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At least 19 records

Risk Ratio and Risk Difference Estimation in Case-cohort Studies

Background: In case-cohort studies with binary outcomes, ordinary logistic regression analyses have been widely used because of their computational simplicity. However, the resultant odds ratio estimates cannot be interpreted as relative risk measures unless the event rate is low. The risk ratio and risk difference are more favorable outcome measures that are directly interpreted as effect measures without the rare disease assumption. Methods: We provide pseudo-Poisson and pseudo-normal linear regression methods for estimating risk ratios and risk differences in analyses of case-cohort studies. These multivariate regression models are fitted by weighting the inverses of sampling probabilities. Also, the precisions of the risk ratio and risk difference estimators can be improved using auxiliary variable information, specifically by adapting the calibrated or estimated weights, which are readily measured on all samples from the whole cohort. Finally, we provide computational code in R (R Foundation for Statistical Computing, Vienna, Austria) that can easily perform these methods. Results: Through numerical analyses of artificially simulated data and the National Wilms Tumor Study data, accurate risk ratio and risk difference estimates were obtained using the pseudo-Poisson and pseudo-normal linear regression methods. Also, using the auxiliary variable information from the whole cohort, precisions of these estimators were markedly improved. Conclusion: The ordinary logistic regression analyses may provide uninterpretable effect measure estimates, and the risk ratio and risk difference estimation methods are effective alternative approaches for case-cohort studies. These methods are especially recommended under situations in which the event rate is not low.

60 APPLIED LIFE SCIENCES↗

Appendix A: NAS-Wide Encounter Rate Evaluation Using Historical Radar Data and the Airspace Concept Evaluation System (ACES)

Regulations that establish operational and performance requirements for unmanned aircraft systems (UAS) are being developed by a consortium of government, industry and academic institutions. Those requirements will apply to detect-and-avoid (DAA) systems and other equipment necessary to integrate UAS with the National Airspace System (NAS) and are determined according to their contribution to the overall level of safety required to operate in the airspace. Several key gaps must be addressed in order to link equipment requirements to an airspace level of safety. Foremost among these is the calculation of the relative effectiveness of a particular system to mitigate violations of a separation standard with other aircraft, which is known as the systems risk ratio. The risk ratio is calculated as the probability of mid-air collision with a DAA system divided by the probability of mid-air collision without a DAA system. The risk ratio of a DAA system, in combination with the risk ratios of other collision avoidance mitigations, will determine the overall safety of the airspace measured in terms of the number of mid-air collisions per flight hour. Defining the required risk ratio that the DAA system needs to ensure the safety of the airspace requires an evaluation of the current airspace and a simulated evaluation that incorporates UAS aerodynamic performance and the mission characteristics of future UAS operations that are projected to be conducted in areas that interact with current operations. These evaluations will produce the frequency of encounters that currently exist in the airspace and those that could be generated with the introduction of UAS. Together, the frequency of encounters, an evaluation of unmitigated risk of collision, and a desired level of safety of the airspace will yield a required risk ratio of the DAA system. This study will focus on evaluating the encounter rates between aircraft based on historical radar data and encounter rates that could occur based on simulated UAS missions.

Unmanned Aircraft Systems↗

Sense and Avoid Safety Analysis for Remotely Operated Unmanned Aircraft in the National Airspace System. Version 5

This document describes a method to demonstrate that a UAS, operating in the NAS, can avoid collisions with an equivalent level of safety compared to a manned aircraft. The method is based on the calculation of a collision probability for a UAS , the calculation of a collision probability for a base line manned aircraft, and the calculation of a risk ratio given by: Risk Ratio = P(collision_UAS)/P(collision_manned). A UAS will achieve an equivalent level of safety for collision risk if the Risk Ratio is less than or equal to one. Calculation of the probability of collision for UAS and manned aircraft is accomplished through event/fault trees.

