Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

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.

A review of prospective pathways and impacts of COVID-19 on the accessibility, safety, quality, and affordability of essential medicines and vaccines for universal health coverage in Africa.

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.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

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-1ß 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.

Biologic Therapy in Pediatric Chronic Rhinosinusitis: A Systematic Review.

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.

Measuring income-associated inequalities in COVID-19 vaccination on a global scale: a modeling study.

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.

Perceptions of Pediatric Endocrinologists and Neurologists on the Drivers of Telehealth Use.

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.

Pediatric basilar skull fractures from multi-level falls: A systematic review and retrospective analysis.

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 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. 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 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.

Use of Telehealth Across Pediatric Subspecialties Before and During the COVID-19 Pandemic.

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.

Chronic esophageal foreign bodies and secondary mediastinitis in children.

OBJECTIVES: The purpose of this study was to review the clinical presentation, diagnosis, and management of chronic esophageal foreign bodies complicated by mediastinitis in children. METHODS: A retrospective study of children with a chronic esophageal foreign body and secondary mediastinal complications diagnosed at Rady Children's Hospital in San Diego over a 12-month period is reported. RESULTS: Three patients received a diagnosis of an esophageal foreign body, retained from 1 to 12 months, and mediastinitis. Each patient presented primarily with respiratory signs and had been treated previously for alternate diagnoses (ie, asthma, reflux, and upper respiratory tract infection) by emergency or pediatric providers. The diagnosis of a foreign body was made after a chest radiograph was examined. Operative airway evaluation confirmed tracheal narrowing in all patients, and a computed tomographic scan of the chest was performed after removal of the foreign body to confirm mediastinal involvement. After medical and/or surgical treatment, the patients were released from the hospital tolerating soft diets. There were no reports of long-term complications in our series of patients. CONCLUSIONS: It is critical to rule out esophageal and airway foreign bodies in pediatric patients with respiratory symptoms that do not respond to medical treatment. Timely recognition of an esophageal foreign body generally allows for removal with minimal morbidity, whereas the incidence of serious complications increases significantly when the diagnosis is delayed. Our series provides support for conservative management of mediastinal complications after removal of chronically retained esophageal foreign bodies in children.

Equal Access to Telemedicine during COVID-19 Pandemic: A Pediatric Otolaryngology Perspective.

OBJECTIVES/HYPOTHESIS: During the current COVID-19 pandemic, the demand for direct-to-home telemedicine services has risen to an unprecedented level. Equal access to specialty care was assessed to identify potential barriers that may negatively impact telemedicine utilization. STUDY DESIGN: Retrospective case series. METHODS: We examined the 6-week period between March and May 2020 when the only access to nonurgent pediatric otolaryngology service was through telemedicine and compared it to in-person visits during the same period in 2019. We compared patient demographics, including age, gender, preferred language, zip code of residence, and primary insurance plan. RESULTS: A total of 1,495 visits were conducted through telemedicine from March 23, 2020 to May 1, 2020, and 1983 in-person visits were completed in 2019. There was no difference in patient age and gender. The proportions of Spanish-speaking families were similar (15.8% in 2019 vs. 14.4% in 2020, P = .96). The percentage of Medi-Cal-insured patients (51.4% in 2019 vs. 49.8% in 2020, P = .73) and the mean poverty level (12.6% in 2019 vs. 12.2% in 2020, P = .38) also remained the same. Spanish-speaking families were statistically more likely to require rescheduling of their telemedicine visits (17.2%) when compared to the overall rescheduling rate of 11.9% (P = .0083). CONCLUSIONS: We were able to successfully provide access to telemedicine services to our vulnerable populations during the current COVID-19 pandemic. Telemedicine is likely to remain an essential mode of delivering patient care going forward. It is important to evaluate and identify potential disparities to telemedicine access and proactively implement changes to address these barriers. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:1175-1179, 2021.

Pediatric Basilar Skull Fracture Mechanisms and Trends From 2007 to 2018.

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.

What does the COVID-19 pandemic mean for HIV, tuberculosis, and malaria control?

Despite its current relatively low global share of cases and deaths in Africa compared to other regions, coronavirus disease 2019 (COVID-19) has the potential to trigger other larger crises in the region. This is due to the vulnerability of health and economic systems, coupled with the high burden of human immunodeficiency virus (HIV), tuberculosis (TB), and malaria. Here we examine the potential implications of COVID-19 on the control of these major epidemic diseases in Africa. We use current evidence on disease burden of HIV, TB, and malaria, and epidemic dynamics of COVID-19 in Africa, retrieved from the literature. Our analysis shows that the current measures to control COVID-19 neglect important and complex context-specific epidemiological, social, and economic realities in Africa. There is a similarity of clinical features of TB and malaria, with those used to track COVID-19 cases. This coupled with institutional mistrust and misinformation might result in many patients with clinical features similar to those of COVID-19 being hesitant to voluntarily seek care in a formal health facility. Furthermore, most people in productive age in Africa work in the informal sector, and most of those in the formal sector are underemployed. With the current measures to control COVID-19, these populations might face unprecedented difficulties to access essential services, mainly due to reduced ability of patients to support direct and indirect medical costs, and unavailability of transportation means to reach health facilities. Therefore, if not accompanied with appropriate economic and epidemiological considerations, we anticipate that these measures might result in unprecedented difficulties among vulnerable segments of society to access essential services, including antiretroviral and prophylactic drugs among people living with HIV and Acquired Immune Deficiency Syndrome, anti-tuberculosis drugs, and curative and preventive treatments for malaria among pregnant women and children. This might increase the propensity of patients taking substandard doses and/or medicines, which has the potential to compromise drug efficacy, and worsen health inequalities in the region. COVID-19 responses at country level should include measures to protect vulnerable and under-served segments of society.

