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1.
Journal of ISAKOS ; JOUR:551, 6(6).
Article in English | EMBASE | ID: covidwho-2088867

ABSTRACT

We highlight the benefits of a formal preseason in professional football in terms of there being a lower injury rate at the start of the season following a formal preseason. Data Background The 'preseason' is an established period of the professional football season for players to gain fitness and has been demonstrated to subsequently improve player performance following the start of the season. Although players are at greater risk of injury in the preseason period, it is questioned whether a preseason subsequently decreases the risk of injury in the start of the formal season itself. Due to the established nature of the preseason no studies have previously reviewed the effect of the preseason on injury rates in the subsequent season. Our aim was to report the injury rate from post-lockdown professional football games (no preseason programme -NPP) and compare to the start of the season (following a preseason programme -FPP). This would then provide a comparison between the two groups and a determination of the potential beneficial effect of a formal preseason on the injury rates at the start of the formal season. Methods We compared the injuries sustained across 4 European Professional Football Leagues (Premier League, Serie A, Bundesliga, La Liga) from the first 2 games for each team at the start of the 2019-20 season (FPP group) and from the first 2 games for each team after the re-start of football following lockdown (NPP group). We recorded the frequency, injuries per game, contact and soft tissue injuries. An injury was recorded if the player was deemed unable to continue play. Results In total 156 games were reviewed, 78 in the FPP group and 78 in the NPP group. A total of 10 injuries were observed in the FPP group games, 0.13 per game, compared to 30 injuries in the NPP group games, 0.39 per game (p=0.001). The ratio of contact to soft tissue injuries was the same for both groups (1:4). There was no significant difference in the length of downtime between the leagues stopping and restarting (92-103 days) and no correlation between injury rate and length of downtime. Conclusions Injuries in elite professional football were more common in the first 2 games following the restart after lockdown than in the first 2 games of the 2019/20 season. We believe this is due to the beneficial effect of a normal preseason being absent for the restart. We highlight the importance of preseason in reducing injury rates amongst professional footballers.

2.
Open Respiratory Medicine Journal ; 16(1), 2022.
Article in English | Scopus | ID: covidwho-2079931

ABSTRACT

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. Objectives: To study the association of latitude and altitude with COVID-19 symptomatology. Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering. Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms (p<.001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude (p=.026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively). Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude. © 2022 Tekin et al.

3.
Chest ; 162(4):A627, 2022.
Article in English | EMBASE | ID: covidwho-2060651

ABSTRACT

SESSION TITLE: Management of COVID-19-Induced Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Evans syndrome (ES) is a rare autoimmune disorder characterized by the combination of two or more cytopenias with an incidence of 0.8-3.7%.Here we present a case of COVID-19 pneumonia complicated by the development of ES. CASE PRESENTATION: A 75-year-old female with the past medical history of 50 pack-year smoking, recent asymptomatic COVID-19 Pneumonia 2 week ago came to the emergency room (ER) with shortness of breath. Her vitals and physical exam were unremarkable. Labs were significant for leukocytosis of 11.66 and D-dimer of 3.32. CT pulmonary angiogram showed bilateral pulmonary embolism along with a COVID-19 pattern of pneumonia. She was started on heparin drip and was eventually discharged on Warfarin with Prednisone taper. After 3 weeks, she presented to the ER with worsening shortness of breath. She was found to have platelet count of 4k and Hb of 6.6 gm%(compared to 370k and 13.1 gm% on last discharge) and was started on transfusions which could not be completed due to development of mid-transfusion fever. She received Dexamethasone and IVIG. All forms of active bleeding were ruled out by bronchoscopy, CT scans and EGD. Flow cytometry was negative for ADAMTS13 ruling out thrombotic thrombocytopenic purpura. Bone marrow biopsy was unremarkable. She was positive for IgG warm agglutinin hemolytic anemia. She was discharged on long-term Prednisone taper. In the clinic she was given intermittent IVIG and Romiplostim to improve her counts. Due to multiple failed attempts to wean her off steroids, she was started on Rituximab with an excellent response of platelets increment to 450k and Hb to 8.5 gm%. Rituximab will be given for a total of 8 weeks. DISCUSSION: ES is considered to be caused by immune system dysregulation. ES in COVID-19 is a diagnostic dilemma as the thrombocytopenia is usually misdiagnosed as COVID-19 sequelae and leads to delay in diagnosis. The treatment of ES is usually with steroids 1 mg/kg/day but they only provide short term improvement. Rituximab, plasma exchange, IVIG, and splenectomy are second-line treatments for relapsing/refractory ES. Our patient had an acceptable response to steroids but it was transient,demonstrating the limited role of steroids in the long term and was eventually treated successfully with Rituximab. A review of limited published cases of ES caused by COVID-19 suggests that diagnosis, treatments, and prognosis are usually individualized according to patient characteristics, presenting symptoms, physician preference, and disease complications. CONCLUSIONS: ES is a very rare syndrome although it requires prompt treatment. It is important to be mindful about immunological causes when a COVID-19 patient presents with cytopenia, as delay in treatment can cause poor outcomes. Reference #1: Turgutkaya A, Bolaman AZ, Yavaşoğlu Í. COVID-19-associated Evans syndrome: A case report and review of the literature. Transfus Apher Sci. 2021 Dec 7:103339. doi: 10.1016/j.transci.2021.103339. Epub ahead of print. PMID: 34896007;PMCID: PMC8655821. DISCLOSURES: No relevant relationships by Nitesh Jain No relevant relationships by Kashyap Kela No relevant relationships by Princy Shah No relevant relationships by namita sharma No relevant relationships by AMIT SHARMA

4.
HemaSphere ; 6:3284-3285, 2022.
Article in English | EMBASE | ID: covidwho-2032098

ABSTRACT

Background: The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib is approved for treatment of chronic lymphocytic leukemia(CLL). Acalabrutinib induces durable remissions in most CLL patients, which mostly are partial remissions (PR), and therefore treatment typically is given as long-term monotherapy. As a potential alternative we developed a time-limited regimen, combining acalabrutinib with obinutuzumab. Aims: Here, we report early results from 14 treatment-naïve patients with CLL who enrolled in this ongoing phase 2 trial (NCT04505254) since September, 2020 at MD Anderson Cancer Center. Methods: Patients and Study Design: Treatment-naïve CLL patients requiring therapy as per iwCLL criteria receive acalabrutinib 100 mg orally twice a day for 24 cycles, combined with monthly obinotuzumab for 6 doses, starting in cycle 3. The first dose of obinutuzumab is divided into 100 mg on day 1 and 900 mg on day 2 of cycle 3;1000 mg are given during subsequent cycles (cycles 4-8). Patients who do not achieve a complete remission (CR) after cycle 8 can receive an additional 6 monthly doses of obinotuzumab during cycles 9 -14. Treatment is discontinued after 24 cycles, and patients will be monitored. The primary objective is to determine the durability of remissions after treatment discontinuation, secondary objectives are to determine clinical and laboratory characteristics that predict for early versus late relapse after time-limited therapy. Results: The median age of the patients is 70 yrs (range, 40 -83 yrs), 14% had del17p or TP53 mutation, 43% had an unmutated IgHV and 71% advance stage disease (RAI stage III and IV). The median baseline absolute lymphocyte count (ALC) and b2 microglobulin at start of therapy were 39.2x109/L (range: 7.1 - 188.4 x 109/L) and 4.2 mg/L (range: 2.2 - 7.9 mg/L), respectively. After a median follow-up of 7 months (2 - 16 months), 13 (93%) of patients remain on study;one patient died (7%) due from complications from a presumed bacterial (COVID19-negative) pneumonia after 2 months on therapy. The estimated one-year PFS and OS for the cohort is 92.8 %. Seven patients were evaluable for response assessment after 8 months of therapy. No patient has yet discontinued therapy. All patients achieved a PR (one patient with undetectable minimal residual disease/U-MRD in the bone marrow), accounting for an overall responsonse rate of 100%. The median levels of bone marrow infiltration by CLL cells, quantified by flow cytometry, declined from 83.6% (range: 54.3 - 94.0 %) at baseline to 4.1% (range, 0.0 - 63.3%, n=7, p<0.05, see figure) after 6 cycles of combination treatment. Sixty-four percent of patients completed all doses of obinotuzumab, 50% requiered a dose reduction of acalabrutinib to 100 mg per day due to adverse events (AE). Grade 33 AE were observed in 4 patients (29%), which included decreased neutrophil counts (n=2), syncope (n=1), and grade 5 lung infection (COVID19 not detected, n=1). The most frequently reported non-serious related AE (3 2 patients) were anemia (n=5 [36%]), decreased platelets counts (n=3 [21%]), bruising (n=3 [21%]), limbs edema (n=2 [15%]) and headache (n=2 [15%]). All these events were grade 1. Importantly, no bleeding or atrial fibrillation events were observed. 3285 (Figure Presented ) Summary/Conclusion: Our preliminary data indicate that combination therapy of acalabrutinib plus obinotuzumab induces remissions with a major reduction in bone marrow disease after 6 months of combination therapy. Longer treatment and follow-up is warranted to determine the durability of responses after therapy discontinuation.

5.
Sci Total Environ ; 852: 158421, 2022 Dec 15.
Article in English | MEDLINE | ID: covidwho-2008099

ABSTRACT

Wastewater-based surveillance (WBS) has been an effective tool for monitoring and understanding potential SARS-CoV-2 transmission across small and large-scale communities. In this study at the University of Saskatchewan, the assessment of SARS-CoV-2 was done over eight months during the 2021-2022 academic year. Wastewater samples were collected using passive samplers that were deployed in domestic sewer lines near adjacent campus residences and extracted for viral RNA, followed by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The results showed similar trends for SARS-CoV-2 detection frequencies and viral loads across university residences, the whole campus, and from related WBS at Saskatoon Wastewater Treatment Plant. The maximum daily detection frequency for seven dormitories considered was about 75 %, while maximum daily case numbers for the residences and campus-wide were about 11 and 75 people, respectively. In addition, self-reported rates of infection on campus peaked during similar time frames as increases in viral load were detected at the Saskatoon wastewater treatment plant. These similarities indicate the usefulness and cost-effectiveness of monitoring the spread of COVID-19 in small-scale communities using WBS.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Waste Water/analysis , COVID-19/epidemiology , RNA, Viral , Universities , Wastewater-Based Epidemiological Monitoring
6.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2005680

ABSTRACT

Background: In the face of the COVID 19 pandemic, goal-concordant care has been gaining further significance. Discussions about the care goals are best when they are exploratory, conversational, and longitudinal. Complex information processing is best done outside of a crisis. Ideally, these conversations should start with the primary care clinician who has a longitudinal clinical relationship with the patient. Methods: A quality initiative project was conducted at the Internal Medicine Residency Clinic located in Northwestern Medicine Woodstock Hospital. Review of order entry in electronic medical records and charts for code status was assessed for data gathering. Patients above the age of 65 years presenting for their annual physical visit were included in the study. Various interventions were done, including educating residents through didactic lectures, sending electronic reminders to the residents and formatting a template note including code status documentation. Pre and post-intervention data was gathered. Results: A total of 104 patients were in the pre-intervention group and 94 patients in the post-intervention group. Pre-intervention, code status was addressed in 33% of total patients interviewed during their annual physical visit. Post intervention, code status was addressed in 48% of the patients. Conclusions: This project was undertaken to increase awareness on a crucial aspect of the addressing code status in outpatient setting. Post intervention studies showed that addressing code status significantly increased. In order to fill the gap, we propose that addressing code status be a mandatory process or a reminder be generated in electronic health records.

7.
Management Decision ; 2022.
Article in English | Scopus | ID: covidwho-1961350

ABSTRACT

Purpose: The research aims to measure the effectiveness of collaborative learning exchanges transpired through digital tools and technologies (DT&Ts) employed by the mentor universities during the COVID-19 pandemic by conducting an empirical study on undergraduate students in Indian higher educational institutions (HEIs) under the mentorship program based on the corporate social responsibility (CSR) initiative. The pandemic scenario, its impact on the mentor university's social responsibility and the way DT&Ts can assist are investigated in this article. Design/methodology/approach: The interactions with experts and students were conducted to explore the DT&Ts for learning exchanges. Next, structural equation modeling (SEM) was performed to validate the model and perform regression analysis. The quantitative data collection was made through questionnaires during the second deadly wave of COVID-19 that hit India. Findings: The independent variables (IVs) such as the IT infrastructure support (IT_IS), virtual collaborative tools (VCTs) and future-oriented technologies (FOTs) have a significant impact on the CSR learning outcomes (CSR_LOs) of undergraduate students under the mentorship program. However, IV research instruments for innovation could not make a significant effect. Research limitations/implications: The IVs IT_IS, VCTs and FOTs influence the CSR_LOs, while RII does not have an influential impact. Practical implications: As the online learning environment is expected to stay at least in a blended form, adequate CSR funding in infrastructure is necessitated to harness the full potential of this important resource, technology. The results of this empirical investigation affirm that IT_IS, VOTs and FOTs significantly impact CSR_LOs during the crisis. The study findings would encourage the mendtor universities and their stakeholders, including the mentee universities, to evolve and create an ecosystem for effective management of these resources to attain positive outcomes. The study findings can guide the mentor universities in managing uncertainties like pandemics and effectively using the earlier-mentioned critical resources for social responsibility. This research also allows the development of future applications adnd models in mentor-mentee universities for social responsibility, post-pandemic transformation and resilience. Social implications: The DT&Ts came to the immediate rescue during the pandemic and positively affected collaborative CSR_LOs by the mentor universities, but they have not evolved to a level where offline learning can be replaced entirely. Hence, it can be inferred that a hybrid model is preferable. The study also improves the understanding of how DT&Ts are being harnessed to aid collaborative learning in fulfilling the mentors' CSR in fatal emergencies. The purpose is to equip the education system through mentorship so that universities can sustain, innovate and grow even in trying times. Also, it discusses the dynamics of various DT&Ts for creating a sustainable learning environment and utilizing them to make the teaching prolific and influential. Originality/value: There is a scarcity of literature regarding the learning outcomes realized through CSR initiatives and collaboration between mentor-mentee institutions. There is a need to understand how these knowledge exchanges continued despite the physical restrictions during the pandemic. In this direction, this study helps to understand how the DT&Ts played a critical role in continuing learning and keeping abreast in a knowledge society from the perspective of resource-based view (RBV) in these precarious situations. © 2022, Emerald Publishing Limited.

8.
Indian Journal of Rheumatology ; 17(2):208-209, 2022.
Article in English | EMBASE | ID: covidwho-1928758
9.
Thailand and the World Economy ; 40(2):1-17, 2022.
Article in English | Scopus | ID: covidwho-1918788

ABSTRACT

Aside from various economic crises faced by different countries are different time, the countries, and sometimes the world as a whole, have faced serious pandemics such as Spanish Flu, Ebola, bubonic plague and the recent COVID 19, among others. In order to boost the economy, the government tends to introduce different stimulus, relief and financial packages in favour of the citizens of its country. The government is inclined to follow the Keynesian model as it focuses on increasing the demand of consumers. It is the need of the hour to realise the importance of health care for the growth and development of the economy as it has been observed that countries where the economic impact of the crisis is huge and prolonged, also suffer from a great impact on healthcare services. The following study concludes, after both theoretical and empirical analysis, that health expenditure plays a major role in increasing global GDP. Thus, the government should focus on increasing expenditures on health during any crisis. This reduces the amount of income spent by consumers on health care and provides them with security. Further, workers' efficiency increases at a great rate, as does their life expectancy. Higher efficiency is associated with higher output and thus higher growth. © 2022 Thailand and the World Economy. All Rights Reserved.

10.
IEEE Engineering Management Review ; : 1-20, 2022.
Article in English | Scopus | ID: covidwho-1901433

ABSTRACT

COVID-19 has shocked global humanity and forced the world for continued lockdown and sudden economic turmoil. The oil and gas (O&G) sectors has experienced a nearly catastrophic besides undergoing supply-demand stalemate and free fall of crude price. Such an unbalance has impacted the supply chain of the O&G industry, having diverse ‘Hotspots.’Besides the growth of green energy, the oil sector contributes significantly to the energy security for the majority of the countries. Hence, the O&G sector needs to consider resilience strategies against such hotspots critically. This research has identified such critical hotspots and analyzed their moderation by developing a STELLA software model with system dynamics (SD) approach. The SD model is simulated with the data input of crude price, forecast demand, and strategy for the upcoming fiscal years. The Indian O&G sector is chosen as a case study;however, globally, the uniformity of the oil and gas supply chain could be effectively applied. The results indicate a drastic decline in production, revenue, sustainability, and net profits, though the critical resilience strategies are suggested. Despite a comprehensive exhibit of difficulties, the oil industry is expected to stay innovative, resilient, and compelling and eventually balances the slump as economic situations improve. IEEE

11.
American Journal of Respiratory and Critical Care Medicine ; 205:1, 2022.
Article in English | English Web of Science | ID: covidwho-1880374
12.
Journal of Vascular and Interventional Radiology ; 33(6, Supplement):S129-S130, 2022.
Article in English | ScienceDirect | ID: covidwho-1867441
13.
International Journal of Pharmacy and Pharmaceutical Sciences ; 14(4):44-50, 2022.
Article in English | EMBASE | ID: covidwho-1822680

ABSTRACT

Objective: The aim of the present study was to assess bioactive compounds found in Tulsi as potential COVID-19 Mpr °inhibitor using molecular docking and to provide scientific justification in term of its active ingredient to target protein for prevention and symptomatic treatment of COVID-19. Methods: COVID-19 Mpr °was docked with eight phytochemicals of Ocimum sanctum Linn. Using Autodock 4.2. Determination of active site and visualization of molecular interactions between ligands and target enzyme was done by Biovia Discovery Studio 4.5. Results: Our result demonstrates that Vicenin, Caryophyllene, Cirsimaritin, Isothymusin and Isothymonin have a better binding affinity to target enzyme. However, only Vicenin exhibited better binding energy i.e.-7.02 kcal/mol to COVID-19 Main protease among other phytochemicals through some responsible interactions to inhibit the replication of SARS-CoV-2 in the human body, whereas Caryophyllene and Cirsimaritin exhibited similar binding affinity i.e.-6.46 kcal/mol but different interactions with target enzyme. Conclusion: Tulsi (Ocimum sanctum Linn.) is a preeminent traditional drug of Ayurveda for prophylaxis and treatment of various ailments, including respiratory disorders like cough, cold and flu. With no specific therapies available, reevaluating and repurposing traditional drugs could be an effective approach for the prevention and treatment of SARS-CoV-2 infection. Therefore our study provides scientific evidence for the potential use of Tulsi as an adjunct therapy for the prevention and symptomatic treatment of COVID-19. However, further in vitro and in vivo studies should be conducted to validate use of proposed compounds in drug discovery and as therapeutics against COVID-19.

14.
Wearable Telemedicine Technology for the Healthcare Industry: Product Design and Development ; : 33-52, 2021.
Article in English | Scopus | ID: covidwho-1797350

ABSTRACT

Blockchain has three main features-decentralization, immutability, and encryption-that can cover multiple fields of use in the healthcare industry. Telemedicine, a relatively new field, stems from telecommunications' contribution to healthcare services' remote delivery. This area has observed many benefits of Blockchain technology. However, innovative techniques for secured and authenticated data transfers still need to be put forward in this new digitization era. Healthcare professions use the opportunities provided by the Blockchain technology (BCT) in accessing the patient's information in a decentralized format. Though the decentralization aspect improves the overall robustness of current healthcare systems, trust and traceability are the key action points that need to be focused on. BCT paired with smart contracts automates operations and services of telehealth and telemedicine in an efficient and trustful way. Several case studies and models have been discussed and proposed, demonstrating the practicality of secured data transfers using BCT in the telehealth and telemedicine domain. BCT has hopefully assisted in the safe sharing of data information, from cryptographic record keeping of a person's information to easy access and access everywhere. Telemedicine has had significant security issues, but Blockchain's ability to develop and maintain a secure network when exchanging data has allowed easy information flow. This chapter presents various models and frameworks proposed in the state-of-the-art and discusses their implications for patient engagement and empowerment. These models are discussed in terms of their performance and cost in providing secured and private data sharing. Cost, lack of awareness on how to implement it, and lack of standardization are obstacles preventing Blockchain's adoption in telemedicine. The COVID-19 pandemic has boosted telehealth and telemedicine technology uptake, where BCT could be a prevailing solution. The interest in providing hospital care in the patient's home is also growing, an approach where multiple investors are pouring money into companies working on remote monitoring of different health and telemedicine parameters. There is currently limited research on Blockchain applications for telemedicine, but more research is available every day. Blockchain is now one of the most active fields of software science, and by restoring authority over medical records and health data to the patient, it will shift the hierarchy of healthcare. © 2022 Elsevier Inc. All rights reserved.

15.
Indian Journal of Clinical Biochemistry ; 36(SUPPL 1):S25-S26, 2021.
Article in English | EMBASE | ID: covidwho-1767678

ABSTRACT

In healthcare today, medical laboratories are key partners in ensuring and maintaining patient safety, Iand it is seen that laboratory results influence approx. 70% of medical decisions. Quality standards of the laboratory plays a major role in ensuring the correctness of these results, providing better patient care as a whole and promoting excellence. While the absence of the same may lead to unreliable results, causing a delay in treatment, misdiagnosis and an increase in cost due to a need for retesting. COVID-19 Pandemic has affected everyone globally & correct lab diagnosis is very important. Therefore, ICMR has made it mandatory to allow only accredited labs to perform RT-PCR test. Good quality is never brought about by accident;it is almost always the cumulative result of sincere intentions, dedicated effort, intelligent direction and skilful execution. As a choice, good qualitymay not necessarily be the easiest or the cheapest;however it is definitely the wisest for both patient health and welfare as well as laboratory credibility. International standard ISO15189, based upon ISO17025 and ISO9001 standards, provides the basic requirements for establishing competence and serves as the bible for quality in medical laboratories. And while this serves as an excellent guiding principle, no matter how good the quality mechanisms are on paper, truly good quality cannot be achieved if theory is not translated into practice day-in and day-out. The entire process of managing a sample must be considered including the beginning i.e sample collection to end i.e reporting and saving results.

16.
18th IEEE India Council International Conference, INDICON 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1752411

ABSTRACT

This article attempts to discover the novel association of vaccines (administered for other diseases) and vitamin A supplement coverage across different countries and the spread of COVID-19.This relation may be affected by several unknown factors as the disease spreads over regions with diverse economic, cultural and climatic conditions. In this situation, relevant associations between features may exist for a subset of countries rather than the entire set of countries.We use a machine learning method named RelDenClu to identify the effects of vaccines or vitamin supplements on the spread of COVID-19. RelDenClu is a non-linear relation based biclustering technique. From the experiment, it was found that countries providing the Tetanus-Toxoid vaccine have lower COVID-19 infection rates. The performance of the proposed technique is also compared with decision tree, LASSO and CBSC and it is noticed that all these methods discover the same association (i.e., countries with a higher rate of administering Tetanus-Toxoid vaccine show lower COVID-19 infection). However, the proposed method can discover the said association in less computation time. Additionally, the proposed method is general enough to be applied to other datasets for finding associations between different local factors affecting the proliferation of any disease across different regions. © 2021 IEEE.

17.
Education Sciences ; 11(12):13, 2021.
Article in English | Web of Science | ID: covidwho-1613679

ABSTRACT

Increasing interest in the digitization of education raises the question of the specifics of the use of digital devices in preschool education and the perception of these new practices by educators. The primary purpose of this study was to examine educators' beliefs about distance education for preschool children in Russia and India, given their professional education and cultural background. These two countries were chosen to explore how the education system has dealt with emergency remote teaching in countries with social and economic diversity. The study involved 909 preschool educators (623 from Russia and 286 from India). An exploratory factor analysis of educators' responses to the Educators' Beliefs about Distance Education for Preschoolers Questionnaire identified three factors. The first factor reflects the degree of positive or negative beliefs about the promotion potential of distance education for preschool children's development. The second represents educators' beliefs about the effectiveness of distance education depending on different teacher, child, and environmental conditions. The third is manifested in the belief among educators that distance education is ineffective in preschool education. The findings suggest that the years of professional education in early childhood pedagogy impacts educators' beliefs about distance education for preschool children. Regardless of the number of years of education training, educators in India were more likely to believe in the high promotion potential of distance education in early childhood.

18.
Blood ; 138:2626, 2021.
Article in English | EMBASE | ID: covidwho-1582154

ABSTRACT

Background: Dysfunction of T cells, NK cells and other immune subsets is common in patients (pts) with CLL. Venetoclax (VEN), a BCL-2 inhibitor and obinutuzumab (OBIN), a CD20 monoclonal antibody (mAb) are approved for pts with CLL (Fischer, NEJM 2019). Atezolizumab, a PD-L1 checkpoint inhibitor (CPI), is approved for melanoma, lung cancer and other solid tumors. Preclinical studies showed synergy of VEN and CD20 mAb with CPI (Kohlhapp, Cancer Discovery 2021;Westin, Lancet Oncology 2014). Clinical studies showed activity of PD1 inhibition in pts with Richter's transformation, but not CLL (Ding, Blood 2017;Jain, ASH 2018). To our knowledge, no prior study has evaluated PD-L1 inhibition in pts with CLL, nor combined CPI, VEN and OBIN. We hypothesized that combined VEN, OBIN and atezolizumab will be synergistic. Methods: This is an investigator-initiated Phase II trial of combined VEN, OBIN and atezolizumab in pts with previously untreated CLL meeting 2008 IWCLL treatment criteria (NCT02846623). Eligibility criteria included age ≥18 years, adequate organ function (total bilirubin ≤1.5 x ULN, ALT and AST ≤2.5 x ULN, creatinine ≤1.5 x ULN). OBIN was given at a flat dose of 100mg IV Cycle (C)1 Day (D)1, 900 mg C1D2, 1000mg on C1D8, 1000mg on C1D15 and then 1000mg on C2-9 D1. Atezolizumab was given at a flat dose of 1680 mg IV (split over 2 days) on C1D3-4 and then C2-9D1-2. VEN was initiated at the start of C3 with the weekly dose-escalation (20mg daily to a target dose of 400mg daily) and continued daily until end of C14 (total 12 cycles of VEN). All pts stopped therapy at the end of C14. Response assessments were done with CT imaging and bone marrow aspirate/biopsy with MRD assessment (multi-color flow cytometry;sensitivity 10 -4) at the end of C2 (prior to VEN initiation), end of C6, end of C9, and end of C14. Results: From July 2019 to December 2020, a total of 26 pts were enrolled. The median age was 60 years (range, 21-74). The baseline characteristics are shown in Table 1. A total of 19/26 (73%) had unmutated IGHV gene. Though the study did not restrict pts with del(17p) or mutated TP53, no pt in the current cohort had del(17p)/ mutated TP53. A total of 14 (54%) pts had a baseline lymph node >5cm. The median follow-up is 13.3 months. One pt came off study in C1 (details below). A total of 25 pts initiated VEN. The TLS risk categories at the start of C1 were high (n=9, 36%), medium (n=12, 48%), and low (n=4, 16%). After 2 cycles of OBIN and atezolizumab (prior to VEN initiation), the majority of pts had downgrading of TLS risk category [high (n=2, 8%), medium (n=3, 12%), and low (n=20, 80%)]. After C6 (about 3 cycles of VEN 400mg daily), bone marrow undetectable (U)-MRD rate was 19/25 (76%);4/25 (16%) had low+ MRD and 2/25 (8%) had high+ MRD. After C9 (about 6 cycles of VEN 400mg daily), among the 21 pts (4 pts have not reached this time-point), the bone marrow U-MRD rate was 18/21 (86%);2/21 (10%) had low+ MRD and 1/21 (5%) had high+ MRD. A total of 14 pts completed C14 (9 pts have not reached this time-point;2 pts came off study prior to completing C14, details below);13/14 (93%) achieved bone marrow U-MRD and 1/14 (7%) has low+ MRD. No patient had disease progression or MRD relapse so far. One pt died (details below). Three pts came off study (one developed retroperitoneal hematoma after receiving enoxaparin for DVT in C1;one developed CPI-induced colitis and removed from the study in C10;one died from COVID-19 pneumonia in C14 while in bone marrow U-MRD remission). Grade 3-4 neutropenia occurred in 14/26 (54%) pts. Grade 3 thrombocytopenia occurred in 5/26 (19%) pts;no pt had G4 thrombocytopenia. A total of 4 pts developed CPI-induced toxicities (colitis, G3, n=1;mucositis, G3, n=1;nephritis, G2, n=1;myositis, G2, n=1). A total of 10/25 (40%) pts had dose reduction of VEN, the majority due to neutropenia. Atezolizumab was discontinued early in 3 pts due to CPI-induced toxicities. Laboratory correlative studies including scRNAseq and CyTOF are ongoing. Conclusions: Treatment with combined VE , OBIN and atezolizumab leads to high rate of early U-MRD remission with 76% bone marrow U-MRD remission at the end of C6 (about 3 cycles of VEN 400mg daily). Four pts had CPI-induced toxicities. The enrollment in this trial continues and updated data and correlative studies will be presented at the ASH meeting. [Formula presented] Disclosures: Jain: Pfizer: Research Funding;Bristol Myers Squibb: Honoraria, Research Funding;Precision Biosciences: Honoraria, Research Funding;Aprea Therapeutics: Research Funding;AstraZeneca: Honoraria, Research Funding;Servier: Honoraria, Research Funding;Incyte: Research Funding;Pharmacyclics: Research Funding;Genentech: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;TG Therapeutics: Honoraria;Janssen: Honoraria;Beigene: Honoraria;Fate Therapeutics: Research Funding;Adaptive Biotechnologies: Honoraria, Research Funding;Cellectis: Honoraria, Research Funding;ADC Therapeutics: Honoraria, Research Funding. Ferrajoli: Janssen: Other: Advisory Board;AstraZeneca: Other: Advisory Board, Research Funding;BeiGene: Other: Advisory Board, Research Funding. Yilmaz: Daiichi-Sankyo: Research Funding;Pfizer: Research Funding. Thompson: AbbVie: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Gilead: Other: Institution: Advisory/Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Pharmacyclics: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Adaptive Biotechnologies: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding, Expert Testimony;Genentech: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Amgen: Other: Institution: Honoraria, Research Grant/Funding. Konopleva: Novartis: Other: research funding pending, Patents & Royalties: intellectual property rights;Reata Pharmaceuticals: Current holder of stock options in a privately-held company, Patents & Royalties: intellectual property rights;Eli Lilly: Patents & Royalties: intellectual property rights, Research Funding;KisoJi: Research Funding;Stemline Therapeutics: Research Funding;Sanofi: Other: grant support, Research Funding;Rafael Pharmaceuticals: Other: grant support, Research Funding;AstraZeneca: Other: grant support, Research Funding;Cellectis: Other: grant support;F. Hoffmann-La Roche: Consultancy, Honoraria, Other: grant support;Calithera: Other: grant support, Research Funding;Ascentage: Other: grant support, Research Funding;Ablynx: Other: grant support, Research Funding;Genentech: Consultancy, Honoraria, Other: grant support, Research Funding;Forty Seven: Other: grant support, Research Funding;AbbVie: Consultancy, Honoraria, Other: Grant Support, Research Funding;Agios: Other: grant support, Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties;Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding;Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees;Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria. Takahashi: Symbio Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene/BMS: Consultancy;Novartis: Consultancy;GSK: Consultancy. Burger: TG Therapeutics: Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau;Beigene: Research Funding, Speakers Bureau;Novartis: Other: Travel/Accommodations/Expenses, Speakers Bureau;Pharmacyclics LLC: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau;Gilead: Consultancy, Other: Travel/Accommodations/Expenses, Rese rch Funding, Speakers Bureau;AstraZeneca: Consultancy;Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Khoury: Stemline Therapeutics: Research Funding;Kiromic: Research Funding;Angle: Research Funding. Kantarjian: Jazz: Research Funding;NOVA Research: Honoraria;Novartis: Honoraria, Research Funding;KAHR Medical Ltd: Honoraria;Precision Biosciences: Honoraria;Amgen: Honoraria, Research Funding;Astra Zeneca: Honoraria;AbbVie: Honoraria, Research Funding;Ipsen Pharmaceuticals: Honoraria;Pfizer: Honoraria, Research Funding;Astellas Health: Honoraria;Aptitude Health: Honoraria;Taiho Pharmaceutical Canada: Honoraria;Immunogen: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Ascentage: Research Funding. Wierda: Karyopharm: Research Funding;Miragen: Research Funding;Acerta Pharma Inc.: Research Funding;Cyclacel: Research Funding;Oncternal Therapeutics, Inc.: Research Funding;Pharmacyclics LLC, an AbbVie Company: Research Funding;Sunesis: Research Funding;Juno Therapeutics: Research Funding;Gilead Sciences: Research Funding;AstraZeneca: Research Funding;Genentech: Research Funding;Loxo Oncology, Inc.: Research Funding;Janssen: Research Funding;Xencor: Research Funding;GSK/Novartis: Research Funding;KITE Pharma: Research Funding;Genzyme Corporation: Consultancy;AbbVie: Research Funding. OffLabel Disclosure: Atezolizumab is not approved for CLL

