Omicron driven ECMO in a vaccinated critically ill patient

Objectives: Reporting a case of a COVID-19 vaccinated patient admitted to our intensive care unit with severe acute respiratory failure due to SARSCoV2 - Omicron variant, rapidly deteriorating requiring intubation, prone ventilation, and ECMO support. Method(s): A 62 years old Caucasian male was admitted in ICU for rapidly deranging respiratory failure and fever which occurred over the previous 24h. The patient received two doses of SARS-CoV2 vaccine (Oxford, AstraZeneca), the last one over five months before onset of symptoms. The patient was admitted to the intensive care unit (ICU) with tachypnea, low peripheral saturation (80%), elevated serum creatinine (2.4 mg/dl), and mild obesity (BMI 34,6). Pressure support ventilation trial (2 hours) failed carryng out to orotracheal intubation and protective ventilation. Worsening of respiratory exchanges (5 th day from the admission) required a rescue prone ventilation cycle, in the meantime an indication was given to the placement of veno-venous ECMO. The cannulation site was femoro-femoral and the configuration used was Vivc25- Va21, according to the current ELSO nomenclature;ECMO flow was progressively increased until a peripheral saturation of 95% was obtained. Result(s): The patient passed out after 2 month of extracorporeal support with no sign of recovery of pulmonary and renal function. Conclusion(s): Unlike evidences showing a lower symptomatic engagement of the Omicron variant SARSCoV2 positive patients, we have witnessed a rapid and massive pulmonary involvement. The short time that passed from the onset of symptoms and the rapid decay of respiratory function required rapid escalation of the intensity of care up to extracorporeal support. The patient showed previous pathologies that can lead to suspicion of a loss of immune coverage given by the vaccine, in addition to the long time elapsed since the last dose. (Figure Presented).

Teaching menopause to health care professionals

The menopause is a stage in the life cycle that affects all women. Managing perimenopausal and postmenopausal health is therefore a key issue for all healthcare professionals, not just gynecologists. The curriculum should include terminology and definitions, assessment, diagnosis and evidence-based management strategies. Healthcare professionals should be aware that women have different perceptions and experiences of the menopause which may be determined by: age and type of menopause, pre-existing health conditions, disability, employment and adverse childhood events. Specialist services may be required for some. These include women with chronic disease, premature ovarian insufficiency or early menopause or pre-existing health conditions and disability, as well as transgender and gender-nonconforming people. The COVID-19 pandemic has changed the mode of delivering healthcare from face-to-face only to include virtual consultations. Teaching now needs to include both types of consultations. A holistic approach is required and teaching should be provided by an accredited expert. Rees M, Abernethy K, Bachmann G, et al. The essential menopause curriculum for healthcare professionals: A European Menopause and Andropause Society (EMAS) position statement. Maturitas. 2022;158:70-77. doi: https://doi.org/10.1016/j.maturitas.2021.12.001Copyright © 2023

First isolation and characterization of the prototype strain of the SARSCoV-2 virus at the beginning of the COVID-19 pandemic in Peru

Introduction: Currently, isolated from SARS-CoV-2 virus exceed 600 million cases in the world. Objective(s): Isolation and characterization of the SARS-CoV-2 virus causing COVID-19 at the beginning of the pandemic in Peru. Method(s): Twenty nasal and pharyngeal swab samples were isolated from SARS-CoV-2 using two cell lines, Vero ATCC CCL-81 and Vero E-6;virus identification was performed by RT-PCR and the onset of cytopathic effect (CPE) was evaluated by indirect immunofluorescence and subsequent identification by genomic sequencing. One of the most widely circulating isolates were selected and named the prototype strain (PE/B.1.1/28549/2020). Then 10 successive passages were performed on Vero ATCC CCL-81 cells to assess mutation dynamics. Result(s): Results detected 11 virus isolates by cytopathic effect, and subsequently confirmed by RT-PCR and indirect immunofluorescence. Of these, six were sequenced and identified as the lineages B.1, B.1.1, B.1.1.1, and B.1.205 according to the Pango lineage nomenclature. The prototype strain corresponded to lineage B.1.1. The analysis of the strains from the successive passages showed mutations mainly at in the spike (S) protein of the virus without variation in the identity of the lineage. Conclusion(s): Four lineages were isolated in the Vero ATCC CCL-81 cell line. Subcultures in the same cell line showed mutations in the spike protein indicating greater adaptability to the host cell and variation in pathogenicity in vitro, a behavior that allows it to have more survival success.Copyright © 2023 Anales de la Facultad de Medicina. All rights reserved.

