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1.
Mol Ther Nucleic Acids ; 31:29-42, 2023.
Article in English | PubMed Central | ID: covidwho-2170615

ABSTRACT

To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine. We compared a cationic polymer (pABOL), a lipid emulsion (nanostructured lipid carrier, NLC), and three lipid nanoparticles (LNP). After immunization, we measured serum cytokines and compared the response to induced antibodies against influenza virus. Formulations that induced a greater cytokine response induced a greater antibody response, with a significant correlation between IP-10, MCP-1, KC, and antigen-specific antibody titers. We then investigated how innate immune sensing and signaling impacted the adaptive immune response to vaccination with LNP-formulated saRNA. Mice that lacked MAVS and are unable to signal through RIG-I-like receptors had an altered cytokine response to saRNA vaccination and had significantly greater antibody responses than wild-type mice. This indicates that the inflammation induced by formulated saRNA vaccines is not solely deleterious in the induction of antibody responses and that targeting specific aspects of RNA vaccine sensing might improve the quality of the response.

2.
Journal of the American Society of Nephrology ; 33:890-891, 2022.
Article in English | EMBASE | ID: covidwho-2125197

ABSTRACT

Background: Dialysis nurses have long working hours and provide high-quality care for immunocompromised patients. During COVID-19, dialysis nurses are confronted with life and death situations in fast-paced and demanding environments. Thus, they are vulnerable to mental health problems which may influence organizational productivity and pose serious health and safety hazards. Method(s): This was a quality improvement project to evaluate depression (Patient Health Questionnaire-9, PHQ9), anxiety (General Anxiety Disorder-7, GAD7) and stress (Perceived Stress Scale, PSS) in dialysis nurses between November 2021 and January 2022 at a large academic medical center. Descriptive statistics were computed for all variables. Result(s): A total of 24 nurses [54% outpatient hemodialysis (HD), 17% outpatient peritoneal dialysis, 25% inpatient HD nurses] with a mean age of 49 (SD=10) years old participated in the survey. Most were female (71%), married or with a significant other (79%), and had children (75%). Majority was Asian (63%), followed by Caucasian (29%), Hispanic (4%) and African American (4%). Almost half of them had a bachelor's degree (46%), were licensed vocational nurses (29%), had an associate degree (13%), and had a master's or doctoral degree (13%). The majority (75%) worked full-time, 13% worked overtime and 7% worked part-time. The mean PHQ9 score was 4+/-4 (minimal depression), GAD7 score was 4+/-4 (minimal anxiety) and PSS score was 21+/-3 (moderate stress). Eighteen (75%) dialysis nurses had prayed to control their mood and 85% of these said praying helped. Four nurses (16.7%) started or tried counseling to control their mood and three (75%) of them mentioned it helped. Two nurses (8.3%) started a new medication to control their mood and both nurses said it helped. Conclusion(s): Dialysis nurses showed minimal depression and anxiety despite the moderate stress level associated with their work. Most dialysis nurses found praying to be helpful to control their moods.

3.
Sci Transl Med ; : eadd6383, 2022.
Article in English | PubMed | ID: covidwho-2137395

ABSTRACT

The U.S. Food and Drug Administration only gave emergency-use-authorization of the BNT162b2 and the mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet, questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3 M-052, a synthetic toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3 M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOC), as well as T cell responses, persisted for 12 months. At one year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched non-vaccinated controls intranasally and intratracheally with a high-dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3 M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. Notably, the observed efficacy of both vaccines one year after vaccination supports the implementation of an early life SARS-CoV-2 vaccine.

