Reconsidering stepped wedge cluster randomized trial designs with implementation periods: Fewer sequences or the parallel-group design with baseline and implementation periods are potentially more efficient.

BACKGROUND/AIMS: When designing a cluster randomized trial, advantages and disadvantages of tentative designs must be weighed. The stepped wedge design is popular for multiple reasons, including its potential to increase power via improved efficiency relative to a parallel-group design. In many realistic settings, it will take time for clusters to fully implement the intervention. When designing the HEALing (Helping to End Addiction Long-termSM) Communities Study, implementation time was a major consideration, and we examined the efficiency and practicality of three designs. Specifically, a three-sequence stepped wedge design with implementation periods, a corresponding two-sequence modified design that is created by removing the middle sequence, and a parallel-group design with baseline and implementation periods. In this article, we study the relative efficiencies of these specific designs. More generally, we study the relative efficiencies of modified designs when the stepped wedge design with implementation periods has three or more sequences. We also consider different correlation structures. METHODS: We compare efficiencies of stepped wedge designs with implementation periods consisting of three to nine sequences with a variety of corresponding designs. The three-sequence design is compared to the two-sequence modified design and to the parallel-group design with baseline and implementation periods analysed via analysis of covariance. Stepped wedge designs with implementation periods consisting of four or more sequences are compared to modified designs that remove all or a subset of 'middle' sequences. Efficiencies are based on the use of linear mixed effects models. RESULTS: In the studied settings, the modified design is more efficient than the three-sequence stepped wedge design with implementation periods. The parallel-group design with baseline and implementation periods with analysis of covariance-based analysis is often more efficient than the three-sequence design. With respect to stepped wedge designs with implementation periods that are comprised of more sequences, there are often corresponding modified designs that improve efficiency. However, use of only the first and last sequences has the potential to be either relatively efficient or inefficient. Relative efficiency is impacted by the strength of the statistical correlation among outcomes from the same cluster; for example, the relative efficiencies of modified designs tend to be greater for smaller cluster auto-correlation values. CONCLUSION: If a three-sequence stepped wedge design with implementation periods is being considered for a future cluster randomized trial, then a corresponding modified design using only the first and last sequences should be considered if sole focus is on efficiency. However, a parallel-group design with baseline and implementation periods and analysis of covariance-based analysis can be a practical, efficient alternative. For stepped wedge designs with implementation periods and a larger number of sequences, modified versions that remove 'middle' sequences should be considered. Due to the potential sensitivity of design efficiencies, statistical correlation should be carefully considered.

Alternatives to dental opioid prescribing after tooth extraction (ADOPT): protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. METHODS: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12-25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant's electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants' perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). DISCUSSION: This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. CLINICALTRIALS: GOV: NCT06275191.

A New Look at Barriers to Clinical Care Among Appalachian Residents Living With Diabetes.

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.

Effects of dynamic body weight support on functional independence measures in acute ischemic stroke: a retrospective cohort study.

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 < 0.0001) was observed at discharge compared to at admission. Improvements for the DBWS group were significantly greater than the SOC group as evidenced by higher gains in total FIM (p = 0.04) and this corresponded to a medium effect size (Cohen's 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.

Examination of Dry Needling Dose and Effect Duration for Individuals With Chronic Ankle Instability.

OBJECTIVE: The purpose of this study was to evaluate the effect of a single treatment vs serial dry needling (DN) treatments of the fibularis longus on individuals with chronic ankle instability and to determine the longevity of any effect found. METHODS: Thirty-five adults with chronic ankle instability (24.17 ± 7.01 years, 167.67 ± 9.15 cm, 74.90 ± 13.23 kg) volunteered for a university laboratory repeated-measures study. All participants completed patient-reported outcomes and were objectively tested using the Star Excursion Balance Test (SEBT), threshold to detect passive motion (TTDPM) measurements, and single limb time-to-boundary measurements. Participants received DN treatment to the fibularis longus once weekly for 4 weeks on the affected lower extremity by a single physical therapist. Data were collected 5 times: baseline 1 week before initial treatment (T0), pre-treatment (T1A), immediately after the first treatment (T1B), after 4 weekly treatments (T2), and 4 weeks after the cessation of treatment (T3). RESULTS: Significant improvements were found for clinician-oriented (SEBT-Composite P < .001; SEBT-Posteromedial P = .024; SEBT-Posterolateral P < .001; TTDPM-Inversion P = .042) and patient-oriented outcome measures (Foot and Ankle Ability Measure-Activities of Daily Living P < .001; Foot and Ankle Ability Measure-Sport P = .001; Fear Avoidance Belief Questionnaire P = .021) following a single DN treatment. Compounding effects from additional treatments exhibited improvement of TTDPM (T1B to T2). No significant losses were noted 4 weeks after cessation of treatment (T2 to T3). CONCLUSION: For the participants in this study, outcomes improved immediately following the first DN treatment. This improvement was sustained but not further improved with subsequent treatments.

