Long-term outcomes of patients with large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel: Results from the us lymphoma CAR-T cell consortium

Introduction: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy that induces durable responses in patients with relapsed or refractory large B-cell lymphoma. At a median of 27.1 months follow-up on the ZUMA-1 trial, median overall survival (OS) was 25.8 months with 39% progression free survival (PFS) at 2 years post-infusion (Locke, Lancet Onc 2019). We previously reported outcomes of axi-cel patients treated with standard of care therapy at a median follow up of 12.9 months, including 42% who did not meet eligibility criteria for ZUMA-1 based on co-morbidities (Nastoupil, JCO 2020). Here we report results from this cohort at a median follow up of 32.4 months, as well as late outcomes of interest including cytopenias, infections and secondary malignancies. Methods and Results: The US Lymphoma CAR-T Consortium comprised of 17 US academic centers who contributed data independent of the manufacturer. Two hundred and ninety-eight patients underwent leukapheresis with intent to manufacture standard of care axi-cel as of September 30, 2018. In infused patients (n=275), OS and PFS were calculated from date of infusion. After median follow-up of 32.4 months (95% CI 31.1 - 34.3), median OS was not reached (95% CI 25.6 - not evaluable) (Figure 1A) with 1-, 2- and 3-year OS of 68.5% (95% CI 62.6-73.7), 56.4% (95% CI 50.1-62.2) and 52.2% (95% CI 45.7-58.2%), respectively. Median PFS was 9 months (95% CI 5.9-19.6) (Figure 1B);1-, 2- and 3-year PFS was 47.4% (95% CI 41.4-53.2), 41.6% (95% CI 35.6-47.5) and 37.3% (95% CI 31.3-43.2), respectively. Twenty-seven PFS events occurred at or after 1 year post infusion;19 events were progressive lymphoma, with the latest relapse observed 28 months after axi-cel infusion. Eight patients died while in remission from their lymphoma: 4 from secondary malignancy, 3 from infection, and 1 from unknown causes. Results of multivariable modeling were similar to our prior analysis: factors associated with both a shorter PFS and shorter OS included male sex, elevated pre-lymphodepletion LDH, and poor ECOG status. Complete blood count and B- and T-cell recovery data were collected at 1 and 2-years post-infusion, excluding patients who had relapsed or been treated for secondary malignancy at time of collection (Table 1). Rates of neutropenia (absolute neutrophil count ≤1000) at 1- and 2- years were 9.2% (10/109) and 11.2% (9/80) and rates of CD4 count ≤200/ul were 62% (23/37) and 27% (7/26). Recovery of B cells was seen in 54% (15/28) and 57% (13/23) at 1-and 2-years post infusion. Infections were reported in 31.2% (34/109) patients between 6- and 12-months post infusion, and 17% (18/109) were severe, requiring either hospitalization and/or IV antibiotics. Twenty-one patients (24%, 21/89) had an infection between 1- and 2- years, 11% of which were severe. Twenty percent (10/49) of patients between 2- and 3-years had an infection and 4 (8%) were severe. Neutropenia, low CD4 counts, and IgG levels were not associated with infection, though patients with infection between 6-12 months were more likely to have received IVIG (p<0.001). No patient in this cohort died of COVID-19. Twenty-two of 275 (8%) patients were diagnosed with subsequent malignancy after axi-cel treatment: 14/275 (5%) patients were diagnosed with myeloid malignancies (MDS (n=12), AML (n=1), CMML (n=1));other malignancies included squamous cell carcinoma of skin (n=3);sarcoma (n=1);endometrial (n=1);lung (n=1);mesothelioma (n=1) and AITL (n=1). Patients with myeloid malignancy had a median age of 62 at axi-cel apheresis (IQR 56-67), 64% were male and median lines of prior therapy was 4 (IQR 3-6), including 36% with a prior autologous stem cell transplant. Eleven patients were in remission from lymphoma at myeloid malignancy diagnosis, while 3 were diagnosed after progression and interval therapy. Conclusion: This multi-center retrospective study showed similar long-term results to the ZUMA-1 trial, despite including patients who did not meet ZUMA-1 eligibility criteria ba ed on comorbidities. Sixteen percent of PFS events were seen after 1 year, largely due to disease progression. Late infection was common but was not explained by persistent neutropenia or low CD4 counts. Subsequent malignancy, including MDS, occurred in 8% of patients and require further study to better identify patients at risk. (Figure Presented).

