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BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.
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Background High rate of people infected with SARS-CoV-2 and their contacts in Cologne, Germany required innovative tools for notification, monitoring and reporting. The digital tool for COVID19 (DiKoMa) provides self-service symptom diaries allowing (a) the stratification for prioritized telephone contact by the health authority and (b) training a machine learning (ML) model that predicts infections with prevailing dominant variant (PDV) from early symptom profiles (SP). Methods Pseudononymized SP covering the first week of diary recordings were included for training (16646 index, 11582 contacts). A balanced random forest (BRF) model was trained to differentiate early predictive symptom patterns of different PDV and contact persons. Model evaluation was performed using sex and age stratified cross validation (CV), the model was validated on SP recorded from days 1 and 6. Results From 03/20 to 02/22, 90478 indeces and 75444 contact persons reported symptoms and health status, covering 46% and 42% of all reported cases, respectively. Diaries contained between 1-52 entries (566791, median 2). Daily analysis of entries, prioritized according to age, prevalent co-morbidities and detoriation of symptoms allowed risk adjusted follow up even during phases with high case notification rates. The top 5 predictive factors of the BRF were immunization, cough, dysgeusia and dysnosmia, fatigue, and sniffles to differentiate infection between wildtype, three PDV and contact persons (CV AUC 80.6%, Validation AUC 77.1%). Conclusions The use of digital symptom diary surveillance helps to provide appropriate medical support for patients on a large scale. Machine learning shows potential for symptom based risk assessment to differentiate PDV for future outbreaks and can thus become a valuable tool alongside specific laboratory diagnostics. Key messages • Digital symptom diaries are a powerful and widely accepted tool to attend COVID19 patients in isolation. They allow risk stratification for follow up and are a low-threshold service. • Machine learning supports index case identification by symptom analysis and can thus become a valuable tool alongside specific laboratory diagnostics.
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Location data is used in many aspects of journalism today. For example, journalists can identify the number of COVID-19 cases by neighborhood, map those, and then share hot spots with their audiences. They can break down political allegiances, block by block, and predict elections. They can tag location data on reported events and filter those to provide a neighborhood-specific newsletter, and so on. But how is this location data acquired and attended to? This study examines how location data is being used by journalists and the ethical concerns that can arise with such data. Recent location data breaches with third-party technology companies have raised questions about how this kind of data is collected, stored, maintained, and shared on a wider scale. This study used the Delphi method of progressive interviews with a panel of subject matter experts and consisted of three rounds of discussions with U.S. journalists and journalism ethicists. The findings identify several themes of how location data poses new storytelling opportunities and significant ethical issues related to privacy, transparency, and validity. Implications for future uses of location data in journalism are discussed, including placing such data into contexts both in the profession and in the academy.
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Purpose: According to the US Census 2019 Income and Poverty report, 10.5% of the population lives below the poverty line, and approximately 10.5 million individuals below 18 years were in poverty in 2019. Children and adolescents in poverty are at risk for poor developmental and psychosocial outcomes, presenting a significant financial burden for families and the general public. Yet low-income populations continue to face barriers to healthcare, leaving them vulnerable to worse health outcomes. Unfortunately, medical students may adopt unfavorable attitudes toward low-income patients due to lack of empathy, poor understanding, and burnout, which negatively affects patient care. A poverty simulation module was included in the medical student curriculum at our institution to improve understanding and empathy toward low-income patients. Methods: IRB approval was obtained prior to data collection. Participants included medical students in one US medical school from 2018 to 2021. In 2021, students participated virtually due to the COVID-19 pandemic, though the objectives and methods remained the same as in person. Participants were placed in a poverty simulation, roleplaying as one of 26 different families facing poverty across four, 15-minute weeks with limited resources and additional social and medical challenges. Students completed a pre-simulation and post-simulation survey with free response and 23-items questioning perceptions of socioeconomic barriers (Perceptions), confidence in handling low-income populations (Confidence), and