4.
J Endocr Soc ; 6(Suppl 1):A24-5, 2022.
Article in English | PubMed Central | ID: covidwho-2119542

ABSTRACT

Background: Obesity is a multifactorial chronic disease for which treatment remains challenging and combination anti-obesity medications including glucagon-like peptide-1 receptor agonists (GLP1-RAs) can be highly effective. Clinical Case: We report the case of a 23-year-old male, previously followed in a pediatric weight management clinic, who presented to an adult weight management program with a body mass index (BMI) of 84.3 kg/m2 and impaired glucose tolerance. Factors contributing to his obesity status included a family history, strong hunger and food cravings, and binge eating tendencies. He lost 30% body weight after the addition of semaglutide (a GLP1-RA) 0.5 mg weekly to an anti-obesity medication regimen.At his initial presentation to the adult weight management clinic, with a weight of 643 pounds and hemoglobin A1c 6.4%, he was started on phentermine 15 mg, topiramate 75 mg, and metformin 500 mg daily. Over the next year, he was followed virtually due to the COVID pandemic and, therefore, weight and BMI could not be ascertained. His dose of metformin was increased to 1000 mg, phentermine to 18.75 mg, and topiramate to 100 mg daily during this time. Additionally, extended release bupropion 150 mg daily was added given a history of depression, which was then increased to 300 mg daily. When he was able to return to the clinic in-person, his weight and BMI remained unchanged and, therefore, semaglutide 0.5 mg weekly was added, in addition to monthly virtual registered dietician (RD) visits and a low calorie diet. He reported a significant reduction in hunger after the addition of semaglutide. Eight months later, he had lost 193 pounds, his BMI had decreased to 66.5 kg/m2, and his hemoglobin A1c normalized. The 30% total body weight loss and improved glucose tolerance achieved in less than one year mirrors that typically achieved by metabolic/bariatric surgery. Conclusion: This case highlights the potential benefit of combination anti-obesity medication regimens that include GLP1-RAs. Specifically, while some patients may experience suboptimal response to combination anti-obesity therapies, it may be that the addition of GLP1-RAs to such regimens, namely semaglutide, can provide a synergistic effect leading to substantial weight loss approaching that achieved from metabolic/bariatric surgery. This may result from targeting multiple eating behavior pathways simultaneously, including appetite, satiety, and binge eating tendencies. Further studies are needed to evaluate the efficacy of GLp1-RAs as part of combination anti-obesity medication regimens, especially among those who achieve suboptimal response to regimens not including GLP1-RAs.Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

5.
American Journal of Transplantation ; 22(Supplement 3):404, 2022.
Article in English | EMBASE | ID: covidwho-2063367

ABSTRACT

Purpose: The OPTN DTAC, a multidisciplinary group, evaluates potential donor derived transmission events (PDDTE) to assess the likelihood of disease transmission. Method(s): Retrospective study of PDDTE cases reported to the OPTN between 01/20 and 12/20. DTAC reviewed cases using a standardized classification algorithm. Result(s): During 2020, there were 18,318 donors and 37,583 unique recipients. DTAC reviewed 261/427 PDDTE from donor (111) or recipient (150) findings. 64/261 (25%) donors had proven/probable transmission (P/P Tr) of infection, malignancies or other to 84/206 (41%) exposed recipients [figure]. 12 involved living donors. Infection occurred with 44/64 P/P cases affecting 63 recipients. Viruses were most frequent P/P infections with 29 recipients having P/P Tr from 19 donors. COVID-19 PDDTE represented 11% (29/261) of all cases reviewed involving 29 donors and 15 lung and 76 non-lung recipients. One lung recipient had P/P Tr and died;none of the non-lung recipients developed P/P Tr. For bacteria, 20 recipients had P/P Tr from 14 donors. Deaths from infection (N=10) occurred at a median of 20 days (5-89 days). Attributable death was highest for fungal (4/12, 33%) and bacterial infections (6/20, 30%). 7 donors with malignancies were classified as P/P impacting 15 recipients with 1 attributable death. 53 non-infection, non-malignancy PDDTE were reported;13 resulted in P/P Tr to 14 recipients. Conclusion(s): Although P/P events remain rare, 1/4 reviewed cases resulted in unanticipated P/P Tr. This is a conservative estimate due to passive reporting and empiric interventions. In 29 COVID-19 PDDTE only 1 lung recipient had P/P Tr. The DTAC continues to evaluate PDDTE to maximize organ use and minimize the risk of transmission. (Table Presented).

