Effects of triple combination therapy on quality of life and psychosocial outcomes: A longitudinal study

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator triple combination therapy (TCT) is available to approximately 85% of the U.S. CF population. Clinical trials of TCT demonstrate numerous improvements in physical health and healthrelated quality of life (HRQoL), but fewstudies have examined the effects of TCTon mental health and psychosocial outcomes, and little is known about whether gains in HRQoL are sustained over time.We aimed to describe the HRQoL and psychosocial outcomes of people with CF (PwCF) initiating TCT and explored changes in these outcomes up to 1 year after starting TCT. Method(s): This longitudinal study enrolled PwCF aged 14 and older who were followed at a large, combined pediatric and adult CF center. Questionnaires were administered within 6 months of initiating TCT (baseline) and 3, 6, and 12 months later. Study self-report measures evaluated were HRQoL (Cystic Fibrosis Questionnaire-Revised;CFQ-R), optimism, self-efficacy, medication-related beliefs (Medication Beliefs Questionnaire;MBQ), perceived social stigma of illness, and body image. Data were also collected from medical charts on measures of health and mental health screening. Four open-ended questionswere included at each timepoint to elicit qualitative data on experiences starting TCT. Longitudinal data were analyzed using linear mixed-effects models for repeated measures. Result(s): Sixty-three adults and adolescents with CF completed the full set of surveys at baseline. Mean participant age was 30.0 +/- 14.2. Fifty-four percent identified as female, 43% as male, and 2% as nonbinary. Seventyfour percent had private insurance. Mean percentage predicted forced expiratory volume in 1 second (FEV1pp) at baseline was 76.0 +/- 24.1%, and mean body mass index (BMI) was 22.9 +/- 3.1 kg/m2. At 12 months, mean FEV1pp was 80.8 +/- 21.9%, and mean BMI was 24.5 +/- 4.1 kg/m2. On standard measures used in CF mental health screening, mean baseline Patient Health Questionnaire (PHQ-9) score was 3.4 +/- 3.5, and mean General Anxiety Disorder score was 3.4 +/- 3.7. Mean PHQ-9 (3.5 +/- 4.0) and GAD-7 (3.4 +/- 3.7) scores at 12 months were similar to baseline. We found no statistically significant differences between the survey time points in participants' physical, respiratory, or emotional functioning on the CFQ-R, but there was a significant change in social functioning ( p < 0.001). There was no statistically significant change over time in optimism or selfefficacy, but there was a significant difference in CF medication beliefs between the four survey time points ( p = 0.008 for MBQ Importance subscale), with a decrease in perceived importance from baseline to 12 months. Conclusion(s): Whereas lung function and BMI increased in our sample by 12 months, similar improvementswere not seen in standard mental health outcomes. There was no change over time in physical, respiratory, or emotional functioning, optimism, or self-efficacy. Only CFQ-R social functioning had changed by 12 months, perhaps reflecting decreased COVID-related social isolation. There was also a change in medicationrelated beliefs, with a decrease in perceived importance of taking CF medications at 12 months. Future directions include conducting qualitative analyses of open-ended questions and further examining data on social stigma, motivation to take medications, and body image, as well as examining relationships between outcome variables and baseline FEV1 and BMICopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Exploring Inequities in Adolescent Sexual and Reproductive Health and Rights During the COVID-19 Pandemic: A Youth-Led Study in Ontario, Canada

