Evaluation of a Novel Battery-Operated Tumbler Device for Use in the Detection of Mouse Pathogens for Rodent Health Monitoring.

The search for alternatives to live animal sentinels in rodent health monitoring programs is fundamental to the 3Rs (Reduction, Replacement, and Refinement) of animal research. We evaluated the efficacy of a novel battery-operated tumbler device that rotates soiled bedding in direct contact with sample media against the use of exhaust sample media and soiled bedding sentinel (SBS) mice. Four rodent racks were used, each with 3 test cages: a cage with a tumbler device that rotated for 10 min twice a week (TUM10), a cage with a tumbler device that rotated for 60 min twice a week (TUM60), and a cage housing 2 female Crl:CD1(ICR) mice. Every 2 wk, each test cage received soiled bedding collected from all cages on each respective rack. In addition to soiled bedding, the tumbler device contained various sample collection media: a contact Reemay filter (3 mo-cRF) that remained in the tumbler for the duration of the study, a contact Reemay filter (1 mo-cRF) that was replaced monthly, adhesive swabs (AS) that were added at every biweekly cage change, and an exhaust Reemay filter located at the exhaust outlet of the cage. All analyses were performed by direct PCR for both sample media in the animal-free methods, and fecal pellet, body swab, and oral swabs were collected from sentinel mice. Out of 16 total pathogens detected, assessment of 1 mo-cRF from both TUM10 and TUM60 cages detected 84% and 79% of pathogens, respectively, while SBS samples detected only 47% of pathogens. AS in TUM60 and TUM10 cages detected the fewest pathogens (24% and 13%, respectively). These results indicate that the novel tumbler device is an effective and reliable tool for rodent health monitoring programs and a suitable replacement for live animal sentinels. In this study, 1 mo-cRF in TUM10 cages detected the highest number of pathogens.

Mortality and Ankylosing Spondylitis in the US population: leading causes and associated factors.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic inflammatory condition that affects the axial skeleton. Recent studies have shown that mortality risk is higher in AS patients and that it is possibly related to disease activity and duration. Our aim was to investigate the leading causes and factors associated with mortality in hospitalized AS patients in the USA. METHODS: This is a case-control study using the Cerner Health Facts® database between 2015 and 2017. The search was done using ICD codes and administrative claims. Cases were hospitalized AS patients who died during that hospitalization, while controls were patients who survived. In addition to demographics, we collected data on the inpatient use of medications such as NSAIDs, as well as different comorbidities and systemic disease manifestations. The discharge diagnoses for deceased patients were collected to infer causes of mortality. Analysis of association was performed using chi-square tests, t-tests, Wilcoxon rank-sum tests, and logistic regression methods. RESULTS: The leading causes of death were cardiovascular, infectious, respiratory, and traumatic. The Elixhauser comorbidity index was the factor most associated with mortality (p-value < 0.0001), with congestive heart failure and renal disease the most contributing. Drug use disorder was associated with mortality (adjusted OR = 10.9; p = 0.001). Inpatient NSAIDs use was not associated with increased odds for mortality (p-value 0.33). CONCLUSION: Cardiovascular and renal comorbidities are associated with mortality and need to be targeted early on to lower the odds of mortality as patients age. Strategies to prevent opioid and drug abuse should be strengthened in the AS population. Key Points • Cardiovascular and renal comorbidities are associated with mortality and need to be screened for and targeted early on to lower the odds of mortality as patients age. • Drug use disorder including opioid dependence is associated with mortality, and strategies to prevent opioid and drug abuse should be strengthened in the AS population.

Oral Health and Behavior Patterns of Women with Eating Disorders-A Clinical Pilot Study.

BACKGROUND: Chronic stomach regurgitation associated with eating disorders (EDs) poses a high risk for tooth erosion. This study investigated oral health conditions, behavioral patterns, and tooth erosion in women with EDs. METHODS: 16 ED and 13 healthy women were enrolled; 14 ED and 10 healthy control subjects completed the study. Subjects completed demographic, medical, oral, and behavioral health history questionnaires. Dental caries status was recorded as Decayed, Missing and Filled Teeth (DMFT)index and the severity of tooth erosion as Basic Erosive Wear Examination (BEWE) scores. Saliva was collected for flow rate, pH, and buffering capacity analysis. RESULTS: The ED group had a lower stimulated saliva flow rate and higher DMFT index but no significant difference in BEWE scores compared to the controls (t-test, significance level 0.05). Five of the fourteen ED subjects exhibited extensive tooth erosion, which may have been exacerbated by their tooth-brushing behavior. CONCLUSIONS: Although some ED subjects showed extensive tooth erosion in this pilot study, the average BEWE score of the ED group was not significantly different from the controls. Extensive tooth erosion in ED may relate to the low stimulated salivary flow. A larger-scale clinical study is necessary to validate these results.

Plant-based dietary patterns and fasting insulin: a cross-sectional study from NHANES 2017-2018.

BACKGROUND: Previous studies have created plant-based diet indices to assess the health effects of specific dietary patterns. OBJECTIVE: To examine the association between the plant-based content of diet and fasting insulin in adults from the NHANES 2017-2018 database. METHODS: Demographic, dietary, lab and clinical data and fasting insulin were obtained from the NHANES 2017-2018 database. From two 24-h dietary recalls, we created a plant-based diet index (PDI) and a healthy plant-based diet index (hPDI). A high PDI score indicated more plants were consumed versus animal foods. A high hPDI score indicated healthier, plant materials (whole grains, whole fruits, vegetables, legumes, vegetable oils, seeds and nuts) were consumed. The relationships between the natural log of fasting insulin, PDI, and hPDI were analyzed using multiple linear regression adjusting for body mass index (BMI) and alanine aminotransferase (ALT). RESULTS: Analyses were based on 1,714 participants, 897 women and 817 men with a median age of 52 years. In this sample, 610 (35.6%) were white, 407 (23.8%) were black, 231 (13.5%) were Mexican, 207 (12.1%) were Asian, 157 (9.2%) were other Hispanic, and 102 (6%) were other or mixed race. Median fasting insulin was 9.74 µU/mL (IQR: 6.2, 15.56). For every 1 unit increase in PDI, the natural log of fasting insulin decreased 0.0068 ± 0.003 µU/mL (CI: -0.00097, -0.013) (p = 0.02). After adjusting for BMI and ALT, the PDI did not significantly predict fasting insulin as the association was not robust due to multicollinearity. The hPDI was inversely and significantly associated with the natural log of fasting insulin (-0.0027 ± 0.00134, CI: -0.000087, -0.0053) (p = 0.043) in a multivariable model including BMI and ALT. CONCLUSION: A healthy plant-based diet is associated with a decrease in fasting insulin levels. Healthfulness of the diet is an important factor when considering the benefit of a plant-based diet.

Nationwide analysis of unplanned conversion during minimally invasive distal pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Utilization of minimally-invasive distal pancreatectomy (MIDP) for pancreatic adenocarcinoma has increased. While unplanned conversion to an open procedure during MIDP is associated with inferior short-term outcomes, the long-term consequences of conversion have not been adequately examined. METHODS: Patients with pancreatic adenocarcinoma undergoing MIDP were selected from the National Cancer Database (2010-2015) and subdivided based on the occurrence of unplanned conversion. Post-operative outcomes and overall survival (OS) were examined. Conversion was additionally compared to a matched group of planned open resections. RESULTS: Among 592 patients undergoing attempted MIDP, unplanned conversion occurred in 23.1%. Despite increased 90-day mortality among patients experiencing conversion, there was no difference in median OS between groups (25.0 vs 27.8 months, p = 0.095). For patients undergoing conversion, post-operative outcomes and long-term survival were similar when compared to a propensity-matched group of patients undergoing planned open resection. On multivariable analysis, treatment at an academic facility (OR 0.63) and a robotic approach (OR 0.50) were both significantly associated with completed MIDP. CONCLUSION: Despite inferior post-operative outcomes compared to successful MIDP, unplanned conversion did not result in significantly reduced long term survival. MIDP can be attempted selectively but treatment at experienced centers via a robotic approach should be considered.

Opinion: Common Errors, Omissions, and Presentation Problems in the Conduct and Reporting of Animal-based Research.

As experienced authors, statisticians, editors, and scientists, we present the following comments to highlight some usages or omissions that are common in research manuscripts. Consideration of these comments will improve practices of data analysis and reporting.

Topical Anesthetics for Analgesia in Acute Corneal Abrasion: Eye Care Providers Survey.

STUDY OBJECTIVES: To evaluate the current attitudes of ophthalmologists and optometrists regarding topical anesthetic (TA) use in the emergency department (ED) for analgesia in corneal abrasions. METHODS: A survey was distributed through email to ophthalmologists and optometrists, and their responses were deidentified. Three scenarios were presented involving the addition of tetracaine in addition to usual care in the setting of uncomplicated corneal abrasion. A 250-character space for comments and demographic questionnaire followed. A chi-square test, Fisher exact test, or sign test, at a significance level of 0.05, was used. RESULTS: Of the 978 individuals surveyed, 486 responded (MD/DOs: 47.1% and ODs: 52.9%). Topical anesthetic favorability significantly decreased with shorter practice length when the patient was only examined by an ED provider. Topical anesthetic favorability was significantly impacted by respondents' degree type. When respondents were posed with using TAs if the respondents were the patient, the respondents were 22.6% more likely to use TA when compared with their answers in the scenario where the ED provider examined the patient and 20.0% more likely when compared with the scenario where a MD/OD examined the patient. Most did not support tetracaine use. CONCLUSIONS: Although treating pain is associated with improved quality of life, most respondents did not support TA use in the ED. Practice length and degree type significantly impacted responses. Respondents were more inclined to use TAs when the respondents were the patient. Results suggest that eye care providers need additional research data supporting safety before routine use in the ED, given the potential for adverse events with TAs.

Predictors of early neurologic deterioration (END) following stroke thrombectomy.

BACKGROUND: Early neurologic deterioration (END) following ischemic stroke is a serious event and is associated with poor outcomes. However, the incidence and predictors of END after stroke thrombectomy for emergent large vessel occlusion are largely unknown. METHODS: The baseline characteristics of patients enrolled in the COMPASS trial (NCT02466893) were analyzed. The primary outcome was worsening of ≥4 National Institutes of Health Stroke Scale (NIHSS) points 24 hours post thrombectomy (4+ END24) and the secondary outcome was deterioration of ≥2 points (2+ END24). RESULTS: Among 270 patients, 27 (10%) developed 4+ END24 and 42 (16%) had 2+ END24. Those with 4+ END24 were older (76.4±12.9 vs 70.9±12.9 years; p=0.04), had a higher prevalence of hypertension (96% vs 69%; p=0.003), diabetes (41% vs 27%; p=0.13) and higher pretreatment systolic blood pressure (SBP) (170.4±32.6 vs 157.6±28.1 mmHg; p=0.03). More 4+ END24 patients had failed reperfusion: Thrombolysis in Cerebral Infarction ≤2a (26% vs 8%; p=0.003). In unadjusted analysis, older patients and those with hypertension, diabetes, elevated SBP and failed reperfusion had higher odds of 4+ END24. In adjusted analysis, age increase by 5 years led to an increase in 4+ END24 of 28%, diabetes increased odds of 2.6 and failed reperfusion increased odds of 4.5. In the multivariable analysis for the secondary outcome, age (OR 1.33; 95% CI 1.109 to 1.593), diabetes (OR 2.7; 95% CI 1.247 to 5.764) and failed reperfusion (OR 7.2; 95% CI 0.055 to 0.349) were also significant predictors of 2+ END24. CONCLUSIONS: Older patients with acute ischemic stroke who have a history of diabetes or hypertension, with elevated pretreatment SBP and failed reperfusion are at a higher risk of END following stroke thrombectomy for emergent large vessel occlusion.

Characterization of the Metabolome of Breast Tissues from Non-Hispanic Black and Non-Hispanic White Women Reveals Correlations between Microbial Dysbiosis and Enhanced Lipid Metabolism Pathways in Triple-Negative Breast Tumors.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that is non-responsive to hormonal therapies and disproportionately impact women of African ancestry. We previously showed that TN breast tumors have a distinct microbial signature that differs from less aggressive breast tumor subtypes and normal breast tissues. However, it is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The goal of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in normal and breast tumor tissues, including TNBC, of non-Hispanic black (NHB) and non-Hispanic white (NHW) women. In this study, we profiled the microbiome (16S rRNA) from breast tumor tissues and analyzed 984 metabolites from a total of 51 NHB and NHW women. Breast tumor tissues were collected from 15 patients with TNBC, 12 patients with less aggressive luminal A-type (Luminal) breast cancer, and 24 healthy controls for comparison using UHPLC-tandem mass spectrometry. Principal component analysis and hierarchical clustering of the global metabolomic profiling data revealed separation between metabolic signatures of normal and breast tumor tissues. Random forest analysis revealed a unique biochemical signature associated with elevated lipid metabolites and lower levels of microbial-derived metabolites important in controlling inflammation and immune responses in breast tumor tissues. Significant relationships between the breast microbiome and the metabolome, particularly lipid metabolism, were observed in TNBC tissues. Further investigations to determine whether alterations in sphingolipid, phospholipid, ceramide, amino acid, and energy metabolism pathways modulate Fusobacterium and Tenericutes abundance and composition to alter host metabolism in TNBC are necessary to help us understand the risk and underlying mechanisms and to identify potential microbial-based targets.

Feasibility of a Brief Intervention to Increase Rapid Primary Care Follow-Up Among African American Patients With Uncontrolled Diabetes.

The management of diabetes, like many other chronic conditions, depends on effective primary care engagement. Patients with diabetes without a usual source of care have a higher risk of uncontrolled disease, hospitalizations, and early death. Our objective was to study the effect of a brief intervention to help patients in medically underserved areas obtain rapid primary care follow-up appointments following hospitalization. We performed a pilot pragmatic randomized controlled trial of adult patients with uncontrolled diabetes who had been admitted to one of three hospitals in the Memphis, TN, area. The enhanced usual care arm received a list of primary care clinics, whereas the intervention group had an appointment made for them preceding their index discharge. Patients in both groups were evaluated for primary care appointment attendance within seven and fourteen days of index discharge. In addition, we examined barriers patients encounter to receiving rapid primary care follow-up using a secret shopper approach to assess wait times when calling primary care offices. Twelve patients were enrolled with six in each trial arm. Baseline demographics, access to medical care, and health literacy were similar across the groups. Primary care follow-up was also similar across the groups; no improvements in follow-up rates were seen in the group receiving assistance with making appointments. Identified barriers to making primary care follow-up appointments included inability to schedule an urgent appointment, long hold times when calling doctor's offices and lack of transportation. Additionally, hold times when calling primary care offices were found to be excessively long in the medically underserved areas studied. The study demonstrates the feasibility of providing patient assistance with scheduling rapid primary care follow-up appointments at the time of discharge and the potential to improve care transitions and access to primary care among patients living in medically underserved areas. Larger pragmatic trials are needed to further test alternative approaches for insuring rapid primary care follow-up in vulnerable patients with ambulatory care-sensitive chronic conditions.

Long-term functional outcomes after traumatic spine fractures.

BACKGROUND: Traumatic spine fractures can result in chronic pain, disability, and prolonged rehabilitation. The purpose of this study is to determine the long-term effects of traumatic spine fractures on patients' functional outcomes after nonoperative and operative management. METHODS: Patients with traumatic spine fractures over a 5-year period were identified and stratified by management strategy (nonoperative and operative) and compared. Functional outcomes were measured using the Boston Activity Measure for PostAcute Care to assess basic mobility and daily activity. Multiple linear regression was used to identify predictors of functional outcome after traumatic spine fractures. RESULTS: In total, 488 patients were identified: 271 nonoperative and 217 operative. Follow-up was obtained in 168 (34%) patients: 95 nonoperative and 73 operative. Mean follow-up was 5.7 years (range 3-8 years). Mean Activity Measure for PostAcute Care scores in patients managed nonoperatively for basic mobility (68 vs 64, P = .09) and daily activity (69 vs 66, P = .26) were clinically similar to those managed operatively. Multiple linear regression identified increasing age as a predictor of decreased basic mobility (ß = -0.50, P < .0001, ß = -0.17, P = .022) and daily activity (ß = -0.58, P < .0001, ß = -0.35, P = .003) in nonoperative and operative groups, respectively. In nonoperative patients, thoracic spine fracture was predictive of both decreased basic mobility (ß = -5.88, P = .041) and daily activity (ß = -8.62, P = .043). In operative patients, lower extremity fractures (ß = -8.86, P = .012), discharge location (ß = -6.91, P = .003), and time to operative fixation (ß = -0.77, P = .040) were associated with decreased basic mobility. CONCLUSION: All patients with traumatic spine fractures displayed mild to moderate functional impairment. Age, thoracic fractures, lower extremity fractures, discharge location, and time to operative fixation were associated with poor functional outcomes.

Conditional loss of Engrailed1/2 in Atoh1-derived excitatory cerebellar nuclear neurons impairs eupneic respiration in mice.

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but studies of cerebellar involvement in eupneic breathing have been inconclusive. Here we investigated temporal aspects of eupneic respiration in the Atoh1-En1/2 mouse model of cerebellar neuropathology. Atoh1-En1/2 conditional knockout mice have conditional loss of the developmental patterning genes Engrailed1 and 2 in excitatory cerebellar nuclear neurons, which leads to loss of a subset of medial and intermediate excitatory cerebellar nuclear neurons. A sample of three Atoh1-derived extracerebellar nuclei showed no cell loss in the conditional knockout compared to control mice. We measured eupneic respiration in mutant animals and control littermates using whole-body unrestrained plethysmography and compared the average respiratory rate, coefficient of variation, and the CV2, a measure of intrinsic rhythmicity. Linear regression analyses revealed that Atoh1-En1/2 conditional knockouts have decreased overall variability (p = 0.021; b = -0.045) and increased intrinsic rhythmicity compared to their control littermates (p < 0.001; b = -0.037), but we found no effect of genotype on average respiratory rate (p = 0.064). Analysis also revealed modestly decreased respiratory rates (p = 0.025; b = -0.82), increased coefficient of variation (p = 0.0036; b = 0.060), and increased CV2 in female animals, independent of genotype (p = 0.024; b = 0.026). These results suggest a cerebellar involvement in eupneic breathing by controlling rhythmicity. We argue that the cerebellar involvement in controlling the CV2 of respiration is indicative of an involvement of coordinating respiration with other orofacial rhythms, such as swallowing.

Intensive sick day rules to prevent recurrent diabetic ketoacidosis- An intervention that exemplifies health disparities.

OBJECTIVE: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). In established T1D patients, DKA is frequently a result of insulin omission or inadequate insulin administration during illness or stress. Ethnic minorities and patients with lower socioeconomic status are affected disproportionately. We hypothesized that implementation of intensive sick day rules with frequent reinforcement would reduce hospitalizations secondary to DKA in T1D youth irrespective of their demographics. METHODS: Intensive sick day rules were implemented beginning January 2016. All T1D patients seen in the pediatric endocrinology clinic or hospital between January 1st 2015 through December 31st 2017 were included for chart review. Categorical variables were analyzed with Chi-square test. For the continuous variables, t test was used. Episodes of DKA per 100 patients were compared using the trends test over the three-year period. Patients who had DKA in 2015 were analyzed as a subgroup. RESULTS: The frequency of DKA episodes per 100 patient years for 2015 was 19.1, for 2016 was 15.2 and was 12.4 for 2017. This decrease was statistically significant (p=0.006). The decline was also statistically significant for the subgroup of patients who developed DKA in 2015 and followed longitudinally. The decline was not uniform across all patient groups and DKA episodes remained associated with African- American race, Medicaid insurance status and higher HbA1c throughout the years. CONCLUSION: Implementation of intensive sick day rules led to a decrease in total number of DKA admissions in our population with T1D youth. However, this intervention did not reduce the health disparity in this population and African-Americans on Medicaid insurance continued to form the disproportionate majority of admissions with DKA. This study highlights the need for further research into interventions that can improve outcomes across racial and socio-economic barriers.

Refining a traditional urban-rural classification approach to better assess heterogeneity of treatment effects in patient-centered outcomes research.

This article describes a rationale and approach for modifying the traditional rural-urban commuting area (RUCA) coding scheme used to classify U.S. ZIP codes to enable suburban/rural vs. urban core comparisons in health outcomes research that better reflect current geographic differences in access to care in U.S. populations at risk for health disparities. The proposed method customization is being employed in the Patient-Centered Outcomes Research Institute-funded Management Of Diabetes in Everyday Life (MODEL) study to assess heterogeneity of treatment effect for patient-centered diabetes self-care interventions across the rural-urban spectrum. The proposed suburban/rural vs. urban core classification scheme modification is based on research showing that increasing suburban poverty and rapid conversion of many rural areas into suburban areas in the U.S. has resulted in similar health care access problems in areas designated as rural or suburban.•The RUCA coding scheme was developed when a much higher percentage of U.S. individuals resided in areas with very low population density.•Using the MODEL study example, this study demonstrates that the RUCA classification scheme using ZIP codes does not reflect real differences in health care access experienced by medically underserved study participants.•Both internal and external validation data suggest that the proposed suburban/rural vs. urban core customization of the RUCA geographic coding scheme better reflects real differences in healthcare access and is better able to assess the differential impact of clinical interventions designed to address geographic differences in access among vulnerable populations.

Association of persistent tachycardia with early myocardial dysfunction in children undergoing allogeneic hematopoietic cell transplantation.

Cancer survivors who have undergone hematopoietic cell transplantation (HCT) are at risk for myocardial dysfunction. Children who receive allogenic HCT encounter systemic inflammation resulting in tachycardia and hypertension. The effect of these abnormalities on myocardial function is not known. The aim of this study was to determine whether cardiac dysfunction early after HCT can be predicted by tachycardia or hypertension, within a retrospective single-center sample of pediatric HCT recipients. Early tachycardia or hypertension was defined as a majority of values taken from infusion date to 90 days post-infusion being abnormal. Ejection fraction <53% determined systolic dysfunction. A composite score of accepted pediatric diastolic abnormalities determined diastolic dysfunction. Among 80 subjects (median age 8 years), early tachycardia, systolic dysfunction, and diastolic dysfunction were present in 64%, 25%, and 48% of the sample, respectively. In multivariable models, early tachycardia was an independent predictor of early systolic dysfunction (OR = 12.6 [1.4-112.8], p = 0.024) and diastolic dysfunction (OR = 3.9 [1.3-11.5], p = 0.013). Tachycardia and cardiac dysfunction are common and associated with one another in the early period after pediatric HCT. Future studies may elucidate the role of tachycardia and myocardial dysfunction early after HCT as important predictors of future cardiovascular dysfunction.

Relationship Between Standardized Test Scores and Board Certification Exams in a Combined Internal Medicine/Pediatrics Residency Program.

Background Combined Internal Medicine/Pediatrics (Med/Peds) residencies rely on categorical program data to predict pass rates for the American Board of Internal Medicine Certifying Exam (ABIM-CE) and the American Board of Pediatrics Certifying Exam (ABP-CE). There is insufficient literature describing what best predicts a Med/Peds resident passing board exams. In this study, we aimed to determine how standardized test scores predict performance on ABIM-CE and ABP-CE for Med/Peds residents. Methodology We analyzed prior exam scores for 91/96 (95%) residents in a Med/Peds program from 2008 to 2017. Scores from the United States Medical Licensing Examination (USMLE) Steps 1 and 2 Clinical Knowledge (CK) and In-Training Exams in Internal Medicine (ITE-IM) and Pediatrics (ITE-P) were analyzed with the corresponding ABIM-CE and ABP-CE first-time scores. Linear and logistic regression were applied to predict board scores/passage. Results USMLE 1 and 2 CK, ITE-IM, and ITE-P scores had a linear relationship with both ABIM-CE and ABP-CE scores. In the linear regression, adjusted R2 values showed low-to-moderate predictive ability (R2 = 0.11-0.35), with the highest predictor of ABIM-CE and ABP-CE being USMLE Step 1 (0.35) and Postgraduate Year 1 (PGY-1) ITE-IM (0.33), respectively. Logistic regression showed odds ratios of passing board certifications ranging from 1.05 to 1.53 per point increase on the prior exam score. The PGY-3 ITE-IM was the best predictor of passing both certifying exams. Conclusions In one Med/Peds program, USMLE Steps 1 and 2 and all ITE-IM and ITE-P scores predicted certifying exam scores and passage. This provides Med/Peds-specific data to allow individualized resident counseling and guide programmatic improvements targeted to board performance.

