Viral Identification Using Multiplex Polymerase Chain Reaction Testing Does Not Reduce Antibiotic Prescribing in Paediatric Intensive Care Units.

PCR tests for viral identification, performed on nasopharyngeal secretions, have experienced a major boom in the last few years. Their use is very frequent, but their indications are still not well defined, especially in Paediatric Intensive Care Units (PICU). These tests are used for the microbiological diagnosis of lower respiratory infections but can be used in other situations. The aim of the study was to investigate the effect of viral identification on antibiotic therapy management. We conducted a single-centre retrospective study from 1 October 2017 to 31 December 2019. This study included all consecutive FilmArray® Respiratory Panel tests performed in patients hospitalised in a PICU. Patients were identified using the microbiology laboratory prospective database and data were extracted from the medical record. 544 tests corresponding to 408 patients were included. The main reasons for testing were pneumonia (34%) and bronchiolitis (24%). In 70% of cases, at least one virus was identified, with Human Rhinovirus (56%) and Respiratory Syncytial Virus (28%) being the two predominant. Bacterial co-infection was present in 25% of cases. Viral identification was not associated with reduced antibiotic therapy. On multivariate analysis, antibiotic management was significantly associated with clinical gravity, CRP value or radiology findings regardless of virus identification. Viral identification has an epidemiological value, but antibiotic prescription relies on other factors.

A Web-Based Platform for the Automatic Stratification of ARDS Severity

Acute respiratory distress syndrome (ARDS), including severe pulmonary COVID infection, is associated with a high mortality rate. It is crucial to detect ARDS early, as a late diagnosis may lead to serious complications in treatment. One of the challenges in ARDS diagnosis is chest X-ray (CXR) interpretation. ARDS causes diffuse infiltrates through the lungs that must be identified using chest radiography. In this paper, we present a web-based platform leveraging artificial intelligence (AI) to automatically assess pediatric ARDS (PARDS) using CXR images. Our system computes a severity score to identify and grade ARDS in CXR images. Moreover, the platform provides an image highlighting the lung fields, which can be utilized for prospective AI-based systems. A deep learning (DL) approach is employed to analyze the input data. A novel DL model, named Dense-Ynet, is trained using a CXR dataset in which clinical specialists previously labelled the two halves (upper and lower) of each lung. The assessment results show that our platform achieves a recall rate of

A Web-Based Platform for the Automatic Stratification of ARDS Severity.

Acute respiratory distress syndrome (ARDS), including severe pulmonary COVID infection, is associated with a high mortality rate. It is crucial to detect ARDS early, as a late diagnosis may lead to serious complications in treatment. One of the challenges in ARDS diagnosis is chest X-ray (CXR) interpretation. ARDS causes diffuse infiltrates through the lungs that must be identified using chest radiography. In this paper, we present a web-based platform leveraging artificial intelligence (AI) to automatically assess pediatric ARDS (PARDS) using CXR images. Our system computes a severity score to identify and grade ARDS in CXR images. Moreover, the platform provides an image highlighting the lung fields, which can be utilized for prospective AI-based systems. A deep learning (DL) approach is employed to analyze the input data. A novel DL model, named Dense-Ynet, is trained using a CXR dataset in which clinical specialists previously labelled the two halves (upper and lower) of each lung. The assessment results show that our platform achieves a recall rate of 95.25% and a precision of 88.02%. The web platform, named PARDS-CxR, assigns severity scores to input CXR images that are compatible with current definitions of ARDS and PARDS. Once it has undergone external validation, PARDS-CxR will serve as an essential component in a clinical AI framework for diagnosing ARDS.

Risk of Admission to the Pediatric Intensive Care Unit for SARS-CoV-2 Delta and Omicron Infections.