Creative collaboration in the cloud: Using Splice Studio and Audiomovers to enhance online music education outcomes

This article details online education design at an Australian university undergraduate music program. The author reviews the rapid development of online learning activities relating to music performance in response to the COVID-19 pandemic enforced lockdown. The lockdown imposed serious challenges for music educators, the overarching one being how to engage students via a screen rather than in a rehearsal room. As the unit designer/assessor, the author utilized specific cloud-based audio software networking tools that are accessible to students (Audiomovers, Splice Studio) to devise learning activities that encouraged creative interactive learning. The author details the advantages and disadvantages of each learning activity. As a substitute for face-to-face interaction, online learning has substantial limitations in relation to music education. Student engagement with accessible online audio tools can enhance skills and knowledge development and interactive learning, thus maximizing student satisfaction and collaborative learning outcomes. © Equinox Publishing Ltd 2021

Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab Versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Evolve CLL/SLL Study (SWOG S1925;NCT#04269902)

Background: Currently, asymptomatic patients with CLL/SLL are observed without treatment until development of symptoms or cytopenias. Historically, early intervention studies in patients with CLL/SLL with non-specific chemoimmunotherapy agents have not resulted in an overall survival (OS) benefit and have resulted in toxicity. The introduction of targeted therapies, such as venetoclax (an oral BCL2 inhibitor;V) and obinutuzumab (an intravenous anti-CD20 monoclonal antibody;O), have provided tolerable/efficacious options for patients with CLL. In the CLL14 study, symptomatic patients with CLL receiving frontline therapy with VO had longer progression-free survival (PFS) and deeper remissions [more undetectable minimal residual disease (uMRD)] compared with those receiving chlorambucil and O (Fischer 2019). The CLL-International Prognostic Index (CLL-IPI;Table 1) is a validated prognostic model to predict which patients are at highest risk of a shorter time to first therapy and shorter OS. A score of ≥4 is considered high-risk on this scale. We aim to use VO as early intervention in asymptomatic, high-risk CLL patients, assessed by CLL-IPI, to potentially improve OS and thus alter the natural history of the disease. Methods: On 12/14/20, we activated the S1925 study (NCT#04269902 ) for adult patients with CLL or SLL, who were diagnosed within 12 months of enrollment. Eligible patients have a CLL-IPI score ≥4 (Table 1) or complex cytogenetics (≥3 cytogenetic abnormalities) and do not meet any criteria for initiation of treatment by the International Working Group for CLL (IWCLL;Hallek 2018) guidelines. Enrolled patients are randomized in a 2:1 manner to early versus delayed (at the time IWCLL indication for treatment is met) therapy with VO (Figure 1). VO is administered as previously described (Fischer 2019). The primary endpoint is OS. We hypothesize that early intervention with VO will improve the rate of 6-year OS from 60% to 80%. This design requires 222 eligible patients for 88% power (2-sided a=0.05) for the primary comparison. To allow for 10% ineligibility, we will enroll 247 patients. Estimated accrual time is 4 years. Secondary endpoints include: rates of response, PFS, and relapse-free survival;safety;time to second CLL-directed therapy;and quality of life (assessed by FACT-Leukemia). As COVID19 is an infection with particularly high morbidity and mortality in patients with CLL, incidence of this infection and complications including death will be recorded and compared between patients followed on the early versus delayed intervention arms. The primary translational objective is to evaluate the prognostic association between OS and peripheral blood MRD status at 15 months after treatment initiation by flow cytometry. Secondary translational objectives include describing the association of other clinical outcomes, baseline prognostic factors, and IWCLL-defined response with MRD status at multiple timepoints. Current Status: At the time of submission, 7 patients have been registered and randomized per protocol. Accrual is ongoing. [Formula presented] Disclosures: Stephens: Adaptive: Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees;Epizyme: Membership on an entity's Board of Directors or advisory committees;Beigene: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Consultancy;CSL Behring: Consultancy;Celgene: Consultancy;Novartis: Research Funding;Abbvie: Consultancy;JUNO: Research Funding;Arqule: Research Funding;Mingsight: Research Funding;Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Moseley: BioSight Ltd: Consultancy. Hill: AbbVie: Consultancy, Honoraria, Research Funding;Gentenech: Consultancy, Honoraria, Research Funding;Beigene: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria;Kite, Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding;Karyopharm: Consultancy, Honoraria, Research Funding;AstraZenica: Consultancy, Honoraria;Celgene (BMS): Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Epizyme: Consultancy, Honoraria;Incyte/Morphysis: Consultancy, Honoraria, Research Funding. Pagel: Pharmacyclics/AbbVie: Consultancy;Actinium Pharmaceuticals: Consultancy;Incyte/MorphoSys: Consultancy;BeiGene: Consultancy;Epizyme: Consultancy;Kite, a Gilead Company: Consultancy;AstraZeneca: Consultancy;Gilead: Consultancy;MEI Pharma: Consultancy. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding;Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio and Atara Biotherapeutics: Consultancy. Danilov: Genentech: Consultancy, Honoraria, Research Funding;Takeda Oncology: Research Funding;TG Therapeutics: Consultancy, Research Funding;Abbvie: Consultancy, Honoraria;Beigene: Consultancy, Honoraria;Pharmacyclics: Consultancy, Honoraria;Gilead Sciences: Research Funding;Bristol-Meyers-Squibb: Honoraria, Research Funding;Rigel Pharm: Honoraria;Bayer Oncology: Consultancy, Honoraria, Research Funding;SecuraBio: Research Funding;Astra Zeneca: Consultancy, Honoraria, Research Funding. Mato: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding;DTRM BioPharma: Consultancy, Research Funding;Acerta/AstraZeneca: Consultancy, Research Funding;Sunesis: Consultancy, Research Funding;BeiGene: Consultancy, Research Funding;Johnson and Johnson: Consultancy, Research Funding;Genentech: Consultancy, Research Funding;AbbVie: Consultancy, Research Funding;Nurix: Research Funding;Genmab: Research Funding;LOXO: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;AstraZeneca: Consultancy;Adaptive Biotechnologies: Consultancy, Research Funding;MSKCC: Current Employment;TG Therapeutics: Consultancy, Other: DSMB, Research Funding. Brander: Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding;Pfizer: Consultancy, Other: Biosimilars outcomes research panel;TG Therapeutics: Consultancy, Research Funding;Novartis: Research Funding;ArQule/Merck: Consultancy;Verastem: Consultancy;BeiGene: Research Funding;ArQule: Research Funding;NCCN: Other: panel member;AstraZeneca: Research Funding;Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding;LOXO: Research Funding;Ascentage: Research Funding;Genentech: Consultancy, Research Funding;DTRM: Research Funding;MEI Pharma: Research Funding;AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding. Coutre: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees;Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta: Other: Data Safety Monitoring Committee, Research Funding. O'Brien: Kite, Regeneron, Acerta, Caribou, Gilead, Pharmacyclics, TG Therapeutics, Pfizer, Sunesis: Research Funding;Amgen, Astellas, Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Biosciences Inc., Vaniam Group LLC, AbbVie, Alexion, Verastem, Juno Therapeutics, Vida Ventures, Autolus, Johnson and Johnson, Merck, Bristol Myers Squibb, NOVA Research Company, El Lill: Consultancy. Erba: AbbVie Inc;Agios Pharmaceuticals Inc;Bristol Myers Squibb;Celgene, a Bristol Myers Squibb company;Incyte Corporation;Jazz Pharmaceuticals Inc;Novartis: Speakers Bureau;AbbVie Inc: Other: Independent review committee;AbbVie Inc;Agios Pharmaceuticals Inc;ALX Oncology;Amgen Inc;Daiichi Sankyo Inc;FORMA Therapeutics;Forty Seven Inc;Gilead Sciences Inc;GlycoMimetics Inc;ImmunoGen Inc;Jazz Pharmaceuticals Inc;MacroGenics Inc;Novartis;PTC Therapeutics: Research Funding;AbbVie Inc;Agios Pharmaceuticals Inc;Astellas;Bristol Myers Squibb;Celgene, a Bristol Myers Squibb company;Daiichi Sankyo Inc;Genentech, a member of the Roche Group;GlycoMimetics Inc;Incyte Corporation;Jazz Pharmaceuticals Inc;Kura Oncology;Nov: Other: Advisory Committee. OffLabel Disclosure: The trial studies early intervention with venetoclax and obinutuzumab in patients with CLL/SLL who are asymptomatic and observation would be standardly recommended.

