Impact of admission viral load on respiratory outcomes in hospitalized SARS-CoV-2 infected patients with cancer and without cancer: A 2-, 4- and 6-months follow-up prospective study.

BACKGROUND: This prospective follow-up study aimed to determine the temporal changes in respiratory outcomes over 6 months period in patients with and without cancer hospitalized for severe COVID-19 and to determine the associated risk factors based on admission viral load. METHODS: All adult patients hospitalized with a confirmed diagnosis of severe SARS-CoV-2 infection were investigated using rRT-PCR on nasopharyngeal swab specimens. Patients were divided into three arbitrary groups according to their cycle threshold (CT) values obtained at admission as high (CT<25.0), medium (CT between 25.0 and 30.0), and low (CT>30.0) viral load. Patients had pulmonary function tests, chest high-resolution computed tomography (HRCT), and a 6-minute walking time distance measured at each follow-up visit. RESULTS: This follow-up study had a total of 112 participants, of which 75 were cancer-free and 37 had active cancer. Overall, 29.5% had a low viral load, compared to 48.2% who had a high viral load, and 22.3% had a medium viral load. For patients who did not have cancer, the mean age was 57.3 (SD 15.4) and for those who had cancer, it was 62.3 (SD 18.4). Most patients had overall better temporal changes in pulmonary function and tolerance, as well as exercise capacity, even though severe and chronic respiratory abnormalities persisted in a fraction of the patients. In patients without cancer who had a high viral load, we have seen a substantial reduction in diffusion capacity of the lungs for carbon monoxide (DLCO) predicted value with a median of 65 (IQR 63-70) while in patients with cancer, it was 60 (IQR 56-67) at 2 months. At 4 and 6 months, the predicted DLCO values for patients without cancer were 65 (IQR 61-70), whereas the predicted DLCO values for patients with active cancer were 62 (IQR 60-67) and 67 (59-73). Importantly, radiological abnormalities persisted in 22 (29%) non-cancer patients and 16 (43%) cancer patients. Multivariate regression analysis showed an increased odds ratio of impaired HRCT associated with a high viral load of 3.04 (95% CI:1.68-6.14; p < 0.001) for patients without cancer and 5.07 (95% CI: 4.04-10.8; p < 0.0001) for patients with cancer. The CT pneumonia score at hospitalization was 2.25 (95% CI:1.76-3.08; p = 0.041) and 2.85 (95% CI:1.89-5.14; p = 0.031) for non-cancer and cancer patients respectively. CONCLUSIONS: The evidence of persistent pulmonary abnormalities and radiographic changes was found in both patient groups who had high viral load at hospital admission and suggesting that SARS-CoV-2 viral load might serve as a useful indicator to predict the development of respiratory complications in patients with COVID-19.

Results from Expanded Access Programs: A Review of Academic Literature.

BACKGROUND: Although expanded access is an increasingly used pathway for patients to access investigational medicine, little is known on the magnitude and content of published scientific research collected via expanded access. METHODS: We performed a review of all peer-reviewed expanded access publications between January 1, 2000 and January 1, 2022. We analyzed the publications for drugs, diseases, disease area, patient numbers, time, geographical location, subject, and research methodology (single center/multicenter, international/national, prospective/retrospective). We additionally analyzed endpoints reported in all COVID-19-related expanded access publications. RESULTS: We screened 3810 articles and included 1231, describing 523 drugs for 354 diseases for 507,481 patients. The number of publications significantly increased over time ([Formula: see text]). Large geographical disparities existed as Europe and the Americas accounted for 87.4% of all publications, whereas Africa only accounted for 0.6%. Oncology and hematology accounted for 53% of all publications. Twenty-nine percent of all expanded access patients (N = 197,187) reported on in 2020 and 2021 were treated in the context of COVID-19. CONCLUSIONS: By summarizing characteristics of patients, diseases, and research methods described in all scientific literature published on expanded access, we provide a unique dataset for future research. We show that published scientific research on expanded access has surged over the past decades, partly due to COVID-19. However, international collaboration and equity in geographic access remain an issue of concern. Lastly, we stress the need for harmonization of research legislation and guidance on the value of expanded access data within real-world data frameworks to improve equity in patient access and streamline future expanded access research.