Background: COVID-19 posed a significant threat to adolescents' sexual and reproductive health and rights (ASRHR), with disproportionate impacts on disadvantaged groups. However, existing research has not centered adolescents' experiences or expertise. Youth-led participatory action research (YPAR) is a collaborative approach to research that recognizes young people as experts to generate knowledge, empower youth, and catalyze action to improve their health. The objective of this study was to support three teams of youth researchers in developing and implementing their own research projects examining the impact of COVID-19 on an ASRHR issue of their choosing, using YPAR methodology. Method(s): Purposive sampling was used to recruit four teams of female-identified youth researchers (ages 16-19 years) in three high-priority regions of Ontario, Canada. Interested youth were interviewed to gauge motivation, relevant intersectional experiences, interest in collaborating, and sense of service to their communities. Selected youth completed a five-day virtual training covering critical thinking, ASRHR, qualitative/quantitative data collection and analysis, research ethics, and project logistics. Each youth team was paired with two adult research mentors and engaged in a four step YPAR process depicted in Figure 1. Youth researchers received compensation for their work and were included as study collaborators. This study was approved by IRB. Result(s): Team 1 identified barriers to having SRH needs met during COVID-19 for assigned females 13-21 yrs old in London, Ontario, using survey methodology. They found that among 58 assigned-female youth, 50% reported difficulties accessing sexual health-related treatment during COVID-19. Team 2 sought to understand how the intersectional identities of youth in Hamilton and Niagara Falls regions influenced experiences of sex education, using in-depth interviews. Key themes were the need to recognize diversity, that the relevance of sex ed changes as adolescence progresses, and that sex ed should focus on positive sexuality. Team 3 identified factors that influenced access to SRH products for teens in Northern Ontario using a survey of 114 adolescents. They found 32% of respondents experienced barriers to buying sexual health products locally, including stigma, cost, distance, disability, and 2SLGBTQIA+ identity. See https://www.shareproject.ca Conclusion(s): This study amplified youth voices through a social justice-framed approach to examining ASRHR during the COVID-19 pandemic. Centering the perspectives, values and experiences of youth introduced the potential to positively impact the youth researchers themselves, while yielding results that were relevant, meaningful, adolescent-responsive and culturally-informed. Supporting Figures or Tables https://www.abstractscorecard.com/uploads/Tasks/upload/19245/RGXGDRUQ-1380706-1-ANY.docxCopyright © 2023

Counselling support for the mental health of children in Hong Kong's international schools during the COVID-19 pandemic: parents' perspectives

Objective: This study investigated how school counsellors in international schools in Hong Kong supported the wellbeing of students and families during the period of school closure caused by the COVID-19 pandemic from the perspective of parents. Method: Sixteen parents with children in eleven different international schools in Hong Kong were interviewed and the data were analysed thematically. Results: Strong pre-existing relationships, role clarity, and open communication between counsellors and parents were associated with the effective adaptation of counselling services to the changing needs of parents during the school closure period, but these characteristics were often weak or absent. Conclusions: Parents' perceptions of counselling during the school closure period provide important feedback that schools can use to build more integrated and responsive support services. Counsellors can support students' wellbeing more effectively during crises by communicating their roles clearly, building strong relationships with parents, and helping students to maintain a diverse experience in their schooling. © 2021 Australian Psychological Society.

Police Powers and Public Assemblies: Learning from the Clapham Common ‘Vigil’ during the Covid-19 Pandemic

The policing of peaceful public assembly during the Covid-19 pandemic has been one of the most central challenges to police legitimacy. This is arguably because mass gatherings are assumed to carry a high risk of contagion yet, at the same time, peaceful public assembly is a protected human right. In this article, we explore this issue by using a case study to provide a detailed chronological interactional analysis of the policing operation surrounding a highly controversial public assembly that took place on Clapham Common in March 2021 in London, England. We explore the utility of a research and theory-based model for public order policing in pandemics as a framework for understanding the way the event evolved and identifying what lessons can be learnt for policing assemblies, both in future pandemics and more generally. We contend that ambiguity in the application of emergency powers and the potential for heavy fines to be applied using the legislation created a divergence between stakeholders and culminated in a leadership vacuum among protesters. Moreover, the context of acute political sensitivity led to a highly centralized public order operation that limited the capacity of police to enact dialogue-based solutions when leadership (re)emerged during the event. We conclude by discussing the implications of our analysis for understanding the inherent dangers of regulatory frameworks that place too heavy a burden of discretionary power into the hands of police in determining whether public assemblies are ‘lawful’, and under what conditions they can occur. © The Author(s) 2021.

