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.

Mindfulness-based Interventions Across the Cancer Continuum in the United States: A Scoping Review.

OBJECTIVE: To review mindfulness-based interventions (MBIs) tested in randomized controlled trials (RCT) across the cancer continuum. DATA SOURCE: Articles identified in PubMed, CINAHL, Web of Science, PsycINFO, and Embase. STUDY INCLUSION AND EXCLUSION CRITERIA: Two independent reviewers screened articles for: (1) topic relevance; (2) RCT study design; (3) mindfulness activity; (4) text availability; (5) country (United States); and (6) mindfulness as the primary intervention component. DATA EXTRACTION: Twenty-eight RCTs met the inclusion criteria. Data was extracted on the following variables: publication year, population, study arms, cancer site, stage of cancer continuum, participant demographic characteristics, mindfulness definition, mindfulness measures, mindfulness delivery, and behavioral theory. DATA SYNTHESIS: We used descriptive statistics and preliminary content analysis to characterize the data and identify emerging themes. RESULTS: A definition of mindfulness was reported in 46% of studies and 43% measured mindfulness. Almost all MBIs were tested in survivorship (50%) or treatment (46%) stages of the cancer continuum. Breast cancer was the focus of 73% of cancer-site specific studies, and most participants were non-Hispanic white females. CONCLUSION: The scoping review identified 5 themes: (1) inconsistency in defining mindfulness; (2) differences in measuring mindfulness; (3) underrepresentation of racial/ethnic minorities; (4) underrepresentation of males and cancer sites other than breast; and (5) the lack of behavioral theory in the design, implementation, and evaluation of the MBI.

Video brochures in a mailed fecal immunochemical test outreach program provide cancer screening information in a user-friendly format for rural Appalachian community members.

PURPOSE: Colorectal cancer (CRC) screening is recommended for average-risk adults, yet many adults are not up-to-date with screening. One recommended CRC screening approach is the annual completion of a fecal immunochemical test (FIT). However, usually, fewer than half of mailed FIT tests are returned. METHODS: To address barriers to FIT return, a video brochure was developed providing targeted CRC screening information and step-by-step FIT instructions as a component in a mailed FIT program. This pilot study occurred in 2021-2022 and partnered with a federally qualified health center in Appalachian Ohio to send a FIT to patients who were 50-64 years old, of average risk, and not up-to-date on CRC screening. Patients were randomly assigned to 1 of 3 groups that differed on materials sent with the FIT: usual care (manufacturer's instructions), a video brochure (video instructions, disposable gloves, disposable stool collection device), or an audio brochure (audio instructions, disposable gloves, disposable stool collection device). FINDINGS: Overall, 16 of 94 patients (17%) returned the FIT, and return was higher among those sent the video brochure (28%) compared to the other 2 groups (OR: 3.1; 95% CI: 1.02, 9.2; P = .046). Two patients had positive tests and were referred for colonoscopy. Patients sent the video brochure reported the content was important, relevant, and made them think about completing the FIT. CONCLUSIONS: Using a video brochure to provide understandable information in a mailed FIT kit is a promising strategy to improve CRC screening outreach programs in rural regions.

Predictors of Stress Exposure in Hospitalized Preterm Infants.

BACKGROUND: Stress exposure in the neonatal intensive care unit (NICU) is associated with poor outcomes in preterm infants. However, factors predicting subsequent NICU stress exposure have not been identified. PURPOSE: To characterize NICU stressors experienced by preterm infants during the first 2 weeks of life and identify demographic, perinatal, and institutional variables associated with stress exposure. METHODS: A secondary analysis of data from a nonexperimental, prospective study was conducted using data from 60 very preterm infants born 28 to 31 weeks gestational age. Stress exposures during the first 2 weeks of life, operationalized as number of invasive procedures, were characterized by type and quantity for each infant using data extracted from electronic health records. Associations between number of invasive procedures and demographic, perinatal, or institutional variables were analyzed using linear regressions with robust standard errors. RESULTS: Preterm infants experienced, on average, 98 (SD = 41.8) invasive procedures. Of these invasive procedures, nasal and/or oral suctioning episodes (58.1%), followed by skin-breaking procedures (32.6%), were most frequent. Differences in the number of invasive procedures were found for maternal race; infants born to Black mothers experienced fewer total invasive procedures than infants born to White mothers. The number of invasive procedures also varied across NICUs. IMPLICATIONS FOR PRACTICE AND RESEARCH: Preterm infant stress exposure differed by maternal race and NICU, consistent with research findings of differential treatment of diverse infants. Further research is needed to understand the reasons for these differences and to identify best practices to standardize neonatal care.