WORKING PRINCIPLE AND INTELLIGENCE OF SMART INFUSION PUMP

There is a tremendous demand on the critical care resources due to the extensive spread of the ongoing coronavirus pandemic and the large number of patients requiring critical care. The efficacy of a device directly influences how long a patient lives since patients are often receiving critical care. Smart infusion pump is a medical device that can drip fluids into the patient's body. This device is considered as one of the most safety-critical medical devices due to the way it functions and the risks it presents. The main objective of this work is to develop an affordable infusion pump usin g embedded technology. The main tactic is to develop equipment that can identify air bubbles in infusion pump tubing since even a little one might obstruct blood flow and result in mortality. This method may provide consumers an accurate result, making it the greatest method for identifying bubbles and saving lives.

Finding and Categorizing COVID-19 Papers in CS Education

In the first 2 years following the outbreak of COVID-19, many papers have been published regarding the impacts and adaptations of the pandemic on computer science education. As a first step towards a systematic literature mapping, this study attempts to develop a process for searching and a categorization schema for papers. The goal of this project is to produce a literature map which will be used to provide an initial assessment of the state of research, as well as a framework for future research directions. Limiting our search to papers published in the ACM Digital Library in the publications sponsored by SIGCSE, we first create and validate a query and inclusion/exclusion criteria for papers. Using a double evaluator model, we find high agreement with a Cohen's Kappa of 0.93, resulting in 42 papers across 6 conference proceedings. We further validate these findings by independent checking against all papers from SIGCSE2021 TS. We then develop categories across three dimensions: In activity: we find remote teaching, remote assessment, remote work, virtual events and general impact of pandemic. In measurement: we find grades, non-grade assessment, attendance/retention, affect/perception, and mental health. In population: we find K-12 students, university/college students, Educators, and the sub-categories of introductory/CS0/CS1 students, gender, and race. Double rater assessments initially produced a relatively low Kappa score of 0.58, but after protocol revision, and the production of additional categories, the kappa score was raised to a very high 0.94. © 2022 Owner/Author.

Reflective monitoring as an iterative process in clinical teaching: lessons from online undergraduate psychiatry teaching during COVID-19

Purpose: During the COVID-19 outbreak, clinical schools across the UK were forced to switch their learning from face-to-face to online platforms. This paper aims to describe the experiences of psychiatry teachers and medical students at Cambridge University of the online psychiatry case-based tutorials during the COVID-19 outbreak and the lessons learned from this implementation. Design/methodology/approach: The authors conducted qualitative focus groups with students followed by in-depth individual interviews with students and teachers. Findings: In a data-led systematic text condensation analysis, this study found seven themes: the COVID-19 context, the structure of the course, teachers' educational ethos, beyond the (teaching) script, possibilities for learning or teaching reflective practice, attitudes to online learning and suggestions for future development. The authors then applied the normalisation process theory (NPT) as the theoretical frame of reference. This model has previously been applied to the implementation of telemedicine in psychiatry, to understand how new technology can become embedded in clinical care. Originality/value: This study's results show how the NPT model can be modified to support the delivery of medical education online, including reflective learning and practice as an iterative process at every stage of the implementation and delivery of the teaching. © 2022, Emerald Publishing Limited.