The challenges of embedding advanced care planning into a Haematology service

Following an increased need for individual patient escalation plans during the COVID-19 pandemic we recently created a working group to embed Advance Care Planning (ACP) into our service. Modern ACP is not only about end-of- life planning, it involves meaningful conversations and supporting patients to make decisions throughout all stages of their disease and treatment. With early conversations and the opportunity to pre plan, the stress and anxiety attached to the difficult decisions at a time when someone may be acutely unwell should become easier (from the perspective of both staff and patients). We carried out a preproject audit to ascertain patient opinions on how we could embed ACP into our service. 50 patients were offered a questionnaire, 38 chose to partake. Result(s): 100% (38) of patients had never been approached by a nurse to discuss ACP. 82% (31 out of 38) said they would not want to be approached about ACP. 18% (7 pts) would like to be approached but 13% (5pts) noted only if end of life. On asking when the best time to be approached: three patients said 'at diagnosis', two said 'anytime', one said 'never', five said 'when ready' and seven said 'end of life only'. Suggestions on the best way to raise ACP issues, five said poster displays (one noting the need for this poster to be positive and also available in Welsh), four suggested routine discussions in the current appointment and five people suggested a separate appointment. Other comments included, I only want to discuss these issues with my solicitor, I would like my family to be involved, make sure the nurses can answer questions. Average age was 68.5 years (range 49-85). Discussion(s): This was a limited audit on an outpatient population, but it raised a number of important issues. The actual carrying out of an audit on an emotive subject highlighted one the difficulties of embedding ACP initiatives into a service with a quarter of patients choosing not to answer the questionnaire, and of those who chose to answer 83% said they did not necessarily want to be approached to discuss ACP. In addition, the terminology 'ACP' appeared confusing, many people linking it to end-of- life discussions or to legal aspects such as writing of Wills. The barriers this audit has highlighted, has helped to shape the future direction of our working group and highlighted the need for increased training.

Persons Diagnosed with COVID-19 in the Clinical Practice Research Datalink (CPRD) Primary Care Dataset: A Cohort Description

Objectives: Clinical Practice Research Datalink (CPRD) Aurum contains primary care electronic health records, including vaccinations and nearly complete capture of SARS-CoV-2 PCR test results between August 2020-March 2022. Our objective was to build code lists to define a cohort of persons diagnosed with COVID in England using routinely collected health data. Method(s): Persons aged 1 year or older were indexed on first COVID diagnosis from August 1, 2020 - January 31, 2022. We developed SNOMED code lists to define high risk of severe disease: 1) National Health Service's (NHS) list of highest risk conditions;2) PANORAMIC trial inclusion criteria;3) UK Health Security Agency (UKHSA) clinical risk groups. COVID vaccinations were defined as of December 1, 2021 using medical and product codes. Code lists were developed using wildcard search terms which were reviewed by multiple independent reviewers, and inclusion/exclusion was determined by consensus. All lists for diagnoses were reviewed by a UK physician. Result(s): We identified 2,257,907 people diagnosed in primary care with COVID;46% were male and mean age was 34 years, comparable to governmental data for the same period reporting 47% of cases in England were male and mean age was 34 years. We identified 12% at high risk of severe disease using the NHS definition, 31% using the PANORAMIC trial criteria, and 10% using the UKHSA clinical risk groups. Among adults, 86.1% had >=1 and 80.2% had >=2 COVID vaccine doses (2% and 0.2% lower than official reports, respectively). Conclusion(s): This cohort represented the age and sex distribution of COVID cases, and the COVID vaccination coverage, in England through January 2022. Definitions were built using reproducible methods that can be leveraged for future work. The high capture of COVID vaccinations supports the use of this cohort to examine clinical and societal benefits of COVID vaccination in England.Copyright © 2023

Development and Evaluation of a Textanalytics Algorithm for Automated Application of the Bsr Covid-19 Shielding Criteria in Rheumatology Patients

