Effectiveness of elbasvir/grazoprevir plus ribavirin for hepatitis C virus genotype 1a infection and baseline NS5A resistance.

INTRODUCTION AND OBJECTIVES: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. MATERIALS AND METHODS: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. RESULTS: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. CONCLUSIONS: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

The first days of diagnostic ultrasound.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

Classification of accurate and misarticulated /ɑr/ for ultrasound biofeedback using tongue part displacement trajectories.

Ultrasound biofeedback therapy (UBT), which incorporates real-time imaging of tongue articulation, has demonstrated generally positive speech remediation outcomes for individuals with residual speech sound disorder (RSSD). However, UBT requires high attentional demands and may therefore benefit from a simplified display of articulation targets that are easily interpretable and can be compared to real-time articulation. Identifying such targets requires automatic quantification and analysis of movement features relevant to accurate speech production. Our image-analysis program TonguePART automatically quantifies tongue movement as tongue part displacement trajectories from midsagittal ultrasound videos of the tongue, with real-time capability. The present study uses such displacement trajectories to compare accurate and misarticulated American-English rhotic /ɑr/ productions from 40 children, with degree of accuracy determined by auditory perceptual ratings. To identify relevant features of accurate articulation, support vector machine (SVM) classifiers were trained and evaluated on several candidate data representations. Classification accuracy was up to 85%, indicating that quantification of tongue part displacement trajectories captured tongue articulation characteristics that distinguish accurate from misarticulated production of /ɑr/. Regression models for perceptual ratings were also compared. The simplest data representation that retained high predictive ability, demonstrated by high classification accuracy and strong correlation between observed and predicted ratings, was displacements at the midpoint of /r/ relative to /ɑ/ for the tongue dorsum and blade. This indicates that movements of the dorsum and blade are especially relevant to accurate production of /r/, suggesting that a predictive parameter and biofeedback target based on this data representation may be usable for simplified UBT.

Three-dimensional echo decorrelation monitoring of radiofrequency ablation in ex vivo bovine liver.

Three-dimensional (3D) echo decorrelation imaging was investigated for monitoring radiofrequency ablation (RFA) in ex vivo bovine liver. RFA experiments (N = 14) were imaged by 3D ultrasound using a matrix array, with in-phase and quadrature complex echo volumes acquired about every 11 s. Tissue specimens were then frozen at -80 °C, sectioned, and semi-automatically segmented. Receiver operating characteristic (ROC) curves were constructed for assessing ablation prediction performance of 3D echo decorrelation with three potential normalization approaches, as well as 3D integrated backscatter (IBS). ROC analysis indicated that 3D echo decorrelation imaging is potentially a good predictor of local RFA, with the best prediction performance observed for globally normalized decorrelation. Tissue temperatures, recorded by four thermocouples integrated into the RFA probe, showed good correspondence with spatially averaged decorrelation and statistically significant but weak correlation with measured echo decorrelation at the same spatial locations. In tests predicting ablation zones using a weighted K-means clustering approach, echo decorrelation performed better than IBS, with smaller root mean square volume errors and higher Dice coefficients relative to measured ablation zones. These results suggest that 3D echo decorrelation and IBS imaging are capable of real-time monitoring of thermal ablation, with potential application to clinical treatment of liver tumors.

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

Reconstruction of shear wave speed in tissue-mimicking phantoms from aliased pulse-echo imaging of high-frequency wavefields.

Quantitative elasticity estimation in medical and industrial applications may benefit from advancements in reconstruction of shear wave speed with enhanced resolution. Here, shear wave speed is reconstructed from pulse-echo ultrasound imaging of elastic waves induced by high-frequency (>400 Hz), time-harmonic mechanical excitation. Particle displacement in shear wavefields is mapped from measured interframe phase differences with compensation for timing of multiple scan lines, then processed by spatial Fourier analysis to estimate the predominant wave speed and analyzed by algebraic wavefield inversion to reconstruct wave speed maps. Reconstructions of shear wave speed from simulated wavefields illustrate the accuracy and spatial resolution available with both methods, as functions of signal-to-noise ratio and sizes of windows used for Fourier analysis or wavefield smoothing. The methods are applied to shear wavefields with frequencies up to six times the Nyquist rate, thus extending the frequency range measurable by a given imaging system. Wave speed measurements in tissue-mimicking phantoms are compared with supersonic shear imaging and mechanical tensile testing, demonstrating feasibility of the wavefield measurement and wave speed reconstruction methods employed.