Using preliminary data and prospective power analyses for mid-stream revision of projected group and subgroup sizes in pragmatic patient-centered outcomes research.

Pragmatic clinical trials are commonly used in patient-centered outcomes research to assess heterogeneity of treatment effects. Patient-Centered Outcomes Research Institute (PCORI) methodology standards for assessing heterogeneity of treatment effects are extremely rigorous, but their implementation in real-world settings can be difficult. Predicting recruitment effectiveness and subgroup characteristics is often challenging and may require mid-stream revision of projected group and subgroup sizes. Yet, little real-world data are available to demonstrate methodologically valid approaches to address situations where such revisions are necessary. These data were used for mid-stream revision of group and subgroup sizes in the Management of Diabetes in Everyday Life (MODEL) clinical trial. The planned number of randomized participants retained over the one-year study period was reduced from 800 to 581 due to recruitment difficulties among potential participants residing in rural areas. Prospective power analyses are based on the revised target of 581 participants retained and the proportions of 167 participants with various key baseline characteristics, who had been randomized in MODEL by January 2018, as reported to the Patient Center Outcomes Research Institute (PCORI) and the MODEL Data Safety and Monitoring Committee. Power calculations are based on two-sided t-tests with type-I error rates of 0.05 and the assumption that effect sizes will range from small (standardized difference = 0.36) to medium (= 0.50). The primary outcome variables are how many days in the previous week participants 1) ate healthy meals, 2) participated in at least 30 minutes of physical activity, and 3) took medications as prescribed. The POWER procedure of SAS 9.4 was used for all analyses. These data, along with the approach, can assist statisticians as they plan future pragmatic clinical trials evaluating heterogeneity of treatment effects. These data can help inform investigators, conducting patient-centered outcomes research, as they define subgroups for either confirmatory analyses for testing heterogeneity of treatment effects or for exploratory analyses where estimation of confidence bounds may be useful for generating future hypotheses. (This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (SC15-1503-28336), www.ClinicalTrials.gov and Identifier: NCT02957513 [1].).

A mid-South chronic disease registry and practice-based research network to address disparities.

OBJECTIVES: To describe an innovative health information technology (HIT) model for supporting community-wide health improvement through multiprovider collaboration in a regional population health registry and practice-based research network (PBRN). STUDY DESIGN: Case study. METHODS: We describe the HIT data structure and governance of the Diabetes Wellness and Prevention Coalition (DWPC) Registry and PBRN based in Memphis, Tennessee. The population served and their characteristics were assessed for all adult patients with at least 1 encounter in a participating health care delivery system from January 1, 2013, to March 31, 2019. Disparities in access and health care utilization were assessed by residential zip code. RESULTS: The DWPC Registry is a chronic disease and population health data warehouse designed to facilitate chronic disease surveillance and tracking of processes and outcomes of care in medically underserved areas of the mid-South. The Registry primarily focuses on obesity-associated chronic conditions such as diabetes, hypertension, hyperlipidemia, and chronic kidney disease. It combines patient data from 7 regional health systems, which include 6 adult hospitals and more than 50 outpatient practices, covering 462,223 adults with 2,032,425 clinic visits and 602,679 hospitalizations and/or emergency department visits from January 1, 2013, to March 31, 2019. The most prevalent chronic conditions include obesity (37.2%), hypertension (34.4%), overweight (26.4%), hyperlipidemia (18.0%), and type 2 diabetes (14.0%). The Registry provides quarterly practice improvement reports to participating clinics, facilitates surveillance of and outreach to patients with unmet health needs, and supports a pragmatic clinical trial and multiple cohort studies. CONCLUSIONS: Regional registries and PBRNs are powerful tools that can support real-world quality improvement and population health efforts to reduce disparities and improve equity in chronic disease care in medically underserved communities across the United States.

