Objective: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). Data Sources: PubMed, MEDLINE, Cochrane, and clinical trial registries. Review Methods: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. Conclusions: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. Implications for Practice: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

OBJECTIVE:To assess the extent and drivers of telehealth use variation across clinicians within the same pediatric subspecialties.METHODS:In this mixed methods study, 8 pediatric medical groups in California shared data for eleven subspecialties. We calculated the proportion of total visits delivered via telehealth by medical group for each subspecialty and identified the 8 most common International Classification of Diseases 10 diagnoses for telehealth and in-person visits in endocrinology and neurology. We conducted semi-structured interviews with 32 pediatric endocrinologists and neurologists and applied a positive deviance approach comparing high versus low utilizers to identify factors that influenced their level of telehealth use.RESULTS:In 2019, medical groups that submitted quantitative data conducted 1.8 million visits with 549,306 unique pediatric patients. For 3 subspecialties, there was relatively little variation in telehealth use across medical groups: urology (mean: 16.5%, range: 9%-23%), orthopedics (mean: 7.2%, range: 2%-14%), and cardiology (mean: 11.2%, range: 2%-24%). The remaining subspecialties, including neurology (mean: 58.6%, range: 8%-93%) and endocrinology (mean: 49.5%, range: 24%-92%), exhibited higher levels of variation. For both neurology and endocrinology, the top diagnoses treated in-person were similar to those treated via telehealth. There was limited consensus on which clinical conditions were appropriate for telehealth. High telehealth utilizers were more comfortable conducting telehealth visits for new patients and often worked in practices with innovations to support telehealth.CONCLUSIONS:Clinicians perceive that telehealth may be appropriate for a range of clinical conditions when the right supports are available.

Inequalities in the accessibility and utilization of quality, safe, and effective coronavirus disease 2019 (COVID-19) vaccines across and within countries limited their value in protecting health during the COVID-19 pandemic. We quantified cross-country, income-associated inequality in COVID-19 vaccination using statistical models based on the data for 79 countries through December 2021. We found notable inequality in vaccinations per capita. At least 11.9% of doses administered in high-income countries could be redistributed to low-income countries to substantially reduce income-associated inequality in vaccinations. The results of this modeling study indicate that reliance on multiple doses of vaccine to attain optimal protection from COVID-19 is a significant contributor to inequality in vaccinations per capita. Dose-sharing mechanisms should account for and include efforts to optimize the capabilities of health systems to deliver vaccines.

Objective: Multi-level fall (MLF) accounts for 26.5%-37.7% of traumatic pediatric basilar skull fractures (BSFs). There is a dearth of information concerning recommendations for work-up, diagnosis, treatment, and otolar-yngological follow-up of pediatric basilar skull fractures secondary to MLFs. Through a systematic literature review and retrospective review of an institution's trauma experience, we sought to identify clinical findings among pediatric MLF patients that indicate the need for otolaryngological follow-up. Methods: A two-researcher team following the PRISMA guidelines performed a systematic literature review. PubMed, Web of Science, and EBSCO databases were searched August 16th, 2020 and again on November 20th, 2021 for English language articles published after 1980 using search terms Pediatric AND (fall OR "multi level fall " OR "fall from height ") AND ( "basilar fracture " OR "basilar skull fracture " OR "skull base fracture " OR "skull fracture "). Simultaneously, an institutional trauma database and retrospective chart review was performed for all patients under age 18 who presented with a MLF to a pediatric tertiary care center between 2007 and 2018. Results: 168 publications were identified and 13 articles reporting pediatric basilar skull fracture data and MLF as a mechanism of injury were selected for review. MLF is the most common etiology of BSF, accounting for 26.5-37.7% of pediatric BSFs. In the retrospective review, there were 180 cases of BSF from MLF in the study period (4.2%). BSF and fall height were significantly associated (p < 0.001), as well as presence of a CSF leak and fall height (p = 0.02), intracranial hemorrhage (ICH) (p = 0.047), and BSF fracture type (p < 0.001). However, when stratified by age, these associations were only present in the younger group. Of those with non-temporal bone BSFs (n = 71), children with hemotympanum (n = 7) were approximately 18 times more likely (RR 18.3, 95% CI 1.89 to 177.02) than children without hemotympanum (n = 64) to have hearing loss at presentation (28.6% vs. 1.6% of patients). Conclusions: MLF is the most common cause of pediatric basilar skull fractures. However, there is limited in-formation on the appropriate work-up or otolaryngologic follow-up for this mechanism of injury. Our retro-spective review suggests fall height is predictive for BSF, ICH, and CSF leak in younger children. Also, children with non-temporal bone BSFs and hemotympanum may represent a significant population requiring otolaryn-gology follow-up.