Background/Aims In April 2020 the British Society for Rheumatology (BSR) issued a risk stratification guide to identify patients at the highest risk of COVID-19 requiring shielding. This guidance was based on patients' age, comorbidities, and immunosuppressive therapies - including biologics that are not captured in primary care records. This meant rheumatologists needed to manually review outpatient letters to score patients' risk. The process required considerable clinician time, with shielding decisions not always transparently communicated. Our aim was to develop an automated shielding algorithm by text-mining outpatient letter diagnoses and medications, reducing the need for future manual review. Methods Rheumatology outpatient letters from Salford Royal Hospital, a large UK tertiary hospital, were retrieved between 2013-2020. The two most recent letters for each patient were extracted, created before 01.04.2020 when BSR guidance was published. Free-text diagnoses were processed using Intelligent Medical Objects software1 (Concept Tagger), which utilised interface terminology for each condition mapped to a SNOMED-CT code. We developed the Medication Concept Recognition tool (MedCore Named Entity Recognition) to retrieve medications type, dose, duration and status (active/past) at the time of the letter. The medication status was established based on the heading where they appeared (e.g. past medications, current medications), but incorporated additional information such as medication stop dates. The age, diagnosis and medication variables were then combined to output the BSR shielding score. The algorithm's performance was calculated using clinical review as the gold standard. Results To allow for the comparison with manual decisions, we focused on all 895 patients who were reviewed clinically. 64 patients (7.1%) had not consented for their data to be used for research as part of the national opt-out scheme. After removing duplicates, 803 patients were used to run the algorithm. 11,558 free-text diagnoses were extracted and mapped to SNOMED CT, with 15,003 free-text medications (that included past, present and any planned treatment). The automated shielding algorithm demonstrated a sensitivity of 80.3% (95% CI: 74.7, 85.2%) and specificity of 92.2% (95% CI: 89.7, 94.2%). Positive likelihood ratio was 10.3 (95% CI: 7.7, 13.7), negative likelihood ratio was 0.21 (95% CI: 0.16, 0.28), F1 score was 0.81. False positive rate was 7.9%, whilst false negative rate was 19.7%. Further evaluation of false positives/negatives revealed clinician interpretation of BSR guidance and misclassification of medications status were important contributing factors. Conclusion An automated algorithm for risk stratification has several advantages including reducing clinician time for manual review to allow more time for direct care, improving efficiency and transparently communicating decisions based on individual risk. With further development, it has the potential to be adapted for future public health initiatives that requires prompt automated review of hospital outpatient letters.

Demonstration of Remote Control of Critical Care Ventilators and the Integrated Clinical Environment

Introduction: The COVID-19 pandemic posed numerous challenges to patient care, including extensive PPE use, patient care in isolation rooms, inadequate numbers of intensivists particularly in rural communities, use of unfamiliar ventilators that would be partially remedied by the ability to remotely control lung ventilation. The goals of the project were to study the intended use, risk management, usability, cybersecurity for remote control of ventilators and demonstrate the use of a single interface for several different ventilators. Method(s): Clinical scenarios were developed including remote control of the ventilator from an antechamber of an isolation room, nursing station within the same ICU, and remote control from across the country. A risk analysis and was performed and a risk management plan established using the AAMI Consensus Report--Emergency Use Guidance for Remote Control of Medical Devices. A cybersecurity plan is in progress. Testing was done at the MDPNP laboratory. We worked with Nihon Kohden OrangeMed NKV-550, Santa Ana, CA, and Thornhill Medical MOVES SLC, Toronto, Canada. Both companies modified their devices to allow remote control by and application operating on DocBox's Apiary platform. Apiary is a commercially available ICE solution, DocBox Inc, Waltham, MA. An expert panel was created to provide guidance on the design of a single common, simple to use graphical user interface (GUI) for both ventilators. Manufacturers' ventilation modes were mapped to ISO 19223 vocabulary, data was logged using ISO/IEEE 11073-10101 terminology using AAMI 2700-2-1, Medical Devices and Medical Systems - Essential safety and performance requirements for equipment comprising the patient-centric integrated clinical environment (ICE): Part 2-1: Requirements for forensic data logging. Result(s): We demonstrated that both ventilators can be controlled and monitored using common user interface within an institution and across the country. Pressure and flow waveforms were available for the NKV-550 ventilator, and usual ventilator measurements were displayed in near-real time. The interface allowed changing FiO2, ventilation mode, respiratory rate, tidal volume, inspiratory pressure, and alarm settings. At times, increased network latency negatively affected the transmission of waveforms. Conclusion(s): We were able to demonstrate remote control of 2 ventilators with a common user interface. Further work needs to be done on cybersecurity, effects of network perturbations, safety of ventilator remote control, usability implications of having a common UI for different devices needs to be investigated.

Beyond Articular Cartilage: A Systematic Review of the Extracellular Matrix in Other Components of the Osteoarthritic Joint

