Case-control Study Of Pediatric Patients Research Articles

Association of autoimmune and autoinflammatory disorders with chronic rhinosinusitis in children

BackgroundIncreasing evidence suggests that autoimmune disorders and their immunomodulating medications may increase the risk of rhinosinusitis. The goal of this study is to determine if autoimmune and autoinflammatory diseases are associated with increased risk of chronic rhinosinusitis (CRS) in children. MethodsA retrospective case-control study of pediatric patients (age 2–18 years) seen in the West Virginia University Hospitals System in the past 10 years was performed. Cases were children with autoimmune or autoinflammatory diseases. Controls were children without any autoimmune or autoinflammatory disorders. Query of our electronic medical record (Epic) was performed using ICD-10 codes. Univariate (unadjusted) and multivariate (adjusted) logistic regression were used to calculate the strength of association of autoimmune or autoinflammatory disorders with CRS and the other airway disorders while adjusting for age, sex, and race. Results420582 pediatric patients were queried with mean age of 10.8 years (SD of 4.8, range of 2–18 years), and 47.9% being female. 1956 (0.5%) had autoimmune disorders and 293 (0.07%) had autoinflammatory disorders. Both autoimmune and autoinflammatory disorders increase the odds of having CRS in the unadjusted [OR = 3.36, p < 0.001 and 5.69, p < 0.001 for the respectively] and the adjusted [OR = 2.90, p < 0.001 and OR = 5.07, p < 0.001 respectively after adjusting for age, sex, and race] models. ConclusionAutoimmune and autoinflammatory disorders increase the risk of CRS and chronic rhinitis in children.

The visual impact of higher-order aberrations in patients with pediatric blepharokeratoconjunctivitis.

To analyze higher-order aberrations (HOAs) and their visual impact in a pediatric blepharokeratoconjunctivitis (PBKC) cohort compared with healthy controls. Prospective case-control study of pediatric patients (≤ 16 years old). Subjects underwent wavefront aberrometry analysis to compare HOAs and their impact on visual quality. A total of 150 eyes from 76 patients were included in the analysis. The PBKC group consisted of 50 eyes and the control group of 100 healthy eyes. Mean age was 10.39 ± 3.81 years for the PBKC group and 10.80 ± 3.61 years for the controls. Mean corrected-distance visual acuity (CDVA) was 0.24 ± 0.21 logMAR in the PBKC group and 0.07 ± 0.1 in the controls (P < 0.001). Mean astigmatism was 1.6 ± 1.98D in the PBKC group vs. 0.67 ± 0.76D in the control group (P = 0.01). Mean RMS of HOAs was 1.05 ± 1.7mm in the PBKC group and 0.41 ± 0.18mm in the controls (P < 0.001). The mean modulation transfer function (MTF) in the PBKC group was significantly lower (16.37 ± 16.32) than controls (30.3 ± 23.57) (P < 0.001). Corneal leukomas, stromal vascularization, peripheral nummular subepithelial scars, and pannus formation are associated with increased HOAs. There was a significant increase in total HOAs of eyes with PBKC compared to healthy controls. Corneal opacity, vascularization, and scarring are associated with increased HOAs. The PBKC eye aberration profile: coma, secondary astigmatism, quadrafoil, and pentafoil, were associated with decreased CDVA and visual quality (PSF and MTF).

Central Line-Associated Bloodstream Infection Risk Factors in a Pediatric Population.

Central venous line (CVL) placement in children is often necessary for treatment and may be complicated by central line-associated bloodstream infection (CLABSI). We hypothesize that line type and clinical and demographic factors at line placement impact CLABSI rates. This is a single-institution case-control study of pediatric patients (≤18years old) admitted between January 1, 2015, and December 31, 2019. Case patients had a documented CLABSI. Control patients had a CVL placed during the study period and were matched by sex and age in a 2:1 ratio. Bivariate and multivariate logistic regression analysis was performed. We identified 78 patients with a CLABSI and 140 patients without a CLABSI. After controlling for pertinent covariates, patients undergoing tunneled or non-tunneled CVL had higher odds of CLABSI than those undergoing PICC (OR 2.51, CI 1.12-5.64 and OR 3.88, CI 1.06-14.20 respectively), and patients undergoing port placement had decreased odds of CLABSI compared to PICC (OR .05, CI 0.01-.51). There were lower odds of CLABSI when lines were placed for intravenous medications compared to those placed for solid tumor malignancy (OR .15, CI .03-.79). Race and age were not statistically significant risk factors. Central lines placed for medication administration compared to solid tumors, PICC compared to tunneled and non-tunneled central lines, and ports compared to PICC were associated with lower odds of CLABSI. Future improvement efforts should focus on PICC and port placement in appropriate patients to decrease CLABSI rates.