BACKGROUND: The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence of French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome in children (MIS-C) during the delta and omicron variant periods. METHODS: This study used the French PICU registry to obtain data on all patients admitted to 41 French PICUs diagnosed with acute COVID-19, incidental positive SARS-CoV-2 test result, or MIS-C between August 30, 2021 and April 20, 2022. Data regarding the total number of positive SARS-CoV-2 polymerase chain reaction results according to the type of variants were obtained from the French National Public Health Agency. RESULTS: Of 745 children, 244 (32.8%) were admitted for acute COVID-19, 246 (33.0%) for incidental positive SARS-CoV-2 test results, and 255 (34.2%) for MIS-C. The incidence of each group was higher with delta than with omicron. The incidence rate ratios with the delta variant were 7.47 (95% CI, 4.22-13.26) for acute COVID-19, 4·78 (95% CI, 2.30-9.94) for incidental positive SARS-CoV-2 test results, and 10.46 (95% CI, 5.98-18.31) for MIS-C compared to the omicron variant. The median age was 66 (7.7-126.8) months; 314 (42%) patients had comorbidities. Patients with acute COVID-19 and incidental positive SARS-CoV-2 test results had similar proportions of comorbidities. No patient with MIS-C died, whereas the mortality rates in the acute COVID-19 and incidental positive SARS-CoV-2 test results groups were 6.8% and 3.8%, respectively. CONCLUSIONS: The incidence of acute COVID-19, incidental positive SARS-CoV-2 test results, and MIS-C admitted to the PICU were significantly higher with the delta variant than with the omicron variant.

Autoimmune diseases and cancers overlapping with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A systematic review.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has various similarities with AQP4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG + NMOSD) in terms of clinical presentations, magnetic resonance imaging (MRI) findings, and response to treatment. But unlike AQP4-IgG + NMOSD, which is known to coexist with various autoimmune diseases and cancers, an association of MOGAD with these conditions is less clear. Methods: We conducted a systematic search in PubMed, Scopus, Web of Science, and Embase based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Duplicates were removed using Mendeley 1.19.8 (USA production) and the citations were uploaded into Covidence systematic review platform for screening. Results: The most common autoimmune disease overlapping with MOGAD was anti-N-Methyl-D-Aspartate receptor encephalitis (anti-NMDAR-EN), followed by autoimmune thyroid disorders, and the most common autoantibody was antinuclear antibody (ANA), followed by AQP4-IgG (double-positive MOG-IgG and AQP4-IgG). A few sporadic cases of cancers and MOG-IgG-associated paraneoplastic encephalomyelitis were found. Conclusion: Unlike AQP4-IgG + NMOSD, MOGAD lacks clustering of autoimmune diseases and autoantibodies associated with systemic and organ-specific autoimmunity. Other than anti-NMDAR-EN and perhaps AQP4-IgG + NMOSD, the evidence thus far does not support the need for routine screening of overlapping autoimmunity and neoplasms in patients with MOGAD.

COVID-19 and the risk of CNS demyelinating diseases: A systematic review

Background Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past 2 years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear. Objective To investigate the relationship between CNS demyelinating disease development and exacerbation with antecedent and/or concurrent SARS-CoV-2 infection. Methods A systematic literature review of all publications describing either a new diagnosis or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach. Results Sixty-seven articles met the inclusion criteria for the study. Most of the reported cases of NMOSD (n = 13, 72.2% of reported cases) and MOGAD (n = 27, 96.5% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases (n = 10, 10.5% of reported cases), relapses (n = 63, 66.4%) and pseudo-relapses (n = 22, 23.2%). The median duration between COVID-19 infection and demyelinating event onset was 11.5 days (range 0–90 days) in NMOSD, 6 days (range−7 to +45 days) in MOGAD, and 13.5 days (range−21 to +180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome. Conclusion Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low considering the prevalence of SARS-CoV-2 infection. The clinical outcomes of new onset or relapsing MS, NMOSD, or MOGAD associated with antecedent or concurrent infection were mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.

Consequences of Social Distancing Measures During the COVID-19 Pandemic First Wave on the Epidemiology of Children Admitted to Pediatric Emergency Departments and Pediatric Intensive Care Units: A Systematic Review.

