related Hospitalizations in Children.

BACKGROUND AND OBJECTIVES: Inflammatory marker testing in children has been identified as a potential area of overuse. We sought to describe variation in early inflammatory marker (C-reactive protein and erythrocyte sedimentation rate) testing for infection-related hospitalizations across children's hospitals and to determine its association with length of stay (LOS), 30-day readmission rate, and cost. METHODS: We conducted a cross-sectional study of children aged 0 to 17 years with infection-related hospitalizations using the Pediatric Health Information System. After adjusting for patient characteristics, we examined rates of inflammatory marker testing (C-reactive protein or erythrocyte sedimentation rate) during the first 2 days of hospitalization. We used k-means clustering to assign each hospital to 1 of 3 groups on the basis of similarities in adjusted diagnostic testing rates across 12 infectious conditions. Multivariable regression was used to examine the association between hospital testing group and outcomes. RESULTS: We included 55 771 hospitalizations from 48 hospitals. In 7945 (14.3%), there was inflammatory marker testing in the first 2 days of hospitalization. We observed wide variation in inflammatory marker testing rates across hospitals and infections. Group A hospitals tended to perform more tests than group B or C hospitals (37.4% vs 18.0% vs 10.4%; P < .001) and had the longest adjusted LOS (3.2 vs 2.9 vs 2.8 days; P = .01). There was no significant difference in adjusted 30-day readmission rates or costs. CONCLUSIONS: Inflammatory marker testing varied widely across hospitals. Hospitals with higher inflammatory testing for one infection tend to test more frequently for other infections and have longer LOS, suggesting opportunities for diagnostic stewardship.

Major Adverse Kidney Events in Pediatric Sepsis.

BACKGROUND AND OBJECTIVES: Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality. RESULTS: Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions. CONCLUSIONS: In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.

Home Health Nursing Care and Hospital Use for Medically Complex Children.

BACKGROUND AND OBJECTIVE: Home health nursing care (HH) may be a valuable approach to long-term optimization of health for children, particularly those with medical complexity who are prone to frequent and lengthy hospitalizations. We sought to assess the relationship between HH services and hospital use in children. METHODS: Retrospective, matched cohort study of 2783 hospitalized children receiving postdischarge HH services by BAYADA Home Health Care across 19 states and 7361 matched controls not discharged to HH services from the Children's Hospital Association Case Mix database between January 2004 and September 2012. Subsequent hospitalizations, hospital days, readmissions, and costs of hospital care were assessed over the 12-month period after the initial hospitalization. Nonparametric Wilcoxon signed rank tests were used for comparisons between HH and non-HH users. RESULTS: Although HH cases had a higher percentage of complex chronic conditions (68.5% vs 65.4%), technology assistance (40.5% vs 35.7%), and neurologic impairment (40.7% vs 37.3%) than matched controls (P ≤ .003 for all), 30-day readmission rates were lower in HH patients (18.3% vs 21.5%, P = .001). At 12 months after the index admission, HH patients averaged fewer admissions (0.8 vs 1.0, P < .001), fewer days in the hospital (6.4 vs 6.6, P < .001), and lower hospital costs ($22 511 vs $24 194, P < .001) compared with matched controls. CONCLUSIONS: Children discharged to HH care experienced less hospital use than children with similar characteristics who did not use HH care. Further investigation is needed to understand how HH care affects the health and health services of children.

Delayed repeat enemas are safe and cost-effective in the management of pediatric intussusception.

BACKGROUND/PURPOSE: The purpose of the study is to compare outcomes between delayed repeat enema (DRE) and immediate surgery (IS) in children with ileocolic intussusception who fail initial enema reduction. METHODS: Retrospective cohort study of children <6 years-of-age from 2008 to 2012 in the Pediatric Health Information System (PHIS) database. Outcomes measured were bowel resection, length of stay (LOS), and adjusted hospital costs (AHC). RESULTS: 4980 of 6889 (72.3%) children with intussusception were discharged without operation following a single successful enema. 1407 of 1909 (73.7%) remaining patients underwent IS while 502 (26.3%) had a DRE. Bowel resection was required in 372 of 1407 (26.4%) patients in IS group compared to 59 of 502 (11.8%) in the DRE group (p<0.001). The number of patients needed to treat by DRE to prevent a bowel resection was 7. In multivariable analysis, the IS patients had a 2.5 times greater likelihood of undergoing bowel resection than the DRE patients (adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.83-3.41, p<0.001). The DRE group had a mean LOS of 3.2 days (95% CI 2.9-3.6) and mean AHC of $9205 (95% CI $7673-$10,735). The IS group had a longer LOS (4.4days, 95% CI 4.0-4.8, p≤0.001) and higher AHC ($14,422, 95% CI $12,631-$16,214, p<0.001). CONCLUSION: Delayed repeat enemas for ileocolic intussusception increase the success of nonoperative reduction, decrease the rate of bowel resection and reduce mean hospital length of stay and costs.

Prevalence and predictors of return visits to pediatric emergency departments.

