REVACCINATION OF PATIENTS WITH SLE OR RA WITHOUT AN INITIAL COVID-19 VACCINE RESPONSE ELICITS SEROCONVERSION IN HALF OF THE PATIENTS

BackgroundTreatment with Rituximab (RTX) in patients with rheumatic diseases (RD) has presented a challenge during the COVID-19 pandemic, as RTX leads to markedly reduced and often undetectable antibody responses after COVID-19 vaccination (1).ObjectivesTo investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with RD who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion.MethodsFrom a RD cohort (COPANARD) vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies (abs) and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralizing abs, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. This study was funded by the Danish Rheumatism Association.ResultsPatient demographics are given in Table 1. Forty-seven percent of cases had detectable total SARS-CoV-2 abs and neutralizing abs after revaccination. However, antibody levels were significantly lower than in controls and blood donors (p<0.008), Figure 1A+B. Revaccination induced an antibody class switch in cases with a decrease in detectable IgM abs (Baseline 11/17, Followup 3/17) and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups, Figure 1C. The proportion of cases with detectable CD4+ T cells increased from 69% to 88% (p=0.25), and for CD8+ T cells, the proportion decreased from 88% to 82% (p=1.00). Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors, Figure 1D. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination, Figure 1D.Univariate logistic regression analysis was performed to analyze if active RTX treatment, the presence of B-cells, or a positive T-cell response prior to revaccination predicted seroconversion of total SARS-CoV-2-abs in the patient cohort. We did not find a significant explanatory effect of either variable in the univariate logistic models, data not shown.Table 1.DemographicsCases Revaccination, n=17Controls Boost, n=29Female sex, no(%)1482%2172%Age, median (IQR)6549 - 706762 - 72Disease duration, years1510 - 18229 - 31Rheumatoid Arthritis/SLE13/410/19None DMARD529%828%Prednisone424%13%Methotrexate741%1241%Hydroxychloroquine212%414%None biologic treatment424%931%Rituximab1271%0TNF-inhibitors16%724%JAK-inhibitors0621%IL-6-inhibitors, Abatacept, Benlysta0724%Previous rituximab treatmentAny rituximab treatment1694%13%RTX within the last 15 months, no1488%0Cumulative total dose, mg134-242Time from RTX to revaccination, months95-1249Figure 1.ConclusionIn conclusion, forty-seven percent of initial non-responders were able to seroconvert after two-dose revaccination. However, plasma concentrations of the antibodies against SARS-COV-2 and the levels of neutralizing capacity remained significantly lower than in immunocompetent blood donors. B-cell levels or T-cell responses before revaccination did not predict seroconversion. Our study suggests that patients with RDs who did not mount a detectable serological response to a COVID-19 mRNA vaccine have a T cell response similar to immunocompetent controls. Future studies should establish the antibody levels that identify RD patients without sufficient protection against SARS-CoV-2 infection.References[1]Troldborg A, et al. Time Since Rituximab Treatment Is Essential for Developing a Humoral Response to COVID-19 mRNA Vaccines in Patients With Rheumatic Diseases. J Rheumatol. 2022.AcknowledgementsThe Danish Rheumatism Association [grant number R203-A7217]. We acknowledge all patients and blood donors contributing to the stud for their invaluable participation. The authors would like to thank Sif Kaas Nielsen and Mads Engelhardt Knudsen, the Laboratory of Molecular Medicine at Rigshospitalet, for their excellent technical assistance in analyzing the samples.Disclosure of InterestsNone Declared.

The economic performance of the EU fishing fleet during the COVID-19 pandemic

The COVID-19 outbreak and subsequent public health interventions have depressed demand and disrupted supply chains for many fishing businesses. This paper provides an analysis of the COVID-19 impacts on the profitability of the EU fishing fleets. Nowcasting techniques were used to estimate the impact of the COVID-19 pandemic on the economic performance for the EU fishing fleet in 2020 and 2021. Our results show that the economic impact of COVID-19 on this sector was smaller than initially expected and overall profits remained positive. This was in part due to low fuel prices that reduced operating costs of fishing, and the early response from governments to support the sector. The results vary by fishing fleet, revealing that small-scale fleets and the fleets in the Mediterranean and Black seas have been more impacted than large-scale fleets and the fleets in the Northeast Atlantic. © G. Carpenter et al., Published by EDP Sciences 2023.