Background/Aims Traditionally viewed from the perspective of cartilage degeneration, osteoarthritis is increasingly seen as a disease of global joint dysfunction. Connective tissue extracellular matrix (ECM) is a crucial determinant of joint mechanobiology, providing cells with scaffolding, topographical cues, and a reservoir of soluble factors. While ECM dysregulation has been extensively studied in osteoarthritic cartilage, it remains poorly defined in other joint tissues. Here, we systematically review the composition, architecture, and remodelling of non-cartilage soft joint tissue ECM in human osteoarthritis and animal disease models. Methods A systematic search strategy was run through the MEDLINE, EMBASE and Scopus databases on 30 October 2020 and repeated on 1 October 2021. The search criteria included disease nomenclature, relevant tissues, as well as structural ECM components and architectural features. All papers were independently screened by two reviewers on the Covidence platform according to predefined eligibility criteria. Relevant clinical, demographic, and biological data were extracted from included studies, which were assessed for bias using the OHAT Risk of Bias Rating Tool for Human and Animal Studies. Results 148 of 8,156 identified studies met all eligibility criteria. 113 papers evaluated human osteoarthritis;of 35 animal studies, the most frequently used models involved surgical joint destabilisation in small mammals. ECM was best defined in menisci, ligaments, and synovium;fewer papers assessed skeletal muscles, tendons, and fat pads. Compared to the healthy joint, osteoarthritis is associated with qualitative and quantitative alterations in structural ECM components, most notably collagens and proteoglycans. In recent years, whole proteome sequencing has been employed to address these changes systematically. The mechanical properties of ECM change significantly in osteoarthritis in response to post-translational modifications, extensive calcification, and the marked loss of matrix organisation across the joint. Notably, some aspects of ECM remodelling in these tissues appear to precede discernible cartilage dysregulation. Similar ECM dysregulation is also observed in animal models, although intermodel variability in arthritogenic precipitant and the range of reported outcomes make comparisons difficult. Many studies are limited by significant bias, notably in the infrequent reporting of investigator blinding, and in the poor demographic matching of osteoarthritic and control patients. Encouragingly, the quality of methodology reporting and use of age-matched control populations have improved in recent years. Conclusion Current data provide compelling evidence of whole joint ECM changes in osteoarthritis and importantly suggest that these changes occur early in the disease process. How ECM dysfunction affects the behaviour of tissue-resident cells remains less well understood. Our work will support the design of disease-relevant biomaterials used to model osteoarthritis in vitro, helping to address this issue, by more accurately recreating the extracellular environment. Furthermore, the development of imaging modalities sensitive to connective tissue ECM changes warrants investigation from both diagnostic and prognostic perspectives.

Hiv Viral Load Suppression and Racial Disparities during the Covid-19 Pandemic in Nyc

Background: Antiretroviral therapy is highly effective in achieving HIV viral load suppression (VLS) but requires sustained engagement in care. The COVID-19 pandemic disrupted medical care, and its impact on engagement in HIV care and VLS remains unclear. Health information exchanges (HIEs) enable examination of patient care across multiple health systems. We sought to leverage HIE data to examine the effect of pandemic-related disruptions in HIV care on VLS and to explore racial/ethnic disparities in VLS. Method(s): We performed a retrospective observational study of people living with HIV (PLWH) using de-identified data from Healthix, an HIE encompassing >20 million patients and 8,000 healthcare facilities in the greater New York City (NYC) region, between 1/1/2018 and 7/14/2022. We identified PLWH based on HIV viral load (VL) tests and HIV diagnosis codes (ICD and SNOMED). We established two cohorts: PLWH engaged in care in 2020 with >=1 VL test in 2019, 2020, and 2021(Group A) and PLWH not engaged in care in 2020 with >=1 VL test in 2019 and 2021 but 0 VL tests in 2020 (Group B). HIV VLS outcomes were categorized as suppressed (< 200 copies/mL) or not suppressed ( >200 copies/mL) using the last VL in 2019, first VL in 2021, and last recorded VL. We compared proportions using X2-tests and fit a group-stratified logistic regression to examine the effect of race/ethnicity on VLS. Result(s): We identified 711,358 VL tests representing 81,122 patients at 249 facilities. Of these patients, 36,199 met our definition of PLWH. Of those, 12,448 met the inclusion criteria for Group A, and 3,377 met the inclusion criteria for Group B. In 2019, Group B had a lower VLS proportion than Group A (85.9% vs 88.1%, X2 = 12.3, p< 0.0001). In 2021, this gap increased;the proportion of VLS was 80.7% in Group B and 88.0% in Group A (X2 = 121.8, p< 0.00001). Most recently, VLS in Group B had increased to 85.6%, but the inter-group gap in VLS had grown from 2.2% to 4.4%. Within both groups, Black and Hispanic patients had lower odds of VLS than white patients. This disparity was greatest in Group B when they reengaged in care in 2021, with 72.0% of Black patients (OR 0.30, 95% CI 0.22-0.42), and 79.1% of Hispanic patients (OR 0.45, 95% CI 0.31-0.63), compared to 89.5% of white patients achieving VLS. Conclusion(s): VLS remained high among PLWH who stayed engaged in care in 2020, dropped among PLWH who disengaged in care, and was lower in minoritized groups even after controlling for engagement in care.