The impact of a 6-week COVID-19 rehabilitation programme on dyspnoea post COVID-19

IntroductionDyspnoea is one of several ongoing symptoms experienced by those recovering from COVID-19 (Arnold et al, 2021). It can impact people for numerous weeks and months following the initial infection. Post COVID-19 rehabilitation may help;however, little is known about the effects of rehabilitation on dyspnoea and the related emotional response. This study aims to explore the impact of an outpatient hospital-based rehabilitation programme on dyspnoea and its emotional burden in those recovering from COVID-19.MethodPeople experiencing ongoing symptoms of COVID-19, both post-hospitalisation and community managed, were referred for assessment of their rehabilitation needs prior to commencing the programme. Consent and ethical approval was gained to allow data collection and analysis for a longitudinal cohort study. The COVID-19 hospital-based programme was twice weekly for 6-weeks. The Multidimensional Dyspnoea Profile (MDP) (Banzett et al, 2015) was completed pre and post-rehabilitation. Data was analysed using a paired t-test. For the MDP, data was explored to understand the most prevalent sensation of dyspnoea. Data is presented as the immediate perception (A1+SQ) and emotional domain (A2).ResultsNineteen people completed the MDP pre-rehabilitation (74% female, mean [SD] age 53.21 [9.99] years). Hospital admissions were 5 (26.3%) and the mean [SD] length of hospital stay was 8.8 [12.66] days. The mean [SD] unpleasantness (A1) score was 5.21 [1.69]. Chest tightness was the most severe and prevalent sensation (SQ). Frustrated was the most severe emotion (A2).Fourteen people completed the MDP Post-rehabilitation. The mean [SD] unpleasantness (A1) score was 4.29 [2.46]. Hyperventilating was the most severe and prevalent sensation (SQ). Frustrated was the most severe emotion (A2). There was no statistically significant difference between the immediate perception pre and post-rehabilitation (-3.37 [10.40]), p=0.22). There was a statistically significant difference between the emotional domain pre and post-rehabilitation (4.36 [5.32]), p< 0.01.ConclusionThese results demonstrate rehabilitation did improve the immediate perception of dyspnoea but this was not statistically significant. Unpleasantness of dyspnoea reduced following rehabilitation. Furthermore, the sensation of dyspnoea changed following the rehabilitation programme. The emotional domain statistically significantly increased following rehabilitation. Further research is required due to the multifactorial nature of dyspnoea.

Experience of COVID-19 and Postpartum Mental Health

Background: Early reports show pregnant and postpartum women have increased rates of anxiety and depression during the COVID-19 pandemic. These elevations could be related to fear of contracting COVID or mitigation strategies, such as social distancing and stay-at-home orders. First-time mothers may be uniquely vulnerable to these stressors. We examined whether 1) exposure to potentially stressful COVID-19 events, perceived impact of COVID-19, and COVID-19 distress are related to anxiety and depression symptoms reported by first-time mothers, and 2) whether the relationship between COVID-19 related stressors and anxiety and depression is stronger for mothers reporting less social support. Methods: We interviewed 125 first-time mothers of infants less than 3 months old from four pediatric primary care offices in Pennsylvania and Delaware (June 2020 - February 2021). Mothers completed a self-report interview asking about social support, COVID-19 experiences, and anxiety and depression symptoms (EPDS Total, Anxiety, Depression). The COVID-19 measure yielded three variables: 1) number of potentially stressful COVID-19 pandemic-related events (Event Exposure), 2) perceived impact of the COVID-19 pandemic on family (Family Impact), and 3) overall perceived distress related to the pandemic (Distress). Results: Participants (mean age = 29.18, SD: 5.50) were racially representative of the recruitment clinics (40.8% White;37.6% Black;11.2% Asian/Asian American;6.4% Latina). Hierarchical linear regression found COVID-19 Event Exposure was unrelated to Depression (β = 0.03, n.s.) and Anxiety (β = 0.04, n.s.). Controlling for Event Exposure, Family Impact was associated with higher EPDS Total (β = 0.32, p = 0.001), Depression (β = 0.29, p =.003), and Anxiety (β = 0.23, p = 0.02). Distress was significantly associated with higher EPDS Total (β = 0.21, p = 0.04) and Depression (β = 0.26, p = 00.01) but not Anxiety (β = 0.08, n.s.). Mothers reporting less social support had higher Depression scores (r = 0.26, p =.003), but social support was unrelated to Anxiety (r = 0.08, p = 0.41). The interaction of Family Impact and social support produced a nonsignificant trend (p = 0.09, Figure). Conclusion: While experience of more COVID-19 related events was unrelated to maternal anxiety and depression symptoms, maternal report of impact of COVID-19 on the family was associated with both anxiety and depression symptoms. Additionally, higher maternal distress reports and less perceived social supports were related to increased maternal depression symptoms. Therefore, future work should explore how to mitigate impact of COVID-19 families and connect mothers to social support to support maternal mental health.