Demographic and Clinical Predictors of Drug Response in Epileptic Children in Jeddah.

Epilepsy is a chronic neurological disease of the brain. Over 20 antiseizure medications are available on the market, but a third of patients still have drug-resistant epilepsy. This study was designed to assess the impact of the demographic and clinical characteristics of epileptic children on their likelihood of developing drug resistance. This study was a multicenter, hospital-based, cross-sectional, case-control study of pediatric patients diagnosed with epilepsy in Jeddah, Saudi Arabia. The study included 101 children with epilepsy. Fifty-six patients showed good response to antiseizure medications (ASMs), and forty-five patients had a poor response. A statistically significant good response to ASMs was reported among younger patients, those who did not report parental consanguinity, those who did not have a family history of epilepsy, and those diagnosed with partial seizures, with no reported adverse effects. The levetiracetam regimen was statistically significant regarding the responsiveness to ASMs. Patients on a monotherapy regimen elicited a significantly better response to levetiracetam than patients on polytherapy (p < 0.001). No significant association was found between the response to ASMs and the sex, nationality, body mass index, complete blood count, or vitamin B12 level. In conclusion, the ASM response in epileptic patients can be predicted by knowing the patient's demographic and epileptic history. However, the complete blood count and vitamin B12 level failed to predict patients' response to ASMs.

Management of children with co-occurring sleep disordered breathing and hearing loss.

To examine hearing loss incidence in a pediatric otolaryngology patients with sleep disordered breathing, and secondarily, identify possible disparities in management. A retrospective case-control study of pediatric patients with sleep-disordered breathing or obstructive sleep apnea from 2012 to 2019 was conducted at a private, not-for-profit, academic, tertiary care center. Study parameters were extracted from the electronic medical record and compared in study groups of patients with sleep-disordered breathing generated based on presence of hearing loss (cases) versus absence (controls). Study parameters were also compared in study groups based on timing of hearing loss onset. 14.8% of patients with sleep disordered breathing had hearing loss. Hearing loss was associated with an increased risk of undergoing adenotonsillectomy (OR 1.632 [1.294-2.058], p<0.001, adjusted for age). In patients who underwent polysomnographic testing, 9.8% patients had pre-existing hearing loss and 12% patients developed hearing loss over the study period. Patients with pre-existing hearing loss and those who developed hearing loss had significantly more visits with otolaryngology compared to controls (p<0.001). Hearing loss did not significantly delay adenotonsillectomy. More patients who developed hearing loss had adenotonsillectomies (OR 2.475 [1.672-3.663], p<0.001, adjusted for age) versus controls. This difference was not identified in patients with pre-existing hearing loss. Patients with evidence of hearing loss in addition to sleep disordered breathing had more adenotonsillectomies performed and more clinic visits. Further work must be done to understand the associations and implications of hearing loss in this population.

Postanesthesia complications in pediatric patients with previous SARS-CoV-2 infection: A cohort study.

Children with SARS-CoV-2 infection are at increased risk for postanesthesia complications. There is minimal data regarding how long that elevated complication risk persists beyond initial SARS-CoV-2 diagnosis. We investigated postanesthesia complications in children with SARS-CoV-2 infection within 90 days of diagnosis. We completed a single-center, retrospective, case-control study of pediatric patients with confirmed SARS-CoV-2 infection within 90 days undergoing anesthesia between January 3-October 7, 2020. Each SARS-CoV-2 positive patient was matched 1:2 by age and type of procedure with a non-SARS-CoV-2 cohort. The primary outcome was the rate of all postanesthesia complications within 30 days of the procedure, defined as unplanned escalations of care within 48 h, cardiac, respiratory, thrombotic, and hemorrhagic events within 30 days. Secondary outcomes were 30-day mortality and hospital length of stay. Of the 341 patients included, 114 patients were SARS-CoV-2 positive and 227 were SARS-CoV-2 negative. Patients with a positive test 0-7 days prior to anesthesia had an increased risk difference in all postanesthesia complications within 30 days (19.9, 95% CI [4.7, 35.1], p= .001) and increased risk difference in length of hospital stay (7.8, 95% CI [1.2, 14.4], p< .001). Patients who underwent anesthesia greater than 42 days from SARS-CoV-2 diagnosis had an increased risk difference in cardiac complications within 30 days (4.3, 95% CI [0.9, 10.0], p= .029). There was no increased hospital length of stay among SARS-CoV-2 positive patients diagnosed greater than 8 days before anesthetic. There were no deaths within 30 days of anesthetic. Postanesthesia complications are higher in children who undergo anesthesia within 7 days of SARS-CoV-2 diagnosis. Additional cardiac risk may persist beyond the immediate period of initial diagnosis. Larger samples are needed to further evaluate the risk of delayed postanesthesia complications and guide optimal timing of surgery.