likelihood of addressing poverty (Likelihood). Each category was scored on a numeric scale that was summed together. The difference in scores between pre- and post-simulation survey responses was measured for significance using Wilcoxon and paired t-tests. The virtual simulation scores of 2021 were also compared with in-person scores from 2018 to 2020. Student free responses were then categorized into 10 topics and measured for variation with standard t-tests. Results: The post-simulation survey results showed increased scores from 2018 through 2021 with an average difference of +1.21 for Perceptions, +1.29 for Confidence, +3.27 for Likelihood. Only Confidence and Likelihood score increases were found to be significant with p-values ranging from 3.66E-17 to 9.95E-05 across all years (p < 0.05). The Perceptions category showed no significant difference from 2018-2020, except 2021 which showed a p-value of 1.26E-04 (p < 0.05). For in-person versus virtual simulation, there was a significant difference in average sum difference across all categories of 7.31 and Z score of <0.0001 (p <0.0001). Students’ free responses commonly focused on the difficulty of budgeting in poverty with no significant variation between years (p < 0.05). Conclusions: A significant improvement was seen in confidence when treating low-income populations and likelihood of addressing poverty in several iterations of a poverty simulation among medical students. This study is limited by variance in student responses, issues with pre- and post-simulation survey matching, and response restriction to numbered scales as opposed to free response. The results of this project encourage the continuation of this simulation among medical students and its expansion to other health professional programs. Sources of Support: ELS Staff at University of Southern Florida Morsani College of Medicine.
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The COVID-19 pandemic has triggered an unprecedented increase in unilateral lawmaking by governors under each state's emergency executive power statute. These actions have been met with controversy and a significant amount of resistance. This Note argues that the resistance to COVID-19 rules in the United States may be partially attributable to the way state emergency power statutes concentrate virtually all the power to enact emergency rules in the hands of governors. As this Note demonstrates, the state executive emergency power regime, like all emergency power frameworks, grapples with the inherent tension between technocratic agility and democratic legitimacy. Drawing on a novel fifty-state survey, this Note shows how, notwithstanding the drafters' attempt to balance executive power with legislative constraint, the statutes as written effectively place all substantive decisionmaking in the hands of the governor, leaving only a binary on/off switch for the legislature to terminate the state of emergency. This consolidation of power in a chronic emergency bypasses the deliberative legislative process, increasing technocratic agility at the expense of democratic legitimacy. This Note suggests a revision to the statutes, inspired by the Congressional Review Act, that would encourage legislative deliberation through a fast-track approval process, while still preserving the prerogative of the governor to enact pandemic policy.
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Background: Little is known on what palliative care (PC) has been provided to patients with COVID-19. Aims: To understand what PC was provided nationwide to patients with COVID-19 and strategies implemented to overcome barriers during the pandemic. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing PC to patients with COVID-19. Thematic analysis was used to describe and interpret overarching themes. Results: Twelve specialized PC (SPC) and 11 primary PC (PPC) were interviewed. Interim analysis of 16 coded interviews demonstrated SPC and PPC physicians used traditional strategies (such as opioids, oxygen and serious illness conversations) to manage symptoms, support end of life, and engage patients and families in goals of care conversations (GOC). Neither SPC nor PPC indicated strong adoption of GOC and symptom management tools circulated early in the pandemic. Both SPC and PPC indicated a shift to virtual communication due to restrictive visitor policies, highlighting the need for distanced support and planned communication. Care coordination for PC patients was challenged by a lack of community resources, family infected with COVID-19, prolonged hospital stays, and increased number of PC patients discharged to rehabilitation services. New PC structures included;GOC teams that functioned in the emergency department and medicine floors, integrated clinical rounding by non-PC clinicians with PC teams, and hospital-based PC outreach to long term care. Strategies to improve PC implementation included: virtual technologies, team collaboration, patient and family engagement tools, and symptom management and GOC conversations tools. Conclusions: While PC management approaches to support patients with COVID-19 were mostly unchanged, new structures and strategies were developed to ensure patients and their families were provided with support.