Identifying Optimal Surgical Timing Relative to SARS-CoV-2 Infection Using COVID-19 Severity in Cancer Patients

INTRODUCTION: Prior literature suggests a need to delay elective surgery up to 8 weeks in patients with a previous SARS-CoV-2 infection to mitigate the risk of adverse postoperative events. However, these recommendations are broad without specific consideration of surgical procedures or factors related to the SARS-CoV-2 infection. The objective of this study was to identify optimal surgical timing in cancer patients with a prior history of COVID-19. METHOD(S): This study was a retrospective cross-sectional study using the National COVID Cohort Collaborative (N3C) centralized data resource. Patients who underwent select major surgeries after January 2020 were assessed for 30-day surgical outcomes. Cancer diagnoses, procedures, and outcomes were identified using standard SNOMED concepts. Patients with a history of COVID-19 prior to surgery were grouped by severity: non-hospitalized vs. hospitalized. Surgical timing relative to previous COVID-19 diagnosis was separated into three groups: 0-4 weeks, 4-8 weeks, and 8+ weeks. All analyses were performed using the N3C Data Enclave. RESULT(S): The study included 133,469 cancer patients with 7,757 (5.8%) who had a history of COVID-19 prior to surgery. Patients with prior COVID-19 did not have significantly increased rates of 30-day mortality (1.1% vs. 0.9%, P=.11) or non-fatal adverse events (23% vs. 22%, P=.33). Of the patients with a history of COVID-19, 1,630 (16%) were hospitalized due to a prior infection. Patients hospitalized for COVID-19 had significantly increased rates of postoperative 30-day mortality (2.9% vs. 0.5%, P< .001) and non-fatal adverse events (38% vs. 20%, P< .001) when compared to patients with a history of non-hospitalized COVID-19. Multivariable regression examining risk for any adverse event in patients with non-hospitalized COVID-19 demonstrated patients to be at baseline risk at 0-4 weeks (aOR 1.02 [0.68-1.50]), 4-8 weeks (aOR 0.98 [0.65-1.43]) and 8+ weeks (aOR 0.97 [0.80-1.17]) when compared to patients without a history of COVID-19. Conversely, patients previously hospitalized for COVID-19 were at increased odds of adverse postoperative events at all assessed time points (Figure). CONCLUSION(S): These data suggest prolonged delays from COVID-19 diagnosis to surgery are unnecessary among cancer patients not hospitalized for SARS-CoV-2 infection. However, there is a persistently elevated postoperative risk in patients who were hospitalized for treatment of COVID-19 prior to undergoing cancer surgery. Additional risk mitigation strategies beyond delaying surgery must be investigated.

Adverse Effects on COVID-19 Vaccination: Myth or Fact?

In the pandemic era, we have started use the vaccination to prevent COVID-19 infection 3-4 months ago. COVID-19 vaccinations may have some unexpected adverse effects in the same as other all medications. In Europe, unusual blood clot after Astrazeneca COVID-19 vaccination (AZ vaccine) were reported to European Medical Agency (EMA) on early March. On 7th April 2021, EMA has declared this event 'possible side effect of AZ vaccine'. The name of this very rare side effect is known as blood clots with low platelet count in common term, and "Thrombosis with Thrombocytopenia Syndrome (TTS)" in scientific term. Unreasonable fears and myths is widely reported in Korean journals about this very rare side effect. The most important issue about this unreasonable fear is improper use of terminology for blood clots or thrombosis. In this presentation, I will explain the exact meaning of this TTS in Korea.

Reset - the First Step in the Clinical Wellbeing Pathway

Background The COVID-19 pandemic has highlighted the importance of wellbeing support for frontline clinical staff. The newly introduced Great Ormond Street Hospital (GOSH) Clinical Wellbeing Pathway aims to provide consistent support to clinical teams following challenging or distressing events at work. RESET is the initial step in this pathway. It is a brief, facilitated conversation between clinical team members, taking place during the shift in which the clinical event has occurred. 'RESET' is an acronym that encompasses five key themes: Recognise, Evaluate, Stuff still to do, Elevate staff, Taking things forward. Method We used an action research methodology, where the design and clinical outcomes were co-created with the relevant staff groups. This comprised of an e-survey on existing clinical practices, expert consultation, facilitator training and pilot with ongoing qualitative feedback from staff on two pilot wards. Results Limited responses from our E-survey on existing hot debrief practices at GOSH highlighted that debriefs did not occur consistently but when they did, they were beneficial. Respondents indicated that training on facilitating debriefs would be well received. Feedback from the expert consultation (n= 14) highlighted the impact of terminology on clinical staff. Therefore, the language of the acronym was adapted accordingly. Feedback also highlighted the important role of the RESET facilitator, being able to respond flexibly and organically to the uncertain and potentially emotive conversations. Preliminary feedback from two facilitator training sessions with senior clinical staff (n= 11) identified the RESET tool and facilitator training is beneficial. Conclusion This phased introduction of the RESET tool has demonstrated that the proforma and accompanying training is viable to assist in the structure of post-event conversations. Clinical impact has yet to be assessed and we continue to pro-actively gather feedback on the utility and barriers to RESET conversations throughout our ongoing pilot study.