Predictive Pediatric Characteristics for Revision Tonsillectomy After Intracapsular Tonsillectomy.

There is little research on the rate and risk factors for revision tonsillectomy after primary intracapsular tonsillectomy. Our study aimed to determine the revision rate following intracapsular tonsillectomy, identify patient characteristics that may increase the probability of revision surgery, and report the tonsillar hemorrhage rate after revision. Level III, retrospective case-control study. A tertiary care pediatric center (Alfred I. duPont Hospital for Children, Wilmington, Delaware). A case-control study of pediatric patients who underwent intracapsular tonsillectomy between January 1, 2004, and December 31, 2018, was performed. Patients aged 2 to 20 years were analyzed and compared with matched controls who underwent intracapsular tonsillectomy within 7 days of the same surgeon's case. In total, 169 revision procedures were included with 169 matched controls. A 1.39% revision rate was observed among a total of 12,145 intracapsular tonsillectomies. Among the 169 patients who underwent a revision procedure, the mean time between cases was 3.5 years. Tonsillitis was the most common diagnosis prompting revision tonsillectomy. Four (2.4%) patients underwent operative control of a postoperative tonsillar hemorrhage after revision surgery. Younger patients (P < .001) and patients with a history of gastroesophageal reflux disease (P = .006) were more likely to undergo revision tonsillectomy. Patients below age 4 years and patients with gastroesophageal reflux disease may be at increased risk of undergoing revision tonsillectomy after primary intracapsular tonsillectomy. These factors should be considered when selecting an intracapsular technique for primary tonsillectomy in pediatric patients.

Viral etiology of life-threatening pediatric pneumonia: A matched case-control study.

BackgroundPediatric pneumonia remains a significant health challenge, while the viral risk factors for adverse outcomes in pediatric pneumonia are not yet fully clear.MethodsA matched case‐control study of pediatric patients with pneumonia was carried out in Beijing, China, between 2007 and 2015. The study enrolled 334 intensive care unit patients who developed life‐threatening diseases and 522 controls matched to the sex, age, ethnicity, admission dates, and residing district of the cases suffered from pneumonia. Nasopharyngeal aspirates were taken from all participants and tested by PCR for 18 common respiratory viruses.ResultsAt least, one virus was detected in 257 (77%) of the cases and 409 (78%) of the controls. We observed no difference in the prevalence of 17 respiratory viruses between cases and controls but found a higher frequency of influenza A virus (IFV‐A) in the cases than in the controls (7% vs 4%, P = .036). After adjusting for comorbid conditions and a history of reactive airway diseases, IFV‐A was associated with an increase in life‐threatening pneumonia (adjusted odds ratio = 2.55, 95% CI = 1.24‐5.24). Young age and congenital heart disease (aOR = 10.16‐10.27, P < .001) were also independent risk factors.ConclusionsThe prevention of IFV infection is critical in decreasing the risk of life‐threatening pneumonia in children.

Comparison of Outcomes of Myeloablative Allogeneic Stem Cell Transplantation for Pediatric Patients with Bone Marrow Failure, Myelodysplastic Syndrome and Acute Myeloid Leukemia with and without Germline GATA2 Mutations.

Germline mutations in GATA2 are associated with an inherited predisposition to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy. However, patients may be at an increased risk for transplant-related toxicity (TRT) and transplant-related mortality (TRM) due to their underlying disease biology. We performed a retrospective case-control study of pediatric patients with BMF/MDS/AML with germline GATA2 mutations, comparing HSCT outcomes to randomly selected patients without germline GATA2 mutations and BMF/MDS (control A) and acute leukemia (control B). The 5-year overall and disease-free survival rates in the GATA2 cohort (65%, 51%) were similar to control A (58%, 49%) and B (45%, 43%) cohorts. In contrast, the 5-year event-free survival rate was significantly lower in the GATA2 cohort (7% ± 6%, 28% ± 10%, and 33% ± 8% for GATA2, A, and B, respectively), due to an increased number of unique TRTs. Specifically, neurologic toxicities occurred significantly more frequently in GATA2 patients than in the control groups, and post-HSCT thrombotic events occurred only in the GATA2 cohort. There was no difference in TRM, infections, or graft-versus-host disease across groups. The higher incidence of thrombotic and neurologic events specific to GATA2 patients warrants further investigation and has potential treatment ramifications.