Effect of a Telephone-Based Lifestyle Intervention on Weight, Body Composition, and Metabolic Biomarkers in Rural Ohio: Results from a Randomized Pilot Study.

Rural residents experience higher rates of obesity, obesity-related chronic diseases, and poorer lifestyle. Promoting physical activity and healthy eating are critical for rural residents; however, lack of resources and access barriers limit the feasibility of in-person lifestyle interventions. There is a need to design and deliver remotely accessible lifestyle interventions in this population. This pilot study examined the effect of a telephone-based lifestyle intervention on weight, body composition, lipids, and inflammatory biomarkers among rural Ohio residents. Rural Ohio adults with overweight/obesity (n = 40) were 2:1 randomized to a 15-week telephone-based lifestyle intervention (n = 27) or control group (n = 13). The lifestyle intervention group received weekly telephone counseling sessions emphasizing healthy eating and increasing physical activity. The control group received educational brochures describing physical activity and dietary recommendations. Weight, body composition, fasting blood lipids, and inflammatory biomarkers were objectively measured at baseline and 15 weeks at local community centers (trial registration#: NCT05040152 at ClinicalTrial.gov). Linear mixed models were used to examine change over time by group. Participants were mostly female, with an average age of 49 years. Over the 15-week trial, the lifestyle intervention showed superior improvements in total cholesterol (∆ = -18.7 ± 7.8 mg/dL, p = 0.02) and LDL (∆ = -17.1 ± 8.1 mg/dL, p = 0.04) vs. control, whereas no significant between-group differences in weight, body composition, or inflammation were observed. Our findings suggest that a 15-week telephone-based lifestyle intervention may offer metabolic benefits that reduce disease risk in rural adults with obesity. Future large-scale studies are needed to determine the efficacy of remotely accessible lifestyle interventions in rural populations, with the goal of reducing obesity-related disparities.

Lower centrifugation speed and time are positively associated with platelet concentration in a canine autologous conditioned plasma system.

OBJECTIVE: To evaluate the effect of variable centrifugation protocols on the cellular composition of the final product of a canine autologous conditioned plasma double-syringe system. ANIMALS: 30 client-owned healthy adult medium- to large-breed (17- to 45-kg) dogs. METHODS: 35 mL of anticoagulated whole blood from each subject was aliquoted into 3 samples: a baseline and 2 double syringes. The syringes were processed for platelet-rich plasma (PRP). Each double syringe was randomly assigned to 1 of 5 groups, which varied in centrifugation settings between 580 and 1,304 X g and 5 and 10 minutes. CBC analysis was performed on each of the samples to determine cellular composition. A mixed-effect linear model was fit to the data. RESULTS: 60 PRP samples and 30 whole blood samples were analyzed. Manufacturer settings generated a platelet fold change > 1 but did not increase concentration to the extent expected. When comparing speed alone, increased centrifugation force was associated with lower platelet fold change. When comparing time alone, increased centrifugation time was also associated with lower platelet fold change and lower leukocyte concentration. CLINICAL RELEVANCE: Autologous conditioned plasma double syringes require a low volume of initial whole blood, making them preferable for canine PRP in clinical settings. This study aimed to evaluate the effect of the centrifugation protocol on the final product cellular composition in dogs and add to the available data on protocols to maximize platelet yield in PRP. Due to inherent individual variability, this study emphasized the importance of evaluating biological samples prior to administration to predict and improve patient outcomes.

Differences in obesity-related health behaviors and health outcomes by rural and Appalachian residency.