Safety and clinical efficacy outcomes from the Long-term extension study of tolebrutinib in patients with relapsing multiple sclerosis: 2-year results

Introduction: Phase 2b trial (NCT03889639) findings in patients with relapsing multiple sclerosis showed central nervous systempenetrant Bruton's tyrosine kinase inhibitor tolebrutinib was well tolerated over 12 weeks and elicited dose-dependent reductions in new gadolinium-enhancing T1 and new/enlarging T2 lesions. Objective/Aim: To characterise tolebrutinib's safety and efficacy at Week 96 (2 years) in the phase 2b trial's long-term safety (LTS) extension (NCT03996291). Method(s): In LTS extension Part A, patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until the phase 3 study dose selection (60 mg/day). In Part B, patients received open-label tolebrutinib 60 mg/day. Safety was assessed via adverse event (AE) reporting. Efficacy outcomes included annualised relapse rate (ARR) and change from baseline Expanded Disability Status Scale (EDSS) score. Result(s): 124 of 125 patients completed Part A and transitioned to Part B;114 (90.5%) remained on study as of 7 March 2022. One patient receiving tolebrutinib 5 mg/day discontinued Part A because of progressive disease and 10 discontinued Part B because of AEs (n=3), perceived lack of efficacy (n=4), emigration (n=2), and patient decision (n=1). At Week 96, no new safety signals have been observed. The most common treatment-emergent AEs (TEAEs) were COVID-19 (20.8% [26/125]), headache (13.6% [17/125]), nasopharyngitis and upper respiratory tract infection (both 11.2% [14/125]), bacterial cystitis (7.2% [9/125]), and pharyngitis and arthralgia (both 5.6% [7/125]). No tolebrutinib dose effects for TEAEs or serious AEs were observed in Part A and no safety signals emerged for patients switching to tolebrutinib 60 mg/day in Part B. Of those who received tolebrutinib 60 mg/day for a minimum of 8 weeks, ARR was 0.17 (95% CI: 0.12, 0.25) and 80.6% remained relapse-free. Mean EDSS remained stable to Week 96. Conclusion(s): Through LTS Week 96, tolebrutinib 60 mg/day continues to show favourable safety, and is associated with a low ARR and stable disability status.

MRI, efficacy, and safety of tolebrutinib in patients with highly active disease (HAD): 2-year data from the phase 2b Long-term safety (LTS) Study

Intoduction: In the phase 2b trial (NCT03889639), brain-penetrant Bruton's tyrosine kinase inhibitor tolebrutinib was well tolerated with dose-dependent reductions in new/enlarging MRI lesions. Objective/Aim: Report MRI, efficacy, and safety outcomes at Week (W)96 (2 years) of the phase 2b trial long-term safety (LTS) extension (NCT03996291) in relapsing MS patients with highly active disease (HAD). Method(s): In the double-blind portion of LTS (Part A), patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day). In the open-label Part B, all participants received 60 mg/day. HAD was defined as one relapse in the year prior to screening and one of the following: >1 gadolinium (Gd)- enhancing lesion within the prior 6 months, or >=9 T2 lesions at baseline (BL) or >=2 relapses in the prior year. Outcomes included Gd-enhancing and new/enlarging T2 lesions, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) score. Result(s): 61 patients met the HAD criteria at BL;60 continued in LTS Part A and 59 transitioned to Part B. As of 7 March 2022, 55 (92%) patients remained on study. New Gd-enhancing lesion counts remained low in the 60/60-mg arm through W96 and were reduced in other arms by W48 through W96, except for 5/60 at W96 (mean+/-SD at W96: 2.00+/-3.83, 0.56+/-1.04, 0.47+/-1.13, 0.23+/-0.44 in 5/60-, 15/60-, 30/60-, 60/60-mg arms, respectively). New/enlarging T2 lesion counts remained low for 15/60, 30/60, and 60/60 mg. T2 lesion volume remained unchanged for 60/60 mg. The most common treatment-emergent adverse events (TEAE) were COVID-19 (20%), nasopharyngitis (16.7%), headache (13.3%), and upper respiratory tract infection (8.3%). There was no dose-relationship for TEAE/serious AE in Part A and no new safety findings for patients switching to 60 mg in Part B. Of the patients who received tolebrutinib 60 mg/day for a minimum of 8 weeks, ARR was 0.10 (95% CI: 0.02, 0.66) and 92.9% remained relapse-free at W96. Mean EDSS scores were stable through W96. Conclusion(s): Through LTS Week 96, in the HAD cohort, tolebrutinib 60 mg demonstrated favourable safety (similar to the overall population), tolerability, and low ARR. New Gd-enhancing lesion counts remained low for the 60/60-mg arm.

Patient satisfaction after remotely delivered gut-directed hypnotherapy for irritable bowel syndrome during the COVID-19 era: implications for future practice.

OBJECTIVE: Gut-directed hypnotherapy (GDH) is an evidence-based treatment for irritable bowel syndrome (IBS). Adoption of remote GDH has been accelerated by the COVID-19 pandemic. We aimed to evaluate patient experience and satisfaction following remote GDH. DESIGN: On completing 12 sessions of remote GDH via Skype using the Manchester protocol, patients with refractory IBS completed a feedback form on their experience. The proportion reporting positive outcomes (≥30% improvement in global IBS symptoms or abdominal pain, satisfaction, recommendation to family/friends) were compared by patient factors (age, gender, proximity, preferences). RESULTS: Of 52 patients completing the feedback form, 27 (52%) indicated that they would have opted for remote over face-to-face GDH, regardless of the pandemic situation. On a five-point scale (5=easy), patients rated the platform easy-to-use (mean 4.5±0.8) without impairment of communication (mean rating 4.6±0.8). Following remote GDH, 30/52 (58%) reported ≥30% global IBS symptom improvement, and 24/52 (46%) reported ≥30% pain reduction. 90% would recommend remote GDH to others. Only 39% felt they would have benefitted more from face to face. Those who would have chosen remote GDH regardless of the pandemic were more likely to be satisfied (p=0.01). Age, gender and proximity did not influence outcomes, satisfaction and likelihood of recommending remote GDH to others. Difficulties during remote sessions were infrequent in both those that were satisfied, and those that would have preferred face to face. CONCLUSION: These data support the need to continue developing remote GDH in the post-COVID era but suggest that there is still a role for face-to-face GDH, with patient choice being an important factor.

Reykjanes Mantle Convection and Climate: Crustal Objectives

The five primary sites proposed for International Ocean Discovery Program (IODP) Expedition 395, which was postponed because of the COVID-19 pandemic, were cored during IODP Expedition 395C. The Expedition 395C operations, shipboard measurements, and sampling were adjusted to account for the absence of a sailing science party. The Expedition 395/395C objectives are (1) to investigate temporal variations in ocean crust generation at the Reykjanes Ridge and test hypotheses for the influence of Iceland mantle plume fluctuations on these processes, (2) to analyze sedimentation rates at the Björn and Gardar contourite drifts, as proxies for Cenozoic variations of North Atlantic deepwater circulation, and for uplift and subsidence of the Greenland-Scotland Ridge gateway related to plume activity, and (3) to analyze the alteration of oceanic crust and its interaction with seawater and sediments. During Expedition 395C, basalt cores were collected at four sites: U1554, U1555, U1562, and U1563. Sediment cores were also collected from these sites as well as from Site U1564, and casing was installed to 602 m at Site U1554. The amount of recovered cores, their preliminary descriptions, and the analyses of shipboard samples show that the results of Expedition 395C will fulfill a significant part of the Expedition 395 objectives. Basalts were collected from two V-shaped ridge and trough pairs, which will allow the investigation of the variability in mantle source and temperature causing this ridge/trough pattern. Basalt cores span an expected age range of 2.8–13.9 Ma, which will allow us to investigate the hydrothermal weathering processes. Sediments from the Björn drift were cored to basement, along with the uppermost 600 m of sediments from the Gardar drift. The data provided by Expedition 395C are a major advancement in achieving the work of Expedition 395. © 2022 Authors. All rights reserved.

