On-time denosumab dosing recovered rapidly during the COVID-19 pandemic, yet remains suboptimal.

Timely administration of denosumab every 6 mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66 yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/-30 d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or ≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: -17.8% (95% CI, -19.6, -16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: -3.2% (95% CI, -5.0, -1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal.

Beyond Acute COVID-19: A Review of Long-term Cardiovascular Outcomes.

Statistics Canada estimated that approximately 1.4 million Canadians suffer from long COVID. Although cardiovascular changes during acute SARS-CoV-2 infection are well documented, long-term cardiovascular sequelae are less understood. In this review, we sought to characterize adult cardiovascular outcomes in the months after acute COVID-19 illness. In our search we identified reports of outcomes including cardiac dysautonomia, myocarditis, ischemic injuries, and ventricular dysfunction. Even in patients without overt cardiac outcomes, subclinical changes have been observed. Cardiovascular sequelae after SARS-CoV-2 infection can stem from exacerbation of preexisting conditions, ongoing inflammation, or as a result of damage that occurred during acute infection. For example, myocardial fibrosis has been reported months after hospital admission for COVID-19 illness, and might be a consequence of myocarditis and myocardial injury during acute disease. In turn, myocardial fibrosis can contribute to further outcomes including dysrhythmias and heart failure. Severity of acute infection might be a risk factor for long-term cardiovascular consequences, however, cardiovascular changes have also been reported in young, healthy individuals who had asymptomatic or mild acute disease. Although evolving evidence suggests that previous SARS-CoV-2 infection might be a risk factor for cardiovascular disease, there is heterogeneity in existing evidence, and some studies are marred by measured and unmeasured confounders. Many investigations have also been limited by relatively short follow-up. Future studies should focus on longer term outcomes (beyond 1 year) and identifying the prevalence of outcomes in different populations on the basis of acute and long COVID disease severity.

Familiar size affects perception differently in virtual reality and the real world.

The promise of virtual reality (VR) as a tool for perceptual and cognitive research rests on the assumption that perception in virtual environments generalizes to the real world. Here, we conducted two experiments to compare size and distance perception between VR and physical reality (Maltz et al. 2021 J. Vis. 21, 1-18). In experiment 1, we used VR to present dice and Rubik's cubes at their typical sizes or reversed sizes at distances that maintained a constant visual angle. After viewing the stimuli binocularly (to provide vergence and disparity information) or monocularly, participants manually estimated perceived size and distance. Unlike physical reality, where participants relied less on familiar size and more on presented size during binocular versus monocular viewing, in VR participants relied heavily on familiar size regardless of the availability of binocular cues. In experiment 2, we demonstrated that the effects in VR generalized to other stimuli and to a higher quality VR headset. These results suggest that the use of binocular cues and familiar size differs substantially between virtual and physical reality. A deeper understanding of perceptual differences is necessary before assuming that research outcomes from VR will generalize to the real world. This article is part of a discussion meeting issue 'New approaches to 3D vision'.

Fracture outcome definitions in observational osteoporosis drug effects studies: a scoping review protocol.

OBJECTIVE: The objective of this review is to describe fracture outcome definitions in observational osteoporosis drug effects studies from Canada and the United States. INTRODUCTION: Health care administrative data are commonly utilized in pharmacoepidemiologic studies. These data are used to define outcomes, such as fractures, and are critical to determining real-world safety and effectiveness of medications. However, there is no current standard for fracture outcome definitions in observational studies. As a result, fractures are inconsistently defined. To inform future research, a synthesis of how fractures are defined in observational studies using health care administrative claims data is needed. Providing clarity on how fractures are defined will provide guidance for future research. INCLUSION CRITERIA: We will include observational studies from the United States and Canada that consider the impact of osteoporosis pharmacotherapies on fracture risk and leverage health care administrative data. METHODS: This review will follow the three-step JBI methodology for scoping reviews. We will search MEDLINE, Embase, and CINAHL for studies published in English from 2000 to the present. Following de-duplication, titles and abstracts will be screened independently by two reviewers. We will then conduct full-text screening for eligible studies. In addition, Canadian and US government pharmacovigilance websites will be searched to identify gray literature. Data extraction will be completed by two reviewers. Results will be presented in figures and in tabular format.

Familiar size affects the perceived size and distance of real objects even with binocular vision.

Although the familiar size of real-world objects affects size and distance perception, evidence is mixed about whether this is the case when oculomotor cues are available. We examined the familiar size effect (FSE) on both size and distance perception for real objects under two viewing conditions with full or restricted oculomotor cues (binocular viewing, which provides vergence and accommodation cues, and monocular viewing through a 1-mm pinhole, which removes those cues). Familiar objects (a playing die versus a Rubik's cube) were manufactured in their typical (1.6-cm die and 5.7-cm Rubik's cube) and reverse (5.7-cm die and 1.6-cm Rubik's cube) sizes and shown at two distances (25 cm versus 91 cm) in isolation. Small near and large far objects subtended equal retinal angles. Participants provided manual estimates of perceived size and distance. For every combination of size and distance, Rubik's cubes were perceived as larger and farther than the dice, even during binocular viewing at near distances (<1 meter), when oculomotor cues are particularly strong. For size perception but not distance perception, the familiar size effect was significantly stronger under monocular pinhole viewing than binocular viewing. These results suggest that (1) familiar size affects the accuracy of perception, not just the speed; (2) the effect occurs even when oculomotor cues are available; and (3) size and distance perception are not perfectly yoked.