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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. [ABSTRACT FROM AUTHOR]

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 otolaryngological 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. 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. 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). MLF is the most common cause of pediatric basilar skull fractures. However, there is limited information on the appropriate work-up or otolaryngologic follow-up for this mechanism of injury. Our retrospective 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 otolaryngology follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Background: Upper airway obstruction in children with Pierre Robin sequence (PRS) may be severe enough to require surgical intervention. Although many studies have demonstrated the effectiveness of mandibular distraction osteogenesis (MDO) in relieving airway obstruction, no study has reported health-related quality of life (QOL) outcomes. The objective of the present study was to conduct the first health-related QOL assessment post-MDO. Methods: The Glasgow Children''s Benefit Inventory (GCBI) questionnaire was distributed in a retrospective manner to the caregivers of all children who had undergone MDO at the authors’ institutions between January 2007 and December 2010. Patients who had other major surgical procedures were excluded. Results: The response rate was 84% (21 of 25 questionnaires completed). The total mean GCBI score was +54 (SD, 19.5), which demonstrated a subjective overall benefit in health-related QOL post-MDO. All of the domains within the GCBI also scored in the positive range, indicating domain specific improvements in health-related QOL. There were no significant differences in the GCBI scores between syndromic-PRS patients and isolated PRS patients; similar results were observed between tracheostomy patients and no tracheostomy patients. Summary: In treating children with PRS and severe upper airway obstruction, MDO resulted in a subjective overall benefit in health-related QOL in our study population. [Copyright &y& Elsevier]

Abstract: Introduction: In addition to upper airway obstruction, many patients with micrognathia and Pierre Robin sequence also have swallowing abnormalities and reflux. Many studies have demonstrated the effectiveness in alleviating the airway symptoms with mandibular distraction osteogenesis, but very few studies have focused on feeding and reflux outcomes. Methods: A retrospective chart review was performed to identify patients with Pierre Robin sequence who underwent mandibular distraction osteogenesis with completed pre- and post-operative upper gastroesophageal series and videofluoroscopic swallow assessments. Results: All six children in our series demonstrated significant improvements in both airway obstructive symptoms and feeding abnormalities. More specifically, all patients showed clinical and objective improvements in reflux and swallowing function after distraction surgery. Conclusion: Objective and symptomatic improvements in swallowing function and reflux disease can be seen after mandibular distraction osteogenesis in children with Pierre Robin sequence. [Copyright &y& Elsevier]

Abstract: Introduction: Ankyloglossia is a congenital condition in which tongue mobility is limited due to an abnormality of the lingual frenulum. The impact of ankyloglossia on breastfeeding is poorly understood but there is a recent trend toward more recognition of this condition and early intervention when needed. Currently, there lacks clear definition of ankyloglossia and different subtypes have been proposed with no clinical correlation. Objective: To determine the prevalence of anterior versus posterior ankyloglossia in a large series of consecutive patients and to assess clinical outcomes after frenotomy. Methods: Retrospective chart review of patients from July 2007 to July 2009 who were diagnosed with ankyloglossia and underwent office frenotomy. Baseline characteristics, specific feeding issues, type of ankyloglossia, and clinical outcomes after frenotomy were reviewed. Results: Of the 341 total patients, 322 (94%) had anterior ankyloglossia and 19 (6%) had posterior ankyloglossia. Median age at presentation was 2.7 weeks (range 1 day of life to 24 weeks); 227 were males and 114 were females. Revision frenotomy rates were significantly higher for the posterior ankyloglossia group (3.7% anterior and 21.1% posterior, p =0.008). Conclusion: Anterior ankyloglossia is much more common and readily managed when compared to posterior ankyloglossia. Posterior ankyloglossia is a poorly recognized condition that may contribute to breastfeeding difficulties. The diagnosis is difficult due to the subtle clinical findings but relevant health care providers should be aware of this condition. Frenotomy is a simple, safe, and effective intervention for ankyloglossia which improves breastfeeding. [ABSTRACT FROM AUTHOR]