Carreno, Victor↗

Piloted Well Clear Performance Evaluation of Detect and Avoid Systems with Suggestive Guidance

Regulations to establish operational and performance requirements for unmanned aircraft systems (UAS) are being developed by a consortium of government, industry and academic institutions (RTCA, 2013). Those requirements will apply to the new detect-and-avoid (DAA) systems and other equipment necessary to integrate UAS with the United States (U.S) National Airspace System (NAS) and will be determined according to their contribution to the overall safety case. That safety case requires demonstration that DAA-equipped UAS collectively operating in the NAS meet an airspace safety threshold (AST). Several key gaps must be closed in order to link equipment requirements to an airspace safety case. Foremost among these is calculation of the systems risk ratio, the degree to which a particular system mitigates violation of an aircraft separation standard (FAA, 2013). The risk ratio of a DAA system, in combination with risk ratios of other collision mitigation mechanisms, will determine the overall safety of the airspace measured in terms of the number of collisions per flight hour. It is not known what the effectiveness is of a pilot-in-the-loop DAA system or even what parameters of the DAA system most improve the pilots ability to maintain separation. The relationship between the DAA system design and the overall effectiveness of the DAA system that includes the pilot, expressed as a risk ratio, must be determined before DAA operational and performance requirements can be finalized. Much research has been devoted to integrating UAS into non-segregated airspace (Dalamagkidis, 2009, Ostwald, 2007, Gillian, 2012, Hesselink, 2011, Santiago, 2015, Rorie 2015 and 2016). Several traffic displays intended for use as part of a DAA system have gone through human-in-the-loop simulation and flight-testing. Most of these evaluations were part of development programs to produce a deployable system, so it is unclear how to generalize particular aspects of those designs to general requirements for future traffic displays (Calhoun, 2014). Other displays have undergone testing to collect data that may generalize to new displays, but have not been evaluated in the context of the development of an overall safety case for UAS equipped with DAA systems in the NAS (Bell, 2012). Other research efforts focus on DAA surveillance performance and separation standards. Together with this work, they are expected to facilitate validation of the airspace safety case (Park, 2014 and Johnson, 2015). The contribution of the present work is to quantify the effectiveness of the pilot-automation system to remain well clear as a function of display features and surveillance sensor error. This quantification will help enable selection of a minimum set of DAA design features that meets the AST, a set that may not be unique for all UAS platforms. A second objective is to collect and analyze pilot performance parameters that will improve the modeling of overall DAA system performance in non-human-in-the-loop simulations. Simulating the DAA-equipped UAS in such batch experiments will allow investigation of a much larger number of encounters than is possible in human simulations. This capability is necessary to demonstrate that a particular set of DAA requirements meets the AST under all foreseeable operational conditions.

detect and avoid↗

Performance assessment for climate intervention (PACI): preliminary application to a stratospheric aerosol injection scenario

As the prospect of exceeding global temperature targets set forth in the Paris Agreement becomes more likely, methods of climate intervention are increasingly being explored. With this increased interest there is a need for an assessment process to understand the range of impacts across different scenarios against a set of performance goals in order to support policy decisions. The methodology and tools developed for Performance Assessment (PA) for nuclear waste repositories shares many similarities with the needs and requirements for a framework for climate intervention. Using PA, we outline and test an evaluation framework for climate intervention, called Performance Assessment for Climate Intervention (PACI) with a focus on Stratospheric Aerosol Injection (SAI). We define a set of key technical components for the example PACI framework which include identifying performance goals, the extent of the system, and identifying which features, events, and processes are relevant and impactful to calculating model output for the system given the performance goals. Having identified a set of performance goals, the performance of the system, including uncertainty, can then be evaluated against these goals. Using the Geoengineering Large Ensemble (GLENS) scenario, we develop a set of performance goals for monthly temperature, precipitation, drought index, soil water, solar flux, and surface runoff. The assessment assumes that targets may be framed in the context of risk-risk via a risk ratio, or the ratio of the risk of exceeding the performance goal for the SAI scenario against the risk of exceeding the performance goal for the emissions scenario. From regional responses, across multiple climate variables, it is then possible to assess which pathway carries lower risk relative to the goals. The assessment is not comprehensive but rather a demonstration of the evaluation of an SAI scenario. Future work is needed to develop a more complete assessment that would provide additional simulations to cover parametric and aleatory uncertainty and enable a deeper understanding of impacts, informed scenario selection, and allow further refinements to the approach.

