Assessment of the Perceived Role and Function of a Community Advisory Board in a NIH Center of Excellence: Lessons Learned

Background: The Community Advisory Board (CAB) was a vital component of the Center for Equal Health. The center addressed health disparities through community-based research and educational outreach initiatives. Objectives: To evaluate the perceived relationship of the CAB and Center, explore members’ perceptions of the CAB’s role, and elicit feedback on how to enhance the relationship between the Center and the CAB. Methods: Ten in-depth, semi-structured interviews were conducted. All interviews were transcribed verbatim and analyzed with a focus on predetermined codes. Results: Main themes focused on perception of CAB roles and need for utilization of board members; overall center challenges; and board member knowledge and communication within the center. Conclusions: Lessons learned mainly focused on clarification of CAB roles as necessary for more effective and efficient communication. Based on feedback, communication channels between the board and center were developed, orientation packets clarifying center roles were provided, and annual retreats were completed. Additional lessons learned for conducting community-academic partnerships are provided

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed

Using Independent Components Analysis to Better Understand the Electrophysiology of Error Processing

Color poster with text, images, charts, and graphs.The Pe (error positivity) is a positive deflection in the electroencephalogram (EEG) peaking around 250ms following a response when a person makes a task error, especially if they are immediately aware of having made that mistake. In our two prior studies of error processing, participants completed a 2-choice response task (the Flanker task) to invoke error-related EEG activity, including the Pe. The Pe normally appears as a positive deflection at posterior electrode sites, and we observed this, but we also saw what appears to be a mirror-image negativity at frontal sites at the same time; we tentatively call this an “inverted Pe”). It is unclear, however, whether these two deflections reflect the same underlying neural activity or separate neurocognitive events. We are currently using independent components analysis (ICA), a computational method for separating complex, mixed signals into simpler subcomponents, to address this question. We predict that the canonical Pe and “inverted Pe” will be appear together in ICA components, suggesting a common neural generator. If they appear in separate ICA components, that will imply distinct neural generators. In either case, resolving this question will advance our knowledge of the electrophysiology of error processing.University of Wisconsin--Eau Claire Office of Research and Sponsored Program

Smartphone Usage : Associations with Cognition, Motivation, and Sleep Patterns

Color poster with text, charts, and graphs.College students’ smartphone use presents concerns with academic dishonesty, distraction, sleep disturbances, and social withdrawal. We conducted a survey to focus on the relationship between phone use/attitudes and attention. We assessed how much students use their phone, how reliant they are on their phone, and their concerns about not having access to their phone. Regarding attention, we asked them about their difficulties with attention and focusing on the present moment, i.e. mindfulness. We also assessed their motivation to seek mental stimulation, i.e. sensation seeking. We predicted positive relationships between smartphone use/problems and both sensation seeking and ADHD-related difficulties. We also predicted negative associations between smartphone use/problems and both mindfulness and sleep amount/quality.Ronald E. McNair Postbaccalaureate Program; University of Wisconsin--Eau Claire Office of Research and Sponsored Program

The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs

<p>Brett MT, Ahopelto SK, Brown HK, Brynestad BE, Butcher TW, Coba EE, Curtis CA, Dara JT, Doeden KB, Evans KR, Fan L, Finley JD, Garguilo NJ, Gebreeyesus SM, Goodman MK, Gray KW, Grinnell C, Gross KL, Hite BRE, Jones AJ, Kenyon PT, Klock AM, Koshy RE, Lawler AM, Lu M, Martinkosky L, Miller-Schulze JR, Nguyen QTN, Runde ER, Stultz JM, Wang S, White FP, Wilson CH, Wong AS, Wu SY, Wurden PG, Young TR, Arhonditsis GB. 2016. The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs. Lake Reserv Manage. 32:246–258.</p> <p>Lake Spokane, a reservoir in eastern Washington State, was previously hypereutrophic due to phosphorus discharges from the City of Spokane wastewater treatment plant (WWTP). This reservoir subsequently recovered to a meso-oligotrophic state after implementation of advanced phosphorus removal. The present study tested whether the mechanistic Lake Spokane water quality (WQ) model realistically represents the sensitivity of this reservoir's hypolimnetic oxygen concentrations to phosphorus inputs. We compared the observed relationship between the mean summer input total phosphorus concentration (TP_IN) and the minimum volume weighted hypolimnetic dissolved oxygen concentration (DO_MIN) to model values for conditions ranging from hypereutrophic to oligotrophic. Prior to advanced phosphorus removal, TP_IN and DO_MIN averaged 86 ± 37 (SD) µg/L and 1.4 ± 1.3 mg/L, respectively. Currently (2010–2014), these values average 14 ± 3 µg/L and 6.5 ± 0.8 mg/L, respectively. By contrast, the model's DO_MIN response for similar TP_IN concentrations was much less pronounced, with hypereutrophic and contemporary DO_MIN averaging 3.8 ± 0.4 and 4.7 ± 0.04 mg/L, respectively. The model also has a structural DO deficit (saturated DO − DO_MIN) of 5.3 mg/L that was evident when all TP inputs to the reservoir were set to zero. Similarly, when all WWTP effluent sources were set to TP_EFF = 0 µg/L, the reservoir epilimnetic TP concentrations were ≈8 µg/L higher than the Spokane River inputs. The water quality model indicates that even if effluent phosphorus concentrations are reduced to zero, the dissolved oxygen goals for Lake Spokane cannot be met.</p

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BackgroundWe aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.MethodsIn this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FindingsBetween Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.InterpretationNeither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FundingUS National Institutes of Health and Operation Warp Speed