High Rates of Undetectable Minimal Residual Disease Remissions with Time-Limited Bendamustine, Rituximab, and Venetoclax (BR-VR) in Untreated Chronic Lymphocytic Leukemia (CLL)

Background: Despite the efficacy of venetoclax (VEN) in frontline CLL, optimal combination regimens and duration of treatment remain unclear. We hypothesized that cytoreduction with bendamustine/rituximab (BR) induction followed by venetoclax/rituximab (VR) consolidation for a fixed 1-year duration would be associated with an increased rate of undetectable minimal residual disease (uMRD) compared to historical controls and a reduction in the risk of tumor lysis syndrome (TLS). Here we report data from an ongoing phase 2 multicenter, US, single-arm, open-label study (NCT03609593) designed to assess the safety and efficacy of BR-VR in previously untreated CLL patients (pts). Methods: Previously untreated CLL/SLL pts ≥ 18 years requiring therapy per iwCLL criteria initially received 3 cycles of bendamustine 50-90 mg/m 2 daily for 2 days and rituximab 375 mg/m 2 every 28 days for 3 cycles. Following BR, VEN was initiated with a standard dose escalation from 20 mg to 400 mg daily over 5 weeks. This was followed by 6 cycles of VR with rituximab given monthly and 5 cycles of VEN alone (12 cycles of VEN in total). Additional eligibility included: ECOG PS ≤ 2, hemoglobin ≥8g/dL, ANC ≥1000/mm 3, and platelets ≥50,000/mm 3. Response was assessed by 2018 iwCLL criteria with uMRD testing by central flow cytometry at a level of <10 -4 in peripheral blood (PB) and bone marrow (BM). The primary endpoint was objective response rate (ORR). Secondary endpoints included uMRD rate, time to uMRD, and adverse events (AEs) assessed by CTCAE v 5.0. Results: As of data cutoff on 30 May 2021, 26 pts were accrued with additional recruitment ongoing. Baseline demographics were as follows: male/female (16/10), median age 60 yrs (range 44-77). Baseline prognostic studies showed unmutated IGHV in 16 (62%) pts, TP53 aberrant (either del(17p) and/or TP53 mutation) in 1 (4%) pt, del(11q) in 3 (12%) pts, and complex karyotype in 4 (15%) pts. TLS risk among 24 evaluable pts at baseline was high (H) in 3 (12.5%), medium (M) in 15 (62.5%), and low (L) in 6 (25%). At a median follow-up of 12.9 mo. (range, 1.9-27.5), 23 pts remain on study. Of 12 pts with at least 15 mo. follow-up (completing all therapy), the ORR was 100% (92% CR/CRi, 8% PR [due to small residual nodes]). 3 pts died on study (2 due to COVID-19 and 1 developed newly metastatic squamous cell carcinoma and taken off study after achieving a CR post-VEN ramp-up). Bendamustine was administered at doses of 50 mg/m 2 in 47%, 70 mg/m 2 in 11%, and 90mg/m 2 in 42% of pts. In 20 evaluable pts, response assessments after cytoreduction with BR demonstrated 15% of pts achieved CR/CRi and 85% achieved PR. For evaluable pts at 16 mo., uMRD (<0.01%) in the PB and BM was observed in 100% (10/10) and 90% (9/10) of pts, respectively. MRD was intermediate (0.01% - <1.0%) in 10% (1 patient) in BM (Figure 1 ORR and MRD). Median time to uMRD was 12 mo. (range 3-15) in PB and 14 mo. (range 5.5-15) in BM. The most common treatment-emergent AEs during BR induction were (any grade/grade ≥3) anemia in 6/2 (21%/7%) pts, nausea in 6/0 (21%/0%), neutropenia in 5/2 (18%/7%), rash in 5/0 (18%/0%), constipation 4/0 (14%/0%), and transaminitis in 3/0 (11%/0%). 2 pts (7%) developed febrile neutropenia during BR. Emergent AEs during VEN treatment included diarrhea in 10/0 (36%/0%) pts, neutropenia in 6/3 (21%/11%), leukopenia in 5/2 (18%/7%), and nausea in 4/0 (14%/0%). TLS risk was substantially reduced after BR lead-in. Of 3 H-risk pts at baseline, none remained H-risk after BR;of 15 M-risk pts, only 1 remained M-risk, with the remainder at L-risk (94% reduction in H- or M- risk TLS). Conclusions: BR-VR is a safe and well-tolerated regimen in untreated CLL pts. BR debulking substantially reduces TLS risk, and this sequential strategy achieves high rates of PB and BM uMRD across all prognostic risk groups. [Formula presented] Disclosures: Hill: Celgene (BMS): Consultancy, Honoraria, Research Funding;AstraZenica: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Gentenech: Consultancy, Honoraria, Research Funding;AbbVie: Consultancy, Honoraria, Research Funding;Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding;Karyopharm: Consultancy, Honoraria, Research Funding;Beigene: Consultancy, Honoraria, Research Funding;Epizyme: Consultancy, Honoraria;Novartis: Consultancy, Honoraria, Research Funding;Incyte/Morphysis: Consultancy, Honoraria, Research Funding. Jurcic: AbbVie, BMS/Celgene, Novartis: Consultancy;AbbVie, Arog Pharmaceuticals, Astellas, BMS/Celgene, Forma Therapeutics, Genentech, Gilead Sciences, PTC Therapeutics, Syros Pharmaceuticals: Research Funding. Heaney: CTI: Honoraria, Research Funding;Blueprint: Honoraria, Research Funding;Novartis: Honoraria;Sierra Oncology: Research Funding;Cogent: Research Funding;BMS: Research Funding;Kartos: Research Funding. Lamanna: MingSight Pharmaceuticals, Inc.: Research Funding;Gilead Sciences, Inc.: Consultancy;AbbVie: Consultancy, Research Funding;AstraZeneca: Consultancy, Research Funding;Juno Therapeutics, Inc.: Research Funding;Oncternal Therapeutics: Research Funding;Celgene Corporation: Consultancy;Genentech, Inc.: Consultancy, Research Funding;Verastem Oncology: Research Funding;TG Therapeutics, Inc: Research Funding;Janssen Pharmaceuticals, Inc.: Consultancy;BeiGene: Consultancy;Pharmacyclics: Consultancy. OffLabel Disclosure: Venetoclax, Bendamustine, and Rituximab are all FDA approved for use in first-line CLL. The combination of these three agents and dosing schedule utilized in this clinical trial is novel and therefore technically reflects an off-label use.

