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

ObjectiveTo quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.MethodsOver 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.ResultsStaffing 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.ConclusionsUnderstanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics

A multisite study of performance drivers among institutional review boards.

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

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

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

Objectives/hypothesisDuring 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 designRetrospective case series.MethodsWe 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.ResultsA 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).ConclusionsWe 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 evidence4. Laryngoscope, 131:1175-1179, 2021

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.

ObjectiveTo quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.MethodsOver 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.ResultsStaffing 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.ConclusionsUnderstanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics

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

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 &lt; 0.01), CD19+ B cells (51% vs. 35%, p &lt; 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p &lt; 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