Numerical analysis of three-dimensional echo decorrelation imaging.

A numerical model for three-dimensional echo decorrelation imaging, a pulse-echo ultrasound method applicable to thermal ablation monitoring, is presented. Beam patterns for steered transmit and receive array apertures are combined with a three-dimensional numerical tissue model to yield beamformed scan lines in a pyramidal configuration, volumetric B-mode images, and spatial maps of normalized decorrelation between sequential image volumes. Simulated three-dimensional echo decorrelation images of random media are analyzed as estimators of local tissue reflectivity decoherence, mimicking thermal ablation effects. The estimation error is analyzed as a function of correlation window size, scan line density, and ensemble averaging of decorrelation maps.

The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update.

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences.

Characterization of cavitation-radiated acoustic power using diffraction correction.

A method is developed for compensating absolute pressure measurements made by a calibrated passive cavitation detector (PCD) to estimate the average acoustic power radiated from a region of interest (ROI) defined to encompass all cavitating bubbles. A diffraction correction factor for conversion of PCD-measured pressures to cavitation-radiated acoustic power per unit area or volume is derived as a simple analytic expression, accounting for position- and frequency-dependent PCD sensitivity. This approach can be applied to measurements made by any PCD without precise knowledge of the number, spatial, or temporal distribution of cavitating bubbles. The diffraction correction factor is validated in simulation for a wide range of ROI dimensions and frequencies. The correction factor is also applied to emission measurements obtained during in vitro ultrasound-enhanced sonophoresis experiments, allowing comparison of stable cavitation levels between therapeutic configurations with different source center frequencies. Results incorporating sonication at both 0.41 and 2.0 MHz indicate that increases in skin permeability correlate strongly with the acoustic power of subharmonic emissions radiated per unit skin area.

Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence.

BACKGROUND: Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. METHODS: Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. RESULTS: A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. CONCLUSIONS: Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI. CLINICAL TRIALS REGISTRATION: NCT00350298.

Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach.

BACKGROUND: Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs. METHODS: A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI. RESULTS: Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization. CONCLUSIONS: A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552).

Echo response and clinical outcome in CRT patients.

BACKGROUND: Change in left ventricular end-systolic volume (∆LVESV) is the most frequently used surrogate marker in measuring response to cardiac resynchronisation therapy (CRT). We investigated whether ∆LVESV is the best measure to discriminate between a favourable and unfavourable outcome and whether this is equally applicable to non-ischaemic and ischaemic cardiomyopathy. METHODS: 205 CRT patients (age 65 ± 12 years, 69 % men) were included. At baseline and 6 months echocardiographic studies, exercise testing and laboratory measurements were performed. CRT response was assessed by: ∆LVESV, ∆LV ejection fraction (LVEF), ∆ interventricular mechanical delay, ∆VO2 peak, ∆VE/VCO2, ∆BNP, ∆creatinine, ∆NYHA, and ∆QRS. These were correlated to the occurrence of major adverse cardiac events (MACE) between 6 and 24 months. RESULTS: MACE occurred in 19 % of the patients (non-ischaemic: 13 %, ischaemic: 24 %). ∆LVESV remained the only surrogate marker for CRT response for the total population and patients with non-ischaemic cardiomyopathy, showing areas under the curve (AUC) of 0.69 and 0.850, respectively. For ischaemic cardiomyopathy, ∆BNP was the best surrogate marker showing an AUC of 0.66. CONCLUSION: ∆LVESV is an excellent surrogate marker measuring CRT response concerning long-term outcome for non-ischaemic cardiomyopathy. ∆LVESV is not suitable for ischaemic cardiomyopathy in which measuring CRT response remains difficult.

Clinical characterisation and risk stratification of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy ≥50 years of age.