The management of diabetes in everyday life study: Design and methods for a pragmatic randomized controlled trial comparing the effectiveness of text messaging versus health coaching.

Background African American patients with uncontrolled diabetes living in medically underserved areas need effective clinic-based interventions to improve self-care behaviors. Text messaging (TM) and health coaching (HC) are among the most promising low-cost population-based approaches, but little is known about their comparative effectiveness in real-world clinical settings. Objective Use a pragmatic randomized controlled trial design to determine the comparative effectiveness of TM and HC with enhanced usual care (EC) in African American adults with uncontrolled diabetes and multiple chronic health conditions. Methods/design The Management of Diabetes in Everyday Life (MODEL) study is randomizing 646 patients (n = 581with anticipated 90% retention) to 3 intervention arms: TM, HC, and EC. Participants are African American adults living in medically underserved areas of the Mid-South, age ≥ 18, with uncontrolled diabetes (A1c ≥ 8), one or more additional chronic conditions, and who have a phone with texting and voicemail capability. Primary outcome measures: the general diet, exercise, and medication adherence subscales of the revised Summary of Diabetes Self-Care Activities questionnaire assessed at one year. Secondary outcomes: diabetes-specific quality of life, primary care engagement, and average blood sugar (A1c). The study will also assess heterogeneity of treatment effects by six key baseline participant characteristics. Conclusions We describe the design and methods of the MODEL study along with design revisions required during implementation in a pragmatic setting. This trial, upon its conclusion, will allow us to compare the effectiveness of two promising low-cost primary care-based strategies for supporting self-care behaviors among African Americans individuals with uncontrolled diabetes. ClinicalTrials.gov registration number: NCT02957513.

Beta-adrenergic blockade for attenuation of catecholamine surge after traumatic brain injury: a randomized pilot trial.

BACKGROUND: Beta-blockers have been proven in multiple studies to be beneficial in patients with traumatic brain injury. Few prospective studies have verified this and no randomized controlled trials. Additionally, most studies do not titrate the dose of beta-blockers to therapeutic effect. We hypothesize that propranolol titrated to effect will confer a survival benefit in patients with traumatic brain injury. METHODS: A randomized controlled pilot trial was performed during a 24-month period. Patients with traumatic brain injury were randomized to propranolol or control group for a 14-day study period. Variables collected included demographics, injury severity, physiologic parameters, urinary catecholamines, and outcomes. Patients receiving propranolol were compared with the control group. RESULTS: Over the study period, 525 patients were screened, 26 were randomized, and 25 were analyzed. Overall, the mean age was 51.3 years and the majority were male with blunt mechanism. The mean Injury Severity Score was 21.8 and median head Abbreviated Injury Scale score was 4. Overall mortality was 20.0%. Mean arterial pressure was higher in the treatment arm as compared with control (p=0.021), but no other differences were found between the groups in demographics, severity of injury, severity of illness, physiologic parameters, or mortality (7.7% vs. 33%; p=0.109). No difference was detected over time in any variables with respect to treatment, urinary catecholamines, or physiologic parameters. Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation scores all improved over time. GCS at study end was significantly higher in the treatment arm (11.7 vs. 8.9; p=0.044). Finally, no difference was detected with survival analysis over time between groups. CONCLUSIONS: Despite not being powered to show statistical differences between groups, GCS at study end was significantly improved in the treatment arm and mortality was improved although not at a traditional level of significance. The study protocol was safe and feasible to apply to an appropriately powered larger multicenter study. LEVEL OF EVIDENCE: Level 2-therapeutic.