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Background: Specialized palliative care (SPC) teams are well placed to support patients with advanced COVID-19 in Canada, but evidence indicates integration so far has been variable. Aim: To understand barriers and facilitators of SPC integration in the management of patients with COVID-19. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing care to patients with COVID-19. Thematic analysis was used to describe and interpret overarching themes. Results: Twenty-three physicians (12 SPC, 5 intensivists, 6 general internists) were interviewed. Interim analysis of 16 coded interviews demonstrated that facilitators/barriers to providing COVID-19 care fell into 5 main categories: patient-related, provider-related, Disease-specific, SPC service, and leadership factors. Patient-related items included age, comorbidities, goals, speed of decline and clustering of patients. Non- SPC provider-related factors included experience providing palliative care and working with the SPC team, time, and motivation. Uncertainty around COVID-19 progression, management and infection control practices were identified disease-specific barriers. SPC service factors included stigma related to palliative care, the accessibility, availability, and readiness of SPC services to meet the perceived needs of patients with COVID-19. Leadership facilitators included institutional mandated or supported integration, and SPC? presence at COVID-19 planning tables. Ways to improve integration included educational initiatives, relationship building, formal integrated structures and presence at institutional COVID-19 planning tables. Conclusion: Preliminary analysis highlights the need for high-level support for formal SPC integrated structures, a SPC role in pandemic planning, and the need for ongoing educational and relationship building initiatives to overcome barriers of SPC integration in COVID-19 care.
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Background: Restrictive institution visitor policies were implemented to minimize infection risks during the COVID-19 pandemic. Little data exists on the relationship between these policies and the provision of palliative care(PC). Aim: To describe the experiences and reflections of PC physicians on the effects of restrictive visitor policies. Methods: Semi-structured interviews were conducted with physicians about their experience providing PC in institutions with restrictive visitor policies. Thematic analysis was used to describe and interpret overarching themes. Results: Twelve specialized PC and 11 primary PC were interviewed. Interim analysis of 16 coded interviews demonstrates 4 main thematic categories including patient, caregiver, provider, and system effects. Patient-related items included isolation, dying alone, lack of caregiver advocacy and forced care decisions to allow for visitor presence. Caregiver factors included the inability to support or provide care to patients, poor communication with care teams, poor illness understanding, the need to make distanced care decisions, and challenges in identifying visitors. Provider factors included increased time and effort on communication, lack of caregiver input on patient status, increased complaints, the need to be a caregiver surrogate, visitor advocate or gatekeeper. System effects included the increased interest to be provided care in the community and the lack of interest in palliative care units. These factors were often exacerbated by several issues including the lack of clear evidence on their validity, and inconsistent enforcement or interpretation of policies at the unit, which led to patient and caregiver anger and distrust, and provider frustration. Conclusion: Preliminary analysis highlights substantial negative consequences of restrictive visitor policies at the patient, caregiver, provider and system levels which were exacerbated by their lack of evidence and inconsistent enforcement.
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Background: Exploring patients' goals of care (GOC) is integral to palliative care practice. COVID-19 may present new challenges to establishing GOC. Aim: To describe the experiences and reflections of physicians regarding exploring GOC for patients with COVID-19. Methods: Semi-structured interviews were conducted with physicians about their experience assessing GOC for patients with COVID-19. Thematic analysis was used to describe and interpret over-arching themes. Results: Twenty-three physicians (12 Palliative Care, 5 Internal Medicine, and 6 Critical Care) were interviewed. Interim analysis of 16 coded interviews revealed 4 thematic categories of factors influencing establishment of GOC: resource availability, COVID-19 factors, patients' baseline health, and unusual communication challenges between health care providers and substitute decision makers (SDMs) or patients. Resourcerelated factors included impact of ICU/ventilator availability and personal protective equipment (PPE) shortages on GOC discussions. COVID-19 factors affecting GOC conversations included physician uncertainty of the course of illness;lack of definitive, evidence-based treatment;patient and family preconceived ideas about COVID-19;and risk of rapid decline. Factors associated with patients' baseline health included comorbid disease and ability to treat comorbid disease in parallel with COVID-19. Unusual communication challenges impacting GOC discussions included a high level of SDM involvement for GOC conversations, visitor policies potentially limiting SDMs' illness understanding, and virtual discussions or discussions taking place under layers of PPE creating barriers to effective communication between physicians, patients, and SDMs. Conclusion: Preliminary analysis highlights the unique challenges faced by both health care providers and patients/SDMs to facilitate and participate in GOC conversations in the context of the COVID-19 pandemic.