Postpartum Mental Health and Infant Development During the COVID-19 Pandemic

Background: Infection mitigation strategies implemented during the COVID-19 pandemic influenced social experiences for new mothers and their infants, with potential to negatively impact infant development. Early reports during the pandemic show postpartum women have increased rates of anxiety and depression which are known risk factors for developmental delay. Additionally, stay-at-home orders, social distancing, and use of face masks may alter visual input (facial expressions and oral motor movements) infants receive with the potential to negatively impact social-emotional and communication development. Thus, there is need to examine the developmental trajectory of infants born during the COVID-19 pandemic. We hypothesized that higher COVID impact and maternal symptoms of anxiety and depression would be linked to greater risk for developmental delay. Methods: We recruited 125 first-time mothers of infants less than 3 months of age from four pediatric primary care offices in Pennsylvania and Delaware (June 2020 - February 2021). Mothers completed a self-report interview when their infants were less than 3 months of age (baseline) and again at 6 months of age (follow-up), asking about COVID-19 family impact, anxiety and depression symptoms (EPDS Total, Anxiety, Depression), infant development (ASQ-3 at 3 months and 6 months and ASQ-SE at 6 months), and items inquiring about the frequency of mother-child caretaking activities across a range of behaviors. Results: Bivariate correlations found that while perceived family impact from COVID-19 was related to maternal self-report of postpartum depression symptoms at baseline (r = .32, p = .001), it was not related to the frequency of mother-child caretaking activities or infant development in the first 6 months of life. However, hierarchical linear regression found when controlling for COVID-19 family impact, baseline postpartum depression symptoms were related to fewer concurrent motherchild caretaking activities (β =.24, p = .007) and predicted poorer infant social-emotional development at 6 months of age (β = .23, p = .013). Conclusion: Consistent with prior literature, maternal postpartum depression symptoms were related to fewer concurrent mother-child caretaking activities and poorer infant social-emotional development at 6 months of age. However, despite anecdotal maternal concern, there was not a relationship between the effect of COVID-19 on the family unit and infant development. It is possible that COVID-19 pandemic effects will play a more prominent role as infants' complex language and social skills emerge. However, the current findings do not support a direct effect of pandemic family impact on infant development during the first six months of life, instead underscoring the importance of maternal wellbeing and functioning for infant social-emotional development.

Understanding the role of Mesothelioma UK clinical nurse specialists in meeting the palliative care needs of patients and families: a mixed methods study

Introduction: Patients with mesothelioma and their families have palliative care needs throughout the trajectory of their illness. In the UK, Mesothelioma UK clinical nurse specialists (MCNS’s) are key providers of generalist palliative care. The aim of this study is to explore the palliative care needs of people with mesothelioma and their families, and to explore the role of MCNS’s in supporting patients with palliative care needs. Methods: The study used a mixed methods design involving two workstreams. Workstream one comprised a systematic review and secondary data analysis. Workstream two involved a cross sectional study of MCNS’s using quantitative and qualitative data collection methods. Findings: Eight key findings were generated from the research: (1) Patients with mesothelioma and (2) their families have significant palliative care needs, from early in the disease trajectory;(3) MCNS’s are highly skilled at providing palliative care, the majority have received training or education in palliative care;(4) There is an important distinction between ‘specialist’ palliative care and ‘generalist’ palliative care in mesothelioma;(5) Good partnership working between MCNS’s and specialist palliative care is crucial to ensure patients receive seamless care;(6) A co-ordinated approach to a patients care is crucial;(7) Patients and families can be reluctant to accept palliative care due to preconceptions about the term ‘palliative’;(8) COVID-19 has presented significant challenges to both patients and healthcare professionals. Conclusion: This study provides valuable insights into palliative care needs in mesothelioma, and the role of Mesothelioma UK clinical nurse specialists and others in meeting these palliative care needs. A range of recommendations have been developed for practice, further research and policy which focus on acknowledging and supporting the MCNS role in palliative care provision, integrated working with specialist palliative care and identifying/supporting patient and family needs in a timely way. Disclosure: No significant relationships.