6.
American Journal of Transplantation ; 22(Supplement 3):333, 2022.
Article in English | EMBASE | ID: covidwho-2063353

ABSTRACT

Purpose: Decision to transplant organs from SARS-CoV-2 NAT+ donors(N+D) balances risk of donor-derived infection with the scarcity of available organs to meet the needs of waitlisted candidates. Method(s): OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC) reports on the use of organs from N+D from the onset of required SARS-CoV-2 lower respiratory tract(LRT) testing for lung donors (May 27, 2021) through August 31, 2021. OPTN data were analyzed for donors with a positive LRT or upper respiratory tract (URT) test reported in DonorNet discrete data fields (N+D), compared with donors who did not have positive LRT or URT in the discrete data fields (N-D). Result(s): Organs were recovered from 120 N+D (all OPTN Regions and 40/57 OPOs (70%)). Median donor age was 42 (IQR: 32-52) for N+D and 43 (30-56) for N-D. There was a greater proportion of DCD N+D than N-D (37.5% vs 28.3%, p=0.04). Underlying COD of anoxia and other were different (N+D 31.7%, 16.7% vs N-D 48%, 2.7%, respectively). Transplanted N+D and N-D did not differ by KDPI, LDRI or LVEF for kidney(KT), liver(LT) or heart(HT), respectively (Table 1). Median time from donor admission to first reported test (any result) was 0 and 4 days for URT and LRT, respectively. N+D recovery occurred a median of 2 (IQR: 1-6) days from last positive test. 246 organs (152KT, 50LT, 22HT, 22other) were transplanted from 107 N+D compared to 8969 organs from 3348 N-D. Recipients from N+D and N-D were similar in age, MELD/PELD (LT) and medical urgency status (HT). Median time from listing to transplant similar for N+D for all organs. The match run sequence number for final acceptor was higher for N+D for all organ types (Table 2). Median length of stay was similar for N+D and N-D for KT and LT (5d and 12-13d, respectively). For HT, median stay was shorter for N+D (30 vs 34d). For N+D, 3 of 50 LT died within 30d of transplant. During this timeframe, no PDDTEs were reported for any N+D at the time of transplant. Conclusion(s): N+D and N-D were similar in terms organ quality characteristics. Recipients receiving organs from N+D had higher match run sequence numbers, suggesting use of organs from N+D is not widespread across centers;however, with small numbers, this data will need to be verified. We cannot assess the relatedness of the three early mortality events in N+D recipients to donor or recipient characteristics. However, these data highlight the importance of ongoing outcome review of N+D recipients. (Figure Presented).

7.
American Journal of Transplantation ; 22(Supplement 3):452, 2022.
Article in English | EMBASE | ID: covidwho-2063348

ABSTRACT

Purpose: The OPTN implemented emergency policy on 5/27/21 requiring lower respiratory testing (LRT) by nucleic acid test (NAT) for SARS-CoV-2 (COVID-19) for all potential deceased lung donors. Our objective was to assess the policy's impact on organ utilization and patient safety. Method(s): OPTN data were analyzed for LRT information reported in discrete data fields or attachments in DonorNet for deceased lung donors recovered 5/27/21- 10/31/21. We used natural language processing to identify donor attachments with terminology related to COVID-19 (e.g., "COVID", "SARS-COV-2") and LRT (e.g., "BAL", "tracheal aspirate") in the attachment filename or description. Result(s): In the first 5 months since implementation, lungs were transplanted from 1037 donors (963 (92.9%) non-DCD, 74 (7.1%) DCD) (Figure). Lung utilization decreased slightly from pre- to post-policy for both non-DCD and DCD donors (overall: 17.7% vs 16.2%;non-DCD: 22.9% vs 21.7%;DCD: 5.1% vs 3.8%). 99.8% (N=1035/1037) of transplanted lung donors had LRT;the majority (99.2%) had LRT results reported in DonorNet on/before day of lung transplant. There have been no reported potential donor-derived SARS-CoV-2 transmissions to lung recipients since implementation. 58 donors had a positive LRT (LRT+), including 27 (46.6%) with a negative upper respiratory test. Lungs were not transplanted from 57/58 LRT+ donors;1 LRT+ donor was believed to be a false positive based on confirmatory test results and had lungs transplanted. Non-lung organs were recovered and transplanted from LRT+ donors without evidence of disease transmission (Table). While the kidney discard rate was higher for LRT+ donors relative to donors without LRT+ (30.2% vs 24.8%), liver discards were lower (5.6% vs 9.9%), and heart utilization was similar (27.6% vs 28.0%). Conclusion(s): Early results suggest that the LRT policy has minimized the risk of donor-derived COVID-19 transmission to lung recipients with minimal impact on lung utilization and allowing transplantation of non-lung organs from LRT+ donors. (Figure Presented).