Importance:The identification of variation in health care is important for quality improvement. Little is known about how different pediatric subspecialties are using telehealth and what is driving variation. Objective:To characterize trends in telehealth use before and during the COVID-19 pandemic across pediatric subspecialties and the association of delivery change with no-show rates and access disparities. Design, Setting, and Participants:In this cohort study, 8 large pediatric medical groups in California collaborated to share aggregate data on telehealth use for 11 pediatric subspecialties from January 1, 2019, to December 31, 2021. Main Outcomes and Measures:Monthly in-person and telehealth visits for 11 subspecialties, characteristics of patients participating in in-person and telehealth visits, and no-show rates. Monthly use rates per 1000 unique patients were calculated. To assess changes in no-show rates, a series of linear regression models that included fixed effects for medical groups and calendar month were used. The demographic characteristics of patients served in person during the prepandemic period were compared with those of patients who received in-person and telehealth care during the pandemic period. Results:In 2019, participating medical groups conducted 1.8 million visits with 549 306 unique patients younger than 18 years (228 120 [41.5%] White and 277 167 [50.5%] not Hispanic). A total of 72 928 patients (13.3%) preferred a language other than English, and 250 329 (45.6%) had Medicaid. In specialties with lower telehealth use (cardiology, orthopedics, urology, nephrology, and dermatology), telehealth visits ranged from 6% to 29% of total visits from May 1, 2020, to April 30, 2021. In specialties with higher telehealth use (genetics, behavioral health, pulmonology, endocrinology, gastroenterology, and neurology), telehealth constituted 38.8% to 73.0% of total visits. From the prepandemic to the pandemic periods, no-show rates slightly increased for lower-telehealth-use subspecialties (9.2% to 9.4%) and higher-telehealth-use subspecialties (13.0% to 15.3%), but adjusted differences (comparing lower-use and higher-use subspecialties) in changes were not statistically significant (difference, 2.5 percentage points; 95% CI, -1.2 to 6.3 percentage points; P = .15). Patients who preferred a language other than English constituted 6140 in-person visits (22.2%) vs 2707 telehealth visits (11.4%) in neurology (P < .001). Conclusions and Relevance:There was high variability in adoption of telehealth across subspecialties and in patterns of use over time. The documentation of variation in telehealth adoption can inform evolving telehealth policy for pediatric patients, including the appropriateness of telehealth for different patient needs and areas where additional tools are needed to promote appropriate use.