Objectives: To synthesize knowledge describing the impact of social distancing measures (SDM) during the first wave of the COVID-19 pandemic on acute illness in children by focusing on the admission to pediatric emergency departments (PED) and pediatric intensive care units (PICU). Methods: We searched Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, EPOC Register, MEDLINE, Evidence-Based Medicine Reviews, EMBASE, WHO database on COVID-19, Cochrane Resources on COVID-19, Oxford COVID-19 Evidence Service, Google Scholar for literature on COVID-19 including pre-print engines such as medRxiv, bioRxiv, Litcovid and SSRN for unpublished studies on COVID-19 in December 2020. We did not apply study design filtering. The primary outcomes of interest were the global incidence of admission to PICU and PED, disease etiologies, and elective/emergency surgeries, compared to the historical cohort in each studied region, country, or hospital. Results: We identified 6,660 records and eighty-seven articles met our inclusion criteria. All the studies were with before and after study design compared with the historical data, with an overall high risk of bias. The median daily PED admissions decreased to 65% in 39 included studies and a 54% reduction in PICU admission in eight studies. A significant decline was reported in acute respiratory illness and LRTI in five studies with a median decrease of 63%. We did not find a consistent trend in the incidence of poisoning, but there was an increasing trend in burns, DKA, and a downward trend in trauma and unplanned surgeries. Conclusions: SDMs in the first wave of the COVID-19 pandemic reduced the global incidence of pediatric acute illnesses. However, some disease groups, such as burns and DKA, showed a tendency to increase and its severity of illness at hospital presentation. Continual effort and research into the subject should be essential for us to better understand the effects of this new phenomenon of SDMs to protect the well-being of children. Systematic Review Registration: Clinicaltrials.gov, identifier: CRD42020221215.

Neuro-Ophthalmological Complications of the COVID-19 Vaccines: A Systematic Review.

BACKGROUND: A worldwide mass vaccination campaign against the coronavirus disease 2019 (COVID-19) pandemic is currently underway. Although the safety data of the clinical trials did not report specific concerns regarding neuro-ophthalmological adverse events, they involved a limited number of individuals and were conducted over a relatively short time. The aim of the current review is to summarize the available postmarketing data regarding the occurrence of neuro-ophthalmological and other ocular complications of the COVID-19 vaccines. EVIDENCE ACQUISITION: Electronic searches for published literature were conducted using Ovid MEDLINE, Embase, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search strategy incorporated controlled vocabulary and free-text synonyms for the concepts of COVID, vaccines, and visual and neuro-ophthalmologic diseases and symptoms. RESULTS: A total of 14 case reports and 2 case series have been selected for inclusion in the final report, reporting 76 cases of post-COVID-vaccination adverse events. The most common adverse event was optic neuritis (n = 61), followed by uveitis (n = 3), herpes zoster ophthalmicus (n = 2), acute macular neuroretinopathy (n = 2), optic disc edema as an atypical presentation of Guillain-Barré syndrome (n = 1), (arteritic anterior ischemic optic neuropathy; n = 1), abducens nerve palsy (n = 1), oculomotor nerve palsy (n = 1), Tolosa-Hunt syndrome (n = 1), central serous retinopathy (n = 1), acute zonal occult outer retinopathy (n = 1), and bilateral choroiditis (n = 1). Most cases were treated with high-dose steroids and had a favorable clinical outcome. CONCLUSION: Since the implementation of the COVID-19 vaccination campaign in the past year, several post-COVID-vaccination neuro-ophthalmological complications have been described. However, considering the number of individuals that have been exposed to the vaccines, the risk seems very low, and the clinical outcome in most cases is favorable. Therefore, on a population level, the benefits of the vaccines far outweigh the risk of neuro-ophthalmological complications.

Educational Setting and SARS-CoV-2 Transmission Among Children With Multisystem Inflammatory Syndrome: A French National Surveillance System.