Surgery for urologic cancers after SARS-CoV-2 infection: Adverse outcomes and optimal delay

Background: Perioperative SARS-CoV-2 infection has been associated with increased adverse outcomes. Research conducted early in the COVID-19 pandemic suggested an 8 week delay after SARSCoV-2 infection prior to undergoing surgery. The aim of this study is to determine if prior COVID-19 infection is an independent risk factor for adverse outcomes following surgery for urologic cancers. A secondary objective was to determine the optimal duration to delay surgery, specifically cystectomy, prostatectomy, or nephrectomy, after COVID-19 infection. Method(s): Data from the National COVID Cohort Collaborative (N3C) data enclave was used to conduct this retrospective cross-sectional study. Patients with cancer diagnoses that underwent surgery for urologic cancers after January 2020 were included in the analyses. Urologic surgeries were queried using standard SNOMED concepts corresponding to cystectomy, nephrectomy, and prostatectomy. Patients were assessed for adverse postoperative events that were defined using standard SNOMED clinical concepts. COVID-19 positive patients were identified via the N3C Knowledge Store using positive lab measurement or a positive SARS-CoV-2 diagnosis. Analyses were conducted in the N3C data enclave. Result(s): The study cohort included 38,974 total patients with 15,216, 14,778, and 8,980, undergoing cystectomy, prostatectomy, and nephrectomy, respectively. 2,807 had a history of COVID-19 infection greater than 20 days prior to surgery. Prior history of COVID-19 was independently associated with adverse outcomes for cystectomy (OR 1.21 [1.03-1.43], p<0.05) and nephrectomy (OR 1.27 [1.06-1.52], p<0.05), but not prostatectomy (OR 1.14 [0.95-1.36]). Multivariable regression assessing time to surgery and risk for any adverse events, did not reveal significant benefit to waiting greater than 20 days after COVID-19 infection to operate. Conclusion(s): Patients with known prior COVID-19 infection who underwent surgical treatment of urologic cancers experienced increased risk of adverse surgical outcomes. Among this group, those who delayed surgery greater than 20 days after infection did not demonstrate decreased risk of these negative outcomes across the procedures studied. Optimal surgical delay in the treatment of urologic cancers after COVID-19 infection does not appear to be greater than 20 days.

Impact of COVID-19 pandemic on recommended vaccine uptake in a single-practice primary care COPD cohort in the UK

Introduction: Immunisation against vaccine-preventable disease is a critical aspect of COPD care. UK recommendations are annual influenza vaccination, pneumococcal vaccine (as a single-dose) and shingles vaccine if aged >=70 years. Aims and objectives: This retrospective study aimed to determine/characterise influenza, pneumococcal and shingles vaccination status in a single-practice primary care COPD cohort during the COVID-19 pandemic. SARSCoV-2 aspects were also evaluated. Method(s): All registered patients with COPD were identified via ICD-10 codes. Extracted data included COPD parameters and comorbidities. Vaccine-specific details were identified using SNOMED codes. Result(s): Records identified 378 patients with COPD;mean age 71 years (range 29-98). Mean % predicted FEV1 was 66.7%;49.2% reported a score of >=3 on the MRC Breathlessness Scale. Pneumococcal vaccination was reported for 83.1%. Shingles vaccine uptake in eligible patients was 64.3%. Influenza vaccine uptake (for 2021/22) was 87.8% (89.3% in those >=65 years)- higher than in prior influenza seasons;2018/19 (77.7%),2019/20 (77.1%) and 2020/21 (83.1%)-indicating a relative increase during the pandemic;6% in 20/21 and 12.7% in 21/22 versus 18/19 and 19/20 respectively. COPD severity, comorbidities and gender did not influence vaccine uptake. SARSCov-2 vaccine uptake for dose 1 and 2 was 97.4% and 93.4% for a booster dose. From January-December 2021, 22 patients (5.6%;range 52-98 years) had confirmed SARS-Cov-2 infection (all of whom were immunized). Conclusion(s): Uptake of recommended vaccines in COPD patients was high;seasonal influenza vaccine uptake showed a trend increase during the COVID-19 pandemic.