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Background: The need to recognize and attend to physician health and wellness has recently been emphasized, due to high levels of documented distress and burnout. The global pandemic has imposed even greater stressors and novel work demands on clinicians. Aim: To understand the experiences of physicians providing care during a global pandemic. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing care to patients during the COVID-19 pandemic. Thematic analysis methodology was used to describe overarching themes. Results: Twenty-three physicians (12 specialized palliative care, 5 intensivists, 6 general internists) were interviewed. Interim analysis of 16 coded interviews revealed 8 main categories: confusion and uncertainty;exhaustion and burnout;trauma;ethical considerations;isolation;professional re-evaluation;altruism;and cohesion. Confusion and uncertainty related mainly to the novel virus, leadership, and institutional preparedness. Exhaustion and burnout encompassed workload, personal protective equipment, family life, and complexity. The trauma theme included visitor policies, family surrogates, and patient management. Ethical considerations included job demands vs personal and family safety. Isolation was largely related to infection control measures. Professional re-evaluation items included job satisfaction due to changed patient encounters or novel structuring. Altruism items included unique personal contribution to pandemic response and societal needs. Cohesion items included supporting each other and team building. Conclusion: Preliminary analysis revealed trauma and distress, but also altruism and cohesion. These findings may inform interventions for physician health and wellness, as well as indicating ways to integrate meaning and purpose into negative experiences to promote resilience.
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For over 30 years Alan Weiss has consulted, coached, and advised everyone from Fortune 500 executives, state governors, non-profit directors, and entrepreneurs to athletes, entertainers, and beauty pageant contestants. That’s quite an assortment of people, and they run into the thousands. Most of them have had what we euphemistically call “means, " and some of them have had a lot more than that. Others have been aspiring and with more ends in sight than means on hand. Alan Weiss states: I’ve dealt with esteem (low), narcissism (high), family problems, leadership dysfunctions, insecurities, addictions, and ethical quandaries. And I’ve talked with them through the coronavirus crisis. But don’t get the wrong idea. About 95% of these people have been well-meaning, honest (to the best of their knowledge), and interested in becoming a better person and better professional. Otherwise, they wouldn’t be talking to me. I found the equivalent of the “runner’s wall” in their journeys, where they must break through the pain and the obstacles and then can keep going with renewed energy and spirit. But runners know how far they must go after the breakthrough, be it another half lap or another five miles. There is a finish line. I’ve found that people in all positions, even after the “breakthrough, " don’t know where they are in the race, let alone where the finish line is. They do not know what meaning is for them. They may have money in the bank, good relationships, the admiration of others, and the love of their dogs. But they have no metrics for “What now?" They believe that at the end of life there is a tallying, some metaphysical accountant who totals up their contributions, deducts their bad acts, and creates the (hopefully positive) difference. That difference, they believe, is their “legacy.” But the thought that legacy arrives at the end of life is as ridiculous as someone who decides to sell a business and tries to increase its valuation the day prior. Legacy is now. Legacy is daily. Every day we create the next page in our lives, but the question becomes who is writing it and what’s being written. Is someone else creating our legacy? Or are we, ourselves, simply writing the same page repeatedly? Or do we leave it blank? Our organic, living legacy is marred and squeezed by huge normative pressures. There is a “threshold” point, at which one’s beliefs and values are overridden by immense peer pressure. Our metrics are forced to change. In an age of social media, biased press, and bullying, we’ve come to a point where our legacy, ironically, is almost out of our hands. Yet our “meaning” - our creation of meaning and not a search for some illusive alchemy - creates worth and impact for us and all those with whom we interact. © 2021 Taylor & Francis.