PURPOSE: With the increased use of genetic testing for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), this disease is being increasingly recognised among elderly patients. However, elderly ARVD/C patients were underrepresented in prior cohorts. We aimed to describe the phenotypical characteristics and outcomes among ARVD/C patients surviving ≥50 years. METHODS: We assessed detailed phenotypical data of 29 patients who (1) presented at ≥50 years of age; and (2) fulfilled 2010 Task Force Criteria (TFC) for ARVD/C by last follow-up. Primary outcome was the occurrence of a major ventricular arrhythmia (sudden cardiac death, resuscitated sudden cardiac arrest or sustained ventricular tachycardia). RESULTS: The majority (55 %) of elderly ARVD/C subjects were male, with a mean age of 59.0 ± 5.8 years at presentation. Study participants fulfilled a median of six (IQR 5-8) TFC criteria by last follow-up, of which arrhythmia criteria were most frequent (97 %), followed by structural criteria (83 %), depolarisation criteria (72 %) and repolarisation criteria (69 %). By last follow-up, 15 (52 %) patients had experienced major ventricular arrhythmias. Most patients (n = 12) presented with this arrhythmia, while three experienced the event during 5.4 ± 3.2 years of follow-up. Compared with patients without an arrhythmic event, patients with major arrhythmias were more likely to be proband (p < 0.001) and male (p = 0.042). Likewise, survival free from sustained ventricular arrhythmia was lower among probands and males. CONCLUSION: Phenotypic characteristics of elderly ARVD/C patients are characterised by depolarisation abnormalities and structural cardiac changes. Ventricular arrhythmias in this elderly cohort are associated with male gender and proband status.

Efavirenz modulation of sleep spindles and sleep spectral profile.

Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment. Forty healthy male subjects were randomized to receive placebo or efavirenz 600 mg nightly for 7 days after completion of a 3-day placebo run-in period. Treatment with efavirenz was associated with reduced time to sleep onset in the Maintenance of Wakefulness Test, an increase in non-rapid eye movement sleep, a large exposure-related decrease in sigma band spectral density and sleep spindle density during non-rapid eye movement sleep, and reduced performance on an attention switching task. Because efavirenz has been shown to have serotonin 2A receptor partial-agonist properties, we reasoned that antagonism of serotonin 2A receptor signalling in the thalamic reticular nucleus, which generates sleep spindles and promotes attention, may be responsible. Consistent with predictions, treatment of healthy volunteers with a single dose of a serotonin 2A receptor antagonist was found to significantly suppress sigma band spectral density in an exposure-related manner and modulated the overall spectral profile in a manner highly similar to that observed with efavirenz, consistent with the notion that efavirenz exhibits serotonin 2A receptor partial-agonist pharmacology in humans.

Assessing bias in administrative database studies of RotaTeq vaccine completion due to exclusion of subjects with incomplete follow-up.

BACKGROUND: RotaTeq® pentavalent human rotavirus vaccine (RV5) is effective against rotavirus illness and rotavirus-related hospitalizations and death. Effectiveness depends on adherence to the dosing schedule, which includes 3 doses at ages 2, 4 and 6 months. Two studies have used automated claims databases to estimate the proportion of vaccinated infants who complete the dosing schedule, but excluded from analysis vaccinated infants who were not enrolled in the database for a sufficient period to observe all 3 doses. Restricting study populations based on duration of follow-up can introduce bias if a large number of subjects are excluded due to insufficient follow-up, and if their outcomes differ from subjects who are included. To address the possibility that exclusions may have been extensive and led to biased estimates of completion rates, we conducted a claims database analysis in the HealthCore Integrated Research Database(SM) to evaluate the proportion of rotavirus vaccinated infants who completed the 3 dose series of RV5. We evaluated potential error introduced by restricting analyses to infants with complete follow-up by estimating completion rates among infants with complete follow-up, and using Kaplan-Meier analyses to estimate completion rates including infants with incomplete follow-up. RESULTS: The inclusion criterion requiring continuous enrollment for the first year of life resulted in only 108,533 (40%) of 233,143 vaccinated infants from 2006-2012 being included in the analysis. After relaxing inclusion criteria, we were able to include 86% of vaccinated infants. The estimated completion rate among infants with continuous enrollment from birth through the first year of life was 78.1% (95% confidence limits [CLs] 77.8%, 78.3%), and among the expanded population the estimated completion rate was 77.4% (95% CLs 77.2%, 77.6%). CONCLUSIONS: These results indicate that most infants were not followed in the database through the first year of life, but the impact of excluding infants with incomplete follow-up was negligible when assessing RV5 completion rates for this commercially insured population. Nonetheless, to increase the size of study populations and reduce the potential for bias, it is preferable to include subjects with incomplete follow-up in automated database analyses, and adopt more robust approaches to defining and analyzing study populations that account for missing data.