Impact of Student Engagement, Satisfaction, and Perception of Learning in Multi Channel Learning during COVID-19 Pandemic

The worldwide Covid-19 pandemic has altered many things, including the way of learning, the way of learning that is carried out during the pandemic through online to avoid or minimize the spread of the virus. Changes in the way of learning for students provide new experiences for universities and students. Several previous studies have been conducted related to this and several important factors were found such as learning program structure factors, student interaction, lecturer presence, student engagement, student satisfaction and learning perception. This quantitative research was carried out using the SEM-PLS technique to see how the influence of the factors that affect learning perception and student satisfaction during pandemic Covid-19 took place. This study used a sample of 436 respondents and found a very significant relationship between factors. The results of this study found, Learning Program Structure, Student Interaction, Lecture Presence, Student Engagement have an influence on Learning Perception factors and Student Satisfaction. The study results useful for the development of future learning methods. © 2022 IEEE.

RE-VACCINATION COMPARED to BOOSTER COVID-19 MRNA VACCINATION SIGNIFICANTLY INCREASES the SEROLOGICAL RESPONSE in RITUXIMAB-TREATED PATIENTS with INFLAMMATORY RHEUMATIC DISEASES WITHOUT A PRIMARY DETECTABLE SEROLOGICAL COVID-19 VACCINE RESPONSE

Background: Reports of an impaired humoral response after COVID-19 vaccination in patients treated with rituximab (RTX) have raised particular concern for patients with infammatory rheumatic diseases (IRD) receiving RTX (1). This calls for strategies to enhance a humoral response in RTX-treated patients. At present, there is no data on whether it is best to increase the humoral response with a third vaccine dose (a booster) or with a third and fourth dose (re-vaccination). Objectives: In IRD patients treated with RTX, without a detectable humoral response after the frst vaccination course (two shots), we aimed to investigate the difference of either a booster vaccine (dose 3) or a new re-vaccination course (dose 3 + 4) on the serological response of the COVID-19 mRNA vaccines. Methods: We included 84 patients with IRD treated with RTX, all without measurable total SARS-CoV-2 antibodies after a full primary COVID-19 vaccination course (2 doses three weeks apart). All patients were offered a new re-vaccination course with the mRNA vaccine not used primarily (Pfzer/Biontec or Moderna). A small number of patients declined the revaccination, and recieved a booster with the mRNA vaccine used initially. Serum total antibodies were measured before and six weeks after the last dose against recombinant SARS-CoV-2 spike S1 protein (VITROS). In addition, CD19+ B-cells were measured at inclussion. Results: Patient characteristics are in Table 1. The median age was 64 years;68% were female with a disease duration of 5 years. Sixty-nine out of 84 were re-vaccinated (3 + 4 dose). Details previous exposure to RTX are given in Table 1. CD19+ B-cells were measurable in 12/81 at inclusion. We found a combined seroconversion rate of 33% six weeks after the last shot. There was no statistical difference between the booster (38,5%) and the re-vaccination group (32,3%), p=0.67 (Pearson's chi-squared). IRD patients with a humoral response in the re-vaccination group had signifcantly higher levels of total SARS-CoV-2 antibodies (median(IQR) 306(49-464) AU/ml) compared to the booster group (14(4-15) AU/ml) p=0.02, Figure 1A. In multiple logistic regression model, we found that levels of CD19+ B-cells were the only variable able to predict a humoral response, Figure 1B. However, only 39% of the patients with a humoral response to vaccination had measurable CD19+ B-cells before vaccination. We found no effect of age, sex, diagnosis, treatment, and RTX exposure on the chance of seroconversion in multiple logistic regression models when corrected for CD19+ B-cells. Conclusion: We found that re-vaccination (dose 3 + 4) with COVID-19 mRNA vaccines favored a high humoral response in patients with IRD treated with RTX, who did not have a detectable humoral response after the frst two vaccine doses, compared to a booster shot (dose 3). A detectable humoral response after re-vaccination was seen in more than half of the patients with no measurable CD19+ B-cells before vaccination. Presence of circulating CD19+ B-cells are a signifcant predictor of humoral response to mRNA COVID-19 vaccination.