OBJECTIVES:To evaluate the specific mechanism and trend of injury resulting in pediatric basilar skull fractures.STUDY DESIGN:Retrospective chart review of a trauma database.SETTING:Tertiary care children's hospital.METHODS:Patients ≤18 years old with basilar skull fractures were identified via the trauma database for admissions from 2007 to 2018. Patients were identified with ICD-9 codes (801.0, 801.1, 801.2, 801.3 or 801.4) and ICD-10 codes (S02.1, S02.10, S02.11, S02.19) for skull base fractures (International Classification of Diseases, Ninth Revision and Tenth Revision).RESULTS:A total of 729 patients were included: 251 females and 478 males. The 2 most common mechanisms of injury are multilevel falls and unhelmeted rider falls. Multilevel falls occur more in the toddler age group (average age, 4 years), and unhelmeted rider falls are seen in the older age group (average age, 11.2 years). Helmeted rider and motor vehicle accident basilar skull injuries are relatively uncommon. There was a spike in television/entertainment center mechanisms of injury in toddlers from 2007 to 2011 but has since decreased.CONCLUSION:Pediatric basilar skull fractures are costly to the health care system, as patients spent more time in intensive care unit beds with a charge limited to hospital rooms between $1.7 and $2.7 million per year. The protective effect of helmets is demonstrated by unhelmeted rider injuries being the second-most common mechanism of basilar skull fractures and by helmeted rider injuries being rare. The small proportion of basilar skull fractures from motor vehicle accidents is an example of policy and behavioral changes resulting in decreased injury.

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

Background The ongoing pandemic of coronavirus disease 2019 (COVID-19) has the potential to reverse progress towards global targets. This study examines the risks that the COVID-19 pandemic poses to equitable access to essential medicines and vaccines (EMV) for universal health coverage in Africa. Methods We searched medical databases and grey literature up to 2 October 2020 for studies reporting data on prospective pathways and innovative strategies relevant for the assessment and management of the emerging risks in accessibility, safety, quality, and affordability of EMV in the context of the COVID-19 pandemic. We used the resulting pool of evidence to support our analysis and to draw policy recommendations to mitigate the emerging risks and improve preparedness for future crises. Results Of the 310 records screened, 134 were included in the analysis. We found that the disruption of the international system affects more immediately the capability of low- and middle-income countries to acquire the basket of EMV. The COVID-19 pandemic may facilitate dishonesty and fraud, increasing the propensity of patients to take substandard and falsified drugs. Strategic regional cooperation in the form of joint tenders and contract awarding, joint price negotiation and supplier selection, as well as joint market research, monitoring, and evaluation could improve the supply, affordability, quality, and safety of EMV. Sustainable health financing along with international technology transfer and substantial investment in research and development are needed to minimize the vulnerability of African countries arising from their dependence on imported EMV. To ensure equitable access, community-based strategies such as mobile clinics as well as fees exemptions for vulnerable and under-served segments of society might need to be considered. Strategies such as task delegation and telephone triage could help reduce physician workload. This coupled with payments of risk allowance to frontline healthcare workers and health-literate healthcare organization might improve the appropriate use of EMV. Conclusions Innovative and sustainable strategies informed by comparative risk assessment are increasingly needed to ensure that local economic, social, demographic, and epidemiological risks and potentials are accounted for in the national COVID-19 responses.

Background We reviewed current evidence on the impact of COVID-19 on HIV, tuberculosis, and malaria across Africa.Methods We searched medical databases up to 15 September 2020 for epidemiological studies that investigated the impact of COVID-19 on HIV, tuberculosis, and malaria in terms of morbidity, mortality, or healthcare accessibility, covering African countries. We consulted global health and government sources for population surveys providing relevant primary data. We employed meta-study to assess evidence. This study is registered with PROSPERO, number CRD42020209265.Results Of the 128 records screened, 14 epidemiological studies were included in the analysis. We identified 5 population surveys. The largest effect of COVID-19 related disruption of HIV, TB, and malaria services is projected to result from interruption of ART, decline in TB case detection, and interruption of insecticide treated bed nets distribution campaigns, respectively. However, most modelling studies substantially underestimated the potential implications of COVID-19 on HIV, TB, and malaria in Africa and focused on the disruption of healthcare resulting from reduction in the capacity of healthcare provider. Reduced capacity of patients to use health services and adhere to treatment may also contribute to poor outcomes even when health systems capabilities are restored or unaffected. Moreover, these models do not account for any potential interaction of HIV, TB, and malaria with COVID-19, although empirical evidence shows that coinfection between HIV and TB with COVID-19 is significantly associated with increased mortality risk in Africa.Conclusions Current evidence is largely speculative. Innovative COVID-19 resilient solutions calibrated to local vulnerabilities are vital to ensure continuity of care and prevent the emergence of further potentially larger crises.