Reflective monitoring as an iterative process in clinical teaching: lessons from online undergraduate psychiatry teaching during COVID-19

Purpose: During the COVID-19 outbreak, clinical schools across the UK were forced to switch their learning from face-to-face to online platforms. This paper aims to describe the experiences of psychiatry teachers and medical students at Cambridge University of the online psychiatry case-based tutorials during the COVID-19 outbreak and the lessons learned from this implementation. Design/methodology/approach: The authors conducted qualitative focus groups with students followed by in-depth individual interviews with students and teachers. Findings: In a data-led systematic text condensation analysis, this study found seven themes: the COVID-19 context, the structure of the course, teachers’ educational ethos, beyond the (teaching) script, possibilities for learning or teaching reflective practice, attitudes to online learning and suggestions for future development. The authors then applied the normalisation process theory (NPT) as the theoretical frame of reference. This model has previously been applied to the implementation of telemedicine in psychiatry, to understand how new technology can become embedded in clinical care. Originality/value: This study’s results show how the NPT model can be modified to support the delivery of medical education online, including reflective learning and practice as an iterative process at every stage of the implementation and delivery of the teaching. © 2022, Emerald Publishing Limited.

A Rare Case of Severe Manifestation of COVID-19 Infection Presenting as Immune-Related Thrombotic Thrombocytopenic Purpura With Multiorgan Involvement Treated With Plasmapheresis, Steroids, Rituximab, and Caplacizumab

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) caused by decreased activity of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Platelet-rich thrombi in small vessels lead to fragmentation of RBCs causing microangiopathic hemolytic anemia (MAHA). Therapeutic plasma exchange is life-saving and is the mainstay of the treatment of TTP. Higher dose IV steroids along with rituximab are used as an adjunct to plasma exchange. Our case report describes a 26-year-old healthy male who presented with new onset seizures and encephalopathy. Blood work demonstrated anemia, severe thrombocytopenia, elevated lactate dehydrogenase, decreased haptoglobin, and elevated creatinine, and peripheral blood smear showed marked schistocytosis indicating MAHA. Plasma exchange and high-dose steroids were started on a presumptive diagnosis of TTP. ADAMTS13 activity was undetectable and ADAMTS13 inhibitor levels were elevated. Rituximab and caplacizumab were then added. Symptoms of encephalopathy improved by day five and platelet counts started improving by day nine. After several days of plasma exchange, he showed a “clinical response” with several weeks of active treatment. The association between coronavirus disease 2019 (COVID-19) infection and the severity of TTP with multiorgan failure is not well understood yet. Although we describe a successful multimodal approach to the management of TTP, which we believe is secondary to COVID-19 infection, further research is warranted to analyze and understand the pathophysiology by which COVID-19 infection causes TTP. It would help in establishing standardized therapy in the future.

Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Patients With Relapsing Multiple Sclerosis:18-Month Results

Objective: To describe safety and efficacy of tolebrutinib in patients with relapsing multiple sclerosis at Week 72 (Month 18) in the long-term safety (LTS) extension of the phase 2b trial. Background: In the phase 2b trial (NCT03889639), tolebrutinib, a CNS-penetrant Bruton's tyrosine kinase inhibitor, was well tolerated over 12 weeks with dose-dependent reduction in new gadolinium-enhancing T1 and new/enlarging T2 lesions. Design/Methods: The LTS extension (NCT03996291) consists of 2 parts: patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until the phase 3 study dose was selected (Part A), and currently receive tolebrutinib 60 mg/day open-label (Part B). Long-term safety and tolerability is the primary objective. Secondary endpoints include annualized relapse rate (ARR) and change from baseline in Expanded Disability Status Scale (EDSS) score. Results: 124 of 125 patients treated in the extension completed Part A and transitioned to Part B. One patient (on 5 mg/day) discontinued Part A due to progressive disease and 6 discontinued Part B due to a variety of reasons, including adverse event (AE;n=2), lack of efficacy (n=1), progressive disease (n=1), and emigration (n=2). To date, no new safety signals have been observed. The most common treatment-emergent AEs (TEAEs) were headache (12.8% [16/125]), COVID-19 (12.8% [16/125]), nasopharyngitis (10.4% [13/125]), upper respiratory tract infection (8.0% [10/125]), and arthralgia (5.6% [7/125]). There was no suggestion of a dose effect for TEAE or serious AE in Part A and no emergence of new safety signals for patients switching to 60 mg in Part B. ARR on tolebrutinib 60 mg was 0.17 (95% CI: 0.11, 0.27);84.7% of patients were relapse-free at the LTS Week 72 cut-off. Mean EDSS scores remained stable to LTS Week 72. Conclusions: Through LTS Week 72, tolebrutinib 60 mg continues to show favorable safety and tolerability, and low ARR.