climate intervention↗

ACES Study of DAA-Mitigated UAS Operations SC-228 Requirements Sub Group

Realization of the expected proliferation of Unmanned Aircraft System (UAS) operations in the National Airspace System (NAS) depends on the development and validation of performance standards for UAS Detect and Avoid (DAA) Systems. The RTCA Special Committee 228 is charged with leading the development of draft Minimum Operational Performance Standards (MOPS) for UAS DAA Systems. NASA, as a participating member of RTCA SC-228 is committed to supporting the development and validation of draft requirements as well as the safety substantiation and end-to-end assessment of DAA system performance. A recent study conducted using NASA's ACES (Airspace Concept Evaluation System) simulation capability begins to address questions surrounding the development of draft MOPS for DAA systems by assessing DAA performance in a NAS-wide context. ACES analyses were conducted to determine the impact of varying elements of UAS pilot performance and uncertainty mitigations on DAA system performance. Simulations were conducted with recorded cooperative and non-cooperative VFR (Visual Flight Rules) traffic to accurately model UAS encounters with other NAS traffic (ATC (Air Traffic Control) being responsible for separation with other IFR (Instrument Flight Rules) aircraft) and with roughly 25, 000 simulated UAS operations The number of Loss of Well Clear (LoWC) events were recorded across the range of independent variables: pilot response time, horizontal LoWC prediction buffer and horizontal LoWC resolution buffer. The number of LoWC events was compared to the unmitigated case (without the benefit of a DAA system) to determine the resultant risk-ratio for each of 8 simulation conditions. The parameter trades presented by the resultant DAA system performance (risk ratio) will be used by SC 228 to inform decisions about future requirements development and validation efforts.

Detect-and-Avoid↗

Hip Abductor Strength Asymmetry: Relationship to Upper Extremity Injury in Professional Baseball Players

Background: Hip strength is an important factor for control of the lumbo-pelvic-hip complex. Deficits in hip strength may affect throwing performance and contribute to upper extremity injuries. Hypothesis: Deficits in hip abduction isometric strength would be greater in those who sustained an upper extremity injury and hip strength would predict injury incidence. Study Design: Prospective cohort study. Level of Evidence: Level 3. Methods: Minor League baseball players (n = 188, age = 21.5 ± 2.2 years; n = 98 pitchers; n = 90 position players) volunteered. Hip abduction isometric strength was assessed bilaterally with a handheld dynamometer in side-lying position, expressed as torque using leg length (N·m). Hip abduction strength asymmetry was represented by [(trail leg/lead leg) × 100]. Overuse or nontraumatic throwing arm injuries were prospectively tracked. Poisson regression models were used to estimate relative risk ratios associated with hip asymmetry; confounders, including history of prior overuse injury in the past year, were included. Results: Hip abduction asymmetry ranged from 0.05% to 57.5%. During the first 2 months of the season, 18 players (n = 12 pitchers) sustained an upper extremity injury. In pitchers, for every 5% increase in hip abduction asymmetry, there was a 1.24 increased risk of sustaining a shoulder or elbow injury. No relationship between hip abduction strength and injury was observed for position players. Conclusion: Hip abduction asymmetry in pitchers was related to subsequent upper extremity injuries. The observed risk ratio indicates that hip abduction asymmetry may contribute a significant but small increased risk of injury. Clinical Relevance: Hip abduction muscle deficits may affect pitching mechanics and increase arm stress. Addressing hip asymmetry deficits that exceed 5% may be beneficial in reducing upper extremity injury rates in pitchers.