Introduction The rising burden of drug resistance is a major challenge to the global fight against malaria. We estimated national Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) across Africa, from 2000 to 2020. Methods We assembled molecular, clinical and endemicity data covering malaria-endemic African countries up to December 2018. Subsequently, we reconstructed georeferenced patient data, using pfdhps540E and pfdhps581G to measure mid-level and high-level SP resistance. Gaussian process regression was applied to model spatiotemporal standardised prevalence. Results In eastern Africa, mid-level SP resistance increased by 64.0% (95% uncertainty interval, 30.7%–69.8%) in Tanzania, 55.4% (31.3%–65.2%) in Sudan, 45.7% (16.8%–54.3%) in Mozambique, 29.7% (10.0%–45.2%) in Kenya and 8.7% (1.4%–36.8%) in Malawi from 2000 to 2010. This was followed by a steady decline of 76.0% (39.6%–92.6%) in Sudan, 65.7% (25.5%–85.6%) in Kenya and 17.4% (2.6%–37.5%) in Tanzania from 2010 to 2020. In central Africa, the levels increased by 28.9% (7.2%–62.5%) in Equatorial Guinea and 85.3% (54.0%–95.9%) in the Congo from 2000 to 2020, while in the other countries remained largely unchanged. In western Africa, the levels have remained low from 2000 to 2020, except for Nigeria, with a reduction of 14.4% (0.7%–67.5%) and Mali, with an increase of 7.0% (0.8%–25.6%). High-level SP resistance increased by 5.5% (1.0%–20.0%) in Malawi, 4.7% (0.5%–25.4%) in Kenya and 2.0% (0.1%–39.2%) in Tanzania, from 2000 to 2020. Conclusion Under the WHO protocols, SP is no longer effective for intermittent preventive treatment in pregnancy and infancy in most of eastern Africa and parts of central Africa. Strengthening health systems capacity to monitor drug resistance at subnational levels across the endemicity spectrum is critical to achieve the global target to end the epidemic.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1β positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.

OBJECTIVE:Although subject recruitment is one of the most critical aspects of human subject research, there is a lack of studies prospectively examining the recruitment preferences of adults for research involving children. METHODS:This was a cross-sectional study of adults accompanying patients at an otolaryngology clinic in a pediatric medical center. Anonymous questionnaires were distributed in English and Spanish to one adult for every patient. Questions assessed the respondent's preferences for research recruitment including contact method preferences, contact preferences for medical profession type, and whether they would expect a child to receive a small gift for participating in a research study. Fisher's exact tests were used to assess the association between the primary predictor, language, and each outcome. RESULTS:566 surveys were collected. 505 (89.1%) were completed in English and 61 (10.7%) were completed in Spanish. Spanish-speaking respondents were more likely to prefer talking to a doctor (76.7%) than English-speaking respondents (40.1%, p < 0.05). Spanish-speaking respondents were more likely to prefer talking over the phone (48.3%) than English-speaking respondents (17.3%, p < 0.05). Spanish-speaking respondents were more likely to prefer communicating via text messaging (41.7%) than English-speaking respondents (16.3%, p < 0.05). English-speaking respondents were more likely to prefer communicating through the patient portal of an electronic health record (EHR) (19%) than Spanish-speaking respondents(3.3%, p < 0.05). Mothers were more likely to prefer talking to a nurse/physician's assistant (20%) than fathers (10%, p < 0.05). Mothers were more likely to prefer talking to research staff (20%) than fathers (9%, p < 0.05). Mothers were more likely to prefer communication via text-message (22%) than fathers (6%, p < 0.05). Spanish-speaking respondents were more likely to prefer pediatric patients receiving a small monetary gift for participating in clinical research (70%) than English-speaking respondents (30%, p < 0.05). CONCLUSION:There was a significant association between preference for recruitment method and primary language spoken by the respondent. Further inquiry is required to understand these differences between English and Spanish speakers.

