Engaging staff to improve COVID-19 vaccination response at long-term care facilities (ENSPIRE): A cluster randomized trial of co-designed, tailored vaccine promotion materials.

BACKGROUND: COVID-19 vaccination rates among long-term care center (LTCC) workers are among the lowest of all frontline health care workers. Current efforts to increase COVID-19 vaccine uptake generally focus on strategies that have proven effective for increasing influenza vaccine uptake among health care workers including educational and communication strategies. Experimental evidence is lacking on the comparative advantage of educational strategies to improve vaccine acceptance and uptake, especially in the context of COVID-19. Despite the lack of evidence, education and communication strategies are recommended to improve COVID-19 vaccination rates and decrease vaccine hesitancy (VH), especially strategies using tailored messaging for disproportionately affected populations. METHODS: We describe a cluster-randomized comparative effectiveness trial with 40 LTCCs and approximately 4000 LTCC workers in 2 geographically, culturally, and ethnically distinct states. We compare the effectiveness of two strategies for increasing COVID-19 booster vaccination rates and willingness to promote COVID-19 booster vaccination: co-design processes for tailoring educational messages vs. an enhanced usual care comparator. Our study focuses on the language and/or cultural groups that are most disproportionately affected by VH and low COVID-19 vaccine uptake in these LTCCs. CONCLUSION: Finding effective methods to increase COVID-19 vaccine uptake and decrease VH among LTCC staff is critical. Beyond COVID-19, better approaches are needed to improve vaccine uptake and decrease VH for a variety of existing vaccines as well as vaccines created to address novel viruses as they emerge.

Expectancy for Adderall influences subjective mood and drug effects regardless of concurrent caffeine ingestion: A randomized controlled trial.

RATIONALE: Nonmedical prescription stimulant use (NPS; use without a prescription or in ways other than prescribed) is common among college students. Despite the potential for negative consequences, students continue engaging in NPS for cognitive enhancement purposes, which may be maintained by expectancy and placebo effects. OBJECTIVES: This study examined if a placebo administered under the guise of Adderall influenced subjective mood/drug effects and cognitive performance. Furthermore, this study examined if concurrent caffeine ingestion incrementally enhanced Adderall-related placebo effects. METHODS: Undergraduate students with features that put them at elevated risk for NPS (N = 121) completed measures of mood and drug effects and cognitive assessments on two separate laboratory visits in this parallel randomized controlled trial. Visit 1 was a baseline control visit, on which no drug was expected or received. On visit 2, subjects were randomized to: (1) expect/receive no drug (control); (2) expect Adderall/receive placebo; or (3) expect Adderall/receive 200 mg caffeine. RESULTS: There were several significant condition × visit interactions for subjective effects, including amphetamine effects, energy and efficiency effects, and feeling high. In most cases, participants who expected Adderall reported greater positive subjective effects on visit 2 compared to controls; however, there were generally not incremental enhancements for those ingesting caffeine compared to placebo. There were no significant effects for any cognitive tests. CONCLUSIONS: Expectation for prescription stimulant effects influenced subjective outcomes in a sample of high-risk college students. These findings may inform expectancy challenge interventions to reduce NPS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03648684.

Growth Effects on Velopharyngeal Anatomy Within the First 2 Years of Life.

PURPOSE: Limited quantitative data exist regarding growth of the velopharynx within the first 2 years of life. The purpose of this study was to (a) quantify changes in velopharyngeal structures due to growth during the first 2 years of life, (b) examine the impact of sex and race within this age range, and (c) provide normative measures for comparison to individuals with cleft palate. METHOD/DESCRIPTION: A retrospective chart review was completed of all patients up to 24 months of age that underwent magnetic resonance imaging of the head for medical necessity within the past 18 months using a three-dimensional fluid-attenuated inversion recovery sequence. Measurements of the velopharynx were obtained from 200 scans consistent with previous literature. Participants were divided into five groups based on corrected age for comparison. Variables of interest included adenoid depth, angle of origin, effective velopharyngeal ratio, effective velar length, levator veli palatini length, origin-origin distance, pharyngeal depth, sagittal angle, velopharyngeal ratio, velar insertion distance, velar length, and velar thickness. RESULTS: Velopharyngeal dimensions were significantly different among corrected age groups after controlling for sex and race. Regarding age, analyses revealed significant differences in all variables of interest except effective velopharyngeal ratio. Regarding sex, significant differences were observed for angle of origin, effective velopharyngeal ratio, effective velar length, levator veli palatini muscle length, and velar insertion distance. Regarding race, a significant difference was only observed for angle of origin. CONCLUSIONS: Results of this study demonstrate growth of velopharyngeal anatomy in normative infants with race and sex effects apparent in children up to 24 months of age. Variable growth trends were observed among different velopharyngeal measures.

Coordinated speech therapy, physiotherapy, and pharmaceutical care telehealth for people with Parkinson disease in rural communities: an exploratory, 8-week cohort study for feasibility, safety, and signal of efficacy.

INTRODUCTION: The potential for coordinated, multidisciplinary telehealth to help connect people with Parkinson disease (PD) in rural areas to PD specialists is crucial in optimizing care. Therefore, this study aimed to test the feasibility, safety, and signal of efficacy of a coordinated telehealth program, consisting of speech therapy, physiotherapy, and pharmaceutical care, for people with PD living in some rural US communities. METHODS: Fifteen individuals with PD living in rural Wyoming and Nevada, USA, participated in this single-cohort, 8-week pilot study. Participants were assessed before and after 8 weeks of coordinated, one-on-one telehealth using the following outcomes: (1) feasibility: session attendance and withdrawal rate; (2) safety: adverse events; and (3) signal of efficacy: Communication Effectiveness Survey, acoustic data (intensity, duration, work (intensity times duration)), Parkinson's Fatigue Scale, 30 second Sit-to-Stand test, Parkinson's Disease Questionnaire - 39, Movement Disorder Society Unified Parkinson's Disease Rating Scale - Part III, and medication adherence. RESULTS: Average attendance was greater than 85% for all participants. There were no serious adverse events and only nine minor events during treatment sessions (0.9% of all treatment sessions had a participant report of an adverse event); all nine cases resolved without medical attention. Although 14 of 16 outcomes had effect sizes trending in the direction of improvement, only two were statistically significant using non-parametric analyses: 30 second Sit-to-Stand (pre-test median=11.0 (interquartile range (IQR)=6.0); post-test median=12.0 (IQR=3.0) and acoustic data work (pre-test median=756.0 dB s (IQR=198.4); post-test median=876.3 dB s (IQR=455.5), p<0.05. CONCLUSION: A coordinated, multidisciplinary telehealth program was safe and feasible for people in rural communities who have PD. This telehealth program also yielded a signal of efficacy for most of the outcomes measured in the study.

Practicing metacognition through the use of repeated posttest predictions.

BACKGROUND: Development of metacognitive skills is one method to increase self-awareness of pharmacy students. This study sought to assess students' posttest prediction (postdiction) of performance on a series of multiple-choice examinations to determine if feedback regarding predicted and actual performance could improve personal predictive abilities over time. IMPACT: While there was a statistically significant change in the students' predictive abilities from examination one to examination three, lower scores in examination two disrupted the trend we had hoped to see. When broken down by overall course score, the highest performing students rarely overestimated their score (5-21% of the time, depending on examination), while the lowest performing students were more varied (22-56% over prediction, depending on examination). RECOMMENDATIONS: This study used a novel assessment method of postdictions without additional data points such as predictions or grade point average (GPA), which could have helped confirm the value of the method. Additionally, we realized assessing the impact of the qualitative feedback students received could elucidate why and recommend this for future studies. DISCUSSION: While students were generally poor predictors of their performance, repeated use of this skill helped them to reduce the number of over predictions made by the end of the course. This change was greatest for the lowest performing students indicating that they may receive more benefit from this exercise than higher performing students. This method of using postdictions adds to the collection of tools that can be used to measure student metacognitive skills.

Shared parameter models for joint analysis of longitudinal and survival data with left truncation due to delayed entry - Applications to cystic fibrosis.

Many longitudinal studies observe time to occurrence of a clinical event such as death, while also collecting serial measurements of one or more biomarkers that are predictive of the event, or are surrogate outcomes of interest. Joint modeling can be used to examine the relationship between the biomarker and the event, and also as a way of adjusting analyses of the biomarker for non-ignorable dropout. In settings such as registry studies, an additional complexity is caused when follow-up of subjects is delayed, referred to as left-truncation of follow-up in the survival analysis setting. If not adjusted for, this can cause bias in estimation of parameters of the survival distribution for the clinical event and in parameters of the longitudinal outcome such as the profile or rate of change over time because subjects may die or have the clinical event before follow-up starts. This paper illustrates how a broad class of shared parameter models can be used to jointly model a time to event outcome along with a longitudinal marker using available nonlinear mixed modeling software, when follow-up times are left truncated. Methods are applied to jointly model survival and decline in lung function in cystic fibrosis patients.

Developing crash prediction models using parametric and nonparametric approaches for rural mountainous freeways: A case study on Wyoming Interstate 80.

Interstate 80 in Wyoming is one of the busiest freight corridors that is characterized with harsh winter conditions and challenging mountainous roadway sections. The fatality rates in Wyoming are always typically higher than the national level. The 402-mile I-80 corridor in Wyoming was selected by the USDOT FHWA for piloting connected vehicle technology to improve the safety and mobility of heavy trucks. To accurately quantify the effectiveness of the pilot, evaluation of the pre-deployment safety performance is essential. Unlike other studies, the full 402-mile of I-80 corridor passing through Wyoming was investigated as a requirement of the USDOT. Homogeneous segmentation was used to divide the corridor based on horizontal and vertical roadway characteristics. A transferability analysis was conducted to investigate whether a short portion of the corridor would be representative of the whole 402-miles of I-80. Results showed that the whole 402 miles should be considered in the analysis due to the radical changes throughout the corridor. Several SPFs were developed using three models; negative binomial (NB) model, spatial autoregressive (SAR) model, and non-parametric multivariate adaptive regression splines (MARS). Comparisons were performed for the developed models. Crash prediction models for total crashes and Fatal and Injury (F + I) crashes in addition to truck crashes were calibrated utilizing five years of crash data from 2012 to 2016. The results obtained from the three statistical approaches showed that MARS model provided a better model fit compared to NB and SAR models, given the lower AIC values for the developed models. Yet, SAR models showed the significant spatial dependency between the neighbor roadway segments. Additionally, the NB model showed its superiority on SAR when the spatial correlation was not significant. Parametric and non-parametric techniques should be interchangeably used in developing SPFs according to the modeling needs.

Analysis of a large cohort of cystic fibrosis patients with severe liver disease indicates lung function decline does not significantly differ from that of the general cystic fibrosis population.

Previous reports of lung function in cystic fibrosis (CF) patients with liver disease have shown worse, similar, or even better forced expiratory volume in 1 second (FEV1), compared to CF patients without liver disease. Varying definitions of CF liver disease likely contribute to these inconsistent relationships reported between CF lung function and liver disease. We retrospectively evaluated spirometric data in 179 subjects (62% male; 58% Phe508del homozygous) with severe CF liver disease (CFLD; defined by presence of portal hypertension due to cirrhosis). FEV1 values were referenced to both a normal population (FEV1% predicted) and CF population (CF-specific FEV1 percentile). We utilized a linear mixed model with repeated measures to assess changes in lung function (before and after diagnosis of CFLD), relative to both the normal and CF populations. At diagnosis of CFLD, the mean FEV1 was 81% predicted, or at the 53rd percentile referenced to CF patients without CFLD. There was a significant difference in post-CFLD slope compared to pre-CFLD slope (post-pre) using FEV1% predicted (-1.94, p-value < 0.0001). However, there was insignificant evidence of this difference using the CF-specific FEV1 percentile measure (-0.99, p-value = 0.1268). Although FEV1% predicted values declined in patients following CFLD diagnosis, there was not significant evidence of lung function decline in CF-specific FEV1 percentiles. Thus, the observed study cohort indicates diagnosis of severe CFLD was not associated with worsened CF lung disease when compared to a large CF reference population.

Balancing statistical and ethical considerations in planning clinical trials: recommendations for response-adaptive randomization urn designs.

During a clinical trial, balancing statistical and ethical considerations are important. Response-adaptive randomization methods use the information from past patients to increase the probability of the next patient receiving the better treatment while avoiding the statistical concern of selection bias. We compared three response-adaptive randomization urn designs, Randomized Play-the-Winner, Modified Play-the-Winner, and Birth-and-Death Urn with Immigration, to the traditional equal allocation design with respect to power and allocation of patients to the better treatment. Because these designs have been described separately, our motivation was to systematically compare them and provide recommendations. With simulations, we varied sample size and combinations of treatment and control success probabilities. We also compared the response-adaptive randomization designs using exact distribution algorithms and applied them to past clinical trial data that used an equal allocation design. We conclude that Modified Play-the-Winner tends to be unpredictable and can result in allocation of all of the patients to the better treatment. Randomized Play-the-Winner allocates more patients to the better treatment than Birth-and-Death Urn with Immigration, but Birth-and-Death Urn with Immigration is more consistent in its allocations. Randomized Play-the-Winner and Birth-and-Death Urn with Immigration produce allocations that have comparable powers to equal allocation design.

Prediction models for postpartum urinary and fecal incontinence in primiparous women.

OBJECTIVES: This study aimed to develop and internally validate a nomogram that facilitates decision making between patient and physician by predicting a woman's individual probability of developing urinary (UI) or fecal incontinence (FI) after her first delivery. METHODS: This study used Childbirth and Pelvic Symptoms Study data, which estimated the prevalence of postpartum UI and FI in primiparous women after vaginal or cesarean delivery. Two models were developed using antepartum variables, and 2 models were developed using antepartum plus labor and delivery variables. Urinary incontinence was defined by a response of leaking urine "sometimes" or "often" using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire. Fecal incontinence was defined as any involuntary leakage of mucus, liquid, or solid stool using the Fecal Incontinence Severity Index. Logistic regression models allowing nonlinear effects were used and displayed as nomograms. Overall performance was assessed using the Brier score (zero equals perfect model) and concordance index (c-statistic). RESULTS: A total of 921 women enrolled in the Childbirth and Pelvic Symptoms Study, and 759 (82%) were interviewed by telephone 6 months postpartum. Two antepartum models were generated, which discriminated between women who will and will not develop UI (Brier score = 0.19, c-statistic = 0.69) and FI (Brier score = 0.10, c-statistic = 0.67) at 6 months and 2 models were generated (Brier score = 0.18, c-statistic= 0.68 and Brier score = 0.09, c-statistic = 0.68) for predicting UI and FI, respectively, for use after labor and delivery. CONCLUSIONS: These models yielded 4 nomograms that are accurate for generating individualized prognostic estimates of postpartum UI and FI and may facilitate decision making in the prevention of incontinence.

Jointly modeling the relationship between longitudinal and survival data subject to left truncation with applications to cystic fibrosis.

Numerous methods for joint analysis of longitudinal measures of a continuous outcome y and a time to event outcome T have recently been developed either to focus on the longitudinal data y while correcting for nonignorable dropout, to predict the survival outcome T using the longitudinal data y, or to examine the relationship between y and T. The motivating problem for our work is in joint modeling of the serial measurements of pulmonary function (FEV1% predicted) and survival in cystic fibrosis (CF) patients using registry data. Within the CF registry data, an additional complexity is that not all patients have been followed from birth; therefore, some patients have delayed entry into the study while others may have been missed completely, giving rise to a left truncated distribution. This paper shows in joint modeling situations where y and T are not independent, that it is necessary to account for this left truncation to obtain valid parameter estimates related to both survival and the longitudinal marker. We assume a linear random effects model for FEV1% predicted, where the random intercept and slope of FEV1% predicted, along with a specified transformation of the age at death follow a trivariate normal distribution. We develop an expectation-maximization algorithm for maximum likelihood estimation of parameters, which takes left truncation and right censoring of survival times into account. The methods are illustrated using simulation studies and using data from CF patients in a registry followed at Rainbow Babies and Children's Hospital, Cleveland, OH.

Nomograms to predict patency after microsurgical vasectomy reversal.

PURPOSE: After undergoing vasectomy up to 6% of men will elect to undergo vasectomy reversal. For these men paternity can be achieved with vasectomy reversal or surgical sperm retrieval coupled with assisted reproduction. Nevertheless, it remains difficult for surgeons to accurately counsel men on the chance of patency after vasectomy reversal. MATERIALS AND METHODS: A retrospective review was conducted of 548 patients who underwent microsurgical vasectomy reversal. Surgery was considered successful if sperm concentration was 100,000 or more sperm per ml, total count was 100,000 or more sperm per ejaculate, motile sperm were present and there was no evidence of subsequent failure. A multivariate logistic regression model was constructed to calculate the probability of having a successful vasectomy reversal and nomograms for patency were generated from this model. RESULTS: A total of 548 patients met the inclusion criteria for this study. Mean followup was 1.8 ± 0.10 years. Mean patient age was 43.4 ± 0.3 years and mean duration of obstruction was 10.4 ± 0.2 years. Two nomograms to predict patency were generated, one for preoperative counseling and a second for postoperative counseling. The factors with the largest effect on patency were average testicular volume and obstruction duration. The factor with the least effect was the presence of sperm granuloma. The concordance index for the preoperative and the postoperative nomograms was 0.64 and 0.66, respectively. CONCLUSIONS: To our knowledge this represents the first use of nomograms to predict the likelihood of patency after microsurgical vasectomy reversal. These nomograms may prove useful to guide further treatment decisions.