Getting to the root of it: contact anaphylaxis from polyethylene glycol in a dental lubricant

A 46-year-old man with no known allergies or history of atopy was referred for the investigation of a severe anaphylactic reaction following root canal dental treatment. The procedure had been done under local anaesthetic and involved drilling the tooth, removal of dental pulp, cleaning and insertion of a temporary filling. Preliminary skin prick tests (SPTs) and intradermal tests were negative to natural rubber latex, articaine (the local anaesthetic used for his procedure), lidocaine and chlorhexidine. He had negative specific IgE to chlorhexidine and latex, and a negative lidocaine challenge, confirming that he was not allergic to lidocaine. He returned for further dental treatment, which was done without local anaesthetic. As the procedure was completed, he developed severe anaphylaxis again. He made a full recovery and his dentist was asked for detailed information and samples of all the materials used during the procedure. Subsequent SPT showed a positive weal of 12 x 6 mm to the dental lubricant, Glyde, which was used on both occasions. Its ingredients included polyethylene glycol (PEG) 4253. SPT to other high-weight macrogol-containing products showed positive reactions to a 5% lidocaine ointment, Movicol, EMLA cream and Depomedrone. On further questioning he recalled minor immediate irritation after using a brand of children's shampoo, but a SPT to the shampoo was negative. An open test, closed test and SPT to a lower-molecular-weight patch-test allergen (PEG400 in petrolatum) were negative. PEGs or 'Macrogols' are hydrophilic polymers used in food, cosmetics and pharmaceutical reagents. They have recently attracted attention as they are excipients in several COVID-19 vaccines and have been suggested as a possible cause of anaphylaxis. Anaphylaxis to higher-molecular-weight PEGs has been reported from the use of bowel preparations and parenteral steroids. There are a handful of reports of contact urticaria to PEG-containing medicaments. We report this case to raise awareness of severe immediate hypersensitivity to these apparently innocuous ingredients and a novel source of exposure. A low index of suspicion, lack of standardized nomenclature and commercial reagents for testing are current barriers to diagnosis.

Safety and efficacy of apremilast in adults hospitalized with COVID-19

Introduction: Apremilast, a nonbiologic oral phosphodiesterase 4 (PDE4) inhibitor, was evaluated as a treatment for the hyperinflammatory response in patients (pts) hospitalized with severe COVID-19. Aims and Objectives: To assess the safety and effectiveness of apremilast plus standard of care (SoC) in pts hospitalized with severe COVID-19. Method(s): COMMUNITY (EudraCT 2020-002594-10) was a phase 3, double-blind, randomized, multinational, platform trial in adult pts hospitalized with COVID-19. Pts received apremilast 30 mg BID (APR) or placebo (PBO) for 14 days or until hospital discharge, whichever occurred first. Supportive care (per study center practices) was allowed except for CYP3A inducers and concurrent PDE4 antagonists. Result(s): From November 24, 2020 to June 4, 2021, 384 pts were enrolled (APR+SoC: n=194;PBO+SoC: n=190);enrollment halted early due to futility. Mean age was 56.5 years;59% were men. Most pts had a COVID-19 clinical severity score of 4 (48%) or 3 (29%) (range: 1-8, 1=death). Median (95% CI) time to confirmed clinical recovery through Day 29 (primary endpoint) was 14 (11-15) days for both groups (P=0.8779). All-cause mortality incidence rates through Day 29 (key secondary endpoint) were 18% (APR+SoC) and 17% (PBO+SoC) (P=0.9665). Treatmentemergent adverse event (TEAE) rates were similar between APR+SoC (54%;n=189) and PBO+SoC (55%;n=187) groups. TEAEs Common Terminology Criteria AE grade >=3 occurred in 25% of APR+SoC pts and 30% of PBO+SoC pts. Serious TEAE rates were 27% (APR+SoC) and 30% (PBO+SoC). Conclusion(s): Although APR+SoC did not improve survival in pts hospitalized with severe COVID-19, APR was well tolerated with a safety profile consistent with the established safety profile.

Biases in COVID-19 Case and Death Definitions: Potential Causes and Consequences.

This paper investigates three controversies involving potential causes and consequences of information bias in case and death definitions during the coronavirus disease (COVID-19) pandemic. First, evidence suggests China's surveillance data were biased and misinterpreted by the World Health Organization (WHO), prompting the WHO to advise nations to copy China's lockdowns. China appeared to use narrow diagnostic definitions that undercounted cases and deaths. Second, novel genomic data disseminated during the pandemic without adequate guidance from rigorous epidemiologic studies biased infection control policies in many countries. A novel genomic sequence of a virus is insufficient to declare new cases of a novel disease. Third, media reports of COVID-19 surveillance data in many nations appeared to be biased. Broadened surveillance definitions captured additional information, but unadjusted surveillance data disseminated to the public are not true cases and deaths. Recommendations include clarification of the proper use of diagnostic and surveillance case and death definitions to avoid information bias.