VACCINATION AGAINST COVID-19 SHOULD BE ENCOURAGED in PATIENTS with RHEUMATIC DISEASE, AS MOST PATIENTS DEVELOP A SEROLOGICAL RESPONSE AGAINST the VACCINE and VACCINATION REDUCES SELF-IMPOSED ISOLATION and SHIELDING BEHAVIOR

Background: Vaccine trials of the SARS-CoV-2 mRNA vaccines were encouraging but excluded most patients with rheumatic diseases (RD) and patients treated with immunosuppressive therapy. However, reports of a more severe COVID-19 disease course in patients with RDs prompted strategies for expediting vaccination of RD patients in most countries. In addition to the impact experienced by most people of the pandemic, patients with RDs were adversely impacted by the potential risk of severe COVID-19 due to their disease and immunosuppressive treatment. Fear of COVID-19 led to disproportionate anxiety, self-isolation, and shielding behavior for many RD patients at the beginning of the pandemic. Objectives: We investigated antibody levels in serum against SARS-CoV-2 after a two-dose vaccination with an mRNA vaccine in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Further, we examined the association between reactogenicity and immunogenicity and how vaccination influenced patient behavior concerning fear of COVID-19 and shielding. Methods: Patients with SLE or RA from the COPANARD (Corona PANdemic Autoimmune Rheumatic Disease)1 cohort received two doses of an mRNA vaccine between January and August 2021 and had total antibodies against SARS-CoV-2 measured before vaccination and 2 and 9 weeks after the second vaccination. In addition, patients answered an electronic questionnaire before and eight weeks after vaccination concerning behavior, anxiety, and symptoms of depression (PHQ-9). Results: Three-hundred-and-three patients and 44 blood donors (healthy controls) were included. Signifcantly fewer patients (90%) had measurable antibodies against SARS-CoV-2 compared to blood donors (100%) after the second vaccination (p<0.001) (Figure 1). Treatment with Rituximab was the strongest predictor of unfavorable vaccine response, as only 27% were seropositive after vaccination. We found a negative effect of prednisone and methotrexate but no effect of age, comorbidity, or pausing medication on seroconversion. Patients experienced signifcant improvement after vaccination in 10 out of 12 questions regarding behavior and fear of COVID-19, but no change was observed in symptoms of depression (p=0.62) or anxiety (p=0.46). Conclusion: The majority of patients with SLE or RA had a measurable sero-logical response to the COVID-19 mRNA vaccine after two doses. Treatment with Rituximab was the strongest predictor of no seroconversion. Our fndings warrant encouragement of vaccination against COVID-19 for patients with RD, as most patients benefts with both a serological immune response and reduced isolation and shielding behavior.

TIME since LAST RITUXIMAB TREATMENT IS ESSENTIAL for DEVELOPING A HUMORAL RESPONSE to the COVID-19 MRNA VACCINE in PATIENTS with RHEUMATIC DISEASES

