Role of masks, testing and contact tracing in preventing COVID-19 resurgences: A case study from New South Wales, Australia

Objectives The early stages of the COVID-19 pandemic illustrated that SARS-CoV-2, the virus that causes the disease, has the potential to spread exponentially. Therefore, as long as a substantial proportion of the population remains susceptible to infection, the potential for new epidemic waves persists even in settings with low numbers of active COVID-19 infections, unless sufficient countermeasures are in place. We aim to quantify vulnerability to resurgences in COVID-19 transmission under variations in the levels of testing, tracing and mask usage. Setting The Australian state of New South Wales (NSW), a setting with prolonged low transmission, high mobility, non-universal mask usage and a well-functioning test-and-trace system. Participants None (simulation study). Results We find that the relative impact of masks is greatest when testing and tracing rates are lower and vice versa. Scenarios with very high testing rates (90% of people with symptoms, plus 90% of people with a known history of contact with a confirmed case) were estimated to lead to a robustly controlled epidemic. However, across comparable levels of mask uptake and contact tracing, the number of infections over this period was projected to be 2-3 times higher if the testing rate was 80% instead of 90%, 8-12 times higher if the testing rate was 65% or 30-50 times higher with a 50% testing rate. In reality, NSW diagnosed 254 locally acquired cases over this period, an outcome that had a moderate probability in the model (10%-18%) assuming low mask uptake (0%-25%), even in the presence of extremely high testing (90%) and near-perfect community contact tracing (75%-100%), and a considerably higher probability if testing or tracing were at lower levels. Conclusions Our work suggests that testing, tracing and masks can all be effective means of controlling transmission. A multifaceted strategy that combines all three, alongside continued hygiene and distancing protocols, is likely to be the most robust means of controlling transmission of SARS-CoV-2

Mixed methods study protocol: Do national reporting and learning system medication incidents in palliative care reflect patient and carer concerns about medication management and safety?

Abstract Introduction Approximately 20% of serious safety incidents involving palliative patients relate to medication. These are disproportionately reported when patients are in their usual residence when compared with hospital or hospice. While patient safety incident reporting systems can support professional learning, it is unclear whether these reports encompass patient and carer concerns with palliative medications or interpersonal safety. Aim To explore and compare perceptions of (un)safe palliative medication management from patient, carer and professional perspectives in community, hospital and hospice settings. Methods and analysis We will use an innovative mixed-methods study design combining systematic review searching techniques with cross-sectional quantitative descriptive analysis and interpretative qualitative metasynthesis to integrate three elements: (1) Scoping review: multiple database searches for empirical studies and first-hand experiences in English (no other restrictions) to establish how patients and informal carers conceptualise safety in palliative medication management. (2)Medication incidents from the England and Wales National Reporting and Learning System: identifying and characterising reports to understand professional perspectives on suboptimal palliative medication management. (3) Comparison of 1 and 2: contextualising with stakeholder perspectives. Patient and public involvement Our team includes a funded patient and public involvement (PPI) collaborator, with experience of promoting patient-centred approaches in patient safety research. Funded discussion and dissemination events with PPI and healthcare (clinical and policy) professionals are planned. Ethics and dissemination Prospective ethical approval granted: Cardiff University School of Medicine Research Ethics Committee (Ref 19/28). Our study will synthesise multivoiced constructions of patient safety in palliative care to identify implications for professional learning and actions that are relevant across health and social care. It will also identify changing or escalating patterns in palliative medication incidents due to the COVID-19 pandemic. Peer-reviewed publications, academic presentations, plain English summaries, press releases and social media will be used to disseminate to the public, researchers, clinicians and policy-makers

Mixed methods study protocol: Do national reporting and learning system medication incidents in palliative care reflect patient and carer concerns about medication management and safety?

Abstract Introduction Approximately 20% of serious safety incidents involving palliative patients relate to medication. These are disproportionately reported when patients are in their usual residence when compared with hospital or hospice. While patient safety incident reporting systems can support professional learning, it is unclear whether these reports encompass patient and carer concerns with palliative medications or interpersonal safety. Aim To explore and compare perceptions of (un)safe palliative medication management from patient, carer and professional perspectives in community, hospital and hospice settings. Methods and analysis We will use an innovative mixed-methods study design combining systematic review searching techniques with cross-sectional quantitative descriptive analysis and interpretative qualitative metasynthesis to integrate three elements: (1) Scoping review: multiple database searches for empirical studies and first-hand experiences in English (no other restrictions) to establish how patients and informal carers conceptualise safety in palliative medication management. (2)Medication incidents from the England and Wales National Reporting and Learning System: identifying and characterising reports to understand professional perspectives on suboptimal palliative medication management. (3) Comparison of 1 and 2: contextualising with stakeholder perspectives. Patient and public involvement Our team includes a funded patient and public involvement (PPI) collaborator, with experience of promoting patient-centred approaches in patient safety research. Funded discussion and dissemination events with PPI and healthcare (clinical and policy) professionals are planned. Ethics and dissemination Prospective ethical approval granted: Cardiff University School of Medicine Research Ethics Committee (Ref 19/28). Our study will synthesise multivoiced constructions of patient safety in palliative care to identify implications for professional learning and actions that are relevant across health and social care. It will also identify changing or escalating patterns in palliative medication incidents due to the COVID-19 pandemic. Peer-reviewed publications, academic presentations, plain English summaries, press releases and social media will be used to disseminate to the public, researchers, clinicians and policy-makers

