The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study
DISCLAIMER/CONCLUSIONS:In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE/OBJECTIVE:Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS:A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS:A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.
Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial
BACKGROUND:Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS:In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (Ã¢â€°Â¥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (Ã¢â€°Â¤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults Ã¢â€°Â¥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (Ã¢â€°Â¤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS/RESULTS:Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58Ã‚Â·3 years (SD 14Ã‚Â·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87Ã‚Â·0% [95% CI 83Ã‚Â·7 to 89Ã‚Â·6] in the baricitinib plus remdesivir plus placebo group and 87Ã‚Â·6% [84Ã‚Â·2 to 90Ã‚Â·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0Ã‚Â·6 [95% CI -3Ã‚Â·6 to 4Ã‚Â·8]; p=0Ã‚Â·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1Ã‚Â·01 (95% CI 0Ã‚Â·80 to 1Ã‚Â·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7Ã‚Â·5% [1Ã‚Â·6 to 13Ã‚Â·3]; p=0Ã‚Â·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6Ã‚Â·0% [2Ã‚Â·8 to 9Ã‚Â·3]; p=0Ã‚Â·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7Ã‚Â·7% [1Ã‚Â·8 to 13Ã‚Â·4]; p=0Ã‚Â·012). INTERPRETATION/CONCLUSIONS:In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING/BACKGROUND:National Institute of Allergy and Infectious Diseases.
Mastering co-management: A curriculum for hospitalists [Meeting Abstract]
Needs and Objectives: The U.S. surgical population is becoming increasingly medically complex, increasing the risk of post-operative complications. Surgeons have traditionally consulted internists and sub-specialists for medical management during inpatient admissions, but this has failed to decrease complications or healthcare costs. To address this issue hospitalists have taken on the role of co-managing patients admitted to surgical services. However, internal medicine residencies don't adequately prepare trainees for this role. Safe and effective modern medical care requires training in medical co-management (MCM), yet there exists no robust theory-and evidence-based curricula to teach these competencies. We designed a curriculum to fill this need. Setting and Participants: Thirteen hospitalists with 0-7 years' clinical experience in an academic medical center in New York, NY. Hospitalists spend 50% of their clinical time on an MCM service covering general surgery, vascular surgery, neurosurgery, general neurology/epilepsy, and orthopedic surgery. Description: We developed a yearlong curriculum based on the Society for Hospital Medicine's guidelines on creating MCM teams and other published frameworks. We applied evidence-based learning theories including: Adult Learning Theory, Cognitivism, Constructivism, and Ericsson's Theory of Expertise. We developed a conceptual framework incorporating key stakeholders in MCM (medical attending, surgical attending, PCP, mid-levels, and patients/families) and 6 core content topics (Roles & Responsibilities, Communication Strategies, Trust & Respect, Common Complications, Transitions of Care, and Deliberate Practice). The curriculum includes two parts: a week-long intensive orientation with Objective Structured Clinical Examinations (OSCEs) and workshops in the main content areas, and a series of monthly continuing professional development (CPD) sessions to facilitate deliberate practice and improve skills needed to manage niche patients on surgical services. These CPD skills are based upon needs identified by the hospitalists and surgical teams. Evaluation: Effectiveness will be measured at the program and hospitalist level. The program will be assessed by patient quality metrics (eg, LOS and readmission rates) and satisfaction by the surgical teams yearly. We will evaluate the impact on hospitalists using retrospective pre-post surveys to measure changes in clinical knowledge, confidence and engagement. Assessments will be collected using Qualtrics survey software. Discussion/Reflection/Lessons Learned: In the early stages of this curriculum, 79% of participants found the CPD sessions "very or extremely helpful." Participants have shown increasing engagement in the curriculum as evidenced by proposals of future session topics and attendance. Data collection is ongoing
A comparison of methods for tracking RFA probes and sensitivity to RF field and temperature [Meeting Abstract]
Electromagnetic tracking for thermal ablation and biopsy guidance: clinical evaluation of spatial accuracy
PURPOSE: To evaluate the spatial accuracy of electromagnetic needle tracking and demonstrate the feasibility of ultrasonography (US)-computed tomography (CT) fusion during CT- and US-guided biopsy and radiofrequency ablation procedures. MATERIALS AND METHODS: The authors performed a 20-patient clinical trial to investigate electromagnetic needle tracking during interventional procedures. The study was approved by the institutional investigational review board, and written informed consent was obtained from all patients. Needles were positioned by using CT and US guidance. A commercial electromagnetic tracking device was used in combination with prototype internally tracked needles and custom software to record needle positions relative to previously obtained CT scans. Position tracking data were acquired to evaluate the tracking error, defined as the difference between tracked needle position and reference standard needle position on verification CT scans. Registration between tracking space and image space was obtained by using reference markers attached to the skin ("fiducials"), and different registration methods were compared. The US transducer was tracked to demonstrate the potential use of real-time US-CT fusion for imaging guidance. RESULTS: One patient was excluded from analysis because he was unable to follow breathing instructions during the acquisition of CT scans. Nineteen of the 20 patients were evaluable, demonstrating a basic tracking error of 5.8 mm +/- 2.6, which improved to 3.5 mm +/- 1.9 with use of nonrigid registrations that used previous internal needle positions as additional fiducials. Fusion of tracked US with CT was successful. Patient motion and distortion of the tracking system by the CT table and gantry were identified as sources of error. CONCLUSIONS: The demonstrated spatial tracking accuracy is sufficient to display clinically relevant preprocedural imaging information during needle-based procedures. Virtual needles displayed within preprocedural images may be helpful for clandestine targets such as arterial phase enhancing liver lesions or during thermal ablations when obscuring gas is released. Electromagnetic tracking may help improve imaging guidance for interventional procedures and warrants further investigation, especially for procedures in which the outcomes are dependent on accuracy.
Precision instrument placement using a 4-DOF robot with integrated fiducials for minimally invasive interventions - art. no. 65092S [Meeting Abstract]
Minimally invasive procedures are increasingly attractive to patients and medical personnel because they can reduce operative trauma, recovery times, and overall costs. However, during these procedures, the physician has a very limited view of the interventional field and the exact position of surgical instruments. We present an image-guided platform for precision placement of surgical instruments based upon a small four degree-of-freedom robot (B-Robll; ARC Seibersdorf Research GmbH, Vienna, Austria). This platform includes a custom instrument guide with an integrated spiral fiducial pattern as the robot's end-effector, and it uses intra-operative computed tomography (CT) to register the robot to the patient directly before the intervention. The physician can then use a graphical user interface (GUI) to select a path for percutaneous access, and the robot will automatically align the instrument guide along this path. Potential anatomical targets include the liver, kidney, prostate, and spine. This paper describes the robotic platform, workflow, software, and algorithms used by the system. To demonstrate the algorithmic accuracy and suitability of the custom instrument guide, we also present results from experiments as well as estimates of the maximum error between target and instrument tip.
Technologies for guidance of radiofrequency ablation in the multimodality interventional suite of the future
Several new image-guidance tools and devices are being prototyped, investigated, and compared. These tools are introduced and include prototype software for image registration and fusion, thermal modeling, electromagnetic tracking, semiautomated robotic needle guidance, and multimodality imaging. The integration of treatment planning with computed tomography robot systems or electromagnetic needle-tip tracking allows for seamless, iterative, "see-and-treat," patient-specific tumor ablation. Such automation, navigation, and visualization tools could eventually optimize radiofrequency ablation and other needle-based ablation procedures and decrease variability among operators, thus facilitating the translation of novel image-guided therapies. Much of this new technology is in use or will be available to the interventional radiologist in the near future, and this brief introduction will hopefully encourage research in this emerging area.
Radio frequency ablation registration, segmentation, and fusion tool
The radio frequency ablation segmentation tool (RFAST) is a software application developed using the National Institutes of Health's medical image processing analysis and visualization (MIPAV) API for the specific purpose of assisting physicians in the planning of radio frequency ablation (RFA) procedures. The RFAST application sequentially leads the physician through the steps necessary to register, fuse, segment, visualize, and plan the RFA treatment. Three-dimensional volume visualization of the CT dataset with segmented three dimensional (3-D) surface models enables the physician to interactively position the ablation probe to simulate burns and to semimanually simulate sphere packing in an attempt to optimize probe placement. This paper describes software systems contained in RFAST to address the needs of clinicians in planning, evaluating, and simulating RFA treatments of malignant hepatic tissue.
Automatic localization of fiducial markers for Transrectal Ultrasound (TRUS) guided needle biopsy - Phantom study
Respiratory motion compensation with tracked internal and external sensors during CT-guided procedures
This paper investigates the possibility of using the motion of a patient's anterior surface in combination with a motion model to compensate for internal respiratory motion during tracked biopsies. Position data from two electromagnetically tracked sensors, one placed on the patient's sternum, the other incorporated into a biopsy needle, were acquired during a liver biopsy. The data were used to evaluate the correlation between the position measurements of the two sensors and to derive an affine motion model to assess respiratory motion compensation for image-guided interventional procedures. The correlation reached up to 94% for ranges of steady respiration. The residual motion of the internal sensor after compensation is reduced by a factor of approximately four.