PURPOSE: Obesity and health behaviors are the major modifiable contributors to cancer and health disparities. We examined the differences in obesity-related health behaviors, and health outcomes by rural and Appalachian residency in Ohio. METHODS: Cross-sectional survey data from the 2011-2019 Behavioral Risk Factor Surveillance System were obtained from the Ohio Department of Health. County-level identifiers were used to classify urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian residency. Self-reported weight, height, health behaviors, and health conditions were used. Logistic regression was used to assess the difference in health behaviors and health outcomes by rural and Appalachian residency. All analyses incorporated with sample weights. RESULTS: Among Ohio residents, compared to urban non-Appalachian residents, urban Appalachian and rural Appalachian residents had a higher prevalence of obesity, hypertension, high cholesterol, and cardiovascular diseases, as well as lower rates of healthy diet and physical activity. No difference was found in trends of obesity and obesity-related health outcomes in 2011-2019 by rural and Appalachian residency. However, rural Appalachian residents had a greater increase in obesity, hypertension, and diabetes, whereas rural non-Appalachian had favorable changes in obesity-related health behaviors. Additionally, associations between health behaviors and obesity-related health outcomes differed by rural and Appalachian residency. CONCLUSIONS: Findings underscore the importance of distinguishing between urban non-Appalachian, urban Appalachian, rural non-Appalachian, and rural Appalachian populations when assessing health disparities. While the trends of obesity and obesity-related health outcomes did not differ, the association between health behaviors and obesity-related outcomes differed by rural and Appalachian residency.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. RESULTS: The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. CONCLUSIONS: The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

The Role of Cigarillo Flavor in the Co-Use of Cigarillos and Cannabis among Young Adults.

Background: Research suggests flavor facilitates cigarillo use, but it is unknown if flavor impacts patterns of co-use of cigarillos and cannabis ("co-use"), which is common among young adult smokers. This study's aim was to determine the role of the cigarillo flavor in co-use among young adults. Methods: Data were collected (2020-2021) in a cross-sectional online survey administered to young adults who smoked ≥2 cigarillos/week (N = 361), recruited from 15 urban areas in the United States. A structural equation model was used to assess the relationship between flavored cigarillo use and past 30-day cannabis use (flavored cigarillo perceived appeal and harm as parallel mediators), including several social-contextual covariates (e.g., flavor and cannabis policies). Results: Most participants reported usually using flavored cigarillos (81.8%) and cannabis use in the past 30 days ("co-use") (64.1%). Flavored cigarillo use was not directly associated with co-use (p = 0.90). Perceived cigarillo harm (ß = 0.18, 95% CI = 0.06, 0.29), number of tobacco users in the household (ß = 0.22, 95% CI = 0.10, 0.33), and past 30-day use of other tobacco products (ß = 0.23, 95% CI = 0.15, 0.32) were significantly positively associated with co-use. Living in an area with a ban on flavored cigarillos was significantly negatively associated with co-use (ß = -0.12, 95% CI = -0.21, -0.02). Conclusions: Use of flavored cigarillos was not associated with co-use; however, exposure to a flavored cigarillo ban was negatively associated with co-use. Cigar product flavor bans may reduce co-use among young adults or have a neutral impact. Further research is needed to explore the interaction between tobacco and cannabis policy and use of these products.

Efficacy of the Outsmart HPV Intervention: A Randomized Controlled Trial to Increase HPV Vaccination among Young Gay, Bisexual, and Other Men Who Have Sex with Men.

BACKGROUND: Routine human papillomavirus (HPV) vaccination is recommended for young adults, yet many young gay, bisexual, and other men who have sex with men (YGBMSM) remain unvaccinated. We report the efficacy of Outsmart HPV, a web-based HPV vaccination intervention for YGBMSM. METHODS: From 2019 to 2021, we recruited YGBMSM in the United States who were ages 18-25 and unvaccinated against HPV (n = 1,227). Participants were randomized to receive either: (i) Outsmart HPV content online and monthly interactive text reminders (interactive group); (ii) Outsmart HPV content online and monthly unidirectional text reminders (unidirectional group); or (iii) standard information online about HPV vaccine (control group). Regression models compared study groups on HPV vaccination outcomes. RESULTS: Overall, 33% of participants reported initiating the HPV vaccine series and 7% reported series completion. Initiation was more common among participants in the interactive group compared with the control group [odds ratio (OR) = 1.47, 98.3% confidence interval (CI): 1.03-2.11]. Completion was more common among participants in both the interactive group (OR = 3.70, 98.3% CI: 1.75-7.83) and unidirectional group (OR = 2.26, 98.3% CI: 1.02-5.00) compared with the control group. Participants who received Outsmart HPV content reported higher levels of satisfaction with online content compared with the control group. CONCLUSIONS: Outsmart HPV is an efficacious and acceptable HPV vaccination intervention for YGBMSM. Future efforts are needed to determine how to optimize the intervention and disseminate it to settings that provide services to YGBMSM. IMPACT: Outsmart HPV is a promising tool for increasing HPV vaccination among YGBMSM with the potential for wide dissemination.

Postnatal Cytokine Trajectories in Very Preterm Infants.

Inflammation often accompanies preterm birth and contributes to poor neurodevelopment in preterm infants. The purpose of this study was to describe postnatal cytokine trajectories among non-infected very preterm infants during the first weeks of life. Blood samples for cytokine analysis were collected weekly from infants born between 28 and 31 weeks post-menstrual age. We used linear mixed models to calculate slopes for each cytokine and allowed the slopes to differ by infant biological sex and post-menstrual age at birth. Levels of interleukin-6, interleukin-8, and interleukin-1 receptor antagonist decreased, on average, during the neonatal period. Monocyte chemoattractant protein-1 levels increased over time, and tumor necrosis factor-alpha levels were stable. Interleukin-6 and interleukin-8 slopes differed by post-menstrual age at birth but were unaffected by infant sex. Knowledge of average cytokine trajectories may be useful in identifying infants with unresolving inflammation that increases their risk for poor neurodevelopment.

BRCAShare-Assessment of an animated digital message for intrafamilial communication of pathogenic variant positive test results: A feasibility study.

While genetic testing for hereditary breast and ovarian cancer syndrome (HBOC) is well-established in the field of medicine, family members' uptake of cascade genetic testing for known familial pathogenic variants remains low. Probands often become responsible for initiating familial communication about their testing results, and barriers to communication may include difficulty in conveying information to relatives and a lack of communication resources for probands' use. In this study, we tested a two-minute animated digital message (ADM) intervention guided by the Health Belief Model (HBM) in an unselected sample to determine hypothetical individual perceptions of susceptibility and severity and behavioral intention to act on the information provided in the ADM. We recruited genetic testing naïve adults from the United States with no personal history of cancer through Amazon Mechanical Turk to participate in this study. Participants were presented a hypothetical scenario describing a relative's recent HBOC diagnosis, viewed the ADM, and answered a questionnaire assessing participants' perception of the HBM constructs in relation to the hypothetical scenario and participants' intentions to pursue cascade genetic testing, talk to a healthcare professional, or talk to family members after ADM viewing. Participants (n = 373) largely perceived HBOC as serious and believed that they could benefit from the information provided by genetic testing; 76% hypothetically intended to pursue genetic testing at a cost of $100 or less, and 90% intended to either pursue testing or talk to a healthcare provider or family members. This feasibility study in an unaffected population could mimic the experience of distant/less-engaged relatives in HBOC families after receiving unexpected information about cascade genetic testing. Most participants demonstrated behavioral intention toward cascade testing, at a rate higher than literature would suggest is typical in high-risk families, indicating that a theory-supported, simple to use intervention may be useful in clinical practice.

Effects of a web-based HPV vaccination intervention on cognitive outcomes among young gay, bisexual, and other men who have sex with men.

Knowledge, attitudes, and beliefs are important antecedents to HPV vaccination, yet remain suboptimal among young gay, bisexual, and other men who have sex with men (YGBMSM). We report the effects of a theoretically-informed, web-based HPV vaccination intervention on these cognitive outcomes. From 2019-2021, we recruited a national sample of YGBMSM ages 18-25 in the United States who were unvaccinated against HPV (n = 1,227). Participants received either standard HPV vaccination information online (control) or population-targeted, individually-tailored content online (Outsmart HPV intervention). Mixed effects models determined if pre-post changes in cognitive outcomes differed between study groups. For five of seven knowledge items about HPV, there were larger pre-post increases among the intervention group than the control group in the percentage of participants who provided correct responses (all statistically significant at p = .05 after Holm's correction). There were also larger pre-post improvements among the intervention group than the control group for most attitudes and beliefs examined, including response efficacy of HPV vaccine (pre-post increases in means: 0.57 vs. 0.38); self-efficacy for the HPV vaccination process (pre-post increases in means: 0.23 vs. 0.10); and intention to get HPV vaccine (pre-post increases in means: 0.70 vs. 0.28) (all statistically significant at p = .05 after Holm's correction). Outsmart HPV is a promising tool for improving key cognitive antecedents to HPV vaccination among YGBMSM, supporting the use of theoretically-informed interventions to affect such outcomes. If efficacious in increasing HPV vaccine uptake in future analyses, this intervention could be utilized in clinical and other healthcare settings that provide services to YGBMSM.

Internet Survey Evaluation of Iliopsoas Injury in Dogs Participating in Agility Competitions.

Objective: To describe risk factors associated with demographics, training, and competition for iliopsoas injury in dogs participating in agility competitions, as well as describe owner reported treatment and return to sport following injury. Procedures: An internet-based survey of agility handlers collected risk factor data for dogs participating in agility. Owners were asked questions about demographics, training, and competition as well as injury treatment and recovery if applicable. Associations between variables of interest and iliopsoas injury were estimated with logistic regression. The final risk factor model was built via modified backward selection, with all variables in the final model showing significant associations at p < 0.05. Results: Of the 4,197 dogs in the sample, 327 (7.8%) reported iliopsoas injury. The final model identified six risk factors for iliopsoas injury. A higher risk of iliopsoas injury was observed for the Border Collie breed, dogs with handlers who are veterinary assistants, dogs competing on dirt, dogs competing on artificial turf 6+ times a year, and dogs that trained with the 2 × 2 method for weave poles. Dogs that were not acquired with agility in mind were observed to have a decreased risk of injury. Factors like number of competition days and jump height were not significantly associated with risk of iliopsoas injury. Owners sought veterinary care for 88% of dogs with iliopsoas injury, including specialty care for 63%. Treatment most often included rest, home rehabilitation, formal rehabilitation, and/or oral medications. Most dogs (80%) were able to return to sport within 6 months, while 20% were out for longer than 6 months, or retired. Conclusion and Clinical Relevance: Iliopsoas injury can necessitate a significant amount of time off from training and competition, and even lead to retirement of dogs competing in agility. Some of the risk factors identified in this study can inherently not be modified (breed, intended use, and handler profession), but can be taken into consideration for injury prevention strategies. Competition and training risk factors that can be modified, such as weave training, may help to inform guidelines for best practices in management of the agility athlete.

Cigarillo Flavor and Motivation to Quit among Co-Users of Cigarillos and Cannabis: A Structural Equation Modeling Approach.

Flavored cigar restrictions have the potential to benefit public health. Flavor availability facilitates cigarillo use, but it is unknown if flavor impacts patterns of co-use of cigarillos and cannabis, an increasingly prevalent behavior among young adults. Data were collected (2020-2021) in a cross-sectional online survey administered to a convenience sample of young adults who smoked cigarillos from 15 areas with high cigar use prevalence. We assessed the relationship between flavored cigarillo use and motivation to quit cannabis and cigarillo use among past 30-day co-users (N = 218), as well as several covariates (e.g., cigarillo price and flavor/cannabis policy). Flavored cigarillo perceived appeal and harm were hypothesized parallel mediators. Most co-users reported usually using flavored cigarillos (79.5%), which was not significantly associated with motivation to quit cigarillos or cannabis. Perceived cigarillo harm (ß = 0.17, 95% CI = 0.00, 0.33), advertising exposure (ß = 0.12, 95% CI = 0.00, 0.24), and income (among racial/ethnic minorities; ß = -0.13, 95% CI = -0.25, -0.02) were significant predictors of motivation to quit cigarillos. There were no significant predictors of motivation to quit cannabis. Cigarillo flavor was not associated with motivation to quit, so findings could suggest that banning flavors in cigars may have a neutral impact on co-use with cannabis among young adults.

Internet Survey Evaluation of Demographic Risk Factors for Injury in Canine Agility Athletes.

Objective: The purpose of this study was to compare previously identified demographic risk factors for injury in agility dogs, and explore other potential associations with demographic risk factors in new populations, and across different levels of injury severity. Procedures: An internet-based survey of agility handlers was conducted. The primary outcome was if the dog had ever had an injury that kept from agility for over a week. Demographic information about the dog and handler were recorded. Logistic regression was used to quantify associations between variables of interest with injury history and all models were adjusted for age. Analyses were stratified by geographic location. Final model building was done via backward selection. Results: The sample included 2,962 dogs from North America and 1,235 dogs from elsewhere. In the North American sample, 8 variables were associated with injury history; dog breed, height and weight, handler age, gender, agility experience, competing at the national level, age dog was acquired, and taking radiographs to assess growth plate closure. In the non-North American sample, 4 variables were associated with injury history; breed, handler age, occupation (dog trainer or not), and handler medical training. In both samples, Border Collies showed a marked increase in injury risk (ORs 1.89 and 2.34) and handler age >65 was associated with lower risk (ORs 0.62 and 0.77). Consistent with previous studies, greater handler experience was associated with reduced risk in the North American sample, but the other sample did not show this pattern, even in unadjusted models. Dog spay/neuter status was not associated with injury risk in either sample. Conclusions and Clinical Relevance: Dogs with radiographs assessing growth plate closure may have increased injury risk as this population of owners may plan to train their dog harder, and at an earlier age. This finding also poses the question of whether or not growth plate closure is a good indicator of safety for increasing training intensity. Knowledge of what risk factors exist for injury in agility dogs is imperative in determining direction for future prospective studies, as well as creating recommendations to help prevent injury in this population of dogs.

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.

Internet-based survey of the frequency and types of orthopedic conditions and injuries experienced by dogs competing in agility.

OBJECTIVE: To describe the frequency and types of injuries experienced by dogs competing and training in agility and identify breed and geographic differences in frequency and types of injuries. SAMPLE: Surveys completed by owners of 4,701 dogs. PROCEDURES: The study involved an internet-based survey. Participants were asked whether their dog had ever had an injury that kept it from participating in agility for > 1 week and, if so, to identify the location and type of injury. RESULTS: Owners of 1,958 (41.7%) dogs reported that their dogs had experienced an injury. The most common injury locations were the shoulder region (n = 589 [30.1% of all dogs with an injury]) and iliopsoas muscle (380 [19.4%]). The percentage of Border Collies sustaining an injury (549/1,052 [51.9%]) was significantly higher than percentages of other breeds. Percentage of dogs that sustained an injury varied by country, with the highest percentage reported in Australia (93/174 [53.4%]) and lowest percentage reported in the US (1,149/2,889 [39.8%]). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that, among dogs competing and training in agility, injuries to the shoulder region were substantially more common than injuries in other anatomic locations, with iliopsoas muscle injuries second most common. The frequency and types of injuries varied among breeds and geographic regions. Findings may help guide clinical evaluations when agility dogs are seen in clinical practice for performance issues or lameness. Further studies regarding regional differences in injury rates are required.

Impact of Previous Genetic Counseling and Objective Numeracy on Accurate Interpretation of a Pharmacogenetics Test Report.

INTRODUCTION: Pharmacogenetic (PGx) testing can be useful for providing information about a patient's drug response by increasing drug efficacy and decreasing the incidence of adverse drug events. While PGx tests were previously only offered to patients under healthcare provider supervision, they are now available as direct to consumer (DTC) tests. This study aimed to assess how accurately individuals from the general population were able to interpret a sample PGx test report and if accuracy differed based on individuals' numeracy or prior genetic counseling (GC). METHODS: We surveyed 293 individuals from the general population, ascertained through ResearchMatch. The survey included questions about PGx test interpretation, numeracy, and genetic literacy. RESULTS: In our cohort, numeracy level impacted PGx result interpretation, with those of high numeracy performing statistically significantly better on both the table format and graphical format (p value = 0.002 and p value <0.001, respectively) and genetic knowledge questions (p value <0.001) than those with low/average numeracy. In addition, previous GC did not impact test interpretation or genetic knowledge, but the number of individuals with prior GC was small (n = 26). DISCUSSION/CONCLUSION: We found that numeracy had a significant impact on correct interpretation of PGx test reports. Because many individuals in the USA have low numeracy levels, it is extremely important that patients do not make their own medication management decision based on the test results and that they consult with their physicians about their PGx testing. The importance of consultation and discussion with providers about results should be emphasized on the test report.