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C. Methods: We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening. Results: We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38). Conclusion: Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C.

Understanding Quality Paradigm Shifts in the Evolving Pharmaceutical Landscape: Perspectives from the USP Quality Advisory Group.

Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts. They also increasingly have recognized that quality needs to be built into systems and processes throughout the lifecycle of the product. Moreover, the recent COVID-19 crisis has emphasized the need to adopt practices that better promote global supply chain resilience. In this paper, the USP Quality Advisory Group explores the various paradigm shifts currently impacting pharmaceutical quality and the approaches that are being taken to adapt to this new environment. Broad adoption of the Analytical Procedure Lifecycle approach, improved data management, and utilization of digital technologies are identified as potential solutions that can help meet the challenges of these quality paradigm shifts. Further discussion and collaboration among stakeholders are needed to pursue these and other solutions that can ensure a continued focus on quality while facilitating pharmaceutical innovation and development.

Lessons from failure: neurosurgical outreach in Managua, Nicaragua.

With respect to the tremendous deficit in surgical care plaguing developing nations, it is critical that medical outreach models be organized in such a fashion that sustainable advancements can be durably imparted beyond the duration of targeted missions. Using a didactic framework focused on empowering host neurosurgeons with an enhanced surgical skillset, a mission was launched in Managua, Nicaragua, after previous success in Kiev, Ukraine, and Lima, Peru. Unfortunately, the failure to critically assess the internal and external state of affairs of the region's medical center compromised the outreach mission. Herein lies the visiting team's lessons from failure and insights on facilitating effective communication with host institutions, circumventing geopolitical instability, and utilizing digital collaboration and video-conferencing tools in the post-COVID-19 era to advance the surgical care of developing regions in a fashion that can be generationally felt.

Improving Medical Practice Management by Recording Interactions on Microsoft Teams

This article presents the ins and outs of recording interactions-including voice, chat and instant messaging, screen sharing, and video meetings-on the Microsoft Teams platform. It details the benefits of interaction recording, how to ensure regulatory compliance, how to choose a recording solution (i.e., what to look for and what to avoid), how to get started, and how to make it easy for users once it is up and running.

Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases.

BACKGROUND: The COVID-19 vaccines are currently recommended for people with rare neuroimmunological diseases such as neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody disease (MOGAD), and transverse myelitis. However, the safety profile of the vaccines in this population is uncertain. OBJECTIVE: To report real-world safety data of the COVID-19 vaccines in persons with rare neuroimmunological diseases. METHODS: An anonymous survey was distributed to patients recruited on social media. Participants answered general demographic and disease-related questions, and specific questions about their experiences with the COVID-19 vaccines. RESULTS: 438 participants completed the questionnaire. The median age was 51 (range 18-82 years); 366 were female (83.6%); 102 (23.3%) had associated comorbidities, and 354 (80.1%) were treated with immunotherapies. 242 participants (55.3%) reported a diagnosis of NMOSD; 99 (22.6%) had MOGAD; 79 (18%) had transverse myelitis. 239 participants (66.2%) were younger than 55 years of age. 138 participants (31.5%) reported earlyadverse events. Of these, 93 (67.4%) were < 55 years old, and 45 (32.6%) were > 55 years old (p=0.0086). The most common adverse events were local reactions, including pain, redness, and swelling at the injection site, reported by 155 participants (35.4%). 73 participants (16.7%) reported new or worsening neurological symptoms following the vaccination. Most symptoms occurred within the first week after vaccination and resolved within three days. CONCLUSIONS: This survey indicates an overall favorable safety and tolerability profile of the COVID-19 vaccines among persons with rare neuroimmunological diseases. Longer-term studies are warranted to confirm these data.

Home epinephrine-treated reactions in food allergy oral immunotherapy: Lessons from the coronavirus disease 2019 lockdown.