Cancer during a Pandemic: A Young Adult Telemental Health Intervention

Background/Purpose: The SARS-II COVID-19 pandemic halted inperson cancer support. Young Adult (YA) cancer survivors (18-39) face physical and mental health challenges unique to their demographic, including fertility, school, and work issues. YAs have benefited from telemental health groups, with outcomes comparable to in-person groups (Oswald et al., 2021). With a lack of evidencebased interventions for YAs, the pandemic presented an opportunity to develop a virtual YA cancer support group designed to increase self-efficacy, reduce distress, and provide coping skills, and facilitate meaningful connections. Methods: Participants (N = 8) were white, 50% female, 19-37 (M = 26), in active treatment or remission with heterogeneous diagnoses. Eight 60-min sessions included interventions derived from ACT (Eilenberg et al., 2014) and MCP (Breitbart and Poppito, 2005), both for group. Participants were surveyed pre- (T1), mid- (T2), and post- (T3) intervention with seven instruments. Longitudinal data were modeled using a repeated measures analysis of variance (ANOVA). Qualitative feedback also was solicited. Results: Participants reported a reduction in anxious preoccupation, helplessness/hopelessness, and psychological inflexibility (T1-T3;p = < 0.05). On average, they would recommend the group to others, 7.5/10 (T2) and 7.8/10 (T3), and felt able to cope with cancer, 8.2/10 (T2) and 8.6/10 (T3) and the pandemic, 10/10 (T2 and T3). Qualitative feedback described the group as “life changing” and “reassuring” and group impact as having “eased fear of exposure. ” Conclusions and Implications: Our data contribute to new norms for an underrepresented population. The lack of participant diversity calls for a needs assessment to identify barriers to reaching communities of color. Cancer was comparatively more disruptive in YAs' lives than COVID-19. Participants preferred unstructured sessions to share experiences. Quantitative data, while significant in areas, did not capture participants' lived experience. Subjective feedback emphasizes the importance of age-related connections and suggests the need for further research.

Community makers: report on developing an online toolkit for supporting people with dementia to connect during the pandemic and beyond

Purpose: Community Makers (https://communitymakers.co) is an active UK wide network that evolved rapidly in response to COVID-19 and the negative impact of social isolation and distancing on people and families affected by dementia. The network is led by the Alzheimer’s Society, UK Dementia Research Institute Care Research and Technology Centre and The Association for Dementia Studies, at the University of Worcester. This study aims to investigate what works for whom and why and in what circumstances as a basis for the development of an online toolkit for people supporting people affected by dementia to connect and reconnect during the pandemic and beyond. Design/methodology/approach: The development of the toolkit was informed by an iterative approach of engagement with people affected by dementia, learning from a network of community organisations and a rapid realist literature review. Findings: Four common factors that combine to make a successful support intervention, regardless of its type, size or location were identified: relationships, purpose, technology and community. The application of the factors, adopted as principles, is illustrated by applying them to three real-world examples. Social implications: The main output was the online tool kit, which is a resource of creative ideas to inspire groups with different approaches to digital involvement and help reduce social isolation. Originality/value: This report offers new insight, based on identification of four principles, into how people affected by dementia can be supported online and offline during a pandemic and beyond. © 2022, Emerald Publishing Limited.

Delivering a first contact practitioner service in East London during a global pandemic

