Adapting Elements of Cleft Care Protocols in Low- and Middle-income Countries During and After COVID-19: A Process-driven Review With Recommendations.

A consortium of global cleft professionals, predominantly from low- and middle-income countries, identified adaptations to cleft care protocols during and after COVID-19 as a priority learning area of need.A multidisciplinary international working group met on a videoconferencing platform in a multi-staged process to make consensus recommendations for adaptations to cleft protocols within resource-constrained settings. Feedback was sought from a roundtable discussion forum and global organizations involved in comprehensive cleft care.Foundational principles were agreed to enable recommendations to be globally relevant and two areas of focus within the specified topic were identified. First the safety aspects of cleft surgery protocols were scrutinized and COVID-19 adaptations, specifically in the pre- and perioperative periods, were highlighted. Second, surgical procedures and cleft care services were prioritized according to their relationship to functional outcomes and time-sensitivity. The surgical procedures assigned the highest priority were emergent interventions for breathing and nutritional requirements and primary palatoplasty. The cleft care services assigned the highest priority were new-born assessments, pediatric support for children with syndromes, management of acute dental or auditory infections and speech pathology intervention.A collaborative, interdisciplinary and international working group delivered consensus recommendations to assist with the provision of cleft care in low- and middle-income countries. At a time of global cleft care delays due to COVID-19, a united approach amongst global cleft care providers will be advantageous to advocate for children born with cleft lip and palate in resource-constrained settings.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. / O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos.

OBJECTIVE: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. METHODS: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. RESULTS: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. CONCLUSION: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

OBJETIVO: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. MÉTODOS: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. RESULTADOS: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). CONCLUSÃO: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

Insomnia prevalence in confined elite athletes

24 Figure 1Insomnia disorder categories: good sleeper (did not score for insomnia disorder);resolved insomnia (scored for insomnia disorder in pre-confinement);confinement insomnia (scored for insomnia disorder in confinement);and persistent insomnia (scored for insomnia disorder in pre and during confinement)[Figure omitted. See PDF]Abstract 24 Table 1Descriptives on demographic, insomnia, and sleep factors (N=74)

Single base mutations in the nucleocapsid gene of SARS-CoV-2 affects amplification efficiency of sequence variants and may lead to assay failure.

Reverse transcriptase quantitative PCR (RT-qPCR) is the main diagnostic assay used to detect SARS-CoV-2 RNA in respiratory samples. RT-qPCR is performed by specifically targeting the viral genome using complementary oligonucleotides called primers and probes. This approach relies on prior knowledge of the genetic sequence of the target. Viral genetic variants with changes to the primer/probe binding region may reduce the performance of PCR assays and have the potential to cause assay failure. In this work we demonstrate how two single nucleotide variants (SNVs) altered the amplification curve of a diagnostic PCR targeting the Nucleocapsid (N) gene and illustrate how threshold setting can lead to false-negative results even where the variant sequence is amplified. We also describe how in silico analysis of SARS-CoV-2 genome sequences available in the COVID-19 Genomics UK Consortium (COG-UK) and GISAID databases was performed to predict the impact of sequence variation on the performance of 22 published PCR assays. The vast majority of published primer and probe sequences contain sequence mismatches with at least one SARS-CoV-2 lineage. We recommend that visual observation of amplification curves is included as part of laboratory quality procedures, even in high throughput settings where thresholds are set automatically and that in silico analysis is used to monitor the potential impact of new variants on established assays. Ideally comprehensive in silico analysis should be applied to guide selection of highly conserved genomic regions to target with future SARS-CoV-2 PCR assays.

Comparison of SARS-CoV-2 N gene real-time RT-PCR targets and commercially available mastermixes.

BACKGROUND: This study aimed to evaluate the impact of four different reverse transcription quantitative PCR (RT-qPCR) master mixes on the performance of SARS-CoV-2 diagnostic PCRs using three primer/probe assays targeting the N gene (A, B and C). The dynamic range and lowest detected quantity was determined using a SARS-CoV-2 partial N gene RNA transcript dilution series (100,000-1 copy/µl) and verified using 72 nose and throat swabs, 29 of which tested positive for SARS-CoV-2 RNA. RESULTS: Assay C consistently detected the lowest quantity of partial N gene RNA transcript with all mastermixes. The Takara One Step PrimeScript™ III RT-PCR Kit mastermix enabled all primer pairs to detect the entire dynamic range evaluated, with the Qiagen Quantifast and Thermofisher TaqPath 1-Step kits also performing well. Sequences from all three primer/probe sets tested in this study (assay A, B and C) have 100 % homology to ≥97 % of the of SARS-CoV-2 sequences available up to 31st December 2020 (n = 291,483 sequences). CONCLUSIONS: This work demonstrates that specific assays (in this case assay C) can perform well in terms of dynamic range and lowest detected quantity regardless of the mastermix used. However we also show that, by choosing the most appropriate mastermix, poorer performing primer pairs are also able to detect all of the template dilutions investigated. This work increases the potential options when choosing assays for SARS-CoV-2 diagnosis and provides solutions to enable them to work with optimal analytical sensitivity.