The Impact of COVID-19 on Breast Cancer Treatment: A Systematic Review

Background: During the COVID-19 pandemic, health resources were stretched, access was impacted by lockdowns and there were concerns about exposure to the virus during visits to hospitals. The purpose of this study was to examine how breast cancer treatments (presentation, surgery, radiotherapy, chemotherapy and/or endocrine therapy) changed or were adapted during the early phase of the pandemic. Methods: A systematic review was conducted using PRISMA guidance. Eligible studies presented original data reporting changes to early breast cancer treatment by comparing ‘pandemic' treatment to a ‘pre-pandemic' cohort or to ‘ideal' treatment of individual cases. Data were extracted into evidence tables and narrative synthesis was used to analyze results. Results: Fifteen studies with paired design were eligible. These reported outcomes for 6,353 people treated for early breast cancer (January 2020–June 2021). All studies reported some change to treatment due to the pandemic. The nature of reported changes was inconsistent. Changes included: more advanced tumours at presentation compared to pre-pandemic, an increase in breast conserving surgery;an increase in simple mastectomy (without breast reconstruction);a trend towards increased wait times, delays to start of treatment, shorter post-operative hospital stay and hypofractionation or omission of radiotherapy. Centres used more or less neoadjuvant chemotherapy or endocrine therapy. Conclusion: In the early stage of the pandemic, fewer early-stage breast cancer cases were treated at many centres. Treatment for breast cancer was impacted and various local solutions were developed. These included less complicated breast surgery, increased use of neoadjuvant therapy, and changes to radiotherapy regimens. Surgery was frequently delayed and breast reconstruction was often unavailable. These results have implications for breast cancer services during the pandemic recovery as a ‘catch-up' increase in cancer diagnoses is expected. Women may wish to access breast reconstruction, unavailable due to COVID-19. The impact of changes to treatment on long-term quality of life should be evaluated. © The Author(s) 2022.

Does Anti-Vaccine Equal Anti-Antibody? Differing Rates of Veteran Acceptance of Monoclonal Antibody Therapies for COVID-19 By Prior Vaccination Status

Background. We assessed correlation between prior acceptance of COVID-19 vaccination and acceptance of monoclonal antibody (MAb) treatment for mild-to-moderate COVID-19. Methods. Adult outpatients evaluated for treatment with MAb between August 31st, 2021 and April 23, 2022 in a large tertiary care VA healthcare system were included. MAb therapies administered over the period included casirivimab-imdevimab, sotrovimab, and bebtelovimab. All patients were screened by a small central clinician team with experience discussing COVID therapies under Emergency Use Authorization (EUA). Baseline characteristics, rationale for not offering MAb, and rates of vaccination and acceptance of therapy were recorded. In addition, rates of acceptance for the initial 4 months were compared to rates during the second 4 months of the program, using Chi-square or Fisher's exact test. Results. 203 patients (mean age 68, 91% male) with early COVID-19 were screened for MAb. 68% were vaccinated. 158 (78%) of those screened were offered MAb. The most common reason MAb was not offered was duration of illness longer than specified by EUA (65%). 112 (71%) patients offered MAb accepted, and 94 (84%) received MAb. Of 106 vaccinated patients offered MAb, 81 (76%) accepted. In contrast, of 52 unvaccinated patients offered MAb, only 31 (60%) accepted (Chi-square p = 0.046). However, when analyzed over time, unvaccinated patients were significantly more likely to accept MAb during the second 4 months of the program (7/7 patients, 100%) than during the first 4 months of the program (24/45 patients, 53%, Fisher's exact p = 0.033). This disparity was not seen in vaccinated patients, who accepted MAb at a rate of 73% during the first half of the program, and 88% during the second half (Chi-square p = 0.19). Conclusion. Vaccinated patients were significantly more likely to accept MAb therapy for COVID-19 than unvaccinated patients, suggesting that willingness to accept COVID-19 vaccination predicts willingness to accept other COVID-19 therapeutics. However, disparity in acceptance rates in our population is significantly attenuating over time, suggesting a 'late-adopter,' phenomenon that has implications for continued efforts to encourage therapeutics and vaccines for COVID-19.