Las roturas parciales del manguito rotador no son una única entidad, sino que más bien representan un espectro de diferentes estados de la misma patología. Además, aunque muchas veces son asintomáticas, pueden llegar a ser muy incapacitantes. Los deportistas que realizan lanzamientos sobre la cabeza y que tienen roturas parciales del manguito rotador se diferencian de los pacientes mayores no deportistas con roturas degenerativas del mismo en su etiología, objetivos y tratamiento. La patogenia de las roturas degenerativas parciales del manguito rotador es multifactorial, y existen indicios de que ciertos factores intrínsecos y extrínsecos desempeñan un importante papel en ellas. El diagnóstico de las roturas parciales del manguito rotador debe basarse en los síntomas de cada paciente y en las imágenes de resonancia magnética. En la mayoría de los casos el tratamiento conservador tiene éxito. Por eso la cirugía normalmente se tiene en cuenta en pacientes que presenten síntomas de suficiente duración e intensidad. Todavía no conocemos bien el papel de la acromioplastia, aunque deberemos considerarla cuando haya causas extrínsecas de rotura parcial del manguito rotador. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Despite numerous studies evaluating the anabolic effects of intermittent administration of parathyroid hormone (PTH) on bone, there are no published studies examining its effect on spinal fusion outcomes. Purpose: To determine the effect of daily injection of human recombinant PTH(1–34) on posterolateral lumbar fusions in a rat model. Study design: Prospective, case-controlled, preclinical animal study. Outcome measures: Manual palpation and serum osteocalcin. Methods: Single-level, intertransverse process spinal fusions were performed with iliac crest autograft in 56 Sprague-Dawley rats. Animals received daily injections of placebo or PTH(1–34). At 6 weeks, fusion masses were assessed by manual palpation. Serum osteocalcin levels were assessed in a subset of the animals. Results: Manual palpation revealed the control group to have a fusion rate of 37% (10/27) and the PTH(1–34)-treated group to have a fusion rate of 52% (15/29). Mean serum osteocalcin levels were 59.8 and 88.6 ng/L for the control and PTH(1–34) groups, respectively. Conclusions: There was a trend towards greater fusion rate in the PTH(1–34) group as compared with the placebo group. Further, PTH(1–34) administration was associated with a significant increase in osteocalcin levels. Certainly, further investigations are warranted, as an injectable agent capable of increasing fusion rates would be of great clinical value. [Copyright &y& Elsevier]

Summary: Objective: To evaluate olfactory function in children with blunt head trauma. Methods: Eligible subjects were consecutive children presenting at San Diego Children''s Hospital Emergency Department or Trauma Service with blunt head trauma. Thirty-seven head injured children mean age 10.11±2.74 were evaluated; 36 healthy age and gender matched community children, mean age 10.08±2.99, served as controls. The medical record was reviewed for clinical measures related to head injury (HI). All children underwent olfactory assessment with the San Diego Children''s Odor Identification Test (SDOIT). Olfactory event-related potentials were recorded on a subset of head injured and control children. Results: Three of 37 head injured children had olfactory dysfunction. The head injured hyposmics had signs of more severe head injury represented by lower Glasgow Coma Scores (GCS), 10.33±5.51, when compared to their normosmic counterparts with mean GCS of 14.06±2.82. When stratifying the head injured children by clinical measures, lower Glasgow Coma Score, and abnormalities on head CT scan were associated with poorer olfactory performance. Conclusion: Children with blunt head injury may suffer post-traumatic olfactory impairment. More severe head injuries are more likely to produce olfactory deficits. In cases of significant head injury, cranial nerve I evaluation is imperative. [Copyright &y& Elsevier]

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. • Undefined recurrent fevers comprise a large subset of autoinflammatory patients. • Tonsils from undefined recurrent fever patients are distinct from PFAPA syndrome. • Undefined recurrent fever tonsils have an IL-1 signature. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

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.

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Unprecedented 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., Methods: We 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 Number: CRD42018095138., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 Association for Clinical and Translational Science 2018.)

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.

Objective: Evaluate clinical and radiographic characteristics of spontaneously regressing lymphatic malformations ("lesions")., Subjects and Methods: Retrospective review of 104 consecutive patients with cervicofacial lesions, with 1-year follow-up., Data Collected: patient's age; lesion stage, location, radiographic characteristics; treatment. Data analysis using descriptive and Fischer exact tests., Results: Spontaneously regressing lesions were identified in 13 of 104 (12.5%) patients. Five of 13 had in utero lesions, which persisted at birth; presenting age in the remaining eight patients was 2 to 138 months. Lesions regressed within 2 to 7 months. Lesion stage: I (7 of 13), II (2 of 13), III (4 of 13). Lesion location: left neck (9 of 13), right neck (4 of 13), posterior neck (10 of 13). All 13 resolving lesions were macrocystic with fewer than five septations in 11 of 13. Comparison of a resolving lesion cohort with a nonresolving lesion cohort demonstrated that disappearing lesions are more likely to have fewer than five septae and to be macrocystic (P < 0.05). Treatment was none in seven of 13, antibiotics in four of 13, and redundant skin excision in two of 13., Conclusion: Spontaneous lesion regression can occur, and these lesions have distinct features. Lesions with these characteristics can be observed.

We describe a male neonate who presented at birth with a compressible dermoid cyst that extended from the floor of the mouth to the midline of the neck. Ultrasonography revealed a fluid-filled sublingual mass. Magnetic resonance imaging performed when the patient was 1 week old demonstrated a 2-cm, cystic, left-sided, sublingual mass that crossed the midline without extension inferior to the mylohyoid muscle. At 3 months of age, the patient developed a 1-cm, solid, submental mass. At the time of surgery, the lesion had a fibromembranous tract that extended through the myolohyoid muscle to a 1-cm cyst in the submental region. Histologic sections depicted 2 dermoid cysts and a connecting fistula. This case represents the first report (to our knowledge) of a dermoid cyst presenting in a neonate as a mass in the floor of the mouth with extension to the midline of the neck.