Fetal Medicine Unit: Need of the Hour at Tertiary Care Centers in India?

Aim: The aim of the article was to emphasize the need for a fetal medicine unit at tertiary care hospitals. Background: The incidence of Rh-negative in India is 5–10%. The issue of Rh incompatibility arises when the mother is Rh-negative and the fetus is Rh-positive. Rh alloimmunization can lead to fetal anemia, hydrops fetalis, and even intrauterine death. It leads to perinatal loss of 1–2.5%. Fetal anemia is a serious complication in pregnancy and is associated with perinatal morbidity and mortality. Intrauterine transfusion (IUT) is a good treatment option for fetal anemia due to Rh incompatibility. Intravascular transfusion offers the best chance of survival to fetuses severely affected with Rh isoimmunization, overall survival exceeding 80%. In the cases with detectable antibodies, prenatal monitoring of maternal antibody titers and fetal middle cerebral arterial-peak systolic velocity (MCA-PSV) Doppler ultrasound assessment helps to plan fetal blood sampling and IUT procedures. Thus, the establishment of fetal medicine unit at tertiary care centers in India is need of the hour. Case description: We report a case of 32-year-old G4P3L1END1IUD1 with Rh-negative sensitized pregnancy with fetal anemia, managed successfully with IUT. Clinical significance: Early diagnosis of fetal anemia by serial MCA-PSV measurements and referral to fetal medicine unit are important for improving the outcome in Rh-negative sensitized pregnancies. Conclusion: Establishment of fetal medicine unit at tertiary care centers is the need of the hour to improve the fetal outcome in high-risk pregnancies like Rh-negative pregnancy.

Incidence, clinical associations and outcomes of intrathoracic complications with and without ARDS in COVID-19 pneumonia.

PURPOSE: To determine the incidence and clinical predictors of intrathoracic complications in COVID-19 patients, and the association with outcomes. METHODS: In this retrospective cross-sectional study, we included 976 patients (age 61 ± 17 years, 62% male) who tested positive for SARS-CoV-2 between March 3-April 4, 2020 and underwent chest imaging. 3836 radiographs from 976 patients and 105 CTs from 88 patients were reviewed for intrathoracic complications, including pneumothorax, pneumomediastinum, pneumopericardium, lobar collapse, pleural effusion, and pneumatocele formation. RESULTS: There was a high rate of intrathoracic complications (197/976, 20%). Pleural effusion was the most common complication (168/976, 17%). Pneumothorax (30/976, 3%) and pneumatoceles (9/88, 10%) were also frequent. History of hypertension and high initial CXR severity score were independent risk factors for complications. Patients with any intrathoracic complication during admission had an over 11-fold risk of ICU admission (adjusted odds ratio [aOR] 11.2, p < 0.0001) and intubation (aOR 12.4, p < 0.0001), over 50% reduction in successful extubation (aOR 0.49, p = 0.02) and longer length of stay (median 13 versus 5 days, p < 0.0001). There was no difference in overall survival between patients with and without any complication (log-rank p = 0.94). CONCLUSION: In COVID-19 patients who underwent chest imaging, 1 in 5 patients have an intrathoracic complication, which are associated with higher level of care and prolonged hospital stay. Hypertension history and high CXR severity score confer an increased risk of complication. SUMMARY: Intrathoracic complications in COVID-19 are common and are predictive of ICU admission, need for intubation, less successful extubation, and longer length of stay but are not predictive of mortality.