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Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promotebreast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NETutility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effectivetreatments. Dowsett et al. recently demonstrated that baseline levels of ER, progesterone receptor (PR), Ki67(>15% vs ≤15%), and Ki67 (>10% vs ≤10%) 2-4 weeks (wks) after starting NET may improve appropriate patient(pt) selection for NET (PMC7280290). The ER, PR and Ki67-based prediction model divides pts with primaryER+/HER2- BC into 3 groups for appropriateness for NET: (Group 1) NET is likely to be inappropriate (Allred ER <6or ER 6 and PgR <6), (Group 2) NET may be appropriate and a biopsy for on-treatment Ki67 analysis may beconsidered after 2-4 wks of NET (2A: ER 7 or 8 and PgR <6 and 2B: ER 6 or 7 and PgR ≥6) given that on-treatment Ki67 >10% has been associated with worse outcome (PMC5455353), or (Group 3) NET is appropriate (ER 8 andPgR ≥6). The ALTERNATE trial ( NCT01953588 ) randomized postmenopausal women with clinical stage II or III,ER+ (Allred score 6-8)/HER2- BC to receive anastrozole (ANA), fulvestrant (FUL), or ANA + FUL for 6 months,unless Ki67 was >10% on wk 4 or 12 biopsy, in which case pts were triaged to receive neoadjuvant chemotherapy(NCT) or surgery. As previously reported, the ET-sensitive disease (mPEPI 0 plus pCR) rates were similar acrossthe treatment arms and overall 22% (286 of 1,299) pts had Ki67 >10% at wk 4 or 12. The ALTERNATE trialtherefore provides a large independent data set to evaluate the NET appropriateness model. Results: Among 1,299 eligible pts randomized to receive 6 months of NET, 214 were excluded due to absent HRAllred score (n=41) or absence of pre-treatment and wk 4 Ki67 determinations (n=173). The proportions of theremaining 1,085 pts in Group 1, 2 and 3 were 1% (n=10), 43% (n= 468), and 56% (n=607), respectively. On-studyKi67 >10% prompting conversion from NET to NCT/Surgery occurred in: Group 1 90% (9 of 10), Group 2 30% (141of 468), and Group 3 17% (104 of 607) ( Table 1 ). Among the 1,075 pts in Groups 2 and 3, 260 (24%) pts had Ki67≤15% at baseline (BL), among whom only 14 (5.4%) had Ki67 >10% at wk 4, compared to 231 of the 815 (28.3%)who had BL Ki67 >15% and subsequent Ki67 >10% at wk 4. 2% of pts who remained on NET due to on-treatmentKi67 <10% had PD. Response and PEPI-0 rates by group will be reported. Conclusion: ALTERNATE trial data support a model whereby levels of ER, PR and Ki67 at diagnosis can be usedfor the identification of postmenopausal pts with primary ER+/HER2- BC who are appropriate for NET. Whenbaseline ER Allred scores are >6 and Ki67 ≤15%, there is a low likelihood of ET-resistant disease. When BL Ki67 is>15%, ET sensitivity is variable, and on-treatment biopsy for Ki67 may assist in triaging regarding NETappropriateness, particularly given the extremely low local PD rates seen in ALTERNATE when on-treatment Ki67was <10%. (Table Presented).