Antithrombotics and antihistamine use correlated with increased COVID-19 severity. Antithrombotics and antihistamine use correlated with increased COVID-19 severity

Background: Many medications have been investigated for use in COVID-19 with anticoagulants being recommended as thromboprophylaxis in hospitals. Aim(s): To investigate the effect of prophylactic and prescribed medication on COVID-19 severity. Method(s): An online survey was used to collect patient data relating to medication use prior to COVID-19 diagnosis in recovered patients. Statistics were performed using one-way ANOVA and t-test. This was an international retrospective cohort study approved by the Royal College of Surgeons in Ireland Human Research Ethics Committee. Result(s): 685 participants representing 32 countries responded (age range 18-78 yrs). Antiplatelet and antithrombotic medication was associated with more severe disease, (28% severe vs. 8% mild). Aspirin and ibuprofen use after diagnosis was associated with increased length of disease;(aspirin 54.5 +/- 3.1 days;control 34.8 +/- 2.7 days, (P < 0.05);ibuprofen 54.7 +/- 6.6 days;control 31.8 +/- 2.8 days, P < 0.05). There was an increase in disease severity for patients taking antihistamines both before and after diagnosis (severe 28%, mild 7%;severe 33% mild 10%, respectively). Antihistamine use was associated with longer disease presentation in both groups (before diagnosis: antihistamine 47.5 +/- 7.9 days, control 35.4 +/- 2.7 days, P < 0.01;after diagnosis 51.9 +/- 5.9 days, control 30.8 +/- 2.6 days P < 0.05). Conclusion(s): We anticipated a prophylactic effect of antithrombotic use prior to infection, however, these data do not support this. The association of ibuprofen and aspirin with severe presentation is likely due to their use for patients with more severe COVID-19 or an underlying condition. Antihistamines inhibit the mast cell response which is important for fighting both the initial infection and the subsequent response. These results indicate that antithrombotics should only be used where there is an indicated thrombotic risk and antihistamines should be used with caution. Further work is required in a larger clinical study to confirm these findings.

Scottish COVID CAncer iMmunity Prevalence (SCCAMP): A longitudinal study of patients with cancer receiving active anti-cancer treatment during the COVID-19 pandemic

Background: Cancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aimed to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anticancer treatment during the COVID-19 pandemic and their antibody response following vaccination. Methods: Eligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome (patient death) was obtained from routine electronic health records. Results: The study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. During the study period there were 174 deaths (22%). The median age was 63 years, and 67% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the local adult general population until May 2021, after which population levels appeared higher than the study population. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality rates were similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, Charlson co-morbidity score and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARSCoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type. Conclusions: SCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.

Social Media for the Dissemination of Educational Videos About Inflammatory Bowel Diseases.

INTRODUCTION: To broadly disseminate 5 user-centered educational videos for patients with inflammatory bowel disease and their family and friends on social media. METHODS: Relevant social media users were iteratively identified based on their online behavior. For each video, 2 different accompanying texts were tested. RESULTS: We reached 4.2 million social media users of whom 320,302 watched at least 50% of the video. A short description resulted in higher view rates than posing an open-ended question. DISCUSSION: We showed the feasibility of large-scale dissemination of health-related educational videos through social media. Our findings can inform future online dissemination approaches of educational content.

DEVELOPMENT OF A NATIONAL ACROSS SPECIALTY MULTI-DISCIPLINARY TEAM FOR MANAGEMENT OF HYPERINFLAMMATORY CONDITIONS DURING THE SARS-COV-2 PANDEMIC

Background/Aims Effective multi-specialty team working is extremely beneficial in management of children with hyper-inflammatory conditions. With the recognition of paediatric inflammatory multisystem syndrome (PIMS) it became apparent a standardised process for discussion of patients would be beneficial. This includes urgent discussion, with access to multiple specialties, and sharing knowledge and experience in a novel condition. Delivering equitable healthcare including access to expertise, specific treatments and research is challenging in Scotland due to its geography. This is facilitated by successful clinical networks (Scottish Paediatric & Adolescent Rheumatology Network [SPARN] and Scottish Paediatric& Adolescent Infection & Immunology National Managed Clinical Network [SPAIIN]) and a well-established paediatric transport service (ScotSTAR). Our aim was to develop a multi-specialty multi-disciplinary team (MDT) for management of patients with hyper-inflammatory conditions. Methods Narrative account of MDT and service development Results We identified a core group of individuals with an interest in inflammatory disorders from different centres and specialties across Scotland including Rheumatology, Infectious Diseases, Cardiology, Intensive Care, Academic Paediatrics, Pharmacists and Clinical Nurse Specialists. Three priorities emerged from initial planning stages: urgent discussions around patient management, peer-to-peer learning and information sharing, and effective prioritisation of research. We designed a written framework and referral pathway, including criteria for acute cardiology involvement, ScotSTAR transfer and intensive care. An electronic proforma was designed to guide MDT discussion, medicolegal documentation and audit purposes. Table 1 describes characteristics of the first nine patients discussed. A particular strength was in diagnostics and consideration of differentials;among patients referred we identified those with haematological malignancy, systemic lupus erythematosus and non-accidental injury. Regular peer-review sessions were held, for reflection on cases and their management in both secondary and tertiary care settings. Clinicians throughout Scotland were encouraged to join via SPARN and SPAIIN networks. Conclusion This multi-specialty MDT has been and continues to be beneficial for management of hyper-inflammatory patients. We will review the process but hope the MDT will prove to continue to be beneficial for future patients. The authors would like to acknowledge all members of the MDT. (Table Presented).