9.
Rsc Advances ; 12(30):19327-19339, 2022.
Article in English | Web of Science | ID: covidwho-1927110

ABSTRACT

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.2 stealth) has exacerbated the problem: again raising the issues of infection prevention strategies and the efficacy of personal protective equipment (PPE). Against this backdrop, we report an antimicrobial fabric for PPE applications. We have fabricated a nanofibrous silk-PEO material using electrospinning followed by zinc oxide thin film deposition by employing the atomic layer deposition technique. The composite fabric has shown 85% more antibacterial activity than the control fabric and was found to possess substantial superoxide dismutase-mimetic activity. The composite was further subjected to antiviral testing using two different respiratory tract viruses: coronavirus (OC43: enveloped) and rhinovirus (RV14: non-enveloped). We report a 95% reduction in infectious virus for both OC43 and RV14 from an initial load of similar to 1 x 10 (sample size: 6 mm dia. disk), after 1 h of white light illumination. Furthermore, with 2 h of illumination, similar to 99% reduction in viral infectivity was observed for RV14. High activity in a relatively small area of fabric (3.5 x 10 viral units per mm(2)) makes this antiviral fabric ideal for application in masks/PPE, with an enhanced ability to prevent antimicrobial infection overall.

10.
Topics in Antiviral Medicine ; 30(1 SUPPL):92, 2022.
Article in English | EMBASE | ID: covidwho-1880775

ABSTRACT

Background: Currently available COVID-19 vaccination regimens in the US deliver either a homologous spike (S) mRNA prime-boost or a prime-only S DNA adenovirus-vectored antigen to elicit humoral and cell-mediated responses to confer protection against SAR-CoV-2 infection. Alternatively, heterologous vaccination using two different platforms has the potential to enhance and expand immune protection. Addition of a second SARS-CoV-2 antigen, the nucleocapsid (N) protein that is less subject to mutation and elicits vigorous T-cell responses, may also be advantageous. We report immunological responses to homologous and heterologous prime-boost vaccination regimens with a human DNA adenovirus serotype 5 S plus N (AdS+N) and/or a self-amplifying S-only mRNA vaccine (AAAH) delivered with a nanostructured lipid carrier (NLC). Methods: CD-1 mice received homologous or heterologous prime-boost combinations of AdS+N and AAAH. Priming doses were administered on Day 0, booster doses were delivered on Day 21, and mice were euthanized for blood and organ collection on Day 35. Serum was analyzed for anti-S (both wild type and variant) and anti-N IgG subtypes by ELISA. Spleen-resident CD4+ and CD8+ T cells were tested for IFN-γ, TNF-α, and IL-2 production in response to S-WT, S Delta variant and N protein overlapping peptides by intracellular cytokine staining (ICS). Splenocyte cytokine secretion upon stimulation with S-WT/N peptides was also assessed by IFN-γ and IL-4 ELISpot. Serum neutralization of the original Wuhan strain, Delta, and B.1.351 variants was assessed by a pseudovirus neutralization assay. Results: The highest humoral and T-cell responses were seen with the heterologous AAAH prime-AdS+N boost regimen, with a significant increase in T-cell responses relative to homologous vaccination. S protein-binding IgG was similar between wild type and Delta variant S proteins, with a strong/clear Th1/Th2 bias, and T cells responded to S wild type and S Delta peptides with similar levels of cytokine expression. Sera from AAAH prime-AdS+N boost mice showed the ability to neutralize Wuhan D614G, Delta, and B.1.351 (South Africa) variant pseudoviruses at high levels. Conclusion: Heterologous vaccination with the AAAH RNA vaccine prime and an AdS+N DNA boost may provide substantially improved humoral and cell-based immunity against SARS-CoV-2 variants by leveraging the advantages of each vaccine platform technology and by inclusion of immune responses to N.