Background: Concerns about Rituximab (RTX) treatment and potentially inadequate vaccine response were aired early in the pandemic, and initial data seem to support this concern (1). So far, studies regarding rheumatic patients and the COVID-19 vaccines have included a relatively small number of patients receiving rituximab. Objectives: We aimed to investigate if patients with rheumatic diseases treated with RTX raise a serological response towards the COVID-19 mRNA vaccines and to elucidate the influence of time since the last dose RTX before vaccination on this response. Methods: We included 201 patients followed at the Department of Rheumatology, Aarhus University Hospital. All had been treated with RTX in the period 2017-2021, and had fnished a two-dose COVID-19 mRNA vaccination. All patients and 44 blood donors had total antibodies against SARS-CoV2 spike protein measured. Univariate and multivariate logistic regression were used. Results: Patients were predominantly female (67%) with a median age of 62 years. The most frequent diagnosis was ANCA-associated vasculitis (32%), rheumatoid arthritis (31%), and myositis (14%), and 97% had the Pfzer/Biontic vaccine. Median number of RTX infusions were 5 (IQR 2-8), with a cumulative dose of 4g (2-8), and 72% had received RTX within the last 15 months. Prednisone was used by 43%, followed by methotrexate (25%), hydroxychloroquine (11%) and azathioprine (10%). We observed a time-dependent increase in antibody response as the interval from the last RTX treatment to vaccination increased (Table 1). Only 17.3% of patients developed a detectable antibody response after receiving their vaccination 6 months or less after their previous RTX treatment (Figure 1). Positive antibody response increased to 66.7% in patients who had RTX 9-12 months before vaccination. Neither cumulative treatment time nor cumulative RTX dose seemed to influence the serological response to the vaccine (Table 1). Thus, even in patients who have received RTX for a substantial time, expanding time-since-last-RTX treatment could prove benefcial for increasing the chance of a serological response. We further found that 'months between last Rtx and vaccination', prednisone and azathioprine treatment were alle negatively associated with antibody response in a multivariate logistic regression analysis(Table 1). All blood donors (100%) had detectable antibodies after vaccination. Conclusion: In conclusion, patients with rheumatic diseases treated with RTX have a severely impaired serological response towards the COVID-19 mRNA vaccine. This is especially true if the interval between RTX treatment and vaccination is less than 9 months. For the majority of RTX treated patients, the recommended six months since last RTX is insufficient to develop a humoral response to COVID-19 mRNA vaccines. Our data suggest that the current recommendations of a 6 months interval should be revised.

A novel non-invasive FcRn-targeted mucosal vaccine strategy

While vaccines against the pandemic SARS-CoV-2 are currently given intramuscularly, it may be preferable to deliver vaccines in a needle-free manner by inhalation or a nasal spray to secure mucosal protection at the actual site of infection. This will limit the spread of the virus, ease administration and likely improve vaccine acceptance. Here, we report on a subunit vaccine strategy based on engineered human albumin fused to immunogens, which upon intranasal delivery targets FcRn for transport across the mucosa followed by induction of robust local and systemic antibody responses beyond that gained by intramuscular delivery. This needle-free vaccination principle was shown to block infection by both SARS-CoV-2 and influenza A, and as such should be an attractive strategy for design of subunit vaccines targeting respiratory diseases.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

Humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Introduction: Expert organizations worldwide recommend that all patients with multiple sclerosis (MS) should be vaccinated against acute respiratory syndrome coronavirus 2 disease of 2019 (COVID- 19). However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. There is increasing evidence of altered protective humoral immunity after mRNA-COVID-19 vaccines among patients treated with fingolimod, rituximab and ocrelizumab. However, the role of cellular immunity is still unknown. Appropriate knowledge regarding the development of protective immunity is of paramount importance in respect to medical, political and public health measures to aid the fight against the COVID-19 pandemic. Objectives and Aims: We aimed to characterize humoral and cellular immunity after mRNA-COVID-19 vaccines in patients with MS treated with high-efficacy DMTs (NEVROVAX). Methods: All patients treated with alemtuzumab, natalizumab, fingolimod, rituximab or cladribine, and vaccinated with BNT162b2- or mRNA-1273-COVID-19 vaccine were invited. We assessed protective humoral immunity by measuring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG response using anti-spike protein-based serology in all included patients before, and 3-6 weeks after full vaccination (NEVROVAX-HUMORAL). Cellular immunity was investigated using high dimensionality multiparameter analyses in 50 pre-selected individuals (10 patients in each treatment group;NEVROVAX-CELLULAR) and in all patients not developing protective humoral immunity in the former group (NEVROVAX-EXTENSION). Results and Conclusions: Over 900 patients were invited and, to date, more than 300 patients have been included in our study. Preliminary results show altered protective humoral immunity in MS patients treated with rituximab and fingolimod. Continuous analysis of cellular immunity is conducted in these patients. The percentage of vaccinated inhabitants in Norway is still under 10%. We expect to complete all analyses by September 2021 and will present our results during ECTRIMS 2021.

