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1.
American Journal of Obstetrics and Gynecology ; 228(1):S514-S515, 2023.
Article in English | Web of Science | ID: covidwho-2308796
2.
Annals of Neurology ; 92:S178-S179, 2022.
Article in English | Web of Science | ID: covidwho-2083460
3.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927923

ABSTRACT

Rationale: LAU-7b is developed as a broadly effective oral COVID-19 therapeutic targeting membrane lipids to exert dual antiviral and inflammation-controlling activity. SARS-CoV-2 reprograms host cellular lipid metabolism to favor entry and replication, a mechanism shared by all lipid-enveloped viruses. LAU-7b decreases host cell membrane lipids fluidity, inhibits de-novo cell lipogenesis, and modulates phospholipid signaling promoting resolution of inflammation. Due to its host-directed mutation-agnostic mechanism, LAU-7b utility could span across future variants, as demonstrated in-vitro against multiple SARS-CoV-2 strains and MERS-CoV. RESOLUTION, a large Phase 2/3 study evaluating LAU-7b in hospitalized COVID-19 patients, is ongoing in the US and Canada, and preliminary Phase 2 results are presented. Methods: RESOLUTION is a placebocontrolled study of oral LAU-7b, once-a-day for 14 days on top of standard of care, in hospitalized COVID-19 patients at risk of developing pulmonary complications. The Phase 2 portion of the study randomized 148 patients with moderate-to-severe COVID-19 and 84 patients in critical condition, but not on invasive ventilation. Key endpoints included proportion of patients alive and free of respiratory failure at Day 29, rates of progression to mechanical ventilation and all-causes death by Day 60, time to recovery and length of hospitalization. Results: Both study arms were highly comparable in terms of mean age, number of comorbidities and concomitant medications. LAU-7b demonstrated a 100% reduction in the risk of progressing to mechanical ventilation or death by Day 60 in moderate-to-severe COVID-19 patients. None of the 76 patients on LAU-7b required mechanical ventilation and none died, while 5 out of 72 patients on placebo progressed to mechanical ventilation (6.9% difference, p=0.025), and 4 patients died (5.6% difference, p=0.053). LAU-7b group also showed an increase of 6.9% (p=0.055) in the proportion of patients alive and free of respiratory failure at Day 29, versus placebo. Patients on LAU-7b tended to recover more rapidly and leave hospital faster. LAU-7b was well-tolerated, with safety comparable to placebo. Critically ill patients treated with LAU-7b did not show improvement over placebo, suggesting that COVID-19 patients in respiratory failure at baseline are too severely affected to benefit. Conclusion: LAU-7b showed positive results in the trial's Phase 2 portion on both survival and avoidance of mechanical ventilation in moderate-to-severe COVID-19. The confirmatory Phase 3 portion was triggered and received approval from the FDA and Health Canada, focusing on moderate-to-severe COVID-19 and using the “Proportion of patients requiring mechanical ventilation and/or death by Day 60” as primary efficacy endpoint.

4.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925144

ABSTRACT

Objective: To understand that COVID-19 can cause epochs of sneezing. Background: While Coronavirus 19 has been reported to inhibit sternutation (Mattu, 2021), Coronavirus-induced epochs of sternutation has not henceforth been described. Case Study: 38-year-old right-handed nasute woman, seven months prior to presentation, experienced an acute onset of loss of smell and taste, with a positive nasopharyngeal swab for SARS COV-2. Since then there has been no improvement in her chemosensory complaints and has developed periods of sternutation, whereby she sneezes 18 times in a row every morning. Results: Abnormalities of physical examination: Neurological Examination: Motor Examination: Drift testing: Left pronator drift with left abductor digiti minimi sign. Cerebellar examination: dysmetria in both upper extremities, left more than right. High frequency low amplitude tremor on extension of both upper extremities. Reflexes: 3+ biceps and brachioradialis and absent ankle jerks bilaterally. Bilateral Hoffman reflexes. Chemosensory testing: Alcohol Sniff Test: 0 (anosmia). Olfactory Retronasal Smell Test Index: 0 (anosmia). Gustatory testing: Propylthioruacil Disk Taste Test: 0 (ageusia). Conclusions: The neuroanatomy of the sneeze reflex suggests that it occurs through the afferent pathway from the trigeminal nerve to the rostral dorsolateral medullary sneezing center where the efferent discharge of the autonomic nervous system occurs through the nervous intermedius to the greater superficial petrosal nerve and to the sphenopalatine ganglion. In any of these afferent or efferent pathways or in the central nervous system itself, COVID may have acted to cause intermittent irritation and thus epochs of sneezing (Songu, 2009;Herman, 1983). The common experience of sneezing occurring in threes may be centrally mediated and this occurred with eighteen sneezes may just be a prolonged variant of such a chronobiological reflex. In those who present with COVID-19, query as to epochs of sternutation may be revealing.

5.
Radiotherapy and Oncology ; 163:S50-S51, 2021.
Article in English | EMBASE | ID: covidwho-1747457

ABSTRACT

Purpose: To report the degree to which post-graduate trainees in radiation oncology perceive their education has been impacted by COVID-19. Materials and Methods: A cross-sectional online survey was administered in June 2020 to trainee members of Canadian Association of Radiation Oncology (CARO). The 82-item survey was adapted from a similar survey administered during SARS and included the Stanford Acute Stress Reaction and Ways of Coping Questionnaires. The survey was developed using best practices including expert review and cognitive pre-testing. Frequency statistics are reported. Results: Thirty-four trainees (10 fellows, 24 residents) responded. Nearly half of participants indicated that the overall impact of COVID-19 on training was negative/very negative (n=15;46%) or neutral (n=15;46%) with a small number indicating a positive/very positive (n=3;9%). Majority of trainees agreed/ strongly agreed with the following statements: “I had difficulty concentrating on tasks because of concerns about COVID-19” (n=17;52%), “I had fears about contracting COVID-19” (n=17;52%), “I had fears of family/loved ones contracting COVID-19” (n= 29;88%), “I felt socially isolated from friends and family because of COVID-19” (n=23;70%), “I felt safe from COVID-19 in the hospital during my clinical duties“ (n=15;46%), and “I was concerned that my personal safety was at risk if/when I was redeployed from my planned clinical duties” (n=20;61%). The changes that had a negative/very negative impact on learning included “the impact of limited patient contact” (n=19;58%), “the impact of virtual patient contact” (n=11;33%), and “limitations to travel and networking” (n=31;91%). Most reported reduced teaching from staff (n=22;66%). Two-thirds of trainees (n=22, 67%) reported severe (>50%) reduction in ambulatory clinical activities, 16 (49%) reported a moderate (<50%) reduction in new patient consultations, while virtual follow-ups (n=25: 76%) and in-patient clinical care activities (n=12;36%) increased. Nearly half of respondents reported no impact on contouring (n=16;49%), on-treatment management (n=17;52%) and tumour boards (n=14;42%) with the majority of other respondents reporting a decrease in these activities. Electives were cancelled in province (n=10/20;50%), out-of-province (n=16/20;80%) and internationally (n=15/18;83%). Conclusions: Significant changes to radiation oncology training were wrought by the COVID-19 pandemic and roughly half of trainees perceive that these changes had a negative impact on their training. Safety concerns for self and family were significant and strategies to mitigate these concerns should be a priority.

6.
International Journal of Radiation Oncology Biology Physics ; 111(3):E187-E187, 2021.
Article in English | Web of Science | ID: covidwho-1529316
8.
Ann. Neurol. ; 90:S121-S121, 2021.
Article in English | Web of Science | ID: covidwho-1473020
9.
Ann. Neurol. ; 90:S125-S126, 2021.
Article in English | Web of Science | ID: covidwho-1472948
10.
Neurology ; 96(15 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1407879

ABSTRACT

Objective: To understand that loss of sternutation may be a sequelae of COVID-19 infection. Background: While chemosensory dysfunction has been described with COVID-19 (Moein, 2020), its effects on sternutation have not heretofore been reported. Case Study: A 50 year old right-handed woman was nasute until four months prior to presentation;when she developed a temperature of 102.4°F, nasal congestion, myalgia, rigors and a total loss of smell and taste. Two days later, nasopharyngeal swab for SARS-CoV-2 RNA was positive. Over the next two months, her smell and taste had returned to normal. While prior to the infection, she would sneeze once or twice every day;since having COVID-19, she no longer sneezes. Results: Abnormalities in Neurological Examination: Reflexes: 3+ quadriceps femoris bilaterally and pendular. Bilateral Hoffman reflexes: present. Chemosensory Testing: Brief Smell Identification Test: 10 (normosmia). Retronasal Olfactory Testing: Retronasal Smell Index: 7 (normal). Gustatory Testing: Propylthiouracil Disc Taste Test: 9 (normogeusia). Sensonics Waterless Empirical Taste Test: 53 (normogeusia) Other: Fiberoptic Endoscopy: normal. CT Scan of Sinuses: Right maxillary sinusitis. Conclusions: Coronavirus may have impacted cranial nerve I which may function along with cranial nerve V to precipitate the sternutation reflex. The efferent component of the sternutation center of the pons which generates the sneeze reflex may have been impacted by the coronavirus, peradventure through a lesion of the pontomedullary sneeze center, adjacent to the descending trigeminal nucleus and tract (Hersch, 2000). Alternatively, this may represent dysfunction of pontine trigeminal reticular neurons and the pneumotaxic center (Batsel, 1975). Persistent absence of sternutation may have potential health effects for the sufferer in that it may allow irritants, potential toxins, or pathogens to invade the nasal mucosa, and thus enhance the likelihood of disease. Further investigation into those having COVID-19 for elimination of sternutation reflex is warranted.

11.
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine ; 5(2):108-113, 2021.
Article in English | EMBASE | ID: covidwho-1261002
12.
Journal of the American Geriatrics Society ; 69:S239-S239, 2021.
Article in English | Web of Science | ID: covidwho-1194965
13.
American Journal of Obstetrics and Gynecology ; 224(2):S283-S284, 2021.
Article in English | Web of Science | ID: covidwho-1141051
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