A survey of adult preferences regarding recruitment for pediatric research.

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.

Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in Africa: a systematic analysis of national trends.

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.

The role of tonsillectomy in reducing recurrent pharyngitis: a systematic review.

OBJECTIVE: To determine the evidence for efficacy of tonsillectomy in reducing the incidence of recurrent pharyngitis. DATA SOURCES: Literature databases consisting of PUBMED, SCOPUS, CINHAL AND OVID EMBASE including all languages. REVIEW METHODS: Literature search of database by 2 authors with structured criteria using an online database. Selected studies evaluated with meta-analysis. RESULTS: In four randomized, controlled trials tonsillectomy was favored over medical therapy in reducing pharyngitis. The difference was statistically significant in only one study. Overall meta-analysis results were significant, indicating that tonsillectomy results in a reduction of about 43% in the incidence of pharyngitis. The number needed to treat with tonsillectomy to prevent one sore throat per month for the first year after surgery was 11 (95% CI; 7-23). CONCLUSION: Tonsillectomy reduces the incidence of recurrent pharyngitis to a modest degree.

Trends in comparative efficacy and safety of malaria control interventions for maternal and child health outcomes in Africa: a study protocol for a Bayesian network meta-regression exploring the effect of HIV and malaria endemicity spectrum.

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.

Clinical and radiographic findings in children with spontaneous lymphatic malformation regression.

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.

Clinical practice guideline: cerumen impaction.

OBJECTIVE: This guideline provides evidence-based recommendations on managing cerumen impaction, defined as an accumulation of cerumen that causes symptoms, prevents assessment of the ear, or both. We recognize that the term "impaction" suggests that the ear canal is completely obstructed with cerumen and that our definition of cerumen impaction does not require a complete obstruction. However, cerumen impaction is the preferred term since it is consistently used in clinical practice and in the published literature to describe symptomatic cerumen or cerumen that prevents assessment of the ear. This guideline is intended for all clinicians who are likely to diagnose and manage patients with cerumen impaction. PURPOSE: The primary purpose of this guideline is to improve diagnostic accuracy for cerumen impaction, promote appropriate intervention in patients with cerumen impaction, highlight the need for evaluation and intervention in special populations, promote appropriate therapeutic options with outcomes assessment, and improve counseling and education for prevention of cerumen impaction. In creating this guideline the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of audiology, family medicine, geriatrics, internal medicine, nursing, otolaryngology-head and neck surgery, and pediatrics. RESULTS: The panel made a strong recommendation that 1) clinicians should treat cerumen impaction that causes symptoms expressed by the patient or prevents clinical examination when warranted. The panel made recommendations that 1) clinicians should diagnose cerumen impaction when an accumulation of cerumen is associated with symptoms, or prevents needed assessment of the ear (the external auditory canal or tympanic membrane), or both; 2) clinicians should assess the patient with cerumen impaction by history and/or physical examination for factors that modify management, such as one or more of the following: nonintact tympanic membrane, ear canal stenosis, exostoses, diabetes mellitus, immunocompromised state, or anticoagulant therapy; 3) the clinician should examine patients with hearing aids for the presence of cerumen impaction during a healthcare encounter (examination more frequently than every three months, however, is not deemed necessary); 4) clinicians should treat the patient with cerumen impaction with an appropriate intervention, which may include one or more of the following: cerumenolytic agents, irrigation, or manual removal other than irrigation; and 5) clinicians should assess patients at the conclusion of in-office treatment of cerumen impaction and document the resolution of impaction. If the impaction is not resolved, the clinician should prescribe additional treatment. If full or partial symptoms persist despite resolution of impaction, alternative diagnoses should be considered. The panel offered as an option that 1) clinicians may observe patients with nonimpacted cerumen that is asymptomatic and does not prevent the clinician from adequately assessing the patient when an evaluation is needed; 2) clinicians may distinguish and promptly evaluate the need for intervention in the patient who may not be able to express symptoms but presents with cerumen obstructing the ear canal; 3) the clinician may treat the patient with cerumen impaction with cerumenolytic agents, irrigation, or manual removal other than irrigation; and 4) clinicians may educate/counsel patients with cerumen impaction/excessive cerumen regarding control measures. DISCLAIMER: This clinical practice guideline is not intended as a sole source of guidance in managing cerumen impaction. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.

Impact of Per Capita Income on the Effectiveness of School-Based Health Education Programs to Promote Cervical Cancer Screening Uptake in Southern Mozambique.

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.

Systems approach to assessing and improving local human research Institutional Review Board performance.

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.