Sport Sciences↗

State-level suicide mortality insights: a comparative study of VHA veterans and the whole US population

Background: Suicide is a leading cause of death in the US Comparative State-level spatial analysis between Veterans Health Administration (VHA veterans) and the whole US population can reveal differences in conditions for targeted interventions and intricate geographical patterns. Methods: The study population contains 2018 and 2019 suicide deaths of VHA veterans and the whole US population. They were used to calculate state-level rates. States were classified by whether their VHA veteran and whole US population rates were above or below respective mean rates. Local Moran’s I was leveraged to examine spatial autocorrelation. Results: State-level suicide mortality rates and disparities among states were generally higher for VHA veterans (2018: 37.3 ± 7.2; 2019: 46.8 ± 8.3) than for the whole US population (2018: 16.6 ± 4.3; 2019: 16.4 ± 4.4). For both populations, there were statistically significant clusters with high suicide rates. Over one-fourth of states demonstrated inverse relationships, with rates above mean for one group but below for other. VHA veterans are at higher risk with over one-third of states had greater than average veteran suicide risk ratio. Conclusions: VHA veterans are at higher risk than the whole population across all states. Mortality disparities among states and clusters of states with high and low rates suggest targeted interventions and cooperative health strategies may help address these differences.

60 APPLIED LIFE SCIENCES↗

Impact of Airborne Radar Uncertainties on Detect-and-Avoid Systems’ Performance

Impact of sensor uncertainty on Detect-and-Avoid (DAA) systems’ performance is investigated. Key metrics analyzed are the loss of DAA well clear ratio, the near-mid-air-collision risk ratio, the alert ratio, and the number of maneuvers per loss of DAA well clear. Sensitivity of these metrics to the magnitude of sensor uncertainty, pilots’ selection of maneuver, and surveillance range is investigated. Benefits of a dynamic buffer around the DAA well clear separation boundary, computed based on track accuracies, are also analyzed. These metrics are computed from open- and closed-loop simulations of a large number of representative encounters between an unmanned aircraft system and a manned aircraft. Results show that sensor uncertainty degrades safety metrics considerably but has only a minor effect on the number of maneuvers per loss of DAA well clear. The number of maneuvers, nonetheless, can be reduced by a 5◦ buffer away from the edge of the range of conflict-resulting heading in pilots’ selection of maneuver.

UAS↗

The effect of differences in time to detection of circulating microbubbles on the risk of decompression sickness

Circulating microbubbles (CMB) are frequently detected prior to the appearance of symptoms of Decompression Sickness (DCS). It is difficult to analyze the effect of CMB on symptoms due to differences in the time to detection of CMB. This paper uses survival analysis models to evaluate the risk of symptoms in the presence of CMB. Methods: Information on 81 exposures to an altitude of 6,400 m (6.5 psi) for a period of three hours, with simulated extravehicular activities, was examined. The presence or absence of CMB was included as a time dependent covariate of the Cox proportional hazards regression model. Using this technique, the subgroup of exposures with CMB was analyzed further. Mean (S.D.) time in minutes to onset of CMB and symptoms were 125 (63) and 165 (33) respectively, following the three hours exposure. The risk of symptoms (17/81) increased 14 times in the presence of CMB, after controlling for variations in time to detection of CMB. Further, the risk was lower when time to detection of CMB was greater than 60 minutes (risk ratio = 0.96; 95 percent confidence intervals = 0.94 - 0.99 0.99 P less than 0.01) compared to CMB before 60 minutes at altitude. Conclusions: Survival analysis showed that individual risk of DCS changes significantly due to variations in time to detection of CMB. This information is important in evaluating the risk of DCS in the presence of CMB.

Kumar, K. V.↗

Numerical Characterization of Astronaut CaOx Renal Stone Incidence Rates to Quantify In-flight and Post-flight Relative Risk

Changes in urine chemistry potentially alter the risk of renal stone formation in astronauts. Quantifying spaceflight renal stone incidence risk compared to pre-flight levels remains a significant challenge for assessing the appropriate vehicle, mission, and countermeasure design. A computational biochemistry model representing CaOx crystal precipitation, growth, and agglomeration is combined with a probabilistic analysis to predict the in- and post-flight CaOx renal stone incidence risk ratio (IRR) relative to pre-flight values using 1517 astronaut 24-hour urine chemistries. Our simulations predict that in-flight fluid intake alone would need to increase from current prescriptions of 2.0 - 2.5 L/day to approximately 3.2 L/day to approach CaOx IRR of the pre-flight population. Bone protective interventions would reduce CaOx risk to pre-flight levels if Ca excretion alone is reduced to < 150 mg/day or if current levels are diminished to 190mg/day in combination with increasing fluid intake to 2.5 - 2.7 L/day. This analysis provides a quantitative risk assessment that can influence the critical balance between engineering and astronaut health requirements.