Family role in paediatric safety incidents: a retrospective study protocol

Introduction: Healthcare-associated harm is an international public health issue. Children are particularly vulnerable to this with 15%–35% of hospitalised children experiencing harm during medical care. While many factors increase the risk of adverse events, such as children’s dependency on others to recognise illness, children have a unique protective factor in the form of their family, who are often well placed to detect and prevent unsafe care. However, families can also play a key role in the aetiology of unsafe care. We aim to explore the role of families, guardians and parents in paediatric safety incidents, and how this may have changed during the pandemic, to learn how to deliver safer care and codevelop harm prevention strategies across healthcare settings. // Methods and analysis: This will be a retrospective study inclusive of an exploratory data analysis and thematic analysis of incident report data from the Learning from Patient Safety Events service (formerly National Reporting and Learning System), using the established PatIent SAfety classification system. Reports will be identified by using specific search terms, such as *parent* and *mother*, to capture narratives with explicit mention of parental involvement, inclusive of family members with parental and informal caregiver responsibilities. Paediatricians and general practitioners will characterise the reports and inter-rater reliability will be assessed. Exploratory descriptive analysis will allow the identification of types of incidents involving parents, contributing factors, harm outcomes and the specific role of the parents including inadvertent contribution to or mitigation of harm. // Ethics and dissemination: This study was approved by Cardiff University Research Ethics Committee (SMREC 22/32). Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops

Multiple points of system failure underpin continuous subcutaneous infusion safety incidents in palliative care: A mixed methods analysis

Background: About 25% of palliative medication incidents involve continuous subcutaneous infusions. Complex structural and human factor issues make these risk-prone interventions. Detailed analysis of how this safety-critical care can be improved has not been undertaken. Understanding context, contributory factors and events leading to incidents is essential. Aims: (1) Understand continuous subcutaneous infusion safety incidents and their impact on patients and families; (2) Identify targets for system improvements by learning from recurrent events and contributory factors. Design: Following systematic identification and stratification by degree of harm, a mixed methods analysis of palliative medication incidents involving continuous subcutaneous infusions comprising quantitative descriptive analysis using the PatIent SAfety (PISA) classification system and qualitative narrative analysis of free-text reports. Setting/participants: Palliative medication incidents ( n = 7506) reported to the National Reporting and Learning System, England and Wales (2016–2021). Results: About 1317/7506 incidents involved continuous subcutaneous infusions with 943 (72%) detailing harms. Primary incidents (most proximal to patient outcomes) leading to inappropriate medication use (including not using medication when it was needed) were underpinned by breakdowns in three major medication processes: monitoring and supply (405, 31%), administration (383, 29%) and prescribing (268, 20%). Recurring contributory factors included discontinuity of care within and between settings, inadequate time, inadequate staffing and unfamiliarity with protocols. Psychological harms for patients and families were identified. Conclusions: System infrastructure is needed to enable timely supply of medication and equipment, effective coordinated use of continuous subcutaneous infusions, communication and continuity of care. Training is needed to improve incident descriptions so these pinpoint precise targets for safer care

6637 How do families mitigate paediatric safety incidents in emergency departments? A multi-method national analysis of incident reports

Objectives Healthcare-associated harm is an international public health issue.1 Children are a particularly vulnerable group, with 15%–35% of hospitalised children experiencing harm whilst receiving medical care.2Whilst many factors increase the risk of adverse events, such as a child’s dependency on others to rec- ognise and respond to illness, children have a unique protective factor in the form of their parents (guardians and families), who are well placed to detect and prevent unsafe care. Mar- tha’s Rule highlights the need to more effectively enable parents to function as safety advocates.3 We aimed to characterise the role of parents in mitigating patient safety incidents involving children within Emergency Departments.4 Methods Free text of patient safety incident reports submitted from Emergency Departments in England and Wales between 2014–2020 to the National Reporting Learning System (now the Learning from Patient Safety Events Service) were searched for terms like *parent*, *dad*, and *mother*. We were provided with 12,300 reported and created a weighted sample of 4000 reports.4 Two trained paediatricians and a general practitioner reviewed reports which were included for analysis if there was clear evidence in the narrative of parental involvement directly related to the reported incident. Reports were systematically coded using the Patient Safety (PISA) classification system.5 An inductive thematic analysis in NVivo informed the development of a mitigatory factor framework. An exploratory descriptive analysis identified the most frequent semantic relationships between type of incident, mitigating factors, and harm outcomes. Results A total of 1065 (27%) reports were included for analy- sis. Parents were involved in mitigating incidents in over two thirds of reports (714, 67%). The most common mitigatory factors included: ‘family advocates for child’, ‘parent expresses concern about care given’, and ‘family chases healthcare appointment’. The most frequent incidents with parental mitiga- tory factors related to diagnosis and assessment (157, 22%), e. g., a missed diagnosis, medication (150, 21%), e.g., wrong medication prescribed, and treatment (89, 13%), e.g., insuffi- cient treatment given. In 229 (32%) of these reports, parents prevented harm or further harm. Conclusion Parents play a key role in preventing safety inci- dents and harms when their children receive healthcare in Emergency Departments. Identification of mitigation factors within incident report narratives will support health systems to identify where they should investigate further or intervene to improve safety. Our analysis has identified priority areas to enable the co-development of recommendations and strategies to deliver safer paediatric care and support parents as child safety advocates