11.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816900

ABSTRACT

Introduction: The aim of this study was to evaluate the impact of COVID-19 on pathological diagnoses of cancer in Northern Ireland, and assess potential inequalities across subgroups of the population. Methods: Data from the four Northern Ireland pathology labs were used to assess trends in pathological cancer diagnoses from 1st March to 12th September 2020 overall and by cancer site, gender and age. These trends were compared to the same timeframe from 2017-2019. Results: Between 1st March and 12th September 2020 there was a 23% reduction in cancer diagnoses compared to the same time period in the preceding three years. Although some recovery occurred in August and September 2020, this revealed inequalities across certain patient groups. Pathological diagnoses of lung, prostate and gynaecological malignancies remained well below pre-pandemic levels. Males and younger/middle-aged adults, particularly the 50-59 year old patient group, also lagged behind other population demographic groups in terms of returning to expected numbers of pathological cancer diagnoses. Conclusions: There is a critical need to protect cancer diagnostic services in the ongoing pandemic to facilitate timely investigation of potential cancer cases. Targeted public health campaigns may be needed to reduce emerging inequalities in cancer diagnoses as the COVID-19 pandemic continues.

12.
Molecular Immunology ; 141:181-182, 2022.
Article in English | Web of Science | ID: covidwho-1801366
14.
Journal of Clinical Oncology ; 40(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1704253

ABSTRACT

Background: Primary care physicians (PCPs) provide essential support for cancer patients. Both primary and cancer care have been affected by the COVID-19 pandemic. In the US, cancer related encounters and screening decreased over 40% and 80% respectively in January to April 2020 compared to 2019 (London et al JCO Clin Cancer Inform 2020). However, the impact of the pandemic on primary care access for cancer patients remains unclear. Methods: This was a population-based, retrospective cohort study using administrative healthcare databases held at ICES in Ontario, Canada. Patients with a new gastrointestinal (GI) malignancy diagnosed within the year prior to the pandemic, between July 1 and Sept 30, 2019 (COVID-19 cohort), were compared to patients diagnosed in years unaffected by the pandemic, between July 1 - Sept 30, 2018 and July 1 - Sept 30, 2017 (pre-pandemic cohort). Both groups were followed for 12 months after initial cancer diagnosis. In the COVID-19 cohort, this allowed for at least 4 months of follow-up data occurring during the pandemic. The primary outcome was number of in-person and telemedicine visits with a PCP. Secondary outcomes were number of in-person and telemedicine visits with a medical oncologist, number of emergency department (ED) visits, and number of unplanned hospitalizations. Outcomes, reported as number of visits per person-year, were compared between the COVID-19 and pre-pandemic cohorts. Results: 2833 individuals diagnosed with a new GI malignancy in the COVID-19 cohort were compared to 5698 individuals in the pre-pandemic cohort. The number of in-person visits to PCPs per person-year significantly decreased from 7.13 [95% CI 7.05 - 7.20] in the pre-pandemic cohort to 4.75 [4.66 - 4.83] in the COVID-19 cohort. Telemedicine visits to PCPs increased from 0.06 [0.05 - 0.07] to 2.07 [2.01 - 2.12]. Combined in-person and telemedicine visits to PCPs decreased from 7.19 [7.11 - 7.26] to 6.82 [6.71 - 6.92]. In-person visits to medical oncologists decreased from 3.73 [3.68 - 3.79] to 2.87 [2.80 - 2.94], and telemedicine visits increased from 0.10 [0.10 - 0.11] to 0.95 [0.91 - 0.99]. Combined in-person and telemedicine visits to medical oncologists remained stable (3.84 [3.78 - 3.89] vs. 3.82 [3.74 - 3.90]). The number of ED visits per person-year decreased from 1.04 [1.01 - 1.07] in the pre-pandemic cohort to 0.93 [0.89 - 0.97] in the COVID-19 cohort. Unplanned hospitalizations did not show a significant change (0.56 [0.54 - 0.58] vs. 0.53 [0.50 - 0.56]). Conclusions: PCP visits for patients with newly diagnosed GI malignancies overall decreased during the pandemic, with a dramatic shift from in-person to telemedicine visits. Visits to medical oncologists also shifted from in-person to telemedicine, but the overall combined visits remained the same. While the number of ED visits decreased, the shift in ambulatory practices did not seem to impact the number of unplanned hospitalizations.