Autoimmune Cytopenias Following Allogeneic Hematopoietic Stem Cell Transplant in Pediatric Patients: A Case-Control Cohort Study

Introduction Autoimmune cytopenia (AIC) is a rare, but serious complication of allogeneic hematopoietic cell transplantation (HCT), and treatment for post-HCT AIC can have severe short- and long-term consequences. We sought to identify AIC risk factors and evaluate treatment-related late effects, in order to better guide management. Methods We performed a retrospective case-control study of pediatric patients who underwent HCT at Children's Hospital Colorado from June 2005 to March 2019. We compared clinical and transplant-related characteristics, chimerism, immune reconstitution, outcomes and late effects between patients who developed AICs (n=20) and a control group (n=40) matched by primary disease category and donor source. Results The incidence of AIC was 5.6% amongst all patients who received allogeneic HCT in the study timeframe (n=354). Of these, 75% had non-malignant disease (n=15). Thirteen developed autoimmune hemolytic anemia (65%), 5 had immune thrombocytopenia (25%), 1 had Evans syndrome (5%) and 1 had autoimmune neutropenia (5%). Median time to AIC was 219 days (range 97-1205 days). There was no difference between AIC patients and controls in gender, age at HCT, conditioning regimen, serotherapy, total body irradiation (TBI), GVHD prophylaxis, chronic GVHD, or time to neutrophil and platelet recovery. Compared to controls, more AIC patients had ABO mismatch (50% vs. 40%, p=0.07), and a higher proportion of grade I-II acute GVHD (93.9% vs. 50%, p=0.06), but was not statistically significant. Seventeen patients (85%), had >95% donor chimerism immediately prior to development of AIC. Fifteen patients (75%) received steroids as part of first-line therapy for AIC and 17 patients (85%) received rituximab as part of all therapy. Eleven patients (64.7%) received rituximab as part of first-line therapy. Only 25% of patients (n=5) responded to initial therapy. Median time to resolution of AIC was 12.0 months (range 10 days to 90 months). Strikingly, 12 patients (70.6%) are still receiving intravenous immune globulin (IVIG) replacement for hypogammaglobulinemia at least 1-year after HCT at a median time of 597.5 days (range 83-3715 days) from last rituximab dose. Iron overload was more prevalent in AIC patients compared to controls (n=8 vs n=1, p=0.0004, median of 2.3 years after HCT). The overall survival (OS) of the AIC cohort was similar to the control group (85% vs 82.5%). No patients in the AIC cohort died from AIC-related complications. In the AIC cohort, 2 patients died from sepsis and 1 patient died from relapsed disease. Conclusions In this case-control study of pediatric HCT patients, AIC was not associated with mixed chimerism or GVHD. The majority of AIC cases did not respond to first-line therapy and required multiple treatment modalities to achieve a complete response. Late effects from AIC-directed therapies include prolonged hypogammaglobulinemia and iron overload.

(24) Morbidity of Central Line-Associated Deep Vein Thrombosis in the Pediatric Intensive Care Unit

Purpose: Deep venous thrombosis (DVT) is the second most common preventable in-hospital harm in pediatrics. Central venous catheters (CVCs) are a known risk factor of hospital-acquired DVT but the associated morbidity has not been studied in children. The purpose of this study was to study potential morbidities of CVC-associated DVT in hospitalized, critically-ill children. Methods: A single-center retrospective case-control study of pediatric patients admitted to a tertiary care children’s hospital from 2009 to 2016 who had a CVC placed within 7 …

Risk Factors Associated with Clostridium difficile Infection in A Pediatric Hematology-Oncology Ward with Analysis of the Infection Control Measures