Objectives: To continue assessment of the benefits and risks of intralesional administration of cidofovir, an acyclic nucleoside phosphonate, for treating severe recurrent respiratory papillomatosis (RRP) in pediatric patients, and to discuss guidelines for larger prospective multi-institutional studies of the use of cidofovir., Design: Prospective case series., Setting: Tertiary care children's hospital., Patients: A total of 10 patients with severe RRP (defined as requiring debulking procedures to maintain airway patency at least once a month) underwent intralesional cidofovir therapy. The original 5 patients have received more than 1 year of follow-up since their last cidofovir injection, and 5 subsequent patients have been treated with a revised injection protocol., Intervention: Microsuspension laryngoscopy with intralesional injection of cidofovir after repetitive carbon dioxide laser treatments and mechanical debulking of papillomas., Main Outcome Measures: Papilloma stage at the time of serial laryngoscopies. Histologic examination of biopsy specimens of laryngeal tissue obtained 1 year or more after last cidofovir injection., Results: There was evidence of marked improvement in the 4 of the 5 new patients enrolled under the revised injection protocol, continuation of a disease-free state in 1 of the original 5 patients, and sustained improvement in 4 of the 5 original patients, resulting in a significantly reduced interval of intervention., Conclusions: Intralesional cidofovir therapy continues to show benefit in the treatment of severe RRP in pediatric patients. Safety profiles have not been fully established, but current histologic data are reassuring.

Objective: To assess the potential benefit of intralesional administration of cidofovir, an acyclic nucleoside phosphonate with activity against several DNA viruses, for treating severe respiratory papillomas in pediatric patients., Design: Prospective case series., Setting: Tertiary care children's hospitals., Patients: Five pediatric patients with severe recurrent respiratory papillomatosis requiring laryngoscopy with carbon dioxide laser therapy more frequently than once a month to maintain airway patency. Each patient underwent between 12 and 33 laryngoscopies with laser treatment prior to being injected with cidofovir., Intervention: Microsuspension laryngoscopy with intralesional injection of cidofovir (Vistide) in conjunction with mechanical debulking and carbon dioxide laser of papillomas., Main Outcome Measure: Papilloma stage at time of serial laryngoscopies., Results: One patient was disease free and 3 patients demonstrated a dramatic response to adjuvant therapy with cidofovir at the 9-month follow-up visit after the last injection of cidofovir. One patient showed an improvement in papilloma stage that was possibly related to concurrent therapy with interferon., Conclusions: Intralesional injection of cidofovir seems to be of benefit in the treatment of severe respiratory papillomatosis in pediatric patients. Larger prospective studies with longer follow-up will be required before cidofovir can be considered an accepted means of managing this difficult disease.

Objective: To determine if the polymerase chain reaction (PCR) can detect bacterial DNA in pediatric middle ear effusions that are sterile by standard cultural methods., Design: Single-center, blinded, comparative study of diagnostic assays. The PCR-based detection systems for Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae were designed and validated using a battery of DNAs obtained from cultured bacteria. Chronic middle ear effusion specimens were collected and comparatively analyzed by culture and the PCR., Setting: Tertiary care pediatric hospital., Patients: A total of 97 middle ear effusions were collected from pediatric outpatients at Children's Hospital of Pittsburgh (Pa) during myringotomy and tube placement for chronic otitis media with effusion (duration > 3 months). All patients had failed multiple courses of antimicrobial therapy and were diagnosed by a combination of validated otoscopy and tympanograms., Main Outcome Measure: Differences in the percentage of positive test results between PCR-based assays and culture for M catarrhalis, H influenzae, and S pneumoniae., Results: Of the 97 specimens of otitis media with effusion, 28 (28.9%) tested positive by both culture and PCR for M catarrhalis, H influenzae, or S pneumoniae. An additional 47 specimens (48%) were PCR positive/culture negative for these three bacterial species. Thus, 75 (77.3%) of the 97 specimens tested PCR positive for one or more of the three test organisms. The minimum number of bacterial genomic equivalents present in the average culture-negative ear was estimated to be greater than 10(4) based on dilutional experiments., Conclusions: The PCR-based assay systems can detect the presence of bacterial DNA in a significant percentage of culturally sterile middle ear effusions. While this finding is not proof of an active bacterial infectious process, the large number of bacterial genomic equivalents present in the ears is suggestive of an active process.

In 90% of children, otitis media with effusion resolves within 3 months. When it persists longer, it is considered chronic. Initial treatment of chronic otitis media with effusion is repeated courses of antibiotics, and a short course of steroids may be appropriate. Use of antihistamines and decongestants has not been shown to be efficacious, although they may be beneficial when inhalant allergies contribute to eustachian tube dysfunction. Persistent effusion leads to conductive hearing loss, which may have a significant impact on language, speech, and intellectual development. Thus, surgical therapy consisting of insertion of tympanostomy tubes and, in selected cases, adenoidectomy is indicated to improve hearing and prevent long-term sequelae.