Caught in the currents: evaluating the evidence for common downstream police response interventions in calls involving persons with mental illness

The origins of this report, and of the Mental Health and Policing Working Group, can be traced to the unique situation Canadians have faced as a result of the COVID-19 pandemic. The unique circumstances of this global outbreak, which have for many Canadians resulted in serious illness and death, intensified economic uncertainties, altered family and lifestyle dynamics, and generated or exacerbated feelings of loneliness and social dislocation, rightly led the Royal Society of Canada's COVID-19 Taskforce to consider the strains and other negative impacts on individual, group, and community mental health. With the central role that police too often play in the lives of individuals in mental and (or) emotional crisis, we were tasked with exploring what can be reasonably said about the state of our current knowledge of police responses to persons with mental illness.

Quality of life and fear of COVID-19 in 2600 baccalaureate nursing students at five universities: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data. METHODS: The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents' mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen's d) were evaluated. RESULTS: In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen's d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen's d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen's d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen's d = 0.26), psychological distress (Cohen's d = 0.76) and overall QoL (Cohen's d = 0.18). CONCLUSIONS: Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students' overall QoL.

The COVID-19 pandemic prompts isolation and behavioral changes in patients with chronic rheumatic diseases leading to reduced physical activity, increased pain, disease activity, and low seroprevalence of SARSCOV2 antibodies

Background: The coronavirus disease 2019 (COVID-19) pandemic has complicated the management of chronic rheumatic diseases (CRD). Patients with CRDs are immunocompromised and generally prone to infection. The fear of COVID-19 and the degree of the self-imposed shielding strategy implemented by many patients introduced new challenges for the patients. Although recommendations have been developed to manage patients with CRDs by, i.e., EULAR, strong evidence is still lacking to guide treatment decisions. Objectives: This study aimed to assess the seroprevalence of SARS-CoV-2 antibodies in patients with CRDs and healthy controls during the first wave of the pandemic. We further evaluated the effect of the pandemic on patient behavior regarding medication, exercise, pain, and experienced disease activity. Finally, we investigated the self-perceived consequences of the pandemic and lock-down on anxiety and depression in patients with CRDs compared with healthy controls. Methods: More than 900 participants were included in the study: 405 patients with rheumatoid arthritis or systemic lupus erythematosus and 513 blood donors. All participants had SARS-CoV-2 antibodies measured (Wantai SARS-CoV-2 total antibody ELISA;sensitivity 96.7%, specificity 99.5%) and answered a questionnaire concerning behavior, anxiety, and symptoms of depression (PHQ-9). The participants with CRD were further asked about physical activity, adherence to medication, and disease-related symptoms. Results: CRD patients had a sixfold lower seroprevalence of SARS-CoV-2 antibodies compared to controls (p=0.03) (Figure 1). Almost 60% of patients were unable to exercise as usual, leading to increased pain in 34%, and experience of increased disease activity in 27%. Approximately 10% of patients reduced or discontinued their immunosuppressive treatments at their own initiative. Symptoms of moderate depression were present in 19% of patients compared to 6,8% of controls (p<0.001). Conclusion: Low seroprevalence in patients with CRDs indicates successful mitigation of exposure to SARS-CoV-2. However, this appears to occur at the expense of physical activity and adherence to immunosuppressive treatment. Our results raise an important concern regarding the consequences of isolation for patients with CRDs. The result of physical isolation is a risk of severe mental health issues, physical inactivity, self-medication, increased pain, and increased disease activity. The long-term consequences of recommendations for patients with CRDs should be taken into account when tackling the continuing pandemic.

Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study

Background: Talazoparib (TALA) is a poly(ADPribose) polymerase inhibitor approved as monotherapy for treating adult patients (pts) with gBRCA1/2-mutated HER2-negative locally advanced or metastatic BC. Methods: This phase 2, non-randomized, single-arm, openlabel study (NCT03499353) evaluated the efficacy and safety of TALA in the neoadjuvant setting for pts with early gBRCA1/2-mutated HER2- BC. Primary endpoint was evaluation of pathologic complete response (pCR) as assessed by Independent Central Review (ICR) after completing 24 weeks of neoadjuvant TALA monotherapy 1 mg QD (0.75 mg for moderate renal impairment) followed by surgery. Secondary endpoints included pCR by investigator (INV) and residual cancer burden (RCB) by ICR (RCB: 0 [pCR], I [minimal], II [moderate], III [extensive]). The evaluable population included pts who received at least 80% of the TALA dose prescribed at treatment start and underwent breast surgery and pCR assessment, plus those who progressed before pCR could be assessed. The intent-to-treat (ITT) population included all pts who received at least 1 dose of TALA. Results: Of 61 pts treated with TALA (ITT and safety populations), 48 comprised the evaluable population. All pts had triplenegative BC. 60 pts had adenocarcinoma and 1 had squamous cell histology, with the following staging: I=20, II=27, III=14. Mean age was 44.6 years, mean duration of 4.5 wks since disease onset, mean duration of treatment of 23.3 wks, and mean overall relative dose intensity of 84.5% (ITT population). pCR (assessed by ICR and INV) and RCB (by ICR) for the evaluable and ITT populations are shown in the table below. Ten (16.4%) patients discontinued treatment due to progressive disease. One pt had a disruption of treatment as a result of COVID-19 restrictions, 2 pts for other reasons: to undergo surgery early and consent withdrawal;9 patients received <80% dose. Treatmentemergent adverse events (AEs) were reported in 98.4% of pts (27.9% grade [G] 1, 23.0% G2, 45.9% G3, 1.6% G4);the most common were fatigue (78.7%;G1 54.1%;G2 21.3%;G3 3.3%), nausea (68.9%;G1 54.1%;G2 13.1%;G3 1.6%), and alopecia (57.4%;G1 54.1%;G2 3.3%). Three (4.9%) pts discontinued treatment due to AEs (G3 anemia [n=2] and G3 vertigo [n=1]) and continued on study. Conclusions: TALA monotherapy in the neoadjuvant setting was active and showed pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens and was generally well tolerated (Table Presented).

Pregnant womenʼs concerns and antenatal care during covid-19 lock-down of the danish society

INTRODUCTION: Pandemics are known to cause stress and anxiety in pregnant women. During the coronavirus disease 2019 (COVID-19) lockdown of the Danish society, pregnant women were considered to be at increased risk, and access to antenatal care changed. METHODS: On 8 April 2020A, a questionnaire was sent to 332 pregnant women previously sampled by general practitioners in two Danish regions. The women were contacted via secured e-mail (e-Boks), and questionnaires were returned until 6 May. RESULTS: The questionnaire was returned by 257 women (77%). More than half believed that they were at a high risk of infection with COVID-19, and a third of the women were concerned about the risk of serious disease – especially for their unborn child. Almost 90% isolated at home most of the time. The majority were worried about possible consequences of the pandemic for antenatal care, but very few had actually missed a scheduled preventive consultation with their general practitioner, and only 15% had missed an appointment with their midwife. The majority of the women preferred normal consultations and found no added safety in shifting the consultation from the normal clinical setting. CONCLUSIONS: The COVID-19 pandemic and lockdown have had a major impact on Danish pregnant women. Even so, concerns were more focused on access to care than on the risk of COVID-19 infection. Contacts with the antenatal healthcare system have only been moderately affected. © 2020, Almindelige Danske Laegeforening. All rights reserved.

Effects of hand disinfection with alcohol hand rub, ozonized water, or soap and water: time for reconsideration?

The effect of alcohol hand rub was tested in eradicating Escherichia coli, and compared with hand wash using ozonized tap water or soap and water. Alcohol eradicated all bacteria in 10 out of 35 participants, but with an average (SD) of 2330 (4227) cfu/mL left after disinfection, whereas ozonized water removed all bacteria in 10 out of 55 participants, with an average of only 538 (801) cfu/mL left (P = 0.045). Soap washing was the most effective with total removal of bacteria in six out of 20 participants, with an average of 98 (139) cfu/mL (P = 0.048 and 0.018 versus ozonized water and alcohol, respectively).