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Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS)annually. Without treatment, it is estimated that 20-30% of DCIS will lead to invasive breast cancer. Currently, morethan 97% of women undergo surgery, with many also undergoing radiation. An alternative to surgery for low-riskDCIS is active monitoring (AM), an approach in which regularly scheduled mammography and physical exams areused to monitor breast changes and determine if, or when, surgery is needed. Trial design: COMET, a multicenterphase III prospective randomized trial, opened in the U.S. in June 2017 (clinicaltrials.gov reference: NCT02926911).The hypothesis is that management of low-risk DCIS using an AM approach does not yield inferior invasive breastcancer and/or quality of life outcomes compared to surgery. Eligibility criteria: Patients with a new diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS, or atypia verging on DCIS are eligible. Patients mustbe ≥40 years of age, have no contraindication for surgery, and pathologic confirmation of grade I/II DCIS. DCIS mustbe ER and/or PR≥ 10% and HER2-negative without invasion, diagnosed within 120 days of registration. Breasttissue, blood and imaging are collected at trial entry and if invasive cancer subsequently occurs, and are stored incentral repositories. Specific aims: The primary aim is to assess whether the 2-yr ipsilateral invasive breast cancerrate for AM is non-inferior to surgery. Secondary aims include comparison of 2-, 5-, and 10-yr mastectomy rate, contralateral invasive breast cancer rate, overall survival and invasive breast cancer-specific survival, as well as 5-and 10-yr ipsilateral invasive breast cancer rate between groups. Patient reported outcomes (PRO) using validatedtools are critical secondary endpoints, and will enable comparison of health-related quality of life and psychosocialoutcomes between surgery and AM groups at prespecified time points over a period of 5 years. Statisticalmethods: An accrual goal of 1200 was estimated using a 2-group test of noninferiority of proportions, with the 2-yrinvasive breast cancer rate in the surgery group assumed to be 0.10, including accounting for upstaging. Theprojected drop-out rate is 25%, for a total of 900 patients treated per allocation arm. The non-inferiority boundarywas set at 0.05. Based on a 1-sided un-pooled z-test, with alpha=0.05, a sample size of n=446 per group will have80% power to detect the specified noninferiority margin. Intention-to-treat analysis of the 2-yr invasive breast cancerrate will be conducted using all patients as randomized, and will be completed using Kaplan-Meier estimates,stratified by group, combined with Greenwood's confidence interval. Several sensitivity analyses (per protocol, as-treated, and instrumental variable) are also planned to account for loss of follow-up, rejection of randomizationallocation and withdrawals. Present and target accrual: Trial accrual as of 7/1/20 is 540 randomized patients from84 activated Alliance for Clinical Trials in Oncology sites. Despite logistical challenges posed by the COVID-19crisis, patients continue to be recruited to the COMET trial. Over 80% of patients have sample sets/images stored inthe tissue and image repositories. This trial will provide definitive clinical, quality of life and biomarker evidenceregarding the trade-offs of surgery vs AM in patients with low-risk DCIS.
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Background: Morbidity and mortality due to coronavirus disease 2019 (COVID-19) may in part be due tointerleukin-6 (IL-6)-mediated hyperinflammation. The IL-6 receptor-targeted monoclonal antibody tocilizumab (TCZ)has been repurposed to treat COVID-19-related hyperinflammation, but prospective data are lacking. Given TCZ'srisks of secondary infection and potential blunting of the adaptive immune response and its finite supply, study of theefficacy, safety, and dose response of TCZ for the treatment of COVID-19-related hyperinflammation is needed. Methods: We conducted an adaptive phase 2 study of low-dose (LD) TCZ in hospitalized, non-mechanicallyventilated adult patients with COVID-19 pneumonitis and evidence of hyperinflammatory syndrome, with C-reactiveprotein (CRP) ≥ 40 micrograms per milliliter. Dose cohorts were determined by a trial Operations Committee, withthe initial doses of 80 or 200 milligrams, depending on the magnitude of CRP elevation and epidemiologic riskfactors. Doses were decreased