Real-world comparative effectiveness of mRNA-1273 and BNT162b2 vaccines among immunocompromised adults identified in administrative claims data in the United States.

INTRODUCTION: Head-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences. METHODS: This observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated. RESULTS: Overall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (5-6%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively. CONCLUSIONS: Among immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only. STUDY REGISTRATION: NCT05366322.

Rabbits use both spectral and temporal cues to discriminate the fundamental frequency of harmonic complexes with missing fundamentals.

The pitch of harmonic complex tones (HCTs) common in speech, music, and animal vocalizations plays a key role in the perceptual organization of sound. Unraveling the neural mechanisms of pitch perception requires animal models, but little is known about complex pitch perception by animals, and some species appear to use different pitch mechanisms than humans. Here, we tested rabbits' ability to discriminate the fundamental frequency (F0) of HCTs with missing fundamentals, using a behavioral paradigm inspired by foraging behavior in which rabbits learned to harness a spatial gradient in F0 to find the location of a virtual target within a room for a food reward. Rabbits were initially trained to discriminate HCTs with F0s in the range 400-800 Hz and with harmonics covering a wide frequency range (800-16,000 Hz) and then tested with stimuli differing in spectral composition to test the role of harmonic resolvability (experiment 1) or in F0 range (experiment 2) or in both F0 and spectral content (experiment 3). Together, these experiments show that rabbits can discriminate HCTs over a wide F0 range (200-1,600 Hz) encompassing the range of conspecific vocalizations and can use either the spectral pattern of harmonics resolved by the cochlea for higher F0s or temporal envelope cues resulting from interaction between unresolved harmonics for lower F0s. The qualitative similarity of these results to human performance supports the use of rabbits as an animal model for studies of pitch mechanisms, providing species differences in cochlear frequency selectivity and F0 range of vocalizations are taken into account.NEW & NOTEWORTHY Understanding the neural mechanisms of pitch perception requires experiments in animal models, but little is known about pitch perception by animals. Here we show that rabbits, a popular animal in auditory neuroscience, can discriminate complex sounds differing in pitch using either spectral cues or temporal cues. The results suggest that the role of spectral cues in pitch perception by animals may have been underestimated by predominantly testing low frequencies in the range of human voice.

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.