The Weberian Politics-Administration Dichotomy in Time of Global Crisis: Neutral Competence or Cadre Organizations

The 2020 Coronavirus pandemic placed enormous pressures on local, regional, and national governments to remain responsive, open, and equitable when developing solutions to protect the public. The focus of this article is an examination of these challenges, the insufficient preparedness, and the resulting response to the pandemic through the lens of the Weberian politics-administration dichotomy. Despite the fact that China does not practice a Weberian democratic form of government, the nation has managed to become a global economic powerhouse. Through a high degree of centralized planning, China has implemented market-based economic reforms synchronous with sustained socialist practices. However, this system also presents unique challenges for effective governance. Some of these challenges are the result of the governmental system in China, the relationship between the central government and local cadre organizations. For China to continue to grow as a global leader, leadership will need to balance the pros and cons of the dichotomy between the centralized political planning and the local administration by promoting more flexibility in governance structure and the central-local relationship.

Symptoms of anxiety, depression and fear in healthcare workers and non-healthcare workers undergoing outpatient COVID-19 testing in an urban Australian setting.

This study assessed symptoms of anxiety, depression and fear of COVID-19 in members of the general community and healthcare workers (HCWs) attending for COVID testing. This cross-sectional study was conducted in a public hospital COVID-19 testing clinic (June-September 2020) using self-administered questionnaires (i.e. the Hospital Anxiety and Depression Scale (HADS) and the Fear of COVID-19 Scale). In all, 430 participants who met the criteria for COVID-19 testing with nasopharyngeal and throat swabs completed the questionnaires. The mean (±s.d.) age of participants was 37.6 ± 12.6 years. HCWs made up 35.1% of the sample. Overall, the mean (±s.d.) score for anxiety was 6.09 ± 4.41 and 'case' prevalence (any severity) was 151/430 (35.1%), higher than normative population scores. Higher anxiety was found in women (P = 0.001) and in clients who had previously been tested for coronavirus (P = 0.03). HCWs had lower anxiety scores than members of the general community (P = 0.001). For depression, the mean (±s.d.) score was 4.18 ± 3.60, with a 'case' prevalence (any severity) of 82/430 (19.1%), similar to normative population scores. Women reported a higher level of COVID-19 fear (P = 0.001), as did people with a lower education level (P = 0.001). A greater psychological impact of COVID-19 was observed in women, people undergoing repeat testing and participants reporting lower levels of educational attainment. HCWs had fewer symptoms of anxiety and depression than non-HCWs attending the same clinic for COVID-19 testing. This information can be used to plan mental health interventions in primary care and testing settings during this and future pandemics.

Anti-thrombotics and antihypertensives with direct action against SARSCOV-2

Background: Drug re-purposing is an attractive prospect to identify new treatments quickly for COVID-19 and many approved drugs have now been identified to have in vitro activity against SARSCoV2. Thromboprophylaxis has also now been clearly shown to improve outcomes in patients with severe COVID-19. Aims: We hypothesised that some anti-thrombotic and antihypertensive agents would also have direct anti-viral activity against SARS-CoV-2. Methods: We used virtual-high throughput screening to investigate the interaction between approved drugs and the RNA dependent RNA polymerase (RdRp), the main protease (3CL pro ), the spike protein and ACE2. Docking was performed using the Irish Centre for High End Computing and Molecular Operating Environment (CCG, Montreal, Canada). In vitro and in vivo literature data was further analysed for these drugs. Results: We identified 7 anti-thrombotic agents and 3 antihypertensives. Argatroban, betrixaban, dipyridamole, olmesartan, aliskiren and fosinopril were predicted to bind to the 3CL pro and cangrelor to the RdRp. Dabigatran was predicted to bind to both the RdRp and 3CL pro . Fondaparinux and bivalirudin were predicted to bind to 3CL pro , RdRp, the spike protein and ACE2. Bivalirudin had the strongest binding energy of -15.7kcal/mol to the RdRp, -13.5kcal/ mol to the 3CL pro , -12.6kcal/mol for the spike protein and -13.8kcal/ mol for ACE2. Fondaparinux had binding energies of -10.8kcal/ mol, -11.8kcal/mol, -9.0kcal/mol and -9.0kcal/mol, respectively. Fondaparinux was demonstrated to inhibit viral entry through inhibition of the spike protein-ACE2 interaction. Fondaparinux has also been shown to be equivalent to enoxaparin in terms of thromboprophylaxis in severe COVID-19 patients, and therefore it is worth investigating whether viral clearance is improved by fondaparinux. Conclusions: Consideration of the choice of thromboprophylaxis used may provide direct benefit to viral clearance in patients. Considering the multiple mechanisms of action, further investigation of plasma concentrations achieved and possible increases in doses to achieve therapeutic benefit both from a thromboprophylaxis and viral clearance perspective is necessary.