renal stones↗

Comparison of venous and pooled capillary hemoglobin levels for the detection of anemia among adolescent girls

Introduction: Blood source is a known preanalytical factor affecting hemoglobin (Hb) concentrations, and there is evidence that capillary and venous blood may yield disparate Hb levels and anemia prevalence. However, data from adolescents are scarce. Objective: To compare Hb and anemia prevalence measured by venous and individual pooled capillary blood among a sample of girls aged 10–19 years from 232 schools in four regions of Ghana in 2022. Methods: Among girls who had venous blood draws, a random subsample was selected for capillary blood. Hb was measured using HemoCue® Hb-301. We used Lin’s concordance correlation coefficient (CCC) to quantify the strength of the bivariate relationship between venous and capillary Hb and a paired t-test for difference in means. We used McNemar’s test for discordance in anemia cases by blood source and weighted Kappa to quantify agreement by anemia severity. A multivariate generalized estimating equation was used to quantify adjusted population anemia prevalence and assess the association between blood source and predicted anemia risk. Results: We found strong concordance between Hb measures (CCC = 0.86). The difference between mean venous Hb (12.8 g/dL, ± 1.1) and capillary Hb (12.9 g/dL, ± 1.2) was not significant (p = 0.26). Crude anemia prevalence by venous and capillary blood was 20.6% and 19.5%, respectively. Adjusted population anemia prevalence was 23.5% for venous blood and 22.5% for capillary ( = 0.45). Blood source was not associated with predicted anemia risk (risk ratio: 0.99, 95% CI: 0.96, 1.02). Discordance in anemia cases by blood source was not significant (McNemar p = 0.46). Weighted Kappa demonstrated moderate agreement by severity (k =0.67). Among those with anemia by either blood source (n = 111), 59% were identified by both sources. Conclusion: In Ghanaian adolescent girls, there was no difference in mean Hb, anemia prevalence, or predicted anemia risk by blood source. However, only 59% of girls with anemia by either blood source were identified as having anemia by both sources. These findings suggest that pooled capillary blood may be useful for estimating Hb and anemia at the population level, but that caution is needed when interpreting individual-level data.

59 BASIC BIOLOGICAL SCIENCES↗

Prediction of Calcium Oxalate Stone Risk with Interventions

Introduction Mitigations intended to reduce bone mineral loss in-flight also influence the level of renal stone risk to astronauts. Extending a recent study completed by our group [1], we investigate the likely influence of combined fluid intake and Ca excretion mitigation strategies. Methods A computational biochemistry model representing CaOx crystal precipitation, growth, and agglomeration [2] is combined with a probabilistic analysis to predict the in-flight CaOx renal stone incidence risk ratio (IRR) relative to pre-flight values using 1517 astronaut 24-hour urine chemistries. The output of this simulation is used to assess the combined impact of controlling fluid intake and Ca excretion on maintaining IRR < 1.2 for > 95% of the population, a threshold determined from initial analysis of the model output compared to referent populations [1]. Results and Conclusions Figure 1 illustrates the simulated in-flight astronaut population (n=40000) with CaOx IRR > 1.2. The red lines indicate the known clinical risk boundary of each factor, and the white box is considered the area of high combined clinical risk. The simulation and identified risk threshold conform well to the expected clinical risk boundaries. The results, assuming insensible water losses equal or exceed 0.7 L/day, imply mitigations achieve risks similar to pre-flight levels when either Ca < 150 mg/day or fluid volume intake > 3.2 L/day individually, or combined Ca < 200 and fluid volume intake > 2.5 L/day. We continue to investigate similar compounded effects and look to apprise engineering trades by informing relative risk changes during mission design. References [1] D. A. Goodenow-Messman, S. A. Gokoglu, M. Kassemi, and J. Myers, Jerry G., “Characterization of Astronaut CaOx Renal Stone Incidence Rates to Quantify In-flight and Post-flight Relative Risk,” npj Microgravity, in review, 2021. [2] M. Kassemi and D. Thompson, “Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations,” Am. J. Physiol. Physiol., vol. 311, no. 3, pp. F520–F530, Sep. 2016, doi: 10.1152/ajprenal.00401.2015.