Keywords: Utilised;Integrated;Challenging Purpose: First Contact Practitioners (FCPs) are being rolled out across the UK to help patients see the right person at the right time, first time. We have worked with all of our Primary Care Networks (PCNs), 8 in total, supplying 18 FCPs to deliver a Five day a week service. This service was provided by an NHS physio department. This was rolled out during COVID-19 pandemic and the team were successfully able to support patients at the start of their journey in GP practices while supporting an increasing workload for GPs. Our aim was to provide highly skilled professionals at the start of the patient journey. We have agreed specific KPI's, such as number of investigations performed, referral onwards to physio or secondary care to monitor performance. Should we then focus on the other aims which were to improve communication and liaison with GPs, to improve pathways for patients, to tailor services to local communities. Methods: We have used quantitative data collection for specific KPIs which includes monitoring waiting times, DNA rates, referral for investigation, diagnosis and a mixed quantitative and qualitative approach for patient feedback. A QI forum was set up for administrative staff and GPs within the PCNs to feedback alongside the FCPs themselves. Results: We have been able to demonstrate that the service is highly used across the vast majority of PCNs, 88% of referrals into the service are appropriate in-line with the ideals of a FCP service, onward requests to radiology are low, 1% for MRI and 4% for X-ray, and waiting times are low, 5 days but are increasing as the service grows in popularity. There have been some challenges with certain GP surgeries not engaging in the service, for example space to house the FCP service, being able to request imaging under the individual FCP name or even a pooled list, variability in demand leading to different waiting times. Conclusion(s): The service so far has delivered against all KPIs. However, the overall time required in setting up the FCP service properly, ensuring appropriate governance and support is in place for staff cannot be underestimated. The quality of training and support is reflected in the low referral for diagnostics and the satisfaction of patients within this particular service. GP engagement has been variable, with some fully embracing the role and being mentors to FCPs, whilst others do not wish to have the service and therefore do not utilize it. Longer term funding for permanent substantive roles will be critical in preventing loss of trained staff. Impact: The roll out has the impact to transform our current pathway, as FCPs can support the patient at the start of their journey. Our clinicians work in primary and secondary care therefore can develop their skills across both areas, while developing the teams around them. This also strengthens existing links with our primary care colleagues, improving referral quality, patient experience and outcomes. Funding acknowledgements: Not funded.

A rapid review and meta-analysis of the laboratory phenotype of multisystem inflammatory syndrome in children

Introduction: Laboratory features are included in the current case definitions of the multisystem inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). Objectives: We reviewed the clinical laboratory test values reported in MIS-C, to better characterise the laboratory phenotype. Methods: A comprehensive search of the WHO COVID-19 database was conducted from January to November 2020. The median test values reported in children 0-19 years with MIS-C, were extracted for each laboratory variable reviewed. Random effects meta-analyses were performed and the quantile estimation method used to determine estimates of the pooled median for each variable. The risk of bias was assessed using the QUADAS-2 tool. Results: Twenty-two observational studies were included in the analyses N=831 children. The overall risk of bias was considered moderate with varying heterogeneity between the studies reviewed for each variable (I2 52.4 - 96.63%). The estimated pooled median values which were abnormal included CRP 188.12 mg/L (95% CI 158.54, 217.70), ESR 60.07 mm/hr (95% CI 49.88, 70.26), ferritin (587.63 ng/ml;95% CI (476.29, 698.97), pro-BNP 6927ng/ml (95% CI 794.52, 13061.13), D-dimer 3.03 ng/L (95% CI 2.41, 3.65), absolute neutrophil count 9.61x109L (95% CI 7.72, 11.50), absolute lymphocyte count 0.92 x109/L (95% CI 0.74, 1.10), platelet count 150.82 x109/L (95% CI 135.09, 145.07), albumin 28.89g/L (95% CI 25.56, 32.22) and sodium 132.67mmol/L (95% CI 131.44, 133.89). Limitations The analyses were limited by varying reporting methods and the use of different normal reference ranges across studies. Conclusion: Markers of inflammation, coagulopathy and cardiac dysfunction, were confirmed as important features of the laboratory phenotype of MIS-C. It is necessary however, to further compare the laboratory values of MIS-C to those with COVID-19 and other hyperinflammatory syndromes in children, to develop evidence-based diagnostic criteria.

Dynamic Approach to Pharmacovigilance in the COVID-19 Era: An International Journal of Medical Toxicology and Drug Experience