15.
Blood ; 138:642, 2021.
Article in English | EMBASE | ID: covidwho-1582224

ABSTRACT

Introduction: The most effective chemoimmunotherapy (CIT) in previously untreated CLL is the combination of fludarabine, cyclophosphamide and rituximab (FCR). Ibrutinib (I), the first irreversible inhibitor of Bruton's tyrosine kinase approved for CLL, has improved outcomes in numerous clinical trials compared to different CIT. Methods: FLAIR (ISRCTN01844152) is an ongoing, phase III, multicentre, randomised, controlled, open, parallel group trial for previously untreated CLL requiring therapy according to the IWCLL 2008 guidelines. Patients over 75 years or with >20% 17p-deleted cells were excluded. Participants were randomised on a 1:1 basis to receive 6 cycles of FCR (oral fludarabine 24mg/m 2/day for 5 days, oral cyclophosphamide 150mg/m 2/day for 5 days with IV rituximab [375 mg/m 2 on day 1/2 of cycle 1;500 mg/m 2 on day 1 of cycles 2-6]) every 28-days or IR (Ibrutinib [420mg/day] plus rituximab [6 doses as for FCR]) given for up to 6 years with stratification by disease stage, age, gender and centre. The primary endpoint was to assess whether IR was superior to FCR in terms of investigator-assessed PFS. Secondary endpoints included overall survival,;attainment of undetectable MRD;response to therapy;safety and toxicity;health-related quality of life and cost-effectiveness. A formal interim analysis was planned when 191 events were observed in both arms or 109 events in the FCR arm alone with a p-value of 0.005 leading to reporting of the trial. Here we report the results of this planned interim analysis. Results: A total of 771 patients were randomised (385 to FCR and 386 to IR) from 113 UK Centres between 9/19/2014 and 7/19/2018. The data was locked on 5/24/2021. 73.3% were male, median age was 62 years (33.6% >65yo) and 45.1% were Binet Stage C. IGHV data was available for 728 (94.4%) patients with 53.2% IGHV unmutated (≥98% homology to germline), 40.5% IGHV mutated and 6.3% Subset 2. Hierarchical FISH testing revealed 0.4% 17p del, 15.4% 11q del, 12.3% trisomy 12, 29.7% normal and 35% 13q del;with 7.1% failed. The arms were well-balanced for disease variables with no significance differences. Median follow-up was 52.7 months. IR had a superior PFS compared to FCR (Median PFS not reached for IR versus 67 months for FCR;HR: 0.44;p<0.001;see Figure). The PFS was significantly better for IR in patients with IGHV unmutated CLL (HR: 0.41;p<0.001), but not for patients with IGHV mutated CLL at this follow-up (HR: 0.66;p=0.179). There was no difference in overall survival between the two arms (HR: 1.01;p=0.956) with a total of 29 deaths in FCR arm (including 4 from CLL, 3 Richter's [RT], 3 AML/MDS, 3 COVID-19 and 2 cardiac/sudden) and 30 in the IR arm (including 3 CLL, 1 RT, 0 AML/MDS, 3 COVID-19 and 8 cardiac/sudden). Second line treatment was initiated for 59 patients after FCR (including 38 