IntroductionUnprecedented global efforts to prevent malaria morbidity and mortality in sub-Saharan Africa have saved hundreds of thousands of lives across the continent in the last two decades. This study aims to determine how the comparative efficacy and safety of available malaria control interventions intended to improve maternal and child health outcomes have changed over time considering the varied epidemiological contexts on the continent.MethodsWe will review all randomised controlled trials that investigated malaria control interventions in pregnant women in sub-Saharan Africa and were published between January 1980 and December 2018. We will subsequently use network meta-regression to estimate temporal trends in the relative and absolute efficacy and safety of Intermittent Preventive Treatments, Intermittent Screening and Treatments, Insecticide-treated bed nets, and their combinations, and predict their ranking according to their relative and absolute efficacy and safety over time. Our outcomes will include 12 maternal and 7 child mortality and morbidity outcomes, known to be associated with either malaria infection or control. We will use intention-to-treat analysis to derive our estimates and meta-regression to estimate temporal trends and the effect modification by HIV infection, malaria endemicity and Plasmodium falciparum resistance to sulfadoxine–pyrimethamine, while adjusting for multiple potential confounders via propensity score calibration.PROSPERO registration numberCRD42018095138.

CONTEXT:In the face of rising mortality rates from cervical cancer (CC) among women of reproductive age, a nationwide screening program based on visual inspection with acetic acid was introduced in Mozambique in 2009. OBJECTIVE:The objective of the study is to examine the impact of per capita income on the effectiveness of school-based health education programs to promote the utilization of CC screening services. MATERIALS AND METHODS:We conducted a cross-sectional study in 2013 involving 105 women randomly selected from households of different economic backgrounds. Marginal effect estimates derived from a logit model were used to explore the patterns in the effectiveness of school-based health education to promote CC screening uptake according to household per capita income, based on purchasing power parity. RESULTS:We found a CC screening uptake of 16.1% (95% confidence interval [CI], 9.7%-24.6%) even though 64.6% (95% CI, 54.2%-74.1%) of women had heard of it. There are important economic differentials in the effectiveness of school-based health education to influence women's decision to receive CC screening. Among women with primary school or less, the probability of accessing CC screening services increases with increasing income (P < 0.05). However, income significantly reduces the effect that school-based health education has on the probability of screening uptake among those women with more than 7 years of educational attainment (P = 0.02). CONCLUSION:These results show that CC screening programs in resource-constrained settings need approaches tailored to different segments of women with respect to education and income to achieve equitable improvement in the levels of screening uptake.

Objective To quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations. Methods Over 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies. Results Staffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process. Conclusions Understanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue of Otolaryngology-Head and Neck Surgery featuring the updated Clinical Practice Guideline: Earwax (Cerumen Impaction). To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 11 recommendations emphasize proper ear hygiene, diagnosis of cerumen impaction, factors that modify management, evaluating the need for intervention, and proper treatment. An updated guideline is needed due to new evidence (3 guidelines, 5 systematic reviews, and 6 randomized controlled trials) and the need to add statements on managing cerumen impaction that focus on primary prevention, contraindicated intervention, and referral and coordination of care.

Introduction The time required to obtain Institutional Review Board (IRB) approval is a frequent subject of efforts to reduce unnecessary delays in initiating clinical trials. This study was conducted by and for IRB directors to better understand factors affecting approval times as a first step in developing a quality improvement framework. Methods 807 IRB-approved clinical trials from 5 University of California campuses were analyzed to identify operational and clinical trial characteristics influencing IRB approval times. Results High workloads, low staff ratios, limited training, and the number and types of ancillary reviews resulted in longer approval times. Biosafety reviews and the need for billing coverage analysis were ancillary reviews that contributed to the longest delays. Federally funded and multisite clinical trials had shorter approval times. Variability in between individual committees at each institution reviewing phase 3 multisite clinical trials also contributed to delays for some protocols. Accreditation was not associated with shorter approval times. Conclusions Reducing unnecessary delays in obtaining IRB approval will require a quality improvement framework that considers operational and study characteristics as well as the larger institutional regulatory environment.

