We would like to highlight the apparent potential of the SARS-CoV-2 virus in causing airway oedema and laryngitis;

The COVID-19 pandemic is causing a significant increase in the number of patients requiring relatively prolonged invasive mechanical ventilation and an associated surge in patients who need a tracheostomy to facilitate weaning from respiratory support. In parallel, there has been a global increase in guidance from professional bodies representing staff who care for patients with tracheostomies at different points in their acute hospital journey, rehabilitation and recovery. Of concern are the risks to healthcare staff of infection arising from tracheostomy insertion and caring for patients with a tracheostomy. Hospitals are also facing extraordinary demands on critical care services such that many patients who require a tracheostomy will be managed outside established intensive care or head and neck units and cared for by staff with little tracheostomy experience. These concerns led NHS England and NHS Improvement to expedite the National Patient Safety Improvement Programme's 'Safe Tracheostomy Care' workstream as part of the NHS COVID-19 response. Supporting this workstream, UK stakeholder organisations involved in tracheostomy care were invited to develop consensus guidance based on: expert opinion; the best available published literature; and existing multidisciplinary guidelines. Topics with direct relevance for frontline staff were identified. This consensus guidance includes:

Purpose As the COVID-19 pandemic has unfolded, there has been growing recognition of risks to frontline health care workers. When caring for patients with tracheostomy, speech-language pathologists have significant exposure to mucosal surfaces, secretions, and aerosols that may harbor the SARS-CoV-2 virus. This tutorial provides guidance on practices for safely performing patient evaluation and procedures, thereby reducing risk of infection. Method Data were collated through review of literature, guidelines, and consensus statements relating to COVID-19 and similar high-consequent infections, with a focus on mitigating risk of transmission to health care workers. Particular emphasis was placed on speech-language pathologists, nurses, and other allied health professionals. A multinational interdisciplinary team then analyzed findings, arriving at recommendations through consensus via electronic communications and video conference. Results Reports of transmission of infection to health care workers in the current COVID-19 pandemic and previous outbreaks substantiate the need for safe practices. Many procedures routinely performed by speech-language pathologists have a significant risk of infection due to aerosol generation. COVID-19 testing can inform level of protective equipment, and meticulous hygiene can stem spread of nosocomial infection. Modifications to standard clinical practice in tracheostomy are often required. Personal protective equipment, including either powered air-purifying respirator or N95 mask, gloves, goggles, and gown, are needed when performing aerosol-generating procedures in patients with known or suspected COVID-19 infection. Conclusions Speech-language pathologists are often called on to assist in the care of patients with tracheostomy and known or suspected COVID-19 infection. Appropriate care of these patients is predicated on maintaining the health and safety of the health care team. Careful adherence to best practices can significantly reduce risk of infectious transmission.

BackgroundInconsistent and poorly coordinated systems of tracheostomy care commonly result in frustrations, delays, and harm. Quality improvement strategies described by exemplar hospitals of the Global Tracheostomy Collaborative have potential to mitigate such problems. This three-year guided implementation program investigated interventions designed to improve quality and safety of tracheostomy care. MethodsThe program management team guided implementation of 18 interventions over three phases (baseline/implementation/evaluation). Mixed methods interviews, focus groups, and Hospital Anxiety and Depression questionnaires defined outcome measures, with patient-level databases tracking and benchmarking process metrics. Appreciative Inquiry, interviews and Normalisation Measure Development questionnaires explored change barriers and enablers. ResultsAll sites implemented at least 16/18 interventions, with the magnitude of some improvements linked to staff engagement (1536 questionnaires from 1019 staff). 2405 admissions (1868 ICU/HDU, 7.3% children) were prospectively captured. Median stay was 50 hospital days, 23 ICU days, and 28 tracheostomy days. Incident severity score reduced significantly (n=606, p<0.01). There were significant reductions in ICU (-0.25 days.month -1 ), ventilator (-0.11 days.month -1 ), tracheostomy (-0.35 days.month -1 ) and hospital (-0.78 days.month -1 ) days (all p<0.01). Time to first vocalisation and first oral intake both decreased by 7 days (n=733, p<0.01). Anxiety decreased by 44% (from 35.9% to 20.0%), and depression decreased by 55% (from 38.7% to 18.3%) (n=385, both p<0.01). Independent economic analysis demonstrated £33 251 savings per patient, with projected annual UK National Health Service savings of £275 million. ConclusionsThis guided improvement program for tracheostomy patients significantly improved the quality and safety of care, contributing rich qualitative improvement data. Patient-centred outcomes were improved along with significant efficiency and cost savings across diverse UK hospitals.

A significant proportion of patients admitted to intensive care units require tracheostomies for a variety of indications. Continual cuff inflation to facilitate mechanical ventilatory support may mean patients find themselves awake, cooperative and attempting to communicate but unable to do so effectively. Resulting frustration and anxiety can negatively impact upon care. Through participation in the Global Tracheostomy Collaborative, our unit rapidly implemented novel techniques facilitating communication in such patients. In carefully selected and controlled situations, the subglottic suction port of routinely available tracheostomy tubes can be used to deliver a retrograde flow of gas above the cuff to exit via the larynx, facilitating speech. The resulting above cuff vocalisation is described in detail for five general ICU patients at our institution, highlighting the benefits of multidisciplinary care and the increasingly important role of the speech and language therapists in the critically ill.

Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.

Background:Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer.Methods:CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis.Results:Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts.Conclusions:CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.

Ultrasound training in a rural setting supported remotely is feasible, efficient, and sustainable. It can help local healthcare workers to screen their prenatal populations for obstetric and neonatal risks, and therefore has the potential to improve outcomes at delivery and provide site-specific epidemiologic data that can be used to develop new healthcare provision strategies.