BTKi, 7 venetoclax+R [venR], 4 BendamustineR [BR] and 3 CHOP-R [RT]) and 21 after IR (including 7 FCR, 5 venR, 1 BR, 1 CHOP-R [RT], 1 ABVD [Hodgkin's]). Overall, 88.1% of patients have received targeted therapies for CLL progression after FCR. The overall survival with FCR in FLAIR is significantly improved compared to FCR in previous NCRI trials (ADMIRE and ARCTIC) which had the same inclusion criteria, the same Centres and an identical FCR schedule, but were conducted prior to widespread availability of targeted therapies in the relapse (recruited between 2009 and 2012). The 4 year overall survival for FCR in FLAIR was 94.5% compared to 84.2% for FCR between 2009 and 2012. SAEs were reported in 53.7% of patients on FCR and 53.4% on IR. Notable differences for SAEs by organ class for FCR vs IR: infections in 33.6% of patients vs 27.1%;blood and lymphatic in 19.8% vs 10.7%;and cardiac in 1.1% vs 8.3%. With current follow-up, there were 10 sudden or cardiac deaths: 8 IR and 2 FCR. Further analysis indicated that 7 of the 8 cardiac or sudden deaths in the IR arm had a history of hypertension or cardiac disease (further detailed in additional ;Munir et al.). Neither of the sudden deaths in the FCR arm ad a prior cardiac or hypertensive history or were on cardiac or anti-hypertensive treatment. There were 6 cases of secondary MDS/AML in the FCR arm and 1 in the IR arm. Conclusion: Ibrutinib plus rituximab resulted in a superior PFS compared to FCR. There was no difference in overall survival, most likely due to effective second-line targeted therapy in patients progressing after FCR. [Formula presented] Disclosures: Hillmen: Janssen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding;AbbVie: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding;Pharmacyclics: Honoraria, Research Funding;Roche: Research Funding;Gilead: Research Funding;SOBI: Honoraria;BeiGene: Honoraria;AstraZeneca: Honoraria. Bloor: Novartis: Honoraria;Kite, a Gilead Company: Honoraria. Broom: AbbVie: Honoraria;AstraZeneca: Honoraria;Janssen-Cilag Ltd: Honoraria;Takeda UK Ltd: Honoraria;Celgene Ltd: Honoraria;Gilead: Honoraria. Furtado: Abbvie: Other: Conference support. Morley: Kite: Honoraria;Janssen: Honoraria;AbbVie;Takeda: Other: Conference support;Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference support. Cwynarski: Adienne, Takeda, Roche, Autolus, KITE, Gilead, Celgene, Atara, Janssenen: Other. Paneesha: Celgene: Honoraria;Roche: Honoraria;Janssen: Honoraria;Gilead: Honoraria;Bristol Myers Squibb: Honoraria;AbbVie: Honoraria. Howard: Roche: Current Employment. Cairns: Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding;Celgene / BMS: Other: travel support, Research Funding. Patten: NOVARTIS: Honoraria;ROCHE: Research Funding;JANSSEN: Honoraria;ASTRA ZENECA: Honoraria;ABBVIE: Honoraria;GILEAD SCIENCES: Honoraria, Research Funding. Munir: F. Hoffmann-La Roche: Consultancy;Alexion: Honoraria.