Sport tourism collaboration: a systematic quantitative literature review. (Special Issue: Systematic reviews in sports tourism.)

The development of sport tourism requires the collaborative engagement of sport, tourism, and other diverse sectors and stakeholders. Sport tourism collaboration has received much attention from academic scholars. This study conducted a systemic quantitative review of sport tourism collaboration. In total, 40 peer-reviewed academic manuscripts published in English-language journals between 1996 and February 2020 were considered, based on predefined criteria, and reviewed in order to address several research objectives. More precisely, this review was intended to systematically and quantitatively examine the bibliographic information, theoretical frameworks, research designs and methods, key issues, and the nature of the findings of the selected manuscripts. The study revealed that a wide range of less geographically diverse authors along with few field-dedicated scholars were engaged in publishing research outputs on sport tourism collaboration terrain in a substantial number of journals. The sampled studies were qualitative and conceptual research driven with limited use of theoretical frameworks. This study also found that most of the selected manuscripts focused on sport, sporting events, and sport tourism, along with mutual work and management-related concepts. Finally, future research directions are identified to address the research gaps. Notable future directions indicate additional quantitative and mixed methods research is necessary for bringing methodological diversity and advancing sport tourism collaboration scholarship with more generalised findings and cases. In addition, functional level sport tourism collaboration, design and implementation of strategy for sport tourism collaboration after COVID 19, and leadership processes of sport tourism collaboration need to be examined within established theories from various disciplines.