19.
Blood ; 138:3720, 2021.
Article in English | EMBASE | ID: covidwho-1582144

ABSTRACT

Background: Ibrutinib (IBR) and venetoclax (VEN) combination is a highly effective therapy for patients (pts) with CLL (Jain, NEJM 2019;Wierda, ASH 2020;Kater, EHA 2021). We previously reported results of the first-line cohort of a phase II trial of combined IBR and VEN for high-risk pts with CLL (Jain, NEJM 2019;Jain, JAMA Oncology 2021). Here we report updated data for these pts with focus on MRD. Methods: Pts with previously untreated CLL meeting IWCLL treatment criteria were enrolled. All pts had at least one high-risk feature: del(17p), mutated TP53, del(11q), unmutated IGHV, or age ≥65 years (yrs). Pts received IBR 420 mg daily for 3 cycles followed by addition of VEN (weekly dose-escalation to 400mg daily). Combined therapy was given for 24 cycles (28 days/cycle). Pts with bone marrow (BM) undetectable MRD (U-MRD) (flow cytometry;sensitivity 10 -4) at 24 cycles of combined therapy discontinued both VEN and IBR;MRD+ pts continued IBR. A trial amendment allowed an additional 12 cycles of combined VEN and ibrutinib for pts who remained BM MRD+ after Cycle 24. Response assessments were performed using BM and CT imaging studies (2008 IWCLL criteria). U-MRD was defined as <0.01%;low MRD+ 0.01% to <1%;high MRD+ ≥1%. Progression-free survival (PFS) was assessed as the time from the start of study drug to CLL progression, Richter transformation, or death from any cause. Blood MRD was monitored every 6 months in pts off treatment or on ibrutinib monotherapy beyond 24 cycles of combined treatment. Results: A total of 80 pts were enrolled. Baseline characteristics are shown in Table 1. The median follow-up was 44.1 months. Five pts came off study during 1 st 3 cycles of IBR monotherapy;75 pts initiated VEN. We previously reported that after 12 cycles of the combination, 45/80 (56%) achieved BM U-MRD remission;24/80 (30%) were BM MRD-positive (low MRD+, n=19;high MRD+, n=5). After 24 cycles of the combination, 53/80 (66%) achieved BM U-MRD remission;14/80 (17%) were BM MRD+ (low MRD+, n=13;high MRD+, n=1). Overall, 60/80 (75%) achieved BM U-MRD as the best response. Updated PFS is provided in Figure 1. Of the 53 pts who were BM U-MRD at the end of cycle 24 of the combination, 52 pts had a subsequent blood MRD assessment done in follow-up (1 missed due to COVID-19);51/53 discontinued all therapy, 2 pts continued IBR per treatment physician discretion. With a median time of 18.4 months post Cycle 24, 8 pts had recurrence of blood MRD (defined as MRD ≥ 0.01% in 2 consecutive visits) in follow-up with 1 pt with CLL progression. The sole pt with CLL progression had mutated IGHV with del(11q) and NOTCH1 mutation. The pt had delayed achievement of BM U-MRD with the pt achieving U-MRD for the first time at the end of Cycle 24 of combined therapy. She was noted to have disease progression 22 months off therapy;BTK or PLCG2 mutation were not detected and the patient is currently in clinical remission on acalabrutinib. The time to MRD conversion for these 53 pts is shown in Figure 2. There were 14 pts who were BM MRD+ at the end of cycle 24 of the combination (low MRD+, n=13;high MRD+, n=1). The only pt with high-MRD+ at end of cycle 24 was noted to have Richter transformation at that time. The remaining 13 pts (all low MRD+ in BM, range 0.01-0.56%) continued IBR monotherapy. With a recent trial amendment, MRD+ pts after Cycle 24 could get 12 additional cycles of venetoclax;9/13 pts have resumed VEN. 6/9 pts have achieved U-MRD remission. 2 pts had Richter transformation and 3 pts have died (Jain, JAMA Oncology 2021). Conclusions: We report long term follow-up of combined IBR and VEN in first-line CLL. Remissions were durable with some pts having recurrence of blood MRD in follow-up, which may be an early indicator of relapse. In a small subset of the pts with BM MRD+ disease at 24 cycles of combined therapy, additional VEN appears to lead to U-MRD remission in majority of the pts. Whether this will lead to improved long-term PFS remains to be determined. [Formula presented] Disclosures: Jain: TG Therapeutics: Honoraria;Beigene: Honoraria;Janssen: Honoraria;Fate Therapeutics: Research Funding;Aprea Therapeutics: Research Funding;Precision Biosciences: Honoraria, Research Funding;Incyte: Research Funding;Adaptive Biotechnologies: Honoraria, Research Funding;Cellectis: Honoraria, Research Funding;ADC Therapeutics: Honoraria, Research Funding;Servier: Honoraria, Research Funding;Pfizer: Research Funding;Bristol Myers Squibb: Honoraria, Research Funding;AstraZeneca: Honoraria, Research Funding;Genentech: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;Pharmacyclics: Research Funding. Thompson: AbbVie: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Amgen: Other: Institution: Honoraria, Research Grant/Funding;Genentech: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Adaptive Biotechnologies: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding, Expert Testimony;Pharmacyclics: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding;Janssen: Consultancy, Honoraria;Gilead: Other: Institution: Advisory/Consultancy, Honoraria. Ferrajoli: BeiGene: Other: Advisory Board, Research Funding;Janssen: Other: Advisory Board;AstraZeneca: Other: Advisory Board, Research Funding. Burger: Novartis: Other: Travel/Accommodations/Expenses, Speakers Bureau;TG Therapeutics: Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau;Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau;Beigene: Research Funding, Speakers Bureau;Pharmacyclics LLC: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau;Gilead: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau;AstraZeneca: Consultancy. Borthakur: GSK: Consultancy;ArgenX: Membership on an entity's Board of Directors or advisory committees;University of Texas MD Anderson Cancer Center: Current Employment;Protagonist: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astex: Research Funding;Ryvu: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees. Takahashi: Symbio Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy;Celgene/BMS: Consultancy;GSK: Consultancy. Sasaki: Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding. Kadia: Cellonkos: Other;Aglos: Consultancy;Dalichi Sankyo: Consultancy;AbbVie: Consultancy, Other: Grant/research support;BMS: Other: Grant/research support;Amgen: Other: Grant/research support;Cure: Speakers Bureau;Jazz: Consultancy;Genentech: Consultancy, Other: Grant/research support;Liberum: Consultancy;Novartis: Consultancy;Pfizer: Consultancy, Other;Pulmotech: Other;Sanofi-Aventis: Consultancy;AstraZeneca: Other;Astellas: Other;Genfleet: Other;Ascentage: Other. Konopleva: Sanofi: Other: grant support, Research Funding;Cellectis: Other: grant support;Calithera: Other: grant support, Research Funding;KisoJi: Research Funding;Agios: Other: grant support, Research Funding;Ascentage: Other: grant support, Research Funding;AbbVie: Consultancy, Honoraria, Other: Grant Support, Research Funding;Ablynx: Other: grant support, Research Funding;Stemline Therapeutics: Research Funding;Eli Lilly: Patents & Royalties: intellectual property rights, Research Funding;AstraZeneca: Other: grant support, Research Funding;Rafael Pharmaceuticals: Other: grant support, Research Funding;Genentech: Consultancy, Honoraria, Other: grant support, Research Funding;F. Hoffmann-La Roche: Consultancy, Honoraria, Other: grant support;Forty Seven: Other: grant support, Research Funding;Novartis: Other: research funding pending, Patents & Royalties: intellectual property rights;Reata Pharmaceuticals: Current holder of stock options in a privately-held company, Patents & Royalties: intellectual property rights. Alvarado: BerGenBio: Research Funding;Jazz Pharmaceuticals: Research Funding;Astex Pharmaceuticals: Research Funding;Sun Pharma: Consultancy, Research Funding;MEI Pharma: Research Funding;FibroGen: Research Funding;Daiichi-Sankyo: Research Funding;CytomX Therapeutics: Consultancy. Yilmaz: Pfizer: Research Funding;Daiichi-Sankyo: Research Funding. DiNardo: Notable Labs: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria;Takeda: Honoraria;Celgene, a Bristol Myers Squibb company: Honoraria, Research Funding;Forma: Honoraria, Research Funding;AbbVie: Consultancy, Research Funding;GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Honoraria, Research Funding;ImmuneOnc: Honoraria, Research Funding;Agios/Servier: Consultancy, Honoraria, Research Funding;Foghorn: Honoraria, Research Funding. Bose: Kartos Therapeutics: Honoraria, Research Funding;Sierra Oncology: Honoraria;Novartis: Honoraria;Constellation Pharmaceuticals: Research Funding;NS Pharma: Research Funding;Celgene Corporation: Honoraria, Research Funding;Blueprint Medicines: Honoraria, Research Funding;Pfizer: Research Funding;Promedior: Research Funding;Astellas: Research Funding;Incyte Corporation: Honoraria, Research Funding;BMS: Honoraria, Research Funding;CTI BioPharma: Honoraria, Research Funding. Pemmaraju: Blueprint Medicines: Consultancy;LFB Biotechnologies: Consultancy;Novartis Pharmaceuticals: Consultancy, Other: Research Support, Research Funding;ASCO Leukemia Advisory Panel: Membership on an entity's Board of Directors or advisory committees;Dan's House of Hope: Membership on an entity's Board of Directors or advisorycommittees;Roche Diagnostics: Consultancy;MustangBio: Consultancy, Other;Affymetrix: Consultancy, Research Funding;Samus: Other, Research Funding;ImmunoGen, Inc: Consultancy;ASH Communications Committee: Membership on an entity's Board of Directors or advisory committees;Aptitude Health: Consultancy;Plexxicon: Other, Research Funding;Springer Science + Business Media: Other;Protagonist Therapeutics, Inc.: Consultancy;HemOnc Times/Oncology Times: Membership on an entity's Board of Directors or advisory committees;Clearview Healthcare Partners: Consultancy;Abbvie Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding;CareDx, Inc.: Consultancy;Sager Strong Foundation: Other;Daiichi Sankyo, Inc.: Other, Research Funding;Incyte: Consultancy;Stemline Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding;Bristol-Myers Squibb Co.: Consultancy;DAVA Oncology: Consultancy;Pacylex Pharmaceuticals: Consultancy;Celgene Corporation: Consultancy;Cellectis S.A. ADR: Other, Research Funding. Jabbour: Amgen, AbbVie, Spectrum, BMS, Takeda, Pfizer, Adaptive, Genentech: Research Funding. Wang: Stemline Therapeutics: Honoraria. Kantarjian: Taiho Pharmaceutical Canada: Honoraria;Precision Biosciences: Honoraria;Immunogen: Research Funding;Daiichi-Sankyo: Research Funding;Jazz: Research Funding;BMS: Research Funding;AbbVie: Honoraria, Research Funding;Pfizer: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;NOVA Research: Honoraria;KAHR Medical Ltd: Honoraria;Ipsen Pharmaceuticals: Honoraria;Astra Zeneca: Honoraria;Astellas Health: Honoraria;Aptitude Health: Honoraria;Amgen: Honoraria, Research Funding;Ascentage: Research Funding. Wierda: Juno Therapeutics: Research Funding;AstraZeneca: Research Funding;Xencor: Research Funding;Janssen: Research Funding;Loxo Oncology, Inc.: Research Funding;Cyclacel: Research Funding;Oncternal Therapeutics, Inc.: Research Funding;Miragen: Research Funding;KITE Pharma: Research Funding;Sunesis: Research Funding;Gilead Sciences: Research Funding;Acerta Pharma Inc.: Rese rch Funding;Pharmacyclics LLC, an AbbVie Company: Research Funding;Karyopharm: Research Funding;Genentech: Research Funding;GSK/Novartis: Research Funding;Genzyme Corporation: Consultancy;AbbVie: Research Funding. OffLabel Disclosure: The combination of ibrutinib and venetoclax is not FDA approved