Marginal modeling in community randomized trials with rare events: Utilization of the negative binomial regression model.

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.

A randomized controlled trial to determine whether beta-hydroxy-beta-methylbutyrate and/or eicosapentaenoic acid improves diaphragm and quadriceps strength in critically Ill mechanically ventilated patients.

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. RESULTS: Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. CONCLUSIONS: These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .

The mediating/moderating role of cultural context factors on self-care practices among those living with diabetes in rural Appalachia.

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 .

Which Risk Factors Are Associated with Pain and Patient-reported Function in Patients with a Rotator Cuff Tear?

BACKGROUND: Patient-reported measures guide physicians in clinical decision making and therefore it is critical to determine what clinical factors are associated with these scores. Psychological and physical factors are commonly studied separately in patients with rotator cuff tears to determine their influence on outcomes. It is well established that psychological distress and scapular motion change in the presence of a symptomatic rotator cuff tear. However, these factors have not been studied simultaneously in a clinical setting to determine their association with shoulder outcome scores. QUESTION/PURPOSE: After controlling for relevant confounding variables, what physical and psychological factors are associated with better (1) American Shoulder and Elbow Surgeons (ASES) scores for function, (2) ASES pain scores, and (3) total ASES scores? METHODS: Fifty-nine patients with a potential symptomatic rotator cuff tear were recruited and agreed to participate in this cross-sectional study. Of those, 85% (50 of 59) met eligibility criteria for a primary diagnosis of an MRI-confirmed symptomatic partial-thickness or full-thickness rotator cuff tear without a history of shoulder surgery. Demographics, rotator cuff tear size, arm flexion, and clinical scapular motion during active arm flexion were evaluated by experienced examiners using standardized procedures. Patients completed the ASES questionnaire and the Optimal Screening for Prediction of Referral and Outcomes-Yellow Flag assessment form, which measures 11 different pain-related psychological distress symptoms. Three separate stepwise multiple linear regression analyses were performed for ASES pain, function, and total scores, with significance set at p < 0.05. RESULTS: This model found that ASES function scores were associated with four factors: older age, increased arm flexion, increased percentage of scapular external rotation during arm flexion, and increased scores for acceptance of chronic pain (adjusted r2 = 0.67; p = 0.01). Those four factors appear to explain 67% of the observed variance in ASES function scores in patients with rotator cuff tears. Furthermore, increased percentage of scapular external rotation during arm flexion and decreased fear-avoidance beliefs related to physical activity scores (adjusted r2 = 0.36; p < 0.01) were associated with better ASES pain scores. And finally, better ASES total scores were associated with four factors: increased arm flexion, increased percentage of scapular upward rotation, increased scapular external rotation during arm flexion, and decreased fear-avoidance beliefs related to physical activity scores (adjusted r2 = 0.65; p < 0.001). CONCLUSION: Our results favor adopting a comprehensive biopsychological clinical assessment for patients with rotator cuff tears that specifically includes humeral and scapular motion, fear-avoidance behaviors, and pain coping behaviors along with demographics. These particular physical and psychological variables were found to be associated with the ASES and, therefore, should be clinically examined simultaneously and targeted as part of a tailored treatment plan. LEVEL OF EVIDENCE: Level II, prognostic study.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

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 < 0.01). 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: · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

Are there racial differences between patients undergoing surgery for shoulder instability? Data from the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Group.

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.

Effect of Dry Needling on Spinal Reflex Excitability and Postural Control in Individuals With Chronic Ankle Instability.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Dry needling demonstrated immediate short-term improvement in measures of static and postural control in individuals with CAI as well as healthy controls.

Maintaining the validity of inference in small-sample stepped wedge cluster randomized trials with binary outcomes when using generalized estimating equations.

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.

Results of caring and reaching for health (CARE): a cluster-randomized controlled trial assessing a worksite wellness intervention for child care staff.

BACKGROUND: Child care workers are among the lowest paid US workers and experience a wide array of health concerns. The physical and mental demands of their job and the lack of employer-provided health-insurance increase health risks. The Caring and Reaching for Health (CARE) study evaluated a 6-month Healthy Lifestyles intervention targeting child care workers' physical activity (primary outcome), other health behaviors, and their workplace health environment. METHODS: Eligible child care centers, defined as being in operation for at least 2 years and employing at least four staff, were enrolled into CARE's cluster-randomized trial. Centers and their child care staff were randomly assigned to either the Healthy Lifestyles (HL) intervention arm or the Healthy Finances (HF) attention control arm using a block randomization approach. Intervention components were delivered through in-person workshops, center-level displays, informational magazines, director coaching, electronic messaging, and an interactive website. Outcome measures were collected during center visits at baseline and immediately post-intervention by trained data collectors blinded to center arm assignment. Workers' physical activity was assessed with accelerometers, worn for 7 days. Secondary outcome measures included biometric assessments of health and fitness, web-based surveys about health behaviors, and an environmental audit of workplace supports for health. Multi-level linear mixed models assessed worker- and center-level changes in these outcomes. RESULTS: Participants included 553 child care workers representing 56 centers (HL = 250 staff/28 centers, HF = 303 staff/28 centers). At 6 months, moderate-to-vigorous physical activity declined slightly in both arms (- 1.3 min/day, 95% CI: - 3.0, 0.3 in HL; - 1.9 min/day, 95% CI: - 3.3, - 0.5 in HF), but there was no significant group by time interaction. Several secondary outcomes for other health behaviors and workplace health environment showed improvements in favor of the intervention arm, yet differences did not remain statistically significant after adjustment for multiple comparisons. CONCLUSIONS: While the Healthy Lifestyles intervention did not improve health behaviors or the workplace health environment, results confirmed the pressing need to focus on the health of child care workers. Future interventions should focus on prevalent health issues (e.g., weight, stress), include both high-tech and high-touch intervention strategies, and address work conditions or other social determinants of health (e.g. wages) as a means of improving the health of these essential workers. TRIAL REGISTRATION: Care2BWell: Worksite Wellness for Child Care (NCT02381938).

A readily available improvement over method of moments for intra-cluster correlation estimation in the context of cluster randomized trials and fitting a GEE-type marginal model for binary outcomes.

BACKGROUND/AIMS: Cluster randomized trials are popular in health-related research due to the need or desire to randomize clusters of subjects to different trial arms as opposed to randomizing each subject individually. As outcomes from subjects within the same cluster tend to be more alike than outcomes from subjects within other clusters, an exchangeable correlation arises that is measured via the intra-cluster correlation coefficient. Intra-cluster correlation coefficient estimation is especially important due to the increasing awareness of the need to publish such values from studies in order to help guide the design of future cluster randomized trials. Therefore, numerous methods have been proposed to accurately estimate the intra-cluster correlation coefficient, with much attention given to binary outcomes. As marginal models are often of interest, we focus on intra-cluster correlation coefficient estimation in the context of fitting such a model with binary outcomes using generalized estimating equations. Traditionally, intra-cluster correlation coefficient estimation with generalized estimating equations has been based on the method of moments, although such estimators can be negatively biased. Furthermore, alternative estimators that work well, such as the analysis of variance estimator, are not as readily applicable in the context of practical data analyses with generalized estimating equations. Therefore, in this article we assess, in terms of bias, the readily available residual pseudo-likelihood approach to intra-cluster correlation coefficient estimation with the GLIMMIX procedure of SAS (SAS Institute, Cary, NC). Furthermore, we study a possible corresponding approach to confidence interval construction for the intra-cluster correlation coefficient. METHODS: We utilize a simulation study and application example to assess bias in intra-cluster correlation coefficient estimates obtained from GLIMMIX using residual pseudo-likelihood. This estimator is contrasted with method of moments and analysis of variance estimators which are standards of comparison. The approach to confidence interval construction is assessed by examining coverage probabilities. RESULTS: Overall, the residual pseudo-likelihood estimator performs very well. It has considerably less bias than moment estimators, which are its competitor for general generalized estimating equation-based analyses, and therefore, it is a major improvement in practice. Furthermore, it works almost as well as analysis of variance estimators when they are applicable. Confidence intervals have near-nominal coverage when the intra-cluster correlation coefficient estimate has negligible bias. CONCLUSION: Our results show that the residual pseudo-likelihood estimator is a good option for intra-cluster correlation coefficient estimation when conducting a generalized estimating equation-based analysis of binary outcome data arising from cluster randomized trials. The estimator is practical in that it is simply a result from fitting a marginal model with GLIMMIX, and a confidence interval can be easily obtained. An additional advantage is that, unlike most other options for performing generalized estimating equation-based analyses, GLIMMIX provides analysts the option to utilize small-sample adjustments that ensure valid inference.

Influence of mini-screw diameter and loading conditions on static and dynamic assessments of bone-implant contact: An animal study.

OBJECTIVES: The goal was to compare static versus dynamic bone-implant interface histology of mini-screws and to evaluate its relation to diameter and load. SETTING AND SAMPLE POPULATION: Canine animal model. MATERIAL AND METHODS: Custom-machined, titanium alloy (Ti6AI4V) mini-screws (n = 70) of 1.60, 2.00, 3.00 and 3.75 mm diameter were placed into edentulous sites in five skeletally mature beagle dogs. Using a split-mouth design, no load (NL) was applied to one side while a 2N load (L) was applied by calibrated coil springs on the other side. Intravenous bone labels were administered 21 and 7 days prior to sacrifice. Dogs were euthanized 90 days after screw placement. Bone sections were analysed under bright-field and epifluorescent light. The region of interest was defined as the bone within the threads of the screws. The following parameters were quantified: (a) Static-bone volume/tissue volume (BV/TV %) and bone-implant contact (BIC, %); (b) Dynamic-labelled bone/bone volume (LB/BV, %), and dynamic BIC (DBIC, %). RESULTS: BV/TV ranged from 71.2% to 85.0% of the screw surface. BIC ranged from 45.7% to 55.4% of the screw surface and was not affected by diameter (P = 0.66). In contrast, the percentage of DBIC did not vary with the applied load (P = 0.41); however, it correlated significantly with the diameter of the screw (P = 0.001). CONCLUSION: The percentage of DBIC that is actively remodelling increases with increasing diameter of the screw. Dynamic histomorphometry is more sensitive to detecting changes in bone-implant contact when compared to static measurements.

Novel application and validation of in vivo micro-CT to study bone modelling in 3D.

OBJECTIVES: The aim is to highlight a novel three-dimensional (3D) imaging methodology using micro-CT scans to visualize and measure bone modelling in an animal model. In order to validate the new methodology, we compared the 3D imaging method to traditional two-dimensional (2D) histomorphometry to assess growth changes in the jaws of a rodent. SETTING AND SAMPLE POPULATION: Rodent animal models. MATERIAL AND METHODS: Eleven rats were obtained from a larger previously published study. Sixty undecalcified histological sections from the maxilla and corresponding high-resolution in vivo micro-CT reconstructions were obtained. Bone modelling changes on specific alveolar surfaces were measured using traditional histomorphometry. Measurements of bone growth were also obtained via 3D Slicer software from 3D micro-CT generated models from the same plane containing the histological images. Both qualitative and quantitative 3D methods were compared to traditional histological measurements. Quantitative agreement between methods was categorized as follows: poor (>150 µm), good (150-100 µm) and excellent (<100 µm). RESULTS: Both qualitative (88.3%) and quantitative (86.7%) 3D measurements showed excellent agreement, when compared to histomorphometric measurements. Only 1.7% and 5% of the comparisons exhibited poor agreement (>150 µm) for qualitative and quantitative methods, respectively. DISCUSSION: The new 3D superimposition method compares very favourably with traditional histology. It is likely that in the future, such methods will be used in studies of bone adaptation. CONCLUSION: The 3D micro-CT qualitative and quantitative methods are reliable for measuring bone modelling changes and compare favourably to histology for the specific application described.

A rodent model using skeletal anchorage and low forces for orthodontic tooth movement.

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.

Blood transfusions in preterm infants: changes on perfusion index and intermittent hypoxemia.

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.

A comparison of bias-corrected empirical covariance estimators with generalized estimating equations in small-sample longitudinal study settings.

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.