to 40 mg and 120 mg after interim assessment. The primary objective was to assessthe relationship of dose to clinical improvement in temperature and oxygen requirement and biochemical responseby CRP. Results: 32 patients received LD TCZ. 25 of 32 (78%) patients receiving LD TCZ at any dose achieved feverresolution. In terms of dose-response, fever resolution in 24 hours was observed in 6 of 8 (75%) who received 200milligrams, 3 of 4 (75%) who received 120 milligrams, 11 of 15 (73%) who received 80 milligrams, and 5 of 5 (100%)who received 40 milligrams (p = 0.80 for response rate difference). Biochemical response consistent withinterleukin-6 pathway inhibition, corresponding to a ≥ 25% CRP decline, after a single dose of LD TCZ wasobserved in 5 of 8 (63%) who received 200 milligrams, 4 of 4 (100%) who received 120 milligrams, 10 of 15 (67%)who received 80 milligrams, and 5 of 5 (100%) who received 40 milligrams (p = 0.34 for response rate difference).100% of patients achieved CRP response within two doses of LD TCZ. Within the 28-day follow-up period, 5 (16%)patients died. For patients who recovered, median time to clinical recovery was 4 days (interquartile range, 2-5).Clinically presumed and/or cultured bacterial superinfections were reported in 4 (12.5%) patients. Correlativebiologic studies examining anti-SARS-CoV-2 antibody production across a range of TCZ doses are presentedseparately (abstract A-22514927). Conclusions: LD TCZ, in addition to standard of care, was associated with improvement of clinicalhyperinflammation parameters in hospitalized adult patients with COVID-19 pneumonitis. No relationship betweenTCZ dose and clinical or biochemical response relationship was identified. Results of the COVIDOSE trial provide arationale for a randomized, controlled trial of LD TCZ versus standard of care in those patients with COVID-19pneumonitis who have evidence of hyperinflammation. (COVIDOSE, ClinicalTrials.gov number, NCT04331795 .).
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INTRODUCTION: Approach to biliary obstruction in a patient with altered anatomy is challenging. Current options for evaluation include surgical assisted gastrostomy with endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) procedure, balloon or spiral enteroscopy with ERCP. We present an unusual approach in a patient with Roux-en-Y gastric bypass (RYGB) who presented with cholangitis during the COVID-19 crisis. CASE DESCRIPTION/METHODS: A 57 year old man with history of diabetes, hypertension and RYGB presented with right upper quadrant abdominal pain, fever and vomiting. Initial labs showed leukocytosis and elevated liver tests. CT abdomen revealed a dilated common bile duct (CBD) with dilated intra and extra-hepatic ducts. In light of the COVID-19 pandemic, the decision was made to place a percutaneous transhepatic biliary drainage catheter (PTC). Cholangiogram revealed occlusion at the ampulla with moderate central and intrahepatic biliary dilation without evidence of stone or other biliary filling defect. Given high suspicion for ampullary malignancy, a single operator cholangioscope was introduced through a sheath that was placed in the PTC tract for evaluation and to obtain biopsies. A single irregular stone was seen abutting the wall causing partial obstruction at the lower third of the CBD with a single smooth focal stenosis of benign appearance at the level of the ampulla. The ampulla appeared normal on endoscopic view. A balloon-guided papillotomy and stone removal was done. Repeat cholangiogram showed no intraductal filling defects and decreased size of the ducts. He had resolution of symptoms and improvement of lab values. Biopsies of the stenosis were negative for malignancy. DISCUSSION: While imaging is often useful to help identify cause and guide treatment of biliary obstruction, additional endoscopic evaluation can change outcomes. In our case, the initial cholangiogram suggested a possible ampullary tumor, but the use of endoscopic visualization with single operator cholangioscope significantly altered his hospital course while adding just a few more minutes to procedure. Our case highlights the benefits of multidisciplinary management of hepatobiliary pathology and the utility of using single operator cholangioscopy for direct visualization in patients with altered anatomy without the need of using more invasive and potentially higher risk procedures such as EDGE, surgical gastrostomy with ERCP or balloon enteroscopy with ERCP.