Measurements of electrical and mechanical dyssynchrony are both essential to improve prediction of CRT response.

INTRODUCTION: Predicting reverse remodeling after cardiac resynchronization therapy (CRT) remains challenging and different etiologies of heart failure might hamper identification of predictors. OBJECTIVE: Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response. METHODS: 227 patients (51% ischemic) received CRT. Response was defined as ≥15% left ventricular end systolic volume decrease after six months. Prediction models were developed comprising clinical parameters and electrical dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony (Model B). Models were compared by area under the receiver-operating curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations. RESULTS: Model B performed significantly better than Model A supported by AUC, NRI and IDI. Furthermore, model B significantly better predicted response for NICM than ICM. CONCLUSION: Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response. Nevertheless, response prediction for ICM remains challenging.

Accuracy of a bistatic scattering substitution technique for calibration of focused receivers.

A recent method for calibrating single-element, focused passive cavitation detectors (PCD) compares bistatic scattering measurements by the PCD and a reference hydrophone. Here, effects of scatterer properties and PCD size on frequency-dependent receive calibration accuracy are investigated. Simulated scattering from silica and polystyrene spheres was compared for small hydrophone and spherically focused PCD receivers to assess the achievable calibration accuracy as a function of frequency, scatterer size, and PCD size. Good agreement between measurements was found when the scatterer diameter was sufficiently smaller than the focal beamwidth of the PCD; this relationship was dependent on the scatterer material. For conditions that result in significant disagreement between measurements, the numerical methods described here can be used to correct experimental calibrations.

Methods to calibrate the absolute receive sensitivity of single-element, focused transducers.

Absolute pressure measurements of acoustic emissions by single-element, focused passive cavitation detectors would be facilitated by improved wideband receive calibration techniques. Here, calibration methods were developed to characterize the absolute, frequency-dependent receive sensitivity of a spherically focused, single-element transducer using pulse-echo and pitch-catch techniques. Validation of these calibration methods on a focused receiver were made by generating a pulse from a small diameter source at the focus of the transducer and comparing the absolute pressure measured by a calibrated hydrophone to that of the focused transducer using the receive sensitivities determined here.

Analysis of tissue changes, measurement system effects, and motion artifacts in echo decorrelation imaging.

Echo decorrelation imaging, a method for mapping ablation-induced ultrasound echo changes, is analyzed. Local echo decorrelation is shown to approximate the decoherence spectrum of tissue reflectivity. Effects of the ultrasound measurement system, echo signal windowing, electronic noise, and tissue motion on echo decorrelation images are determined theoretically, leading to a method for reduction of motion and noise artifacts. Theoretical analysis is validated by simulations and experiments. Simulated decoherence of the scattering medium was recovered with root-mean-square error less than 10% with accuracy dependent on the correlation window size. Motion-induced decorrelation measured in an ex vivo pubovisceral muscle model showed similar trends to theoretical motion-induced decorrelation for a 2.1 MHz curvilinear array with decorrelation approaching unity for 3-4 mm elevational displacement or 1-1.6 mm range displacement. For in vivo imaging of porcine liver by a 7 MHz linear array, theoretical decorrelation computed using image-based motion estimates correlated significantly with measured decorrelation (r = 0.931, N = 10). Echo decorrelation artifacts incurred during in vivo radiofrequency ablation in the same porcine liver were effectively compensated based on the theoretical echo decorrelation model and measured pre-treatment decorrelation. These results demonstrate the potential of echo decorrelation imaging for quantification of heat-induced changes to the scattering tissue medium during thermal ablation.

Benefit-risk assessment for the Novavax COVID-19 vaccine (NVX-CoV2373).

A benefit-risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit-risk balance for NVX-CoV2373.