Debra A Goodenow↗

Survival after aortic valve replacement for severe aortic stenosis with low transvalvular gradients and severe left ventricular dysfunction

OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.

NASA Discipline Cardiopulmonary↗

Association Between Dispatch Complaint and Critical Prehospital Time Intervals in Suspected Stroke 911 Activations in the National Emergency Medical Services Information System, 2012–2016

Emergency Medical Services can help improve stroke outcomes by recognizing stroke symptoms, establishing response priority for 911 calls, and minimizing prehospital delays. This study examines 911 stroke events and evaluates associations between events dispatched as stroke and critical EMS time intervals. Data from the National Emergency Medical Services Information System, 2012 to 2016, were analyzed. Activations from 911 calls with a primary or secondary provider impression of stroke were included for adult patients transported to a hospital destination. Three prehospital time intervals were evaluated: (1) response time (RT) ≤8 min, (2) on-scene time (OST) ≤15 min, and (3) transport time (TT) ≤12 min. Associations between stroke dispatch complaint and prehospital time intervals were assessed using multivariate regression to estimate adjusted risk ratios (ARR) and 95% confidence intervals (CIs). Approximately 37% of stroke dispatch complaints were identified by EMS as a suspected stroke. Compared to stroke events without a stroke dispatch complaint, median OST was shorter for events with a stroke dispatch (16 min vs. 14 min, respectively). In adjusted analyses, events dispatched as stroke were more likely to meet the EMS time benchmark for OST ≤15 min (OST, 1.20 [1.20–1.21]), but not RT or TT (RT, [1.00–1.01]; TT, 0.95 [0.94–0.95]). Furthermore, our results indicate that dispatcher recognition of stroke symptoms reduces the time spent on-scene by EMS personnel. These findings can inform future EMS stroke education and quality improvement efforts to emphasize dispatcher recognition of stroke signs and symptoms, as EMS dispatchers play a crucial role in optimizing the prehospital response.

59 BASIC BIOLOGICAL SCIENCES↗

Temporal Trends of Racial and Socioeconomic Disparities in Population Exposures to Upstream Oil and Gas Development in California

People living near oil and gas development are exposed to multiple environmental stressors that pose health risks. Some studies suggest these risks are higher for racially and socioeconomically marginalized people, which may be partly attributable to disparities in exposures. We examined whether racially and socioeconomically marginalized people in California are disproportionately exposed to oil and gas wells and associated hazards. We longitudinally assessed exposure to wells during three time periods (2005–2009, 2010–2014, and 2015–2019) using sociodemographic data at the census block group‐level. For each block group and time period, we assessed exposure to new, active, retired, and plugged wells, and cumulative production volume. We calculated risk ratios to determine whether marginalized people disproportionately resided near wells (within 1 km). Averaged across the three time periods, we estimated that 1.1 million Californians (3.0%) lived within 1 km of active wells. Nearly 9 million Californians (22.9%) lived within 1 km of plugged wells. The proportion of Black residents near active wells was 42%–49% higher than the proportion of Black residents across California, and the proportion of Hispanic residents near active wells was 4%–13% higher than their statewide proportion. Disparities were greatest in areas with the highest oil and gas production, where the proportion of Black residents was 105%–139% higher than statewide. Socioeconomically marginalized residents also had disproportionately high exposure to wells. Though oil and gas production has declined in California, marginalized communities persistently had disproportionately high exposure to wells, potentially contributing to health disparities.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

Abstract Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94; 700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82–1.05 for 7000 mg [ p (overall) = 0.88] and 0.81–1.21 for 700 mg [ p (overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [ p = 0.97], 7000 mg; 24 vs 20.5 days [ p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2. Trial Registration: ClinicalTrials.gov Identifier: NCT04518410.

60 APPLIED LIFE SCIENCES↗