16.
Blood ; 138:4011, 2021.
Article in English | EMBASE | ID: covidwho-1582152

ABSTRACT

Introduction: Primary care physicians are essential to cancer care. They frequently identify signs and symptoms leading to a diagnosis of cancer, and provide ongoing support and management of non-cancer health conditions during cancer treatment. Both primary care and cancer care have been greatly affected by the COVID-19 pandemic. In the United States, cancer-related patient encounters and cancer screening decreased over 40% and 80% respectively in January to April 2020 compared to 2019 (London et al. JCO Clin Cancer Inform 2020). However, the impact of the COVID-19 pandemic on primary care access for cancer patients remain unclear. Methods: We undertook a population-based, retrospective cohort study using healthcare databases held at ICES in Ontario, Canada. Patients with a new lymphoid or myeloid malignancy diagnosed within the year prior to the COVID-19 pandemic, between July 1, 2019 and September 30, 2019 (COVID-19 cohort) were compared to patients diagnosed in years unaffected by the COVID-19 pandemic, between July 1, 2018 - September 30, 2018 and July 1, 2017 - September 30, 2017 (pre-pandemic cohort). Both groups were followed for 12 months after initial cancer diagnosis. In the COVID-19 cohort, this allowed for at least 4 months of follow-up data occurring during the COVID-19 pandemic. The primary outcome was number of in-person and virtual visits with a primary care physician. Secondary outcomes of interest included number of in-person and virtual visits with a hematologist, number of visits to the emergency department (ED), and number of unplanned hospitalizations. Outcomes, reported as crude rates per 1000 person-months, were compared between the COVID-19 and pre-pandemic cohorts using Poisson regression modelling. Results: We identified 2882 individuals diagnosed with a new lymphoid or myeloid malignancy during the defined COVID-19 timeframe and compared them to 5997 individuals diagnosed during the defined pre-pandemic timeframe. The crude rate of in-person primary care visits per 1000 person-months significantly decreased from 574.4 [95% CI 568.5 - 580.4] in the pre-pandemic cohort to 402.5 [395.3 - 409.7] in the COVID-19 cohort (p < 0.0001). Telemedicine visits to primary care significantly increased from 5.3 [4.8 - 5.9] to 173.0 [168.4 - 177.8] (p < 0.0001). The rate of combined in-person and telemedicine visits to primary care did not change from 579.8 [573.8 - 585.8] in the pre-pandemic cohort to 575.5 [566.9 - 584.2] in the COVID-19 cohort (p = 0.43). In-person visits to hematologists decreased from 504.1 [498.5 - 509.7] to 432.8 [425.3 - 440.3] (p < 0.0001), and telemedicine visits to hematologists increased from 6.6 [6.0 - 7.3] to 75.9 [72.8 - 79.1] (p < 0.0001). The rate of combined visits to hematologists did not change from 510.7 [505.1 - 516.4] to 508.7 [500.6 - 516.8] (p = 0.68). The rate of ED visits significantly decreased from 95.1 [92.7 - 97.6] in the pre-pandemic cohort to 84.7 [81.4 - 88.0] in the COVID-19 cohort (p < 0.0001). The rate of unplanned hospitalizations did not change from 64.8 [62.8 - 66.8] to 65.7 [62.9 - 68.7] (p = 0.60). Conclusions: Primary care visits for patients with hematologic malignancies did not significantly change during the pandemic, but there was a sizeable shift from in-person to telemedicine visits. Similar findings were seen for visits to hematologists. While the rate of visits to the ED decreased, potentially due to concern of being exposed to the COVID-19 virus, the shift in ambulatory practices did not seem to impact the rate of unplanned hospitalizations. Disclosures: No relevant conflicts of interest to declare.

19.
IEEE Industry Applications Magazine ; 2021.
Article in English | Scopus | ID: covidwho-1515165
20.
2021 Ieee/Ias 57th Industrial and Commercial Power Systems Technical Conference ; 2021.
Article in English | Web of Science | ID: covidwho-1361872

ABSTRACT

The global pandemic of COVID-19 has impacted the entire world in ways that were unimaginable months ago. It has changed how professionals work and interact with one another. To ensure the safety of experts and attorneys, also forensic inspection procedures must evolve, while still providing a reliable foundation for an expert testimony, relevant to the task at hand. Traditional field inspections require attendees to be physically present and generally in close proximity. Inspecting artifacts may also require that individual components be serially examined by multiple experts, which increases the risk of transmitting the disease. The authors propose a new approach to forensic inspections aimed at protecting consultants from the biological risk due to COVID-19. This approach takes into account the anti-contagion safety protocols established in affected countries around the world.

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