Pediatric Primary Care Clinicians' Perspectives on Telemedicine Use, 2020 Versus 2021.

Objective: We examined the change in pediatric primary care clinician attitudes and perceptions about telemedicine after one year of telemedicine use. Methods: We administered a survey to pediatric primary care clinicians across 50 primary care practices in Pennsylvania in 2020 and 2021. Surveys were linked using a combination of deterministic and probabilistic matching. We used McNemar's test to compare change in responses from 2020 to 2021. Results: Among pediatric primary care clinicians surveyed in 2020 and 2021 (n = 101), clinicians agreed that telemedicine could always or usually deliver high-quality care for mental health (80% in 2020 and 78% in 2021), care coordination (77% in 2020 and 70% in 2021), acute care (33% in 2020 and 34% in 2021), or preventive care (25% in 2020 and 18% in 2021) and this did not significantly change. Clinician perceptions of usability, while high, declined over time with fewer endorsing ease of use (93% in 2020 and 80% in 2021) and reliability (14% in 2020 and 0% in 2021) over time. Despite this, 62% of clinicians agreed that they were satisfied with their use of telemedicine at both time points. Respondents anticipated positive impact on equity and timeliness of care from telemedicine use but did not anticipate positive impact across child health, health care delivery, or clinician experience. Perceptions across these domains did not change over time. Conclusions: With one year of telemedicine experience, primary care clinicians maintained beliefs that telemedicine could deliver high-quality care for specific clinical needs but had worsening perceptions of usability over time.

Nested case-control study designs for left-truncated survival data.

The determination of risk factors for disease incidence has been the subject of much epidemiologic research. With this goal a common study design entails the follow-up of an initially disease-free cohort, keeping track of the dates of disease incidence (onset) and ascertaining covariate (putative risk factor) information on the full cohort. However, the collection of certain covariate information on all study subjects may be prohibitively expensive and, therefore, the nested case-control study has commonly been used. The high cost of full covariate information on all subjects also arises when determining risk factors for "failure," death say, "following" disease onset, in particular, in a prevalent cohort study with follow-up; in such a study a cohort of subjects with existing disease is followed. We here adapt nested case-control designs to the setting of a prevalent cohort study with follow-up, a topic previously not addressed in the literature. We provide the partial likelihood under risk set sampling and state the asymptotic properties of the estimated covariate effects and baseline cumulative hazard. We address the following design questions in the context of prevalent cohort studies with follow-up: How many subjects should be included in the sampled risk sets for efficient estimation? In what way is the proportion of censored subjects associated with the benefit of a nested case-control design? What proportion of overall variance is attributable to risk set sampling? This work is motivated by the anticipated analysis of data on survival with Parkinson's Disease, being collected as part of the ongoing Canadian Longitudinal Study on Aging.

La détermination des facteurs de risque pour l'incidence d'une maladie est le sujet de nombreuses études épidémiologiques. À cet effet, un plan d'expérience commun consiste à suivre une cohorte initialement en santé en prenant note de la date à laquelle la maladie se manifeste (début) et en évaluant les covariables (facteurs de risque présumés) pour la cohorte en entier. Lorsque la collecte de certaines covariables pour tous les individus s'avère trop onéreuse, une étude cas-témoins peut eˆtre considérée. Un problème similaire de couˆts élevés pour la collecte d'information sur tous les sujets peut également se présenter lorsque les facteurs de risque pour un « échec ¼, disons le décès, doivent eˆtre déterminés après le début de la maladie. Une telle situation peut survenir dans une étude sur une cohorte prévalente avec suivi, mais la question n'a pas encore été traitée dans la littérature. Les auteurs développent la vraisemblance partielle pour un échantillonnage dans l'ensemble à risque et décrivent les propriétés asymptotiques des estimés de l'effet des covariables et de la fonction cumulative du risque de base. Ils répondent à certaines questions émergeant d'un plan d'expérience pour une cohorte prévalente avec suivi, notamment le nombre de sujets à inclure dans l'ensemble de risque pour obtenir une estimation efficace, les façons dont la proportion de sujets censurés est liée aux bénéfices d'un plan cas-témoin imbriqué, et la proportion de variance globale attribuable à l'échantillonnage dans l'ensemble à risque. Le développement de ces méthodes est motivé par l'analyse imminente de données de survie de patients atteints de la maladie de Parkinson dont la collecte est en cours dans le cadre de l'é tude longitudinale canadienne sur le vieillissement.

The survival function NPMLE for combined right-censored and length-biased right-censored failure time data: properties and applications.

Many cohort studies in survival analysis have imbedded in them subcohorts consisting of incident cases and prevalent cases. Instead of analysing the data from the incident and prevalent cohorts alone, there are surely advantages to combining the data from these two subcohorts. In this paper, we discuss a survival function nonparametric maximum likelihood estimator (NPMLE) using both length-biased right-censored prevalent cohort data and right-censored incident cohort data. We establish the asymptotic properties of the survival function NPMLE and utilize the NPMLE to estimate the distribution for time spent in a Montreal area hospital.

Quantification of long-term nonlinear stress relaxation of bovine trabecular bone.

The reliability of computational models in orthopedic biomechanics depends often on the accuracy of the bone material properties. It is widely recognized that the mechanical response of trabecular bone is time-dependent, yet it is often ignored for the sake of simplicity. Previous investigations into the viscoelastic properties of trabecular bone have not explored the relationship between nonlinear stress relaxation and bone mineral density. The inclusion of this behavior could enhance the accuracy of simulations of orthopedic interventions, such as of primary fixation of implants. Although methods to quantify the viscoelastic behavior are known, the time period during which the viscoelastic properties should be investigated to obtain reliable predictions is currently unclear. Therefore, this study aimed to: 1) Investigate the duration of stress relaxation in bovine trabecular bone; 2) construct a material model that describes the nonlinear viscoelastic behavior of uniaxial stress relaxation experiments on trabecular bone; and 3) implement bone density into this model. Uniaxial compressive stress relaxation experiments were performed with cylindrical bovine femoral trabecular bone samples (n = 16) with constant strain held for 24 h. Additionally, multiple stress relaxation experiments with four ascending strain levels with a holding time of 30 min, based on the results of the 24-h experiment, were executed on 18 bovine bone cores. The bone specimens used in this study had a mean diameter of 12.80 mm and a mean height of 28.70 mm. A Schapery and a Superposition model were used to capture the nonlinear stress relaxation behavior in terms of applied strain level and bone mineral density. While most stress relaxation happened in the first 10 min (up to 53 %) after initial compression, the stress relaxation continued even after 24 h. Up to 69 % of stress relaxation was observed at 24 h. Extrapolating the results of 30 min of experimental data to 24 h provided a good fit for accuracy with much improved experimental efficiency. The Schapery and Superposition model were both capable of fitting the repeated stress relaxation in a sample-by-sample approach. However, since bone mineral density did not influence the time-dependent behavior, only the Superposition model could be used for a group-based model fit. Although the sample-by-sample approach was more accurate for an individual specimen, the group based approach is considered a useful model for general application.

Simulated microgravity improves maturation of cardiomyocytes derived from human induced pluripotent stem cells.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous potential for basic research and translational application. However, these cells structurally and functionally resemble fetal cardiomyocytes, which is a major limitation of these cells. Microgravity can significantly alter cell behavior and function. Here we investigated the effect of simulated microgravity on hiPSC-CM maturation. Following culture under simulated microgravity in a random positioning machine for 7 days, 3D hiPSC-CMs had increased mitochondrial content as detected by a mitochondrial protein and mitochondrial DNA to nuclear DNA ratio. The cells also had increased mitochondrial membrane potential. Consistently, simulated microgravity increased mitochondrial respiration in 3D hiPSC-CMs, as indicated by higher levels of maximal respiration and ATP content, suggesting improved metabolic maturation in simulated microgravity cultures compared with cultures under normal gravity. Cells from simulated microgravity cultures also had improved Ca2+ transient parameters, a functional characteristic of more mature cardiomyocytes. In addition, these cells had improved structural properties associated with more mature cardiomyocytes, including increased sarcomere length, z-disc length, nuclear diameter, and nuclear eccentricity. These findings indicate that microgravity enhances the maturation of hiPSC-CMs at the structural, metabolic, and functional levels.

Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.