This plain language summary serves as an overview in explaining earwax (cerumen). The summary applies to patients older than 6 months with a clinical diagnosis of earwax impaction and is based on the 2017 update of the Clinical Practice Guideline: Earwax (Cerumen Impaction). The evidence-based guideline includes research that supports diagnosis and treatment of earwax impaction. The guideline was developed to improve care by health care providers for managing earwax impaction by creating clear recommendations to use in medical practice.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an autoinflammatory disorder of childhood and little is known about the underlying etiology. While mutations involving the IL-1 pathway have been identified in other recurrent fever disorders, including TNF-receptor associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndrome (CAPS), there is no clear genetic basis for PFAPA. Patient data and detailed family histories were collected for over 170 children with recurrent fevers including 70 patients with PFAPA to create a prospective cohort over a 4-year period. DNA was isolated from blood or tonsillar tissue from recurrent fever patients, and NLRP3 and TNFRSF1A were sequenced. Quantitative real time PCR was used to evaluate IL-36 transcripts in tonsils. Our cohort reflects the diversity of San Diego, without predilection for any specific ethnic background. Family histories revealed 21% of patients have a first degree relative with recurrent fevers and 12% with tonsillitis in childhood, with only 1.4% reporting a history of recurrent infections. We have identified over 30 families with 2-8 affected members. These patients do not possess mutations commonly seen in other autoinflammatory disorders such as CAPS or TRAPS, suggesting that a novel gene may be involved. Upregulation of IL-36 gene expression in tonsils identifies the IL-1 family member IL-36 as a candidate gene. A substantial portion of our families with PFAPA report childhood histories of recurrent fevers that resolved either spontaneously or with tonsillectomy, indicating a possible dominantly inherited trait that impacts the developing immune system, including the tonsils.

OBJECTIVE:To determine rates of cerebrospinal fluid (CSF) leak, meningitis, and readmission in pediatric and adult patients with isolated basilar skull fracture. STUDY DESIGN:Cross-sectional analysis of a statewide database. SUBJECTS:Patients with isolated basilar skull fracture (1995-2010). METHODS:Patients were identified within the California Office of Statewide Health Planning and Development database using ICD-9 diagnosis codes. RESULTS:A total of 3563 pediatric and 10,761 adult patients met inclusion criteria. In-hospital rates of meningitis (0.48% and 0.64%, P = .3360) and CSF leak (2.33% and 1.75%, P = .0270) were similar among children and adults, respectively. Rates of 90-day meningitis (0.17% and 0.37%, P = .0714) and CSF leak (0.40% and 0.40%, P = .9823) were also similar. Thirty-day readmission was 4.6% for children compared with 12.4% for adults (P < .001). For both pediatric and adult patients, extra-axial hematoma (odds ratio [OR] [confidence interval {CI}] 1.65 [1.05-2.59] and 1.61 [1.34-1.95]) and comorbidities (OR [CI] 2.19 [1.11-4.34] and 1.28 [1.04-1.59]) were associated with significant increases in 30-day readmission. Loss of consciousness greater than 1 hour (OR, 3.05; 95% CI, 1.53-6.08) and CSF leak (OR, 3.28; 95% CI, 1.41-7.64) increased the likelihood of pediatric readmissions. Lack of insurance (OR, 0.67; 95% CI, 0.50-0.90) and female gender (OR 0.83; 95% CI, 0.70-0.99) reduced the likelihood of adult readmission. CONCLUSION:Meningitis and CSF leak following isolated basilar skull fractures are uncommon. Readmission within 30 days was more common in adults than in children. CSF leak, hematoma, and prolonged loss of consciousness increased the likelihood of readmission in children. Intracranial injury, male gender, having insurance, and comorbidities increased the likelihood of readmission in adults.