OBJECTIVE: To determine the rate of return visits to pediatric emergency departments (EDs) and identify patient- and visit-level factors associated with return visits and hospitalization upon return. DESIGN AND SETTING: Retrospective cohort study of visits to 23 pediatric EDs in 2012 using data from the Pediatric Health Information System. PARTICIPANTS: Patients <18 years old discharged following an ED visit. MEASURES: The primary outcomes were the rate of return visits within 72 hours of discharge from the ED and of return visits within 72 hours resulting in hospitalization. RESULTS: 1,415,721 of the 1,610,201 ED visits to study hospitals resulted in discharge. Of the discharges, 47,294 patients (3.3%) had a return visit. Of these revisits, 9295 (19.7%) resulted in hospitalization. In multivariate analyses, the odds of having a revisit were higher for patients with a chronic condition (odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.86-1.96), higher severity scores (OR: 1.42, 95% CI: 1.40-1.45), and age <1 year (OR: 1.32, 95% CI: 1.22-1.42). The odds of hospitalization on return were higher for patients with higher severity (OR: 3.42, 95% CI: 3.23-3.62), chronic conditions (OR: 2.92, 95% CI: 2.75-3.10), age <1 year (1.7-2.5 times the odds of other age groups), overnight arrival (OR: 1.84, 95% CI: 1.71-1.97), and private insurance (OR: 1.47, 95% CI: 1.39-1.56). Sickle cell disease and cancer patients had the highest rates of return at 10.7% and 7.3%, respectively. CONCLUSIONS: Multiple patient- and visit-level factors are associated with revisits. These factors may provide insight in how to optimize care and decrease avoidable ED utilization.

Prevention of central venous catheter-associated bloodstream infections in pediatric intensive care units: a performance improvement collaborative.

OBJECTIVE: The goal of this effort was to reduce central venous catheter (CVC)-associated bloodstream infections (BSIs) in pediatric intensive care unit (ICU) patients by means of a multicenter evidence-based intervention. METHODS: An observational study was conducted in 26 freestanding children's hospitals with pediatric or cardiac ICUs that joined a Child Health Corporation of America collaborative. CVC-associated BSI protocols were implemented using a collaborative process that included catheter insertion and maintenance bundles, daily review of CVC necessity, and daily goals. The primary goal was either a 50% reduction in the CVC-associated BSI rate or a rate of 1.5 CVC-associated BSIs per 1,000 CVC-days in each ICU at the end of a 9-month improvement period. A 12-month sustain period followed the initial improvement period, with the primary goal of maintaining the improvements achieved. RESULTS: The collaborative median CVC-associated BSI rate decreased from 6.3 CVC-associated BSIs per 1,000 CVC-days at the start of the collaborative to 4.3 CVC-associated BSIs per 1,000 CVC-days at the end of the collaborative. Sixty-five percent of all participants documented a decrease in their CVC-associated BSI rate. Sixty-nine CVC-associated BSIs were prevented across all teams, with an estimated cost avoidance of $2.9 million. Hospitals were able to sustain their improvements during a 12-month sustain period and prevent another 198 infections. CONCLUSIONS: We conclude that our collaborative quality improvement project demonstrated that significant reduction in CVC-associated BSI rates and related costs can be realized by means of evidence-based prevention interventions, enhanced communication among caregivers, standardization of CVC insertion and maintenance processes, enhanced measurement, and empowerment of team members to enforce adherence to best practices.

Adverse events in the neonatal intensive care unit: development, testing, and findings of an NICU-focused trigger tool to identify harm in North American NICUs.

OBJECTIVES: Currently there are few practical methods to identify and measure harm to hospitalized children. Patients in NICUs are at high risk and warrant a detailed assessment of harm to guide patient safety efforts. The purpose of this work was to develop a NICU-focused tool for adverse event detection and to describe the incidence of adverse events in NICUs identified by this tool. METHODS: A NICU-focused trigger tool for adverse event detection was developed and tested. Fifty patients from each site with a minimum 2-day NICU stay were randomly selected. All adverse events identified using the trigger tool were evaluated for severity, preventability, ability to mitigate, ability to identify the event earlier, and presence of associated occurrence report. Each trigger, and the entire tool, was evaluated for positive predictive value. Study chart reviewers, in aggregate, identified 88.0% of all potential triggers and 92.4% of all potential adverse events. RESULTS: Review of 749 randomly selected charts from 15 NICUs revealed 2218 triggers or 2.96 per patient, and 554 unique adverse events or 0.74 per patient. The positive predictive value of the trigger tool was 0.38. Adverse event rates were higher for patients <28 weeks' gestation and <1500 g birth weight. Fifty-six percent of all adverse events were deemed preventable; 16% could have been identified earlier, and 6% could have been mitigated more effectively. Only 8% of adverse events were identified in existing hospital-based occurrence reports. The most common adverse events identified were nosocomial infections, catheter infiltrates, and abnormal cranial imaging. CONCLUSIONS: Adverse event rates in the NICU setting are substantially higher than previously described. Many adverse events resulted in permanent harm and the majority were classified as preventable. Only 8% were identified using traditional voluntary reporting methods. Our NICU-focused trigger tool appears efficient and effective at identifying adverse events.

Measurement of cytokine production using whole blood.

Whole blood (WB) ex vivo stimulation assays are useful for measuring cytokine responses due to the easy access of samples from healthy donors and patients and the minimal processing of the sample required. Because the assay mimics the natural environment, WB culture may be the best milieu in which to study cell activation and cytokine production in vitro. Whole blood stimulation has been used to investigate the cellular responsiveness to a variety of stimuli, including bacterial endotoxin (LPS), antigens, allergens, and antibiotics. Various clinical uses of whole blood stimulation assays have been suggested, including the assessment of autoimmune diseases, the monitoring of drug and vaccine efficacy, and immunotoxicity. Thus, whole blood cell culture may be useful in studying the biological effects of potential allergenic and/or antigenic substances or drugs on immune cell activation and cytokine secretion.