Palliative care terminology and practice in intensive care units in the Czech Republic: results of PEOpLE-C19 study

Study goal: Palliative care is an essential part of a complex approach to patients in the intensive care unit (ICU). This study aimed to describe palliative care practice in ICU in the Czech Republic. Study type: a cross-sectional, questionnaire study Material and methods: The inclusion criteria for study participation were nurses or physicians taking care of patients in the ICU for patients with Coronavirus Disease 2019 (COVID-19). The participants could participate by filling out the electronic survey with 40 questions. The questionnaire was evaluated by descriptive statistical analysis. Results: 313 questionnaires were analyzed. Participants reported up to 15 different terms for end-of-life care, the most often being palliative care (75.1%, n=235). The supportive care, especially sedatives, was most frequently adjusted according to the patient's needs. On the other hand, as a standard approach, the parenteral (35.8%, n=112) and enteral (17.3%, n=54) nutrition were most often withdrawn. Regarding organ support, renal replacement therapy (69.7%, n=218) and vasopressors (60.4%, n=189) were often withdrawn. The most rarely withdrawn organ support was artificial ventilation (24.6%, n=77), endotracheal intubation (11.5%,n=36), and tracheostomy cannula (2.9%, n=9). The majority of respondents would appreciate further education in palliative care. Conclusion: Palliative care is an essential theme not only in the COVID-19 pandemic. The palliative care terminology and practice used in the Czech Republic are heterogeneous. There is a space for further research and education in palliative care.

3. Adolescents' Perceptions of Mental Health around the World: Key Findings from a 13-Country Qualitative Study

Purpose: Adolescence (ages 10-19) is a sensitive developmental period for the emergence of mental and behavioral health problems, but there is a lack of multi-country qualitative studies that explore how adolescents themselves understand these critical challenges. As part of UNICEF's 2021 State of the World's Children Report, the Global Early Adolescent Study collaborated with organizations in 13 countries to hold a series of focus group discussions (FGDs) with adolescents focused on mental health. These FGDs aimed to (1) understand adolescents' perspectives on significant mental health challenges in their age group, (2) understand adolescents' perspectives on the key risk and protective factors driving these challenges, and (3) understand the ways in which adolescents cope with these challenges, including barriers and facilitators to help-seeking. Methods: A total of 71 FGDs were conducted across 13 countries between February and June of 2021. Countries were selected to ensure geographic, economic, and cultural diversity, and included: Belgium, Chile, China, the Democratic Republic of Congo, Egypt, Indonesia, Jamaica, Jordan, Kenya, Malawi, Sweden, Switzerland, and the United States. Within each country, FGDs were stratified by sex and age such that there were at least two younger (ages 10-14) and two older (ages 15-19) focus groups. Depending on the COVID-19 restrictions at the time, FGDs were either held in-person or online. All FGDs were held in local languages and lasted between 60 and 90 minutes. FGDs were recorded, transcribed verbatim, and translated into English when necessary. These English translations were then coded and analyzed using an inductive thematic analysis approach. Results: Across diverse cross-cultural settings, a number of consistent findings emerged from the voices of adolescents. In particular, adolescents around the world emphasized the many contexts that drive mental health challenges, including family adversity, community violence, unsupportive school environments, poverty, social media culture, and restrictive gender norms. They also discussed significant barriers to seeking help for mental health challenges, such as community stigma, lack of social support, and fears of invalidation. These barriers frequently resulted in adolescents coping with these challenges without support, often using maladaptive strategies. Importantly, adolescents generally described and understood mental health in terms of distress (e.g., sadness, loneliness, shame, anger) rather than disorder (e.g., depression, anxiety). Conclusions: Above all, it was clear that adolescents around the world need much better formal and informal supports to adequately address mental and behavioral health problems, and that these responses must take into account the many contexts that contribute to these problems. Further, the non-clinical terminology frequently used by adolescents suggests that taking a purely diagnostic approach in addressing mental health challenges may exclude many adolescents in need of assistance. Sources of Support: Wellcome Trust.

On Classification and Taxonomy of Coronaviruses (Riboviria, Nidovirales, Coronaviridae) with Special Focus on Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2)

Coronaviruses are highly virulent and therefore important human and veterinary pathogens worldwide. This study presents the first natural hierarchical classification of Coronaviridae. We also demonstrate a "one-step” solution to incorporate the principles of binomial (binary) nomenclature into taxonomy of Coronaviridae. We strongly support the complete rejection of the non-taxonomic category "virus” in any future taxonomic study in virology. This will aid future recognition of numerous virus species, particularly in the currently monotypic subgenus Sarbecovirus. Commenting on the nature of SARS-CoV-2, the authors emphasize that no member of the Sarbecovirus clade is an ancestor of this virus, and humans are the only natural known host © 2022, Mathematical Biology and Bioinformatics.All Rights Reserved.