BACKGROUND: Oral immunotherapy (OIT) is effective in desensitizing patients with food allergy but adverse reactions limit its use. OBJECTIVE: To study the effect of the coronavirus disease 2019 lockdown in Israel between March 15, 2020, and April 30, 2020, on the incidence of home epinephrine-treated reactions. METHODS: All patients who were in the up-dosing phase of OIT for greater than or equal to 1 month during the lockdown, or a respective period in years 2015 to 2019, were studied. The incidence of home-epinephrine treated reactions during the 2020 lockdown was compared with that in the respective period in 2015 to 2019 and to periods before and after the lockdown. RESULTS: A total of 1163 OIT treatments were analyzed. Two epinephrine injections occurred during 2020 (0.7%) compared with 29 injections (3.28%) during 2015 to 2019 (P = .03). Patients treated in 2020 were older (8.1 vs 7 years, P < .01) and had a significantly lower single highest tolerated dose (12 vs 20 mg protein, P < .01). The rate of milk-OIT was lower (P = .01), but the total number of milk treatments was higher (99 vs 71 to 82) in 2020 compared with 2015 to 2019. On multivariate analysis, treatments during the 2020 lockdown were performed in older patients (P = .001), primarily for nonmilk (P = .03), began with a lower single highest tolerated dose (P = .006), and were associated with significantly less home epinephrine-treated reactions (P = .05) compared with those in 2015 to 2019. Patients treated in 2020 experienced more epinephrine-treated reactions in adjacent periods before (n = 8) and after (n = 6) the lockdown. CONCLUSION: The lower rate of home epinephrine-treated reactions during the coronavirus disease 2019 lockdown in Israel suggests that potentially avoidable triggers contribute significantly to the rate of adverse reactions during OIT.

Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children mimicking Kawasaki disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors, including age>70 years, obesity, diabetes, systemic hypertension and other underlying diseases. During the second week of viral pneumonia, acute respiratory distress syndrome can occur and carries high mortality. Unlike most common respiratory viruses, children seem to be less susceptible to SARS-CoV-2 infection, and generally develop mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have recently been described. Both the clinical symptoms (i.e. high and persistent fever, gastrointestinal disorders, skin rash, conjunctival injection and dry cracked lips) and the biological signs (e.g. elevated C-reactive protein/procalcitonin and high levels of ferritinaemia) mimicked Kawasaki disease. In most cases, intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days. Adjunctive steroid therapy and sometimes biotherapy (e.g. anti-interleukin 1Ra and anti-interleukin 6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them later developed coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory syndrome in children" related to SARS-CoV-2 has recently been described. Similarities with Kawasaki disease and the physiopathology of this syndrome still need further exploration.

The impact of the COVID-19 pandemic on rabies reemergence in Latin America: The case of Arequipa, Peru.

In Latin America, there has been tremendous progress towards eliminating canine rabies. Major components of rabies elimination programs leading to these successes have been constant and regular surveillance for rabid dogs and uninterrupted yearly mass dog vaccination campaigns. Unfortunately, vital measures to control COVID-19 have had the negative trade-off of jeopardizing these rabies elimination and prevention activities. We aimed to assess the effect of interrupting canine rabies surveillance and mass dog vaccination campaigns on rabies trends. We built a deterministic compartment model of dog rabies dynamics to create a conceptual framework for how different disruptions may affect rabies virus transmission. We parameterized the model for conditions found in Arequipa, Peru, a city with active rabies virus transmission. We examined our results over a range of plausible values for R0 (1.36-2.0). Also, we prospectively evaluated surveillance data during the pandemic to detect temporal changes. Our model suggests that a decrease in canine vaccination coverage as well as decreased surveillance could lead to a sharp rise in canine rabies within months. These results were consistent over all plausible values of R0. Surveillance data from late 2020 and early 2021 confirms that in Arequipa, Peru, rabies cases are on an increasing trajectory. The rising rabies trends in Arequipa, if indicative to the region as whole, suggest that the achievements made in Latin America towards the elimination of dog-mediated human rabies may be in jeopardy.