Background/Introduction: The clinical presentation and natural history of infection with the novel SARS-CoV-2 virus are relatively unknown, as are the risks associated with the infection and use of pharmaceutical agents. Objective/Aim: Adapt existing pharmacovigilance capabilities to ensure appropriate evaluation of the benefit-risk profiles of specific therapies during the ongoing pandemic. Methods: Bristol Myers Squibb (BMS) Epidemiology have created a tool to dynamically estimate background COVID-19 incidence rates by country, time-period, demographic categories, standards of care, and reporting practices. Local data were updated through the course of the pandemic with background rates re-estimated at regular intervals. Cases, severe cases, and deaths per 100,000 were rescaled to the age and geographic distribution of treated patients (in clinical programs or real-world use). Drug-specific Safety Management Teams used these background rates to identify potential COVID-19-related safety signals in investigational and marketed drugs. Real-world data sources were utilized to understand testing and treatment patterns. The BMS Clinical Safety Program (CSP), a systematic data collection capability, reduces reporting bias and further enhances our understanding of adverse events of interest through the development and implementation of event-specific, targeted case report forms (CRFs) within BMS interventional clinical trials. The COVID-19 CSP CRFs collect patient-level COVID-19 data (i.e., risk factors, diagnosis, clinical presentation, progression, treatment, and outcomes). Results: To date, we have not identified signals of increased risk related to COVID-19 infection that warrant additional action for any of our treatments. TriNetX COVID-19 Rapid Response Network data (February 2021) showed that among 250,000 patients with cancer, positivity rates were similar across immunotherapy (2.5%), chemotherapy (2.7%), and hormone therapy (2.5%). Explorys data showed a shift in median nivolumab treatment frequency from Q2W to Q3W among 1,114 patients with negative COVID-19 tests and to Q4W among 129 COVID-19-positive patients continuing treatment. Conclusion: Individual case level findings and background incidence rates are mutually informative;remarkable or unexpected insights from one may prompt further analysis and validation from the other. Leveraging these complementary pharmacovigilance capabilities in parallel continues to provide a flexible and innovative means to identify potential safety signals, both quantitatively (epidemiology) and qualitatively (CSP), as the conditions of the pandemic evolve. The latest CSP adaptation has included incorporation of CRF data points focused on COVID-19 vaccination and its impact. Once sufficient CSP data are available, analysis will help us understand the impact of COVID-19 infections on the efficacy and safety of our investigational therapies and allow comparisons to real-world data.

CORONET;COVID-19 in Oncology evaluatiON Tool: Use of machine learning to inform management of COVID-19 in patients with cancer

Background: Patients (pts) with cancer are at increased risk of severe COVID-19 infection and death. Due to COVID-19 outcome heterogeneity, accurate assessment of pts is crucial. Early identification of pts who are likely to deteriorate allows timely discussions regarding escalation of care. Likewise, safe home management will reduce risk of nosocomial infection. To aid clinical decisionmaking, we developed a model to help determine which pts should be admitted vs. managed as an outpatient and which pts are likely to have severe COVID-19. Methods: Pts with active solid or haematological cancer presenting with symptoms/asymptomatic and testing positive for SARS-CoV-2 in Europe and USA were identified following institutional board approval. Clinical and laboratory data were extracted from pt records. Clinical outcome measures were discharge within 24 hours, requirement for oxygen at any stage during admission and death. Random Forest (RF) algorithm was used for model derivation as it compared favourably vs. lasso regression. Relevant clinical features were identified using recursive feature elimination based on SHAP. Internal validation (bootstrapping) with multiple imputations for missing data (maximum ≤2) were used for performance evaluation. Cost function determined cut-offs were defined for admission/death. The final CORONET model was trained on the entire cohort. Results: Model derivation set comprised 672 pts (393 male, 279 female, median age 71). 83% had solid cancers, 17% haematological. Predictive features were selected based on clinical relevance and data availability, supported by recursive feature elimination based on SHAP. RF model using haematological cancer, solid cancer stage, no of comorbidities, National Early Warning Score 2 (NEWS2), neutrophil:lymphocyte ratio, platelets, CRP and albumin achieved AUROC for admission 0.79 (+/-0.03) and death 0.75 (+/-0.02). RF explanation using SHAP revealed NEWS2 and C-reactive protein as the most important features predicting COVID-19 severity. In the entire cohort, CORONET recommended admission of 96% of patients requiring oxygen and 99% of patients who died. We then built a decision support tool using the model, which aids clinical decisions by presenting model predictions and explaining key contributing features. Conclusions: We have developed a model and tool available athttps://coronet.manchester.ac.uk/ to predict which pts with cancer and COVID-19 require hospital admission and are likely to have a severe disease course. CORONET is being continuously refined and validated over time.