Introduction: The impact of clostridium difficile infection (CDI) on patients’ health and hospitals’ cost is significant. Currently CDI is recognized as an increasingly important pathogen in children with increasing incidence among pediatric patients. Data is scarce on the incidence and risk factors of CDI in Saudi Arabia, especially in pediatric oncology population. In this study, we report the first outbreak of CDI in pediatric hematology-oncology ward in Saudi Arabia and describe the associated risk factors for CDI. Methods: This is a descriptive, epidemiologic hospital based case-control study of pediatric Patients in hematology-oncology ward who had CDI in an outbreak from January 2012 to June 2013 at a tertiary hospital in Saudi Arabia, matched randomly to a control group who were admitted in the same ward during the study period. The main outcome measure was the adjusted odds ratio estimates of potential risk factors for CDI infection. We also describe the control measures that were implemented to control this outbreak. Results: Risk factors associated with CDI were antibiotic use with cotrimoxazole being the most used one, and length of hospital stay. Controls were found to have been treated more with penicillins and aminoglycosides. Conclusion: Factors associated with CDI infection are often complex and maybe confounded by local variables, antibiotic exposure and lengthy hospital stays are among many risk factors for CDI in high -risk populations. Our study also highlights the importance of infection control measures in controlling and preventing outbreaks of CDI.

A Risk-Prediction Model For Identifying Venous Thromboembolism In Hospitalized Pediatric Patients: A Single Institution Retrospective Case-Control Analysis

IntroductionVenous thromboembolism (VTE) is increasing in children, especially in the tertiary care setting. Hospital-associated VTE (HA-VTE) is a potentially preventable cause of major morbidity and mortality. However, the incidence of HA-VTE VTE is low in children Risk stratification tools may aid in identification of hospitalized high risk pediatric patients who may benefit from VTE prophylaxis. MethodsWe conducted a case-control study of pediatric patients with HA-VTE (21 years or younger at the time of diagnosis) admitted to the Johns Hopkins Hospital from 2008-2010. Cases were identified using ICD-9 codes for DVT and PE and verified by reviewing hospital records and radiologic imaging reports. HA-VTE was defined as: 1) VTE was diagnosed ≥48 hours after hospital admission without signs/symptoms of VTE on admission, or 2) VTE was diagnosed within 90 days of hospital discharge. Two contemporaneous controls matched for age, sex and admission unit were selected for each case. Records of cases and controls were reviewed for presence of a priori identified putative VTE risk factors at admission. Univariate and conditional multivariable logistic regression analyses with backward elimination were used to develop risk-prediction models. Based on results of univariate analysis, we sought to evaluate two multivariable models, one without length of stay (LOS) with relevance to assessment at admission, and one in which LOS was included with relevance to re-assessment after several days of hospitalization. All variables selected for the multivariable model were tested for interaction with a significance threshold level of p<0.2. Except for this, all hypothesis testing was two tailed and a p value of <0.05 was considered significant. Receiver operator curves (ROC) were constructed using risk factors on multivariate analysis. ResultsTable 1 lists the results putative risk factors by univariate analysis with a) significantly higher odds of VTE and b) higher odds of VTE but not statistically significant. In multivariable logistic regression analysis, central venous catheter (CVC), VTE predisposition and immobility or LOS >5 days were independently associated with HA-VTE. The combination of CVC and VTE predisposition with either immobility or LOS was predictive of HA-VTE (area under the curve for ROC of 76.6% and 80.6%, Table 2). ConclusionWe found independently associated risk factors with that may potentially be used in a predictive model of HA-VTE in children. Further prospective validation studies of these and other risk factors may serve as the basis of future risk-stratified randomized control trials of primary prevention of pediatric HA-VTE. Disclosures:Streiff:Bristol Myers Squibb: Research Funding; Sanofi: Consultancy, Honoraria; Eisai, Daiichi-Sankyo, Boehringer-Ingelheim, Janssen HealthCare: Consultancy. Strouse:NIH: Research Funding; Doris Duke Charitable Foundation: Research Funding; Masimo Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Takemoto:Novonordisk: Research Funding.

Toll-Like Receptor 4 Promoter Polymorphisms: Common TLR4 Variants May Protect against Severe Urinary Tract Infection

BackgroundPolymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses.Methodology/Principal FindingsWe sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. Since TLR4 plays a vital role in susceptibility to urinary tract infection (UTI), promoter sequences were obtained from children with mild or severe disease. We performed a case-control study of pediatric patients with asymptomatic bacteriuria (ABU) or those prone to recurrent acute pyelonephritis (APN). Promoter activity of the single SNPs or multiple allelic changes corresponding to the genotype patterns (GPs) was tested. We then conducted a replication study in an independent cohort of adult patients with a history of childhood APN. Last, in vivo effects of the different GPs were examined after therapeutic intravesical inoculation of 19 patients with Escherichia coli 83972. We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. The ABU associated GPs also reduced innate immune responses in patients who were subjected to therapeutic urinary E. coli tract inoculation.ConclusionsThe results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility.