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No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% delta⁹-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In the United States, diabetes is the seventh leading cause of death and continues to rise in prevalence, with type 2 diabetes accounting for 90–95% of all cases. Rates of diabetes in Kentucky, and, in particular, the Appalachian region, are among the highest in the nation and are increasing faster than the national average. Despite this disproportionate burden, barriers to clinical appointment attendance have not been fully explored in this population. This article examines the association among perceived barriers to clinical attendance, glycemic control, and diabetes self-care as part of an ongoing study. We used a 25-item checklist developed using the Chronic Care Model to assess participants’ barriers to clinic attendance. Glycemic control was assessed via A1C measurement. Diabetes self-care was assessed using the Summary of Diabetes Self-Care Activities measure. At the time of analysis, 123 of the 356 participants (34.6%) did not report any barriers to clinic attendance. For the remainder, the major reported barriers included forgetting appointments, inability to afford medicines or other treatment, and placing faith above medical care. The average A1C was 7.7%, and the average diabetes self-care summary score was 17.1 out of 35 points (with higher values indicating better self-care). Missing clinic appointments is associated with lower health outcomes, especially in vulnerable populations. This study can help educate clinic staff on perceived barriers to type 2 diabetes management among people with diabetes in Appalachia.

Background/aims This work is motivated by the HEALing Communities Study, which is a post-test only cluster randomized trial in which communities are randomized to two different trial arms. The primary interest is in reducing opioid overdose fatalities, which will be collected as a count outcome at the community level. Communities range in size from thousands to over one million residents, and fatalities are expected to be rare. Traditional marginal modeling approaches in the cluster randomized trial literature include the use of generalized estimating equations with an exchangeable correlation structure when utilizing subject-level data, or analogously quasi-likelihood based on an over-dispersed binomial variance when utilizing community-level data. These approaches account for and estimate the intra-cluster correlation coefficient, which should be provided in the results from a cluster randomized trial. Alternatively, the coefficient of variation or R coefficient could be reported. In this article, we show that negative binomial regression can also be utilized when communities are large and events are rare. The objectives of this article are (1) to show that the negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model and to explain why the estimates may differ; (2) to derive formulas relating the negative binomial overdispersion parameter k with the intra-cluster correlation coefficient, coefficient of variation, and R coefficient; and (3) analyze pre-intervention data from the HEALing Communities Study to demonstrate and contrast models and to show how to report the intra-cluster correlation coefficient, coefficient of variation, and R coefficient when utilizing negative binomial regression. Methods Negative binomial and over-dispersed binomial regression modeling are contrasted in terms of model setup, regression parameter estimation, and formulation of the overdispersion parameter. Three specific models are used to illustrate concepts and address the third objective. Results The negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model, although estimates may differ. Practical differences arise in regard to how overdispersion, and hence the intra-cluster correlation coefficient is modeled. The negative binomial overdispersion parameter is approximately equal to the ratio of the intra-cluster correlation coefficient and marginal probability, the square of the coefficient of variation, and the R coefficient minus 1. As a result, estimates corresponding to all four of these different types of overdispersion parameterizations can be reported when utilizing negative binomial regression. Conclusion Negative binomial regression provides a valid, practical, alternative approach to the analysis of count data, and corresponding reporting of overdispersion parameters, from community randomized trials in which communities are large and events are rare.

Background Stroke remains a major public health concern in the United States and a leading cause of long-term disability in adults. Dynamic body weight support (DBWS) systems are popular technology available for use in clinical settings such inpatient rehabilitation. However, there remains limited studies in such inpatient settings that compare DBWS to standard of care (SOC) using real world outcome measures. For survivors of acute ischemic stroke, we determine if incorporating a dynamic body weight support (DBWS) system into inpatient therapy offers greater improvement than standard of care (SOC). Methods A retrospective chart review included 52 individuals with an acute ischemic stroke admitted to an inpatient rehabilitation facility. Functional Independence Measure (FIM) data, specifically changes in FIM at discharge, served as the primary outcome measure. Patient cohorts received either therapies per SOC or therapies incorporating DBWS. Regardless of cohort group, all patients underwent therapies for 3 h per day for 5 days a week. Results For both groups, a statistically and clinically significant increase in total FIM (P d = 0.58). Among FIM subscores, the DBWS group achieved a significant increase in sphincter control while all other subscore changes remained non-significant. Conclusions This preliminary evidence supports the benefit of using DBWS during inpatient rehabilitation in individuals who have experienced an acute ischemic stroke. This may be due to the greater intensity and repetitions of tasks allowed by DBWS. These preliminary findings warrant further investigations on the use of DBWS in inpatient settings.

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21–1.90 mg/kg/day to a maximum dose of 2.86–3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10–1.00 µM) or CD (1.20–120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.

Background The HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests. Methods The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups. Results Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA). Conclusions Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study. Trial registration ClinicalTrials.gov http://www.clinicaltrials.gov; Identifier: NCT04111939

Background The purpose of this study was to identify differences related to race in preoperative and intraoperative findings of patients undergoing operative treatment for shoulder instability. Methods Data from the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort were used. Of 1010 patients, 995 provided race and ethnicity information and were included in the analyses. Demographic characteristics, injury history, radiographic and intraoperative findings, and preoperative patient-reported instability, pain, and function were compared (1) between white and minority patients and (2) in a subgroup analysis between white patients and the 3 largest minority groups. The Distressed Communities Index (DCI) score was recorded for each patient’s home ZIP code. Multiple logistic regressions were performed to determine whether models consisting of race/ethnicity, insurance carrier, and/or DCI score were predictive of bone and cartilage loss at the time of surgery. Results Compared with white patients, a greater percentage of US minority patients had ≥2 dislocations (68.0% vs. 57.1%, P = .01), which corresponded with more frequent articular cartilage lesions (62.2% vs. 51.0%, P = .007) and increased frequencies of glenoid bone loss > 10% (16.2% vs. 8.7%, P = .03) and Hill-Sachs lesions (68.6% vs. 56.0%, P = .004). Specifically, when compared with white patients, African American and Asian patients showed significantly increased frequencies of glenoid bone loss > 10% (19.7% of African American patients, 18.4% of Asian patients, and 8.9% of white patients; P = .01) and Hill-Sachs lesions (65.6%, 71.7%, and 52.4%, respectively; P = .02). Race was an independent predictor of articular cartilage lesions (P = .04) and the presence of Hill-Sachs lesions (P = .01). A higher DCI score (P = .03) and race (P = .04) were both predictive of having glenoid bone loss > 10%. Conclusion We found that minority race was associated with increased number of preoperative dislocations and increased frequency of articular cartilage and Hill-Sachs lesions at the time of surgery, and both minority race and an increased DCI score were associated with glenoid bone loss > 10%. Further research is needed to understand the underlying reason for these differences and to optimize care for all patients with shoulder instability.

Context: Awareness of important injury risk factors associated with excessive pitching volume has been highlighted in the literature, but injury rates remain high. Shoulder pain in baseball players is associated with various changes in musculoskeletal movements, which presents as measurable impairments throughout the kinetic chain. Baseball coaches and rehabilitation professionals have utilized exercise programs targeting strength and flexibility of the throwing arm to prevent injuries. The purpose of this review is to summarize the current evidence regarding the effectiveness of arm care exercise programs in reducing upper extremity injury rates in adolescent baseball players. Evidence Acquisition: A search of electronic databases, including CINAHL with full text, MEDLINE, and SPORTDiscus was conducted to retrieve available articles in English from the years 2010 through 2020. The search terms injury prevention, exercise, and adolescent baseball were used. Study Design: Clinical review. Level of Evidence: Level 4. Results: Improving shoulder internal rotation range of motion by stretching the posterior shoulder muscles daily was associated with a 36% risk reduction of shoulder and elbow injuries. Group-based arm care exercise programs that target multiple musculoskeletal impairments demonstrated an approximately 50% reduced risk of elbow injury. Conclusion: For adolescent baseball players, arm care injury prevention programs focusing on important musculoskeletal impairments are effective at reducing injury incidence rates. Multimodal injury prevention programs that improve multiple musculoskeletal impairments are more comprehensive and may result in better injury reduction than programs focusing on a singular impairment.

The purpose of this study was to compare postural control and neurophysiologic components of balance after dry needling of the fibularis longus between individuals with chronic ankle instability (CAI) and a healthy control group.This quasi-experimental university-laboratory study included 50 adult volunteers-25 with CAI (16 female, 9 male; age: 26 ± 9.42 years; height: 173.12 ± 9.85 cm; weight: 79.27 ± 18 kg) and 25 healthy controls (15 female, 10 male; age: 25.8 ± 5.45 years; height: 169.47 ± 9.43 cm; weight: 68.47 ± 13 kg). Participants completed the Star Excursion Balance Test (SEBT), single-leg balance, and assessment of spinal reflex excitability before and after a single treatment of dry needling to the fibularis longus. The anterior, posterolateral, and posteromedial directions of the SEBT were randomized, and reach distances were normalized to a percentage of leg length. A composite SEBT score was calculated by averaging the normalized scores. Postural control was assessed in single-limb stance on a force plate through time-to-boundary measurements in eyes-open and eyes-closed conditions. Fibularis longus and soleus spinal reflexes were obtained by providing electrical stimulation to the common fibular and tibial nerves with participants lying prone. A Group × Time analysis examined changes in performance, and effect sizes were calculated to assess significance.Significant group × time interactions were identified for composite (P = .006) and posteromedial (P = .017) SEBT scores. Significant time effects for all directions of the SEBT, time to boundary with eyes open, and the mediolateral direction with eyes closed indicate improved postural control following treatment (P.008). Within-group effect sizes for significant time effects ranged from small to large, indicating potential clinical utility.Dry needling demonstrated immediate short-term improvement in measures of static and postural control in individuals with CAI as well as healthy controls.

Stepped wedge cluster trials are an increasingly popular alternative to traditional parallel cluster randomized trials. Such trials often utilize a small number of clusters and numerous time intervals, and these components must be considered when choosing an analysis method. A generalized linear mixed model containing a random intercept and fixed time and intervention covariates is the most common analysis approach. However, the sole use of a random intercept applies a constant intraclass correlation coefficient structure, which is an assumption that is likely to be violated given stepped wedge trials (SWTs) have multiple time intervals. Alternatively, generalized estimating equations (GEE) are robust to the misspecification of the working correlation structure, although it has been shown that small-sample adjustments to standard error estimates and the use of appropriate degrees of freedom are required to maintain the validity of inference when the number of clusters is small. In this article, we show, using an extensive simulation study based on a motivating example and a more general design, the use of GEE can maintain the validity of inference in small-sample SWTs with binary outcomes. Furthermore, we show which combinations of bias corrections to standard error estimates and degrees of freedom work best in terms of attaining nominal type I error rates.

BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

Purpose: Children who are deaf or hard of hearing (DHH) and who use hearing aids or cochlear implants are more likely than their peers with typical hearing to exhibit behavior problems. Although multiple evidence-based interventions for child behavior problems exist, they are rarely delivered to children who are DHH, and no rigorous randomized controlled trials have been conducted to determine their effects with this population. This protocol describes a study aiming to test the effectiveness of an evidence-based behavioral parent training intervention adapted for parents of young children who are DHH and simultaneously to assess key implementation outcomes and multilevel contextual factors influencing implementation. Method: The protocol for a Type 1 hybrid effectiveness–implementation trial of a behavioral parent training intervention for parents of young children who are DHH is presented, including details of the study design, participants, assessments, and analyses. Using a stakeholder-engaged, mixed-methods approach, we will test the effects of the intervention versus treatment as usual on parenting behaviors, child behaviors, and a range of secondary effectiveness outcomes, including adherence to using hearing aids and cochlear implants as well as measures of child speech and language. We will assess the acceptability, feasibility, fidelity, and costs of the intervention from the perspectives of peer coaches who deliver the intervention, hearing health care clinicians (including audiologists and speech-language pathologists), and administrators of programs serving young children who are DHH. Conclusions: Results of this trial will inform future efforts to close the gap between prevalence of behavioral problems in young children who are DHH and access to and use of evidence-based interventions to prevent and treat them. If effective, this intervention could be widely implemented using strategies informed by the findings of this study to benefit young children who are DHH and followed in hearing health care and their families.

Background The HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate Type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests. Methods The primary outcome, number of opioid overdose deaths, is count data assessed at the community-level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the Type I error rates and power for 3 tests: 1) Wald-type t-test with small-sample corrected empirical standard error estimates; 2) Wald-type z-test with model-based standard error estimates; and 3) permutation test with test statistics calculated by the difference in average residuals for the two groups. Results Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper Type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved Type I error rates if the constrained space was not too small. For all tests, power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA). Conclusions Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study. Trial registration: ClinicalTrials.gov http://www.clinicaltrials.gov; Identifier: NCT04111939

Rehabilitation strategies after traumatic spinal cord injury aim to maximize functional recovery by applying principles of neuroplasticity via task-specific, repetitive training. Rehabilitation of patients with traumatic spinal cord injury poses unique challenges, including bilateral limb involvement, autonomic dysfunction, loss of proprioception, and potentially spinal precautions/bracing. The purpose of this retrospective case series was to determine whether use of dynamic body weight support would yield greater improvement in functional recovery compared with standard of care in adults with traumatic spinal cord injury. Data were collected from patients with traumatic spinal cord injury who completed inpatient rehabilitation incorporating dynamic body weight support (n = 5) and who completed inpatient rehabilitation without dynamic body weight support (n = 5). The primary outcome measure was the change in Functional Independence Measures. The dynamic body weight support group had a significantly greater improvement in Total Functional Independence Measures and in Functional Independence Measures motor subscale compared with the standard of care group (P = 0.023 and P = 0.033, respectively). This study presents initial evidence that dynamic body weight support therapy during inpatient rehabilitation has the potential to improve functional independence compared with standard of care in patients with traumatic spinal cord injury. Larger prospective randomized studies need to be conducted to expand on these findings.

The HEALing (Helping to End Addiction Long-termThe primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups.Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA).Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study.ClinicalTrials.gov http://www.gov ; Identifier: NCT04111939.

To assess the proposed shortened tools based on the Finnegan neonatal abstinence scoring tool (FNAS) for relative clinical utility.Retrospective study comparing shortened tools with FNAS on need for treatment, medication initiation cutoff score agreement, and length of treatment in 369 infants with prenatal opioid exposure using estimated areas under the receiver operating characteristic curves, Pearson and Spearman correlations, and proportion correctly classified, sensitivity, and specificity.The tools by Gomez et al. and Chervoneva et al. are most predictive of the FNAS cut-off values to initiate treatment, have cutoff values that best align with the FNAS cutoff values, and strongly correlate with the FNAS (r ≥ 0.88 corresponding to treatment initiation, r ≥ 0.83 during first 10 days of treatment).The tools of Gomez and Chervoneva demonstrated potential clinical usefulness by strongly associating with the need for treatment and monitoring the course of NAS therapy.

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process.

BackgroundThe stepped wedge cluster randomized trial (SW-CRT) design is now preferred for many health- related trials because of its flexibility on resource allocation and clinical ethics concerns. However, as a necessary extension of studying multiple interventions, multiphase stepped wedge designs (MSW-CRT) have not been studied adequately. Since estimated intervention effect from Generalized estimating equations (GEE) has a population-average interpretation, valid inference methods for binary outcomes based on GEE are preferred by public health policy makers.MethodsWe form hypothesis testing of add-on effect of a second treatment based on GEE analysis in an MSW-CRT design with limited number of clusters. Four variance-correction estimators are used to adjust the bias of the sandwich estimator. Simulation studies have been used to compare the statistical power and type I error rate of these methods under different correlation matrices.Results We demonstrate that an average estimator with t(I-3) can stably maintain type I error close to the nominal level with limited sample sizes in our settings. We show that power of testing the add-on effect depends on the baseline event rate, effect sizes of two interventions and the number of clusters. Moreover, by changing the design with including more sequences, power benefit can be achieved. ConclusionsFor designing the MSW-CRT, we suggest using more sequences and checking event rate after initiating the first intervention via interim analysis. When the number of clusters is not very large in MSW-CRTs, inference can be conduct using GEE analysis with an average estimator with t(I-3) sampling distribution.

Background The aim of this study was to examine whether cultural factors, such as religiosity and social support, mediate/moderate the relationship between personal/psychosocial factors and T2DM self-care in a rural Appalachian community. Methods Regression models were utilized to assess for mediation and moderation. Multilevel linear mixed effects models and GEE-type logistic regression models were fit for continuous (social support, self-care) and binary (religiosity) outcomes, respectively. Results The results indicated that cultural context factors (religiosity and social support) can mediate/moderate the relationship between psychosocial factors and T2DM self-care. Specifically, after adjusting for demographic variables, the findings suggested that social support may moderate the effect of depressive symptoms and stress on self-care. Religiosity may moderate the effect of distress on self-care, and empowerment was a predictor of self-care but was not mediated/moderated by the assessed cultural context factors. When considering health status, religiosity was a moderately significant predictor of self-care and may mediate the relationship between perceived health status and T2DM self-care. Conclusions This study represents the first known research to examine cultural assets and diabetes self-care practices among a community-based sample of Appalachian adults. We echo calls to increase the evidence on social support and religiosity and other contextual factors among this highly affected population. Trial registration US National Library of Science identifier NCT03474731. Registered March 23, 2018, www.clinicaltrials.gov.

Background: Preseason movement screening can identify modifiable risk factors, deterioration of function, and potential for injury in baseball players. Limited resources and time prevent high school baseball coaches from performing movement screens on their players. Hypothesis: The arm care screen (ACS) will be highly sensitive to detecting musculoskeletal risk factors. Study Design: Cross-sectional Level of evidence: Level 3 Methods: A total of 150 baseball players were independently scored on the ACS electronically by reviewing a video recording of each player’s screening performance. Discriminability of the ACS was determined with a 2 × 2 contingency table dichotomizing musculoskeletal risk factors as present or absent based on a predetermined cutoff value and those who passed or failed the corresponding ACS subtest. Results: High sensitivity was observed on the reciprocal shoulder mobility (0.89; 95% CI 0.81-0.94), 90/90 total body rotation (0.86; 95% CI 0.79-0.92), and lower body diagonal reach (0.85; 95% CI 0.78-0.91) tests of the ACS suggesting sufficient ability to identify musculoskeletal impairments and risk factors. Conclusion: The ACS is a simplistic screening tool that the coach can administer to discriminate between youth, high school, and college-level baseball players who possess musculoskeletal risk factors. The ACS subtests demonstrated high sensitivity for correctly identifying musculoskeletal risk factors common in baseball players and can be useful as a screening tool for baseball coaches developing arm care exercise programs. Clinical Relevance: A field-expedient screen could provide coaches the ability to identify musculoskeletal risk factors that need to be addressed to minimize injury risk factors in a time-efficient manner.

Objective The objective of the study was to determine the clinical utility of brain natriuretic peptide (NT-proBNP) for prediction of moderate to severe bronchopulmonary dysplasia (BPD). We hypothesized that elevated NT-proBNP levels at 4 weeks of postnatal age may predict the severity of BPD in preterm infants. Study design The study design was a prospective observational study. The research team enrolled and followed a cohort of 70 infants with gestational age less than or equal to 30 weeks. The plasma NT-proBNP levels were measured at the postnatal day 28th. We further followed and categorized infants into two groups. Infants with no or mild BPD (Group 1) and infants with moderate or severe BPD (Group 2). We compared plasma NT-proBNP levels at 28th day of postnatal life between Groups 1 and 2. The difference in NT-proBNP levels on day 28th between groups was used to predict the severity of BPD. Results Plasma NT-proBNP was significantly elevated in Group 2 compared with Group 1, median (IQR) of 845 pg/mL (553, 1632) compared with 726 pg/mL (391, 923), P = 0.02. NT-proBNP had a fair predictive accuracy (C statistics of 0.68) to determine moderate to severe BPD. Conclusion NT-proBNP may be a useful biomarker in conjunction with clinical factors as a predictor of severe BPD. For future directions, the trend of NT-proBNP in infants with BPD may have clinical significance in monitoring of the disease.

Background Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments. Objective To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI. Methods Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = 6) and who received inpatient rehabilitation without DBWS (SOC, n = 6). The primary outcome measure was the change in Functional Independence Measures (FIM) scores from admission to discharge. Results There was significant improvement in total FIM scores at discharge compared to admission for both the DBWS (p = 0.001) and SOC (p = 0.005) groups. Overall, the DBWS group had greater improvement in total FIM score and FIM subscales compared to the SOC group. Conclusions Our results suggest DBWS has the potential to allow a greater intensity of therapy during inpatient rehabilitation and yield better outcomes compared to SOC in patients with TBI.

OBJECTIVES Analyze risk factors affecting length of stay (LOS) for patients presenting with deep neck space infections including care by medical versus surgical team. METHODS This is a retrospective chart review from January 2005 through May 2018 at the University of Kentucky analyzing factors related to deep neck space abscesses. Patients included adults >18 years old admitted for deep neck space infections undergoing surgical intervention. This study compared effects of treatment on a medical versus surgical service on LOS while accounting for patient confounders. Independent variables included age, gender, tobacco use, medical comorbidities, Charlson comorbidity index, American Society of Anesthesiology (ASA) classification, presence of drain, readmissions, and repeat surgical interventions. Univariate and multivariate analysis were performed. RESULTS One hundred sixty-three patients were included in the analysis. LOS was significantly longer for those on medicine services (P

Objective The relationship between hearing loss and cognitive decline is of great importance with growing evidence of hearing loss as an independent modifiable risk factor for dementia. Our goal was to evaluate for differences in dementia neuropathology between subjective normal hearing and hearing loss subjects, as well as subjects who wore hearing aids. Study design Retrospective database. Setting Tertiary academic center. Patients Brain tissue analyzed from our Center on Aging. Demographics, subjective hearing status, hearing aid use, cognitive status, and dementia neuropathology documented. Interventions Dementia neuropathology analyzed in brains of normal hearing and hearing loss subjects. Main outcome measures Differences in dementia neuropathology between hearing groups. Groups were compared using logistic regression and analysis of covariance (ANCOVA). Results Two-hundred and seventy-three subjects were included, 189 normal hearing and 84 subjective hearing loss subjects. No significant difference demonstrated in Alzheimer's disease neuropathology (p > 0.05) or pathologic stage (p = 0.2471). No significant difference observed in neuropathology of other major dementia types, specifically, presence of Lewy bodies (p > 0.05), Lewy body disease pathologic stage (p = 0.9778), or presence of micro-infarcts, macro-infarcts, or arteriosclerosis (p > 0.05). Hearing aid-wearing subjects had a lower prevalence of clinical dementia (39.1% versus 57.9%; p = 0.0208) with no significant difference in dementia neuropathology (p > 0.05). Conclusion Subjective hearing loss was not found to be associated with significantly different dementia neuropathology, which counters hypotheses on hearing loss causing permanent neurodegeneration and cognitive decline. Hearing aid users were found to have a lower prevalence of dementia for similar levels of neurodegeneration, suggesting a potential neuroprotective effect of hearing aids.

Context The gut microbiome is a source of inflammatory factors such as lipopolysaccharide (LPS; endotoxin) that influence metabolic homeostasis. Rifaximin is a well-tolerated antibiotic that may reduce LPS. Objective We sought to develop a method to accurately assess postprandial endotoxemia and to determine whether rifaximin treatment improves metabolic homeostasis in obese humans with metabolic syndrome. Design and Setting Plasma LPS, adipose inflammation, glucose and lipid metabolism, and insulin sensitivity were evaluated in a clinical research setting. Participants Twelve obese human research participants with prediabetes or three features of metabolic syndrome participated. Intervention The research participants were randomized to placebo control or rifaximin soluble solid dispersion (80 mg/d) treatment groups and treated for 12 weeks. Outcome Measures We evaluated changes in insulin sensitivity with a euglycemic clamp; changes in lipid and glucose metabolism with oral lipid and glucose tolerance tests; changes in plasma LPS during the lipid tolerance test; and changes in adipose tissue and systemic inflammation by measuring inflammatory cytokines. Results Rifaximin treatment slightly worsened insulin sensitivity (P = 0.03), did not improve glucose or lipid homeostasis, and did not significantly improve adipose tissue inflammation. Our efforts to accurately assess plasma LPS using limulus amebocyte lysate assays revealed that the majority of LPS is masked from detection by limulus amebocyte lysate assays, but can be unmasked using a pretreatment step with protease. Unmasked LPS increases during the lipid tolerance test, but rifaximin treatment did not reduce this. Conclusions Rifaximin treatment did not lower plasma LPS or improve metabolic homeostasis in obese humans.

OBJECTIVE: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. The present study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease. DESIGN: ALS patients (N = 102) being treated in 3 multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry, and psychological health every 3 months for up to 18 months. MAIN OUTCOME MEASURE: Psychological health composite. RESULTS: In multilevel dyadic models, patients and spouses had similar levels of financial worry and loneliness. Both patients and spouses had worse psychological health with higher loneliness, but only spouses had worse psychological health with higher financial worry. Significant interactions with age and disease severity indicated that older spouses were more affected by loneliness than were younger spouses, and patients with less severe disease were more affected by financial worry than patients with more severe disease. CONCLUSION: The results provide good support for socioemotional selectivity theory’s implications for psychological health in a strong test of the theory.

It has been theorized that incorporating strength, speed, and flexibility training regimes may improve the quality of the tennis serve. Efficient stroke quality during the serve improves velocity and diminishes injury risk in tennis players. However, no study in tennis has identified whether adequate musculoskeletal capacity is a factor that helps drive optimal serve mechanics. The aim of this study was to determine whether musculoskeletal capacity could predict efficient serve mechanics. A total of 46 professional women’s tennis players (age: 26 ± 3 years, body mass: 65 ± 5 kg, height: 1.74 ± 0.06 m) were studied. Musculoskeletal capacity parameters were evaluated by the tennis specific screen (TSS) with strength and flexibility measures. Serve mechanics were evaluated using the observational tennis serve analysis (OTSA) tool. The OTSA is scored using a 0–9 system. Multiple regression analysis revealed scapular dyskinesis on the non-dominant side during flexion to be predictive of OTSA score (r2 = 0.14, p-value = 0.008). However, the correlation is weak (r = 0.38), rendering a non-clinically significant relationship between scapular dyskinesis and serve mechanics. None of the other musculoskeletal parameters generated significant relationships to serve mechanics. This study demonstrated that in professional women’s tennis players there is no meaningful relationship between the TSS measurements and OTSA scores. In conclusion, musculoskeletal capacity and serve mechanics are independent of each another, and should be addressed separately.

Introduction Nonhuman animal models have been used extensively to study orthodontic tooth movement (OTM). However, rodent models have disadvantages, including a reported reduction in bone volume during OTM. The purpose of this study was to determine the viability of a skeletal anchorage and the effect of low force (∼3 cN) on interradicular bone volume during OTM. Methods Ninety Sprague-Dawley rats were divided into 5 time points. A miniscrew and a nickel titanium coil spring placed a load of 3 cN (experimental) or 0 cN (sham) on the maxillary first molar in a split-mouth design. Displacement of the first molar and bone volume/total volume (BV/TV) in the interradicular region were quantified. Results The success rate of the miniscrew was 98.9% (89 out of 90). Linear and angular tooth movement increased steadily (mean 0.1 mm/wk, 0.48 mm at 40 days). BV/TV was significantly reduced between the tooth movement and non–tooth movement sides in the 3 cN group: by 13%, 23%, 15%, 23%, and 16% at 3, 7, 14, 28, and 40 days, respectively. Conclusions Our model resulted in efficient OTM without skeletal anchorage failure. BV/TV reduction was lower than in previous reports. This novel validated model is likely to be the basis for future studies.

Background Non-invasive transcranial direct current stimulation has been shown to modulate cortical excitability in various studies. Similarly, recent preliminary studies suggest that transcutaneous spinal direct current stimulation (tsDCS) may engender a modulation effect on spinal and cortical neurons. Objective The purpose of this study was to evaluate the dose-response effects of tsDCS in healthy subjects and thereby lay groundwork for expanding treatment options for patients with spinal cord injury (SCI). Methods Nine healthy subjects received each of the following 2 tsDCS conditions: Anodal and cathodal, in random order with at least 1 week washout period between each session. In order to test safety and dose response, various current intensities were used (2, 2.5 and 3 mA) for 20 minutes. The active electrode was placed vertically over T10-T11, and the reference electrode was placed over the left shoulder. To evaluate corticospinal excitability, motor evoked potentials over soleus muscle elicited by transcranial magnetic stimulation were measured. To assess spinal cord excitability, H- and M- wave over soleus muscle to calculate Hmax/ Mmax ratio were measured. Results Linear regression showed a dose response with cathodal tsDCS on motor evoked potentials measured from the left leg as well as with anodal tsDCS on Hmax/ Mmax ratio measured from the left leg. Conclusions These findings indicate tsDCS effects are dose-dependent. These effects should be investigated in a larger sample.

Background Arm care programs consisting of upper extremity strengthening and stretching have been recommended for injury prevention for pitchers of all ages. There has been no investigation into high school baseball coaches’ usage and perceptions of arm care programs to mitigate physical impairments associated with injuries in baseball players. # Hypothesis/Purpose The purpose of this study was to investigate the current usage of arm care programs by high school baseball coaches. The primary objective was to determine if coaches use group-based or individualized arm care programs. The secondary objective sought to determine if the use of arm care programs is influenced by coaches’ age, education, and experience level. Finally, this study explored the potential barriers to arm care implementation and high school baseball coaches’ current awareness and beliefs of injury prevention. # Study Design Descriptive cross-sectional survey # Methods A 29-item online survey was emailed to 18,500 high school baseball coaches throughout the United States. Data were collected for three months, and the response rate was 3.7%. # Results A total of 87.3% (n=571/654) of responding coaches use arm care programs with their players. Of coaches performing arm care, only 18.5% of 571 individualize their arm care exercises based on specific player needs. However, older and more experienced coaches are more likely to individualize their programs. Among the 12.7% (n=83/654) of coaches who do not use arm care programs, the two most commonly cited reasons for not implementing arm care were lack of observed benefit (41%) and insufficient staff (31%). Although 42% of 654 coaches recognized reduced shoulder mobility as a major contributor to injury, risk factors such as throwing with a fatigued arm, previous injury history, and throwing \> 8 months per year were not consistently identified as primary risk factors. # Conclusion The results of this study suggest that the majority high school baseball coaches implement group-based arm care exercise programs to prevent injury. Lack of confidence in the effectiveness and staffing limitations were major barriers to implementation of arm care programming. However, the responding coaches exhibited inconsistent risk factor awareness and dated injury prevention beliefs. Therefore, better educational collaboration between rehabilitation professionals and high school coaches regarding injury risk factors and preventative strategies is warranted. # Level of Evidence Level 3

Background: Despite disproportionate rates of diabetes among Appalachian residents, barriers to attending clinical appointments have not been fully explored. We examined the association between barriers to clinic attendance, A1c, and self-care. Methods: We report baseline cross-sectional data from an ongoing study of participants in six counties in rural Appalachia Kentucky. Barriers to clinic attendance were measured using a 25-item checklist adapted from the Chronic Care Model and self-care was measured using a summary score from Toobert’s Diabetes Self-Care Activities. Linear regression models were fit with varying levels of adjustment. Results: Most study participants (N=356) where White (n=349), women (n=230), and had health insurance (n=349). Average A1c was 7.7% (SD=1.7%). No barriers were reported by 37.4% of participants. In fully adjusted models, not being worried about diabetes was significantly associated with diabetes self-care. Inaccessible transportation and co-payment, and the belief that God (but not them) will help their diabetes were significantly associated with A1c (Table 1). Conclusions: Both logistical and cognitive barriers obstruct clinic attendance in this sample. Additional aspects or barriers to clinical attendance could be cognitive or emotional, such as social support and cultural norms. Future research should develop interventions for these logistical and cognitive barriers. Disclosure B. L. Smalls: None. M. Lacy: None. L. Hieronymus: None. P. Westgate: None. M. Azam: None. S. C. Westneat: None. N. Schoenberg: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112136)

BACKGROUND Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders. STUDY DESIGN Respiratory measurements (Resistance, Compliance, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants

BACKGROUND Beige and brown adipose tissue (BAT) are associated with improved metabolic homeostasis. We recently reported that the β3-adrenergic receptor agonist mirabegron induced beige adipose tissue in obese insulin-resistant subjects, and this was accompanied by improved glucose metabolism. Here we evaluated pioglitazone treatment with a combination pioglitazone and mirabegron treatment and compared these with previously published data evaluating mirabegron treatment alone. Both drugs were used at FDA-approved dosages. METHODS We measured BAT by PET CT scans, measured beige adipose tissue by immunohistochemistry, and comprehensively characterized glucose and lipid homeostasis and insulin sensitivity by euglycemic clamp and oral glucose tolerance tests. Subcutaneous white adipose tissue, muscle fiber type composition and capillary density, lipotoxicity, and systemic inflammation were evaluated by immunohistochemistry, gene expression profiling, mass spectroscopy, and ELISAs. RESULTS Treatment with pioglitazone or the combination of pioglitazone and mirabegron increased beige adipose tissue protein marker expression and improved insulin sensitivity and glucose homeostasis, but neither treatment induced BAT in these obese subjects. When the magnitude of the responses to the treatments was evaluated, mirabegron was found to be the most effective at inducing beige adipose tissue. Although monotherapy with either mirabegron or pioglitazone induced adipose beiging, combination treatment resulted in less beiging than either alone. The 3 treatments also had different effects on muscle fiber type switching and capillary density. CONCLUSION The addition of pioglitazone to mirabegron treatment does not enhance beiging or increase BAT in obese insulin-resistant research participants. TRIAL REGISTRATION ClinicalTrials.gov NCT02919176. FUNDING NIH DK112282 and P20GM103527 and Clinical and Translational Science Awards grant UL1TR001998.

Highlights • HEALing Communities Study is a parallel-group cluster randomized controlled trial. • Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. • Structured consensus decision-making strategy guided study measure development. • More than 80 study measure specifications and a common data model were developed. • The study will provide methodology and longitudinal community data for research., Background Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. Methods The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) A community engagement strategy with local coalitions to guide and implement the intervention; 2) A compendium of EBPs coupled with technical assistance; and 3) A series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. Discussion The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

Objective A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants.Study Design Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation.Results A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56–0.74, all p Conclusion We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process.Key Points

Treatment of subjects who are obese/insulin resistant with the β3AR agonist mirabegron resulted in increased beige adipose tissue, without a change in brown adipose tissue (BAT), along with an improvement in glucose tolerance, HbA1c, and an increase in type 1 fibers in skeletal muscle. Pioglitazone has been demonstrated to increase beiging, and it has been demonstrated that combination of a thiazolidinedione with a β3AR agonist further increased beige adipocyte markers in vitro. The goal of this study was to determine whether combination therapy with pioglitazone and mirabegron would further increase beiging, BAT volume or activity, or skeletal muscle fiber type switching, and improve glucose homeostasis more than each drug separately. We randomized obese and insulin-resistant (IR) research participants to mirabegron (50 mg/day), pioglitazone (30 mg/day), or combination treatment groups. Adipose and muscle tissue biopsies and PET-CT scans were performed at baseline and after 10 weeks of treatment. Mitochondrial bioenergetics were determined in purified mitochondria from adipose tissue. Although mirabegron and pioglitazone treatment significantly induced SC WAT beiging separately, the combination of the two drugs resulted in less beiging than mirabegron treatment alone, and did not increase mitochondrial uncoupling. Furthermore, neither pioglitazone nor combination therapy increased BAT or fiber-type switching to type 1 fibers. Although each drug improved glucose homeostasis, the effect of the combination was not significantly additive. Analysis of mRNA expression revealed that pioglitazone or combination treatment induced the expression of p107, which promotes white versus brown adipose gene expression, suggesting a mechanism for inhibition of mirabegron-induced beiging by pioglitazone. These results suggest that pioglitazone inhibits mirabegron-induced beiging and does not augment other beneficial effects of mirabegron treatment. Disclosure P.A. Kern: None. H. Memetimin: None. B. Zhu: None. A.L. Confides: None. Z. Johnson: None. H.J. Vekaria: None. P. Westgate: None. P.G. Sullivan: None. E.E. Dupont-Versteegden: None. B. Finlin: None. Funding National Institutes of Health (DK112282)

Generalized estimating equations (GEE) incorporate a working correlation structure that is important because the more accurately this structure reflects the true structure, the more efficiently reg...

Background Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH. Study design and methods We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO2 ) were monitored with high-resolution pulse oximeters 24 hours before and after RBC transfusion. Data were analyzed at three postnatal periods: Epoch 1, first week of life (1 to 7 days of life); Epoch 2, 2 to 4 weeks of life (8 to 28 days of life); and Epoch 3, 4 to 8 weeks of life. Results A total of 118 transfusions were analyzed. IH measures significantly decreased after transfusion in Epochs 2 and 3. PI significantly increased after transfusion, but it did not correlate with the decrease in IH measures. Mechanical ventilation, fraction of inspired oxygen (FiO2 ), and IH measures influenced the effects on oxygenation. Conclusions RBC transfusion improved IH after the first week of life. The benefit in IH did not correlate with PI increase after transfusion. Pretransfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

Background: This study tested the influence of the ‘Protect Their Future’ video intervention on adult intentions to vaccinate their adolescents.Method: The study included 529 parents of 11- to 19-y...

Data arising from longitudinal studies are commonly analyzed with generalized estimating equations. Previous literature has shown that liberal inference may result from the use of the empirical sandwich covariance matrix estimator when the number of subjects is small. Therefore, two different approaches have been used to improve the validity of inference. First, many different small-sample corrections to the empirical estimator have been offered in order to reduce bias in resulting standard error estimates. Second, critical values can be obtained from a t-distribution or an F-distribution with approximated degrees of freedom. Although limited studies on the comparison of these small-sample corrections and degrees of freedom have been published, there is a need for a comprehensive study of currently existing methods in a wider range of scenarios. Therefore, in this manuscript, we conduct such a simulation study, finding two methods to attain nominal type I error rates more consistently than other methods in a variety of settings: First, a recently proposed method by Westgate and Burchett (2016, Statistics in Medicine 35, 3733-3744) that specifies both a covariance estimator and degrees of freedom, and second, an average of two popular corrections developed by Mancl and DeRouen (2001, Biometrics 57, 126-134) and Kauermann and Carroll (2001, Journal of the American Statistical Association 96, 1387-1396) with degrees of freedom equaling the number of subjects minus the number of parameters in the marginal model.

OBJECTIVES: Determine the incidence of apnea in preterm and term infants after deep sedation (DS) compared with general anesthesia (GA). METHODS: A retrospective chart review was performed on infants who underwent elective DS or GA from January 2008 to December 2013, were RESULTS: There were 61 DS encounters (24 preterm and 37 term) and 175 GA encounters (120 preterm and 55 term) that met inclusion criteria. No recorded apneic events in either preterm or term infants were recorded after DS. After GA, 1.7% of infants had apneic events (2.5% preterm and 0 term; P = .57 versus DS). All events occurred within 2 hours of monitoring in recovery. CONCLUSIONS: None of the infants had apnea after DS. Rates from the literature would suggest that 2 to 6 of the preterm DS subjects should have experienced postsedation apnea. Sampled GA subjects had a rate of 2.5% in preterm infants exhibiting apnea after GA. Although the post-DS apnea rate is lower than what has been previously published, the small sample size and limitations of a retrospective design prevent us from directing a change in postsedation monitoring recommendations. However, we do support the need for prospective studies with strict monitoring criteria to reveal the true risk of post-DS apnea.

Objective: The purpose of this study was to quantitatively assess dentoalveolar and skeletal compensations in patients with untreated unilateral cleft lip and palate (UCLP). We hypothesized that there are significant skeletal and dental adaptations in UCLP cases compared to a comparison maxillary crossbite group. Design: A convenience retrospective sample of 30 patients with UCLP and a comparison group of 30 patients with unilateral posterior crossbite without CLP. Cone-beam computed tomography scans (CBCTs) were used to evaluate dental and skeletal compensations. In addition, alveolar bone thickness was measured at 2-mm increments in mesiodistal and faciolingual cross-sectional views along the long axis of the central incisors. Alveolar bone height was measured, and the percentage of root length supported by bone was calculated. Results: Compensations for unilateral cleft lip and palate were restricted to the cleft site and adjacent structures. Dental compensations include alteration in the position of cleft-adjacent maxillary incisors and maxillary canines. No gross skeletal compensations were found. Alveolar support of cleft adjacent incisors was similar to controls except for measurements in the most coronal and apical regions. The cleft group contralateral incisors exhibited buttressing effects and had significantly higher alveolar thickness in the coronal half of the tooth. There was less (5%) alveolar coverage of the cleft-facing aspect of the central incisor root than all other incisors. Conclusion: The bone adaptation to the presence of a cleft was localized in the vicinity of the cleft, and adaptations in the mandible were not apparent.

OBJECTIVE To compare the prevalence of disruptive behavior problems between preschool-aged children with hearing loss and normal hearing. STUDY DESIGN Cross-sectional study. SETTING Tertiary academic center. PATIENTS Caregivers of children (2-5 yr old) with normal hearing (NH) (n = 39), hearing loss using hearing aid(s) (HA) (n = 29), or cochlear implant(s) (CI) (n = 21). INTERVENTION(S) Demographic information and a mental health history were obtained. Child behavior and language development were assessed. MAIN OUTCOME MEASURE(S) The Young Child-Diagnostic Interview Schedule for Children-IV and the MacArthur-Bates Communication Development Inventory III. RESULTS Distributions of race, socioeconomic status, insurance status, and parental home situation (single versus two parent family) were similar across all groups. Parents of children with hearing loss were significantly more likely to report behavior problems (HA = 41%, CI = 38%) than parents of NH children (10%; p = 0.002). Children with hearing loss were significantly more likely to meet diagnostic criteria for oppositional defiant disorder (HA = 48%, CI = 48%) than NH children (23%; p = 0.02). More NH children (8%) than hearing impaired children (0%) had accessed mental health services (p = 0.08). NH children were found to have more advanced language development than hearing-impaired children (p

Purpose Although computer-aided craniofacial reconstructions allow for simulation of hard tissue changes, the prediction of the final soft tissue facial changes remains a challenge. The purpose of the present study was to evaluate the 3-dimensional (3D) soft tissue changes in patients undergoing 2-jaw orthognathic surgery. Patients and Methods For the present retrospective cohort study, 40 consecutive patients (11 men and 29 women; mean age 23.5 ± 4.9 years) who had undergone 2-jaw orthognathic surgery were selected. We obtained the medical and dental records from 3 weeks before surgery and 6 months after surgery. We used image processing software to segment, superimpose, and quantify the hard and soft tissue displacements in 3 dimensions before and after surgery at 15 paired locations. The soft tissue and hard tissue changes were determined through quantification of homologous landmark displacements between the preoperative and postoperative computed tomography data. We measured the 3D soft and hard tissue changes and the anteroposterior, inferosuperior, and transverse components of the changes. We quantified the ratios between the soft and hard tissue changes, tested Pearson's correlation between these changes, and developed a predictive regression equation for the observations at each location. Results We found that soft tissue movement followed the hard tissue movement, with a correlation nearly equal to 0.9 (range 0.85 to 0.98), suggesting that in general the soft tissues of the maxillary and mandibular landmarks are affected similarly by the skeletal movements. The anteroposterior component of the soft tissue 3D displacements followed the hard tissue movement with a ratio greater than 0.9 and with high correlation (r > 0.9) in the mandible. Conclusion The results of the present study provide surgeons with a ratio of hard to soft tissue change and the strength of the correlations, which will allow for more accurate 3D predictions for both midline and lateral structures in bimaxillary orthognathic surgical cases. In addition, predictive equations for various landmarks were developed and can be used in computer-based prediction programs to aid in treatment planning of soft tissue changes.

Objectives/Hypothesis To assess the efficacy of a patient navigator intervention to decrease nonadherence to obtain audiological testing following failed screening, compared to those receiving the standard of care. Methods Using a randomized controlled design, guardian-infant dyads, in which the infants had abnormal newborn hearing screening, were recruited within the first week after birth. All participants were referred for definitive audiological diagnostic testing. Dyads were randomized into a patient navigator study arm or standard of care arm. The primary outcome was the percentage of patients with follow-up nonadherence to obtain diagnostic testing. Secondary outcomes were parental knowledge of infant hearing testing recommendations and barriers in obtaining follow-up testing. Results Sixty-one dyads were enrolled in the study (patient navigator arm = 27, standard of care arm = 34). The percentage of participants nonadherent to diagnostic follow-up during the first 6 months after birth was significantly lower in the patient navigator arm compared with the standard of care arm (7.4% vs. 38.2%) (P = .005). The timing of initial follow-up was significantly lower in the navigator arm compared with the standard of care arm (67.9 days after birth vs. 105.9 days, P = .010). Patient navigation increased baseline knowledge regarding infant hearing loss diagnosis recommendations compared with the standard of care (P = .004). Conclusions Patient navigation decreases nonadherence rates following abnormal infant hearing screening and improves knowledge of follow-up recommendations. This intervention has the potential to improve the timeliness of delivery of infant hearing healthcare; future research is needed to assess the cost and feasibility of larger scale implementation. Level of Evidence 1b. Laryngoscope, 127:S1–S13, 2017

Objectives/Hypothesis Factors affecting access to healthcare is an expanding area of research. This study seeks to identify factors associated with no-show rates in an academic otolaryngology practice to improve clinical efficiency and patient access to care. Study Design Retrospective review. Methods A retrospective review of scheduled clinical appointments from February 1, 2015 to January 30, 2016 at a single academic otolaryngology department was performed. Statistical analysis was completed to examine the association of no-show rates with the following: otolaryngology subspecialty, clinic location (e.g., main campus vs. satellite), patient demographic factors, attending seniority, temporal factors, insurance types, rurality, and visit type. Results There was an overall no-show rate of 20% for 22,759 scheduled clinic visits. Satellite clinics had the highest no-show rates at 25% (P

Aims: This pilot randomized comparative study investigated changes in motor performance and indices of neuroplasticity associated with occupation-based intervention and repetitive task practice in ...