Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

MTS in False Positive Reduction for Multi-Sensor Fusion

The Mahalanobis Taguchi System (MTS) is a relatively new tool in the vehicle health maintenance domain, but has some distinct advantages in current multi-sensor implementations. The use of Mahalanobis Spaces (MS) allows the algorithm to identify characteristics of sensor signals to identify behaviors in machines. MTS is extremely powerful with the caveat that the correct variables are selected to form the MS. In this research work, 56 sensors monitor various aspects of the vehicles. Typically, using the MTS process, identification of useful variables is preceded by validation of the measurements scale. However, the MTS approach doesn\u27t directly include any mitigating steps should the measurement scale not be validated. Existing work has performed outlier removal in construction of the MS, which can lead to better validation. In our approach, we modify the outlier removal process with more liberal definitions of outliers to better identify variables\u27 impact prior to identification of useful variables. This subtle change substantially lowered the false positive rate due to the fact that additional variables were retained. Traditional MTS approaches identify useful variables only to the extent they provide usefulness in identifying the positive (abnormal) condition. The impact of removing false negatives is not included. Initial results show our approach can reduce false positive values while still maintaining complete fault identification for this vehicle data set

Where Do We Go From Here? Assessing Medical Students' Surgery Clerkship Preparedness During COVID-19.

IntroductionThe impact of COVID-19 on surgical education has been profound, and clinical learning experiences transitioned to virtual formats. This study investigated the impact of virtual experiences created to facilitate learning during the pandemic for medical students.MethodsWe performed a cohort study to determine the perceived clinical preparedness for medical students enrolled in the preclinical surgery pilot course, surgical Extended Mastery Learning Rotation (EMLR), and longitudinal surgical clerkship (LC). The preclinical surgery pilot course took place before COVID-19 disruptions, and the EMLR and LC experiences took place virtually. Specialty choice was examined in the EMLR and LC cohorts. Performance on the NBME surgical assessments was analyzed among students enrolled in the traditional clerkship and pandemic-disrupted courses and compared to national data using a two-sample t-test.ResultsCompared to preclinical students, EMLR and LC students demonstrated improvements in their perceived surgical clerkship readiness. After the 3-week EMLR course, in the setting of completing only one-third of the clerkship year, students had an average NBME Surgical Self-Assessment Exam score of 72 (SD 12), comparable to the national average of 71 (SD 9) p = 0.33. The average shelf exam score for students (N = 24) enrolled in the traditional clerkship (block 1), prior to COVID-19, disruptions was 66 (SD 9) compared to an average score of 69 (SD 9) for the longitudinal clerkship students (N = 20) that took the shelf exam later in the year (p = 0.36). COVID-19 disruptions did not affect specialty choice. All LC students have decided on a specialty; 50% nonsurgical and 50% surgical. From the EMLR cohort, 36% and 38% plan to pursue surgical and nonsurgical specialties, respectively, with 26% still undecided.ConclusionsCourses were well-liked and will be implemented in future clerkships. Surgical educators demonstrated flexibility and creativity in the development of the EMLR. Despite COVID-19 disruptions, medical students made progress in their clinical skills and foundational science knowledge. COVID-19 disruptions did not appear to impact specialty choice

Where Do We Go From Here? Assessing Medical Students' Surgery Clerkship Preparedness During COVID-19.

IntroductionThe impact of COVID-19 on surgical education has been profound, and clinical learning experiences transitioned to virtual formats. This study investigated the impact of virtual experiences created to facilitate learning during the pandemic for medical students.MethodsWe performed a cohort study to determine the perceived clinical preparedness for medical students enrolled in the preclinical surgery pilot course, surgical Extended Mastery Learning Rotation (EMLR), and longitudinal surgical clerkship (LC). The preclinical surgery pilot course took place before COVID-19 disruptions, and the EMLR and LC experiences took place virtually. Specialty choice was examined in the EMLR and LC cohorts. Performance on the NBME surgical assessments was analyzed among students enrolled in the traditional clerkship and pandemic-disrupted courses and compared to national data using a two-sample t-test.ResultsCompared to preclinical students, EMLR and LC students demonstrated improvements in their perceived surgical clerkship readiness. After the 3-week EMLR course, in the setting of completing only one-third of the clerkship year, students had an average NBME Surgical Self-Assessment Exam score of 72 (SD 12), comparable to the national average of 71 (SD 9) p = 0.33. The average shelf exam score for students (N = 24) enrolled in the traditional clerkship (block 1), prior to COVID-19, disruptions was 66 (SD 9) compared to an average score of 69 (SD 9) for the longitudinal clerkship students (N = 20) that took the shelf exam later in the year (p = 0.36). COVID-19 disruptions did not affect specialty choice. All LC students have decided on a specialty; 50% nonsurgical and 50% surgical. From the EMLR cohort, 36% and 38% plan to pursue surgical and nonsurgical specialties, respectively, with 26% still undecided.ConclusionsCourses were well-liked and will be implemented in future clerkships. Surgical educators demonstrated flexibility and creativity in the development of the EMLR. Despite COVID-19 disruptions, medical students made progress in their clinical skills and foundational science knowledge. COVID-19 disruptions did not appear to impact specialty choice

Third year medical student knowledge gaps after a virtual surgical rotation

IntroductionThis study describes perceived knowledge gaps of third-year medical students after participating in a virtual surgical didactic rotation (EMLR) and shortened in-person surgery rotation during the COVID-19 Pandemic.MethodsOpen-ended and Likert questions were administered at the end of the virtual rotation and inperson-surgical rotation to medical students. Three blinded coders identified themes by semantic analysis.Results82 students (51% of all MS3s) participated in the EMLR. Semantic analysis revealed gaps in perioperative management (Post-EMLR:18.4%, Post-Inpatient:26.5%), anatomy (Post-EMLR:8.2%, PostInpatient:26.5%). and surgical skills (Post-EMLR: 43.0%, Post-Inpatient: 44.1%). Students also described gaps related to OR etiquette (Post-EMLR: 12.2%, Post-Inpatient: 8.8%) and team dynamics/the hidden curriculum (Post- Inpatient:26.6%). There was a significant improvement in perceived confidence to perform inpatient tasks after completing the inpatient clinical experience (p ≤ 0.01).ConclusionVirtual interactive didactics for cognitive skills development cannot replace a full clinical surgical experience for third-year medical students. Future curricula should address perceived gaps

Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation

Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants