Estimates of Information Growth in Longitudinal Clinical Trials

In group sequential clinical trials, it is necessary to estimate the amount of information present at interim analysis times relative to the amount of information that would be present at the final analysis. If only one measurement is made per individual, this is often the ratio of sample sizes available at the interim and final analyses. However, as discussed by Wu and Lan (1992), when the statistic of interest is a change over time, as with longitudinal data, such an approach overstates the information. In this paper, we discuss other problems that can result in overestimating the information, such as heteroscedasticity and correlated observations. We demonstrate that when using an inefficient estimator on unbalanced data, the true information growth can be nonmonotonic across interim analyses

Using Trends in Biometric Data to Predict Interest in Enrolling in an Employer-Sponsored National Diabetes Prevention Program Focusing on Diet and Exercise: A Retrospective Cohort Study

Background: Evidence-based lifestyle programs including the Diabetes Prevention Program can delay an individual’s risk of developing type 2 diabetes. Identifying which individuals are less likely to enroll in these programs and tailoring recruitment approaches to encourage participation among those with perceived barriers is an effective strategy to increase engagement in health promotion. This study aimed to identify the pre-enrollment differences in biometric trends between individuals with prediabetes who did and did not express interest in free worksite diabetes prevention programs.Subjects and Method: This retrospective cohort study was conducted among individuals in the Midwest enrolled in a private insurance plan from 2011 to 2014. Data was combined from annual biometric screenings and a health survey. Demographic characteristics were summarized for the study population (n=2,066). The dependent variable for this study was interest in the DPP, while the independent variables included body mass index, waist circumference, body weight, lipid measurements, and blood pressure. Linear mixed models with random intercepts were used to compare bio-metric trajectories for body mass index, waist circumference, body weight, lipid measurements (triglycerides and cholesterol), and blood pressure for the two groups.Results: No differences were observed in biometric trends for those who did and did not choose to enroll in the free worksite program.Conclusion: Examining pre-enrollment biometric trend data is a relatively novel approach to evaluating engagement in health programs. More research is needed to understand how this information can be used to identify an individual’s interest in enrolling in health programming

Risk factors for the development of stifle injuries in canine agility athletes

ObjectivesOur aim was to determine risk factors for developing stifle injuries in canine agility athletes. We hypothesized that increased weight, increased frequency of competing, and greater number of runs/day would increase risk.Study designInternet based survey, n = 4,197.MethodsIndividuals with at least one dog who had competed in agility in the past 3 years were eligible. Injury history was defined as an injury to the stifle that kept the dog from participating in agility for >1 week. Logistic regression models were used to estimate associations between variables of interest and injury history.ResultsHandlers of 216 dogs reported a history of injury. The majority were cranial cruciate ligament (CCL) injury (101/216), and patella luxation (40/216). In the final model, five variables were independently associated with odds of stifle injury (in addition to age). Heavier dogs (adjusted for height), Border Collies, male dogs neutered <10 months, female dogs spayed before their first heat cycle, handlers aged 18–24, and teeter contact behavior were associated with increased risk.ConclusionHeavier dogs were more likely to report injury, but there was no association with injury and increased number of competition days, or runs/day. The Border Collie breed was at the highest risk of injury. There was substantial risk for stifle injury with early spay/neuter. Additionally, a significant increase in risk of injury was reported for younger (18–24) vs. older handlers (65+). Athlete fitness level, conformation, and genetic predisposition to injury may play the most significant role in the development of injury

Owner-reported treatments and outcomes of perceived injuries to the thoracic and pelvic limb of agility dogs

ObjectiveThe aim of this study was to identify the type of veterinary care sought by handlers of injured agility dogs, the types of treatments the dogs received, and the timeframe for return to training and competition.ProceduresOwners of agility dogs completed an internet-based survey. They were instructed to report injuries that had kept the dog from training or competing for over a week, identify which area(s) of the body had been injured and answer questions about the most severe injury to each body part. Additional questions included if handlers had sought veterinary care, who primarily determined treatment, type of treatment(s), and length of time before the dog could return to full training and competition.ResultsThis sample included data on 1,714 total injuries from 1,256 unique dogs. Handlers sought veterinary care for over 80% of injuries across all anatomical locations. Handlers were most likely to seek specialty veterinary care for reported injuries to the stifle (71%), iliopsoas (63%) and tibia (61%), and least likely for reported injuries to the carpus (34%), metatarsus (33%) and metacarpus (22%). Treatment of reported injuries to the antebrachium and stifle were most likely to be directed by a veterinarian (>70%), while reported injuries of the thigh (51%) and hip (53%) were least likely. Rest was the most common treatment for all injuries. Return to sport within 3 months was common (>67%) for most perceived injury locations, though dogs with reported stifle injuries took longer to return to competition and had a higher rate of retirement.Conclusion and clinical relevanceOwners of agility dogs have a high rate of seeking veterinary care for injuries. Overall return to sport rates were high, with the stifle being the notable exception. Future studies regarding specific treatment of injuries in agility dogs, and how injuries and their treatment affect return to agility after injury are required to provide optimal care protocols for these canine athletes

Evaluation of Surface Type and Time of Day on Agility Course Performance

INTRODUCTION: Canine agility competitions are performed on a variety of surfaces. In the equine and human literature, surface type has been associated with speed, performance, and injury risk. The aim of this study was to evaluate the effect of general surface type and time of day on calculated speed (yards per second over a measured course distance) and course performance during the UKI Agility International (UKI) U.S. Open. We hypothesized that surface type would affect calculated speed, with sand being the slowest. MATERIALS AND METHODS: Data on course performance from the 2021 and 2022 events were obtained directly from UKI. The officiating judge measured course length, automatic timers recorded dogs\u27 course times, and speeds were calculated from these values. Three surfaces (dirt, grass, and sand) were compared across three categories of courses (jumpers, standard, and speedstakes). Differences in calculated speeds and qualifying rates were estimated using generalized estimating equations (GEE) to account for multiple runs by the same handler. RESULTS: Among jumpers courses, those run on sand in 2021 were markedly slower than those run on dirt. Grass and dirt were more similar in terms of average calculated speed, though some courses run on grass were significantly faster than courses run on dirt and vice versa. Time of day effects observed were inconsistent, with more variability observed for dirt and sand than for grass. DISCUSSION: There was a notable variation in calculate speed based on surface with sand being slowest, likely due to the increased energy cost required to run on sand due to its high compliance. Calculated speeds on grass and dirt appeared generally similar, but there was substantial variability of calculated speed among various courses, making comparison of surface effects challenging. Variables within the surface itself (such as compaction level and moisture content) likely play a role in the effects of surface on speed and performance. This study provides insight into the complexity of surface effects on performance in agility dogs and highlights the need for canine-specific surface studies on the effect of surface variables and how these relate to risk of development of musculoskeletal injuries

Testing a brief web-based intervention to increase recognition of tobacco constituents

Objective: We examined website formats to increase smokers\u27 recognition of harmful and potentially harmful constituents (HPHCs) in cigarettes. Methods: Adult, daily smokers (N = 279) were randomized to view a brief, single-page study website showing HPHC names and uses. The intervention site was tailored + interactive, labeled by cigarette brand/subbrand showing color imagery and pop-up boxes; the generic + static website (control) was unbranded in greyscale. Eye tracking equipment measured attention (dwell time) to precise website features. Linear regression analyses compared attention to HPHC descriptions and the correct recognition of 15 HPHC chemicals. A randomly selected sub-sample (N = 30) of participants qualitatively rated website usability. Results: Despite spending less dwell time on the HPHC text and entire website, adult smokers who viewed the generic + static website had greater improvement in HPHC recognition compared to the tailored + interactive website (4.6 vs 3.6; p = .02); this finding contrasts with current literature on tailoring and interactivity. Both websites were rated highly on ease-of-use and readability. Conclusions: Basic formats and narrative HPHC Web-based content attracted less visual attention, yet increased recognition of these chemicals in cigarettes, compared to brand-tailored, interactive web-based content

Distribution of cardiovascular health by individual- and neighborhood-level socioeconomic status: Findings from the Jackson Heart Study

BACKGROUND: Data demonstrate a positive relationship between socioeconomic status (SES) and cardiovascular health (CVH). OBJECTIVE: To assess the association between individual- and neighborhood-level SES and CVH among participants of the JHS (Jackson Heart Study), a community-based cohort of African Americans in Jackson, Mississippi. METHODS: We included all JHS participants with complete SES and CVH information at the baseline study visit (n = 3,667). We characterized individual- and neighborhood-level SES according to income (primary analysis) and education (secondary analysis), respectively. The outcome of interest for these analyses was a CVH score, based on 7 modifiable behaviors and factors, summed to a total of 0 (worst) to 14 (best) points. We utilized generalized estimating equations to account for the clustering of participants within the same residential areas to estimate the linear association between SES and CVH. RESULTS: The median age of the participants was 55 years, and 64% were women. Nearly one-third of eligible participants had individual incomes \u3c$20,000 and close to 40$25,480). Adjusted for age, sex, and neighborhood SES, there was an average increase in CVH score of 0.31 points associated with each 1-category increase in individual income. Similarly, each 1-category increase in neighborhood SES was associated with a 0.19-point increase in CVH score. These patterns held for our secondary analyses, which used educational attainment in place of income. These data did not suggest a synergistic effect of individual- and neighborhood-level SES on CVH. CONCLUSIONS: Our findings suggest a potential causal pathway for disparities in CVH among vulnerable populations. These data can be useful to the JHS community to empower public health and clinical interventions and policies for the improvement of CVH

A Comparison of Benefit Limits in Mental Health

This study provides insight to policy makers and stakeholders on how three types of benefits limits on Medicaid-covered mental health services might affect access for consumers diagnosed with severe mental illness. The study used a retrospective cohort design with data for Medicaid-covered, community-based mental health services provided in Ohio during fiscal year 2010. Log-binomial regression was used for the analysis. Results indicate that limits compared have significant, varying consequences based on Medicaid coverage and diagnoses. When constraining Medicaid costs, policy makers should consider how limits will disrupt care and include clinicians in discussions prior to implementatio

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

BackgroundPatients 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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

A Study to Assess the Efficacy of Enasidenib and Risk-Adapted Addition of Azacitidine in Newly Diagnosed IDH2-Mutant AML

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998