Federal, state, and institutional barriers to the expansion of medication and telemedicine abortion services in Ohio, Kentucky, and West Virginia during the COVID-19 pandemic.

OBJECTIVES: We aimed to characterize the combined impact of federal, state, and institutional policies on barriers to expanding medication and telemedicine abortion care delivery during the COVID-19 pandemic in the abortion-restrictive states of Ohio, Kentucky, and West Virginia. STUDY DESIGN: We analyzed 4 state policies, 2 COVID-related state executive orders, and clinic-level survey data on medication abortion provision from fourteen abortion facilities in Ohio, Kentucky, and West Virginia from December 2019 to December 2020. We calculated the percent of medication abortions provided at these facilities during the study period by state, to assess changes in medication abortion use during the pandemic. RESULTS: We ascertained that COVID-19-executive orders in Ohio and West Virginia that limited procedural abortion in Spring 2020 coincided with an increase in the overall number and proportion of medication abortions in this region, peaking at 1613 medication abortions (70%) in April 2020. Ohio and West Virginia, which had executive orders limiting procedural abortion, saw relatively greater increases in April compared to Kentucky. Despite temporary lifting of the mifepristone REMS, prepandemic regulations banning telemedicine abortion in Kentucky and West Virginia and requiring in-person clinic visits for medication abortion distribution in Ohio limited clinics' ability to adapt to offer medication abortion by mail. CONCLUSIONS: Our findings illustrate how restrictive medication and telemedicine abortion policies in Ohio, Kentucky, and West Virginia created additional obstacles for patients seeking medication abortion during the pandemic. Permanently lifting federal regulations on in-clinic distribution of mifepristone would only advantage abortion seekers in states without restrictive telehealth and medication abortion policies. State policies that limit access to comprehensive abortion services should be central in larger efforts toward dismantling barriers that impinge upon reproductive autonomy. IMPLICATION STATEMENT: We find that abolishing the REMS on mifepristone would not be enough to expand access to patients in abortion-restrictive states with telemedicine and medication abortion laws. While the REMS is a barrier, it represents one of several hindrances to the expansion of telemedicine abortion distribution across the United States.

Pseudo-outbreak of coagulase-negative staphylococcus species from blood cultures highlights unique challenges in care of critically ill patients with COVID-19

Background: In response to the COVID-19 pandemic, a dedicated intensive care unit for patients infected with SARS-CoV-2 was created at our institution. We noticed a marked increase in the number of blood cultures positive for coagulase-negative Staphylococcus species (CoNS) that highlights unique challenges that arise with the creation of new units and workflows. Methods: We reviewed all blood culture results from the COVID-19 intensive care unit (CoVICU) from April 15 to May 29. We reviewed all blood cultures taken from the oncology ward, medical intensive care unit (MICU), and emergency department (ED) for the same time frame as a comparison. We calculated contamination rates, using the clinical microbiology laboratory criteria for possible contaminants based on species and number of positive blood cultures. Results: There were 324 total blood cultures collected from the CoVICU with 27/324 (8.3%) positive for organisms deemed contaminant, 10/324 (3.1%) were positive considered bloodstream infections (BSI);the ratio of BSI:contaminant was 1:2.7. For the MICU, ED, and oncology units contamination rates were 2/197 (1%), 33/747 (4.4%), and 2/334 (0.6%), respectively;and the ratio of BSI:contaminant was 5:1, 2.2:1, and 17.5:1, respectively. There was a significant relationship between contamination rates and unit, X2(3, N = 1602) = 30.85, p < 0.001. Conclusion: Upon investigation, peripheral blood draw kits were not stocked in the CoVICU. Additionally, certain components of standard work for blood culture collection (e.g. glove exchange) could not be performed per usual practice due to isolation precautions. Peripheral blood draws were routinely performed by nurses in CoVICU and MICU while phlebotomy performed these in other comparison units. We suspect that lack of availability of blood draw kits and disruption of typical workflow in isolation rooms contributed to an unusually high number of contaminated blood cultures among patients admitted to the CoVICU. Notably, the CoVICU and MICU providers were the same pool of caregivers, further supporting a process issue related to isolation precautions. Institutions should be aware of the need for extra attention to supply chain management and examination of disruption to standard work that arise in the management of COVID-19 patients.