Public Perspectives on Decisions About Emergency Care Seeking for Care Unrelated to COVID-19 During the COVID-19 Pandemic.

Importance: Delaying critical care for treatable conditions owing to fear of contracting COVID-19 in the emergency department (ED) is associated with avoidable morbidity and mortality. Objective: To assess and quantify how people decided whether to present to the ED during the COVID-19 pandemic for care unrelated to COVID-19 using conjoint analysis, a form of trade-off analysis that examines how individuals make complex decisions. Design, Setting, and Participants: This cross-sectional survey study was conducted using a nationwide sample from June 1, 2020, during the initial peak of the COVID-19 pandemic. Included participants were adults aged 18 years or older in the US who self-reported that they had not tested positive for COVID-19. Data were analyzed from July 2020 through May 2021. Exposures: Participants completed a self-administered online survey. Main Outcomes and Measures: Using a choice-based conjoint analysis survey, the relative importance was assessed for the following attributes for individuals in deciding whether to seek ED care for symptoms consistent with myocardial infarction or appendicitis: reduction in chance of dying because of ED treatment, crowdedness of ED with other patients, and chance of contracting COVID-19 in the ED. We also performed latent class analyses using conjoint data to identify distinct segments of the respondent population with similar choice patterns. Logistic regression was then used to explore whether patient sociodemographics and political affiliations were factors associated with decision-making. Results: Among 1981 individuals invited to participate, 933 respondents (47.1%) completed the survey; participants' mean (SD) age was 40.1 (13.0) years, and 491 (52.6%) were women. In latent class analyses, 158 individuals (16.9%) with symptoms of myocardial infarction and 238 individuals (25.5%) with symptoms of appendicitis prioritized avoidance of COVID-19 exposure in the ED (ie, chance of contracting COVID-19 in the ED or crowdedness of ED with other patients) over seeking appropriate care for symptoms. Having a usual source of care was a factor associated with lower odds of prioritizing avoidance of COVID-19 exposure (myocardial infarction scenario: adjusted odds ratio, 0.49 [95% CI, 0.32-0.76]; P = .001; appendicitis scenario: adjusted odds ratio, 0.57 [95% CI, 0.40-0.82]; P = .003), but most sociodemographic factors and political affiliations were not factors associated with decision-making. Conclusions and Relevance: This study found that up to one-quarter of individuals were willing to forgo potentially life-saving ED care to avoid exposure to COVID-19. These findings suggest that health care systems and public health organizations should develop effective communications for patients and the community at large that reassure and encourage timely health care for critical needs during the ongoing COVID-19 pandemic and other scenarios.

A virtual geriatrics and palliative care immersion course for inter-professional teams

Introduction Older adults suffering from multiple progressing illnesses and geriatric syndromes need interprofessional teams to optimize care. There are insufficient number of trained geriatrics experts to serve the ageing population;it is critical to devise practical ways to train frontline clinicians in geriatrics and palliative care principles. During the COVID-19 pandemic, with support from a HRSA grant, the authors adapted an Immersion Course modeled on the successful CRIT program (Chief Resident Immersion Training in the Care of Older Adults). The virtual course focused on the Age Friendly Health System's 4Ms (What Matters, Mentation, Medication, and Mobility) to coach a wide range of trainees and professionals in the care for older adults. Methods The 1.5-day virtual course interspersed mini-lectures with 3 interactive breakout case module discussions depicting a patient with progressing dementia. Lectures were taught by interprofessional faculty pairs and discussion groups were structured to maximize interprofessional learning. Didactic sessions included dementia, depression, deprescribing, non-pharmacological pain management, falls, frailty, community resources, telehealth etc. On day two, attendees were introduced to the principles of an Age Friendly Health System with support from Institute for Healthcare Improvement and participated in interactive quality improvement (QI) breakout exercises with coaching focused on potential QI projects. Results Fifty-seven people attended the course including doctors, MAs, RNs, social workers, chaplains, PAs, NPs, pharmacists and representatives from community-based organizations. The average pre-test score was 66%;the post-test average rose to 80%. Scores improved consistently across all professions and experience levels. The evaluations and comments in the group feedback session were uniformly enthusiastic;they all reported that the content was at the right level. Conclusion We have successfully conducted a 1.5-day virtual immersion course for interprofessional trainees and clinicians. The course was well accepted and successfully imparted core geriatrics, palliative care and quality improvement content while fostering interprofessional teamwork. This conference could serve as a model for training the existing workforce to better care for vulnerable adults during this unprecedented pandemic time and beyond.

Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors.

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.