20.
Indian Journal of Pharmaceutical Sciences ; 83(6):1081-1093, 2021.
Article in English | Web of Science | ID: covidwho-1579180

ABSTRACT

The Coronavirus Disease 2019 pandemic has wreaked havoc on global health infrastructure and personnel, resulting in enormous misery, deaths and economic stagnation. Severe Acute Respiratory Syndrome-Coronavirus-2 respiratory infections are frequently worsened by secondary bacterial infections and co-infections due to prolonged hospitalizations;resulting in irreversible lung damage, respiratory failure, cardiac arrest and death. The high mortality rate of Coronavirus Disease 2019 patients is primarily due to multi drug resistant microbial (viral/bacterial) infections, unrestrained inflammatory response and delayed antibody production. The superfluous use of broad spectrum antimicrobial drugs as the last resort has further aggravated the Coronavirus Disease 2019 crisis by contributing to the global antimicrobial resistance. To overcome these hurdles for effective treatment of Coronavirus Disease 2019 and associated bacterial infections, phage therapy seems to be promising due to a lack of effective antiviral drugs and antimicrobial-resistant superadded bacterial infections. Prior studies suggest that when phages, their cocktails and endolysins are administered alone or in synergism with antibiotics through nebulization or through intravenous and intraperitoneal injections have exhibited greater antibacterial potential to combat even Multidrug-Resistant pulmonary bacterial infections. Bacteriophages and phagicin have also shown potent antiviral activity by triggering the production of antiviral cytokines. Many studies have also indicated phage mediated antiviral immunity by lowering Nuclear Factor Kappa B activation and reactive oxygen species production. Phage display technique can serve as a promising approach for Coronavirus Disease 2019 vaccine development through production of Severe Acute Respiratory Syndrome-Coronavirus-2 specific antibodies. This review illustrates the potential of phage therapy as a double edged sword to combat both Coronavirus Disease 2019 as well as associated bacterial infections.

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