Incidence, nature and causes of avoidable significant harm in primary care in England:retrospective case note review

Objective To estimate the incidence of avoidable significant harm in primary care in England; describe and classify the associated patient safety incidents and generate suggestions to mitigate risks of ameliorable factors contributing to the incidents. Design Retrospective case note review. Patients with significant health problems were identified and clinical judgements were made on avoidability and severity of harm. Factors contributing to avoidable harm were identified and recorded. Setting Primary care. Participants Thirteen general practitioners (GPs) undertook a retrospective case note review of a sample of 14 407 primary care patients registered with 12 randomly selected general practices from three regions in England (total list size: 92 255 patients). Main outcome measures The incidence of significant harm considered at least ‘probably avoidable’ and the nature of the safety incidents. Results The rate of significant harm considered at least probably avoidable was 35.6 (95% CI 23.3 to 48.0) per 100 000 patient-years (57.9, 95% CI 42.2 to 73.7, per 100 000 based on a sensitivity analysis). Overall, 74 cases of avoidable harm were detected, involving 72 patients. Three types of incident accounted for more than 90% of the problems: problems with diagnosis accounted for 45/74 (60.8%) primary incidents, followed by medication-related problems (n=19, 25.7%) and delayed referrals (n=8, 10.8%). In 59 (79.7%) cases, the significant harm could have been identified sooner (n=48) or prevented (n=11) if the GP had taken actions aligned with evidence-based guidelines. Conclusion There is likely to be a substantial burden of avoidable significant harm attributable to primary care in England with diagnostic error accounting for most harms. Based on the contributory factors we found, improvements could be made through more effective implementation of existing information technology, enhanced team coordination and communication, and greater personal and informational continuity of care

Patient safety in prisons: a multi-method analysis of reported incidents in England

Objectives Prisoners use healthcare services three times more frequently than the general population with poorer health outcomes. Their distinct healthcare needs often pose challenges to safe healthcare provision. This study aimed to characterise patient safety incidents reported in prisons to guide practice improvement and identify health policy priorities. Design: We carried out an exploratory multi-method analysis of anonymised safety incidents from prisons. Setting Safety incidents had been reported to the National Reporting and Learning System by prisons in England between April 2018 and March 2019. Participants Reports were reviewed to identify any unintended or unexpected incident(s) which could have, or did, lead to harm for prisoners receiving healthcare. Main outcome measures Free-text descriptions were examined to identify the type and nature of safety incidents, their outcomes and harm severity. Analysis was contextualised with subject experts through structured workshops to explain relationships between the most common incidents and contributory factors. Results Of 4112 reports, the most frequently observed incidents were medication-related (n = 1167, 33%), specifically whilst administering medications (n = 626, 54%). Next, were access-related (n = 559,15%), inclusive of delays in patients accessing healthcare professionals (n = 236, 42%) and managing medical appointments (n =  171, 31%). The workshops contextualised incidents involving contributing factors (n = 1529, 28%) into three key themes, namely healthcare access, continuity of care and the balance between prison and healthcare priorities. Conclusions This study highlights the importance of improving medication safety and access to healthcare services for prisoners. We recommend staffing level reviews to ensure healthcare appointments are attended, and to review procedures for handling missed appointments, communication during patient transfers and medication prescribing

Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection

We reported previously that a proportion of natural CD25+ cells isolated from the PBMC of HCV patients can further upregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory T cells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCV-responsive natural CD25+ cells and show that these cells are not activated conventional T cells expressing FOXP3, but hard-wired Treg with a stable FOXP3 phenotype and function. Of ∼46,000 genes analyzed in genome wide transcription profiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25+ cells and conventional T cells. Expression profiles, including cell death, activation, proliferation and transcriptional regulation, suggest a survival advantage of HCV-responsive Treg over the other cell populations. Since no Treg-specific activation marker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogate marker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previously described effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights the non-self specific nature of Treg during infection

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder