Wisconsin Clinical Research Articles

The correlations among racial/ethnic groups, hypertriglyceridemia, thrombosis, and mortality in hospitalized patients with COVID-19

Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. Our previous study has shown that patients with COVID-19 who developed hypertriglyceridemia during hospitalization have a 2.3 times higher mortality rate. However, whether the correlation between hypertriglyceridemia and mortality has disparity among different racial and ethnic groups is unknown.In this study, we investigated the impact of race/ethnicity on the correlation between hypertriglyceridemia and mortality in hospitalized patients with COVID-19. De-identified information from 904 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted from the Medical College of Wisconsin Clinical Data Warehouse. A multivariable regression analysis suggested that the Asians and non-White Hispanics had 4 or 3.9 times higher mortality rate, respectively, after adjusting for age, morbid obesity (BMI ≥40), and gender. The hypertriglyceridemia (≥150 mg/dL) was associated with higher mortality, after adjusting for age, gender, and morbid obesity. The baseline hypertriglyceridemia occurrence had relevantly more consistent percentages among all racial/ethnic groups. However, non-White Hispanic and Asian patients had the highest frequencies of peak hypertriglyceridemia occurrence during hospitalization. The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombosis after adjusting for morbid obesity, age, and sex. In summary, in this retrospective study of 904 hospitalized COVID-19 patients, Asians and non-White Hispanics had a greater likelihood of developing hypertriglyceridemia during hospitalization and mortality than White patients.

Assessing the implementation of a clinical decision support tool in primary care for diabetes prevention: a qualitative interview study using the Consolidated Framework for Implementation Science

BackgroundIn this paper we describe the use of the Consolidated Framework for Implementation Research (CFIR) to study implementation of a web-based, point-of-care, EHR-linked clinical decision support (CDS) tool designed to identify and provide care recommendations for adults with prediabetes (Pre-D CDS).MethodsAs part of a large NIH-funded clinic-randomized trial, we identified a convenience sample of interview participants from 22 primary care clinics in Minnesota, North Dakota, and Wisconsin that were randomly allocated to receive or not receive a web-based EHR-integrated prediabetes CDS intervention. Participants included 11 clinicians, 6 rooming staff, and 7 nurse or clinic managers recruited by study staff to participate in telephone interviews conducted by an expert in qualitative methods. Interviews were recorded and transcribed, and data analysis was conducted using a constructivist version of grounded theory.ResultsImplementing a prediabetes CDS tool into primary care clinics was useful and well received. The intervention was integrated with clinic workflows, supported primary care clinicians in clearly communicating prediabetes risk and management options with patients, and in identifying actionable care opportunities. The main barriers to CDS use were time and competing priorities. Finally, while the implementation process worked well, opportunities remain in engaging the care team more broadly in CDS use.ConclusionsThe use of CDS tools for engaging patients and providers in care improvement opportunities for prediabetes is a promising and potentially effective strategy in primary care settings. A workflow that incorporates the whole care team in the use of such tools may optimize the implementation of CDS tools like these in primary care settings.Trial registration Name of the registry: Clinicaltrial.gov. Trial registration number: NCT02759055. Date of registration: 05/03/2016. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT02759055 Prospectively registered.

The Correlation between Racial/Ethnic Groups, Thrombosis, and Mortality in Hospitalized Patients with COVID-19

The SARS-CoV-2 virus has infected hundreds of millions of people and caused millions of deaths worldwide. Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. A previous study found an independent and positive association between the Black/African American race and positive COVID-19 testing results in Milwaukee County, WI, while adjusting for age, sex, socioeconomic status, and comorbidities (Munoz-Price. et al, 2020, JAMA Network). Our previous study revealed that patients with COVID-19 who developed hypertriglyceridemia during their hospitalization were associated with a 2.3 times higher mortality rate, after adjusting for age, gender, body mass index, history of hypertension and diabetes (Dai. et al, 2021, manuscript accepted by Journal of Clinical Lipidology). Additionally, adverse blood clotting events is one of the major causes of death for patients with COVID-19. In this study, we investigated the correlation between racial/ethnic groups and mortality, along with potential correlations between hypertriglyceridemia and adverse blood clotting events in hospitalized patients with COVID-19 (ICD10CM:U07.1).De-identified data from 1,441 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted using the Medical College of Wisconsin Clinical Research Data Warehouse. Vital, demographic, and diagnostic information were used for the statistical analysis, specifically: age, gender, body mass index (BMI), race/ethnicity, thrombosis diagnosis and laboratory test results for triglyceride. The thrombotic events included were presence of disseminated intravascular coagulopathy, deep vein thrombosis, myocardial infarction, pulmonary embolism, and stroke diagnosed during their hospitalization. Hypertriglyceridemia was characterized as triglyceride levels greater than 150 mg/dL, with a baseline variable being the first occurrence of hypertriglyceridemia (baseline), and the peak variable being the highest manifestation of hypertriglyceridemia during hospitalization (peak).A binary logistic regression model showed that non-white Hispanic and Asian patients both had a higher correlation with mortality than white patients, with odds ratios (OR) of 4.1 [95% CI (2.2-7.9), p < 0.001] and 4.2 [95% CI (1.8-9.8), p < 0.001], respectively, after adjusting for age, BMI, and sex (Figure A). Additionally, the regression analysis showed that peak hypertriglyceridemia developed during hospitalization was correlated with a 1.8 times higher mortality in the entire inpatient cohort [95% CI (1.2-2.9), p < 0.01], after adjusting for age, sex, and BMI and independent of obesity. Furthermore, myocardial infarction [OR = 1.5, 95% CI (1.-2.5), p < 0.05] and pulmonary embolism [OR = 2.0, 95% CI (1.1-4.1), p < 0.05] were also correlated with a higher mortality, after adjusting for age, BMI, and sex (Figure B). The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombotic events with a borderline significance [OR= 1.5, 95% CI (0.9-2.1), p = 0.05] after adjusting for BMI, age, and sex. Further analysis revealed that non-white Hispanic patients had the highest frequencies of peak hypertriglyceridemia (triglyceride > 150 mg/dL) occurrence during hospitalization than the other race/ethnicity groups (Figure C). On the other hand, 22% of non-white Hispanics had at least one diagnosis of thrombotic event during hospitalization, which was the lowest incidence of thrombosis among all race/ethnicity groups (Figure D).In our current retrospective study of inpatients with COVID-19, race/ethnicity, peak hypertriglyceridemia developed during hospitalization, and thrombosis are independently associated with mortality. The peak hypertriglyceridemia developed during hospitalization is positively correlated with the incidence of thrombosis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cost-effectiveness of stop smoking incentives for medicaid-enrolled pregnant women

Maternal smoking increases mortality and morbidity risks for both mother and infant. The First Breath Wisconsin study examined the cost-effectiveness of providing incentives to pregnant women who smoked to engage in stop smoking treatment. Participants (N = 1014) were Medicaid-enrolled pregnant women recruited from September 2012 to April 2015 through public health departments, private, and community health clinics in Wisconsin. The incentive group (n = 505) could receive $460 for completing pre-birth visits ($25 each), post-birth home visits ($40, $25, $25, $40 for 1-week, 2-month, 4-month and 6-month visits), monthly smoking cessation phone calls post-birth ($20 each), and biochemically-verified tobacco abstinence at 1-week ($40) and 6-months ($40) post-birth. The control group (n = 509) received up to $80 for 1-week ($40) and 6-month ($40) post-birth assessments. Intervention costs included incentive payments to participants, counselor and administrative staff time, and smoking cessation medications. Cost-effectiveness analysis calculated the incremental cost-effectiveness ratio (ICER) per one additional smoker who quit. The incentive group had higher 6-month post-birth biochemically-confirmed tobacco abstinence than the control group (14.7% vs. 9.2%). Incremental costs averaged $184 per participant for the incentive group compared to controls ($317 vs $133). The ICER of financial incentives was $3399 (95% CI $2228 to $8509) per additional woman who was tobacco abstinent at 6 months post-birth. The ICER was lower ($2518 vs $4760) for women who did not live with another smoker. This study shows use of financial incentives for stop smoking treatment is a cost-effective option for low-income pregnant women who smoke.

Assessment of Variation in Electronic Health Record Capabilities and Reported Clinical Quality Performance in Ambulatory Care Clinics, 2014-2017

Electronic health records (EHRs) are widely promoted to improve the quality of health care, but information about the association of multifunctional EHRs with broad measures of quality in ambulatory settings is scarce. To assess the association between EHRs with different degrees of capabilities and publicly reported ambulatory quality measures in at least 3 clinical domains of care. This cross-sectional and longitudinal study was conducted using survey responses from 1141 ambulatory clinics in Minnesota, Washington, and Wisconsin affiliated with a health system that responded to the Healthcare Information and Management Systems Society Annual Survey and reported performance measures in 2014 to 2017. Statistical analysis was performed from July 10, 2019, through February 26, 2021. A composite measure of EHR capability that considered 50 EHR capabilities in 7 functional domains, grouped into the following ordered categories: no functional EHR, EHR underuser, EHR, neither underuser or superuser, EHR superuser; as well as a standardized composite of ambulatory clinical performance measures that included 3 to 25 individual measures (median, 13 individual measures). In 2014, 381 of 746 clinics (51%) were EHR superusers; this proportion increased in each subsequent year (457 of 846 clinics [54%] in 2015, 510 of 881 clinics [58%] in 2016, and 566 of 932 clinics [61%] in 2017). In each cross-sectional analysis year, EHR superusers had better clinical quality performance than other clinics (adjusted difference in score: 0.39 [95% CI, 0.12-0.65] in 2014; 0.29 [95% CI, -0.01 to 0.59] in 2015; 0.26 [95% CI, -0.05 to 0.56] in 2016; and 0.20 [95% CI, -0.04 to 0.45] in 2017). This difference in scores translates into an approximately 9% difference in a clinic's rank order in clinical quality. In longitudinal analyses, clinics that progressed to EHR superuser status had only slightly better gains in clinical quality between 2014 and 2017 compared with the gains in clinical quality of clinics that were static in terms of their EHR status (0.10 [95% CI, -0.13 to 0.32]). In an exploratory analysis, different types of EHR capability progressions had different degrees of associated improvements in ambulatory clinical quality (eg, progression from no functional EHR to a status short of superuser, 0.06 [95% CI, -0.40 to 0.52]; progression from EHR underuser to EHR superuser, 0.18 [95% CI, -0.14 to 0.50]). Between 2014 and 2017, ambulatory clinics in Minnesota, Washington, and Wisconsin with EHRs having greater capabilities had better composite measures of clinical quality than other clinics, but clinics that gained EHR capabilities during this time had smaller increases in clinical quality that were not statistically significant.

Applying the AFIX Quality Improvement Model to Increase Adult Immunization in Wisconsin.

Assessment, Feedback, Incentives, and eXchange (AFIX) is a quality improvement model used to increase childhood and adolescent immunization rates in the United States. We evaluated implementation of a similar quality improvement model to boost adult immunization rates. During November 2016 through May 2017, adult immunization outreach specialists conducted 124 in-person visits to clinics in Wisconsin that immunize adults, submit immunization information to the Wisconsin Immunization Registry (WIR), and agreed to participate in adult AFIX. Outreach specialists ran immunization assessment reports using the WIR and showed a paper copy of the report during the visit. Health care providers were encouraged to implement at least 1 of 18 strategies (eg, reminder-and-recall intervention, giving adult immunization resources to patients) to increase adult immunization rates. Outreach specialists conducted follow-up with health care providers at 3, 6, and 9-18 months after the initial visit to encourage strategy implementation. We compared AFIX sites with control clinics on practice type, geographic location, and clinic size. Clinics that participated in adult AFIX had a significantly larger increase in median adult immunization rates for completion of the human papillomavirus vaccine series at the 9- to 18-month follow-up than control clinics did (10.4% vs 7.7%; P = .02). The median immunization rate for 13-valent pneumococcal conjugate vaccine/23-valent pneumococcal polysaccharide vaccine completed in series was higher, but not significantly so, among adult AFIX clinics than among control clinics (12.6% vs 10.7%; P = .18). Adult AFIX resulted in increased awareness about adult immunization recommendations and may be a useful tool for increasing adult immunization rates.

Time-varying effects of 'optimized smoking treatment' on craving, negative affect and anhedonia.

To identify when smoking cessation treatments affect craving, negative affect and anhedonia, and how these symptoms relate to abstinence, to help evaluate the effects of particular intervention components in multi-component treatments and accelerate treatment refinement. Secondary analysis of data from a two-arm randomized controlled trial. Seven primary care clinics in Wisconsin, United States. Adult primary care patients who smoked daily (n=574). Intervention was abstinence-optimized treatment (A-OT, n=276) comprising 3weeks of nicotine mini-lozenges pre-target quit day (TQD), 26weeks of combination nicotine patch and mini-lozenges post-TQD and extensive psychosocial support. The comparator was recommended usual care (RUC, n=298), comprising brief counseling and 8weeks of nicotine patch post-TQD. Time-varying effect models examined dynamic effects of A-OT (versus RUC) on the primary outcomes of nightly cigarette craving, negative affect and anhedonia from 1week pre- to 2weeks post-TQD. Exploratory models examined within-person relations between nicotine medication use and same-day symptom ratings. Secondary logistic regression analyses examined associations between post-TQD craving, negative affect and anhedonia and 1-month post-TQD abstinence. A-OT significantly suppressed pre- and post-TQD craving (β=-0.27 to -0.46 across days) and post-TQD anhedonia (β=-0.24 to -0.38 across days), relative to RUC. Within individuals, using patches was associated with lower negative affect in RUC (β=-0.42 to -0.52), but not in A-OT. Using more mini-lozenges was associated with greater craving (β=0.04-0.07) and negative affect (β=0.03-0.05) early, and with lower anhedonia (β=-0.06 to -0.12) later. Greater post-TQD craving (OR=0.68) and anhedonia (OR=0.85) predicted lower odds of abstinence 1month post-TQD. Time-varying effect models showed that a multi-component treatment intervention for smoking cessation suppressed significant withdrawal symptoms more effectively than recommended usual care among daily adult smokers motivated to quit. The intervention reduced craving pre- and post-target quit day (TQD) and anhedonia post-TQD.

Differing Collagen Responses in the Right and Left Ventricle Following Postnatal Hyperoxia Exposure

BackgroundPreterm birth affects approximately 1 in 10 pregnancies, and extreme preterm birth is associated with a 17‐fold increased risk of heart failure during childhood and early adulthood. Whether this is related to increase cardiac fibrosis is currently unknown. The objective of this study was to determine if fibrosis is present in an animal model of cardiomyopathy of prematurity using postnatal hyperoxia exposure.MethodsPostnatal hyperoxia exposure in an immature rat heart was used to mimic the relative hyperoxia exposure premature infants experience at birth. Timed‐pregnant Sprague Dawley rats (Rattus norvegicus) were allowed to deliver naturally, and pups randomized to either postnatal hyperoxia (85% FIO2) or normoxia (21%) exposure from 0–14 days of life. Dams were rotated daily to prevent maternal oxygen toxicity. On day 21 of life, cardiac tissue was harvested and prepped for Masson’s trichrome blue stain. Additional hearts were resected and the right ventricle (RV) and left ventricle (LV) were flash frozen. The trichrome stained tissue was analyzed using ImageJ to determine the percent of image that was collagen, and colorimetric collagen assays that measured the hydroxyproline were ran on the flash frozen tissue. Results were compared with t‐tests, with p&lt;0.05 used to determine significance.ResultsOverall, presence of cardiac fibrosis was low. In the LV, trichrome analysis demonstrated no difference between the hyperoxic and normoxic groups (4.56x10−4% vs 3.01x10−4 %, p=0.58). Similarly, the collagen assay showed no difference between the hyperoxic and normoxic LV (1.24 ±0.20 μg/g vs 1.01 ±0.34 μg/g, p=0.231). However, in the RV there was decreased percent fibrosis in hyperoxia relative to normoxia (2.69x10‐3 % vs 4.88x10‐3 %, p=0.03). The collagen assay showed similar results of a trend towards decreased collagen in hyperoxic RV compared to the normoxic RV (2.01±0.45μg/g vs 2.57±0.27μg/g, p =0.09).ConclusionThese results appear to suggest that cardiac fibrosis is not a prominent feature in the animal model of cardiomyopathy of prematurity. Whether this is true for humans born preterm merits further study in the function and structure of the human heart throughout its development. The increased risk of heart failure could be caused by factors other than collagen deposition, or collagen deposition that occurs later in life. Further testing is required to fully understand the relationship between hyperoxygenation and long‐term heart health.Support or Funding InformationUniversity of Wisconsin Clinical and Translational Science Award program, through the NIH National Center for Advancing Translational Sciences grant NIH UL1TR000427

Effects of Chronic Artificial Sweetener Consumption on Type 1 Diabetes Susceptibility

As the diabetes epidemic grows worldwide, there is a heightened awareness of how modern day diets may contribute to the increased incidence of disease. To combat the dietary intake of sugar, there has been a drastic increase in the daily consumption of non‐caloric artificial sweeteners (NCAS). However, a number of studies suggest that NCAS cause counterintuitive metabolic derangements that may contribute to negative health outcomes. Conversely, there are limited duration studies focused on weight management suggesting the opposite, thus creating controversy. The impact of chronic NCAS consumption in type 1 diabetes (T1D) patients or those with a high genetic susceptibility for T1D is also unknown. T1D has a strong genetic basis; however, environmental factors likely underlie the rapid increase in T1D incidence in the past few decades. Children with T1D frequently consume NCAS as a way of managing postprandial hyperglycemia and insulin doses. Increased availability of NCAS within the home likely also translates to more NCAS consumption by non‐diabetic siblings with a higher risk to develop T1D. Our study aimed to test the effects of chronic consumption of NCAS subtypes on high T1D susceptibility backgrounds. To test this, we supplemented the diet of T1D susceptible BioBreeding DR+/+ rats with aspartame (metabolized) and acesulfame potassium (Ace‐K+, not metabolized) for three weeks in their drinking water. DR+/+ rats consuming NCAS water had a significant increase in blood glucose versus normal water controls. Metabolomics analysis of plasma from these rats revealed alterations in lipid and energy metabolism, with a greater effect resulting from Ace‐K+. Using a novel mass spectrometry‐based quantification assay we developed, we found that Ace‐K+ also accumulated in the plasma these DR+/+ rats (21+10 μM; N=6) following chronic consumption. Further follow‐up was performed in vitro using rat cardiac microvascular endothelial cells (RCMVECs) to measure cardiometabolic effects. The RCMVECs were treated with an Ace‐K+ dose‐response for three weeks and they exhibited impairment during in vitro tube formation and cell viability tests (p&lt;0.05; N=3). Gene expression analysis of the RCMVECs displayed significant differences in insulin signaling, glucose metabolism, and inflammatory regulation (p&lt;0.05; N=4). In further tests, we also observed that chronic Ace‐K+ consumption accelerated the rate of type 1 diabetes onset in DRlyp/lyp rats. Overall, these results suggest that the accumulation of absorbed intact NCAS subtypes, like Ace‐K+, have the potential to lead to metabolic flux that may be important in pre‐ and post‐onset T1D, whereas the metabolized aspartame caused less fluctuation. We are now focused on translating these studies to a pediatric T1D population and are implementing a novel NCAS food frequency questionnaire and plasma quantification test to better measure consumption clinically.Support or Funding InformationSupport for this project was provided by the Medical College of Wisconsin Clinical and Translational Science Institute, the Mayo Clinic Metabolomics Resource Core (pilot award provided by the U24DK100469 grant to BRH), and the Children’s Research Institute (CRI19301 to MH).

Strengthening Public Health in Wisconsin Through the Wisconsin Clinical Laboratory Network.

The Wisconsin Clinical Laboratory Network (WCLN) at the University of Wisconsin-Madison is a partnership of 138 clinical and public health laboratories (as of February 2019) coordinated by the Wisconsin State Laboratory of Hygiene. This article describes the WCLN, its current activities, and lessons learned through this partnership. A laboratory technical advisory group, which consists of representatives from clinical laboratories, provides clinical laboratory perspective to the WCLN and fosters communication among laboratories. Activities and resources available through the WCLN include annual regional meetings, annual technical workshops, webinars, an email listserv, laboratory informational messages, in-person visits by a WCLN coordinator to clinical laboratories, and laboratory-based surveillance data and summaries distributed by the Wisconsin State Laboratory of Hygiene. One challenge to maintaining the WCLN is securing continual funding for network activities. Key lessons learned from this partnership of more than 20 years include the importance of in-person meetings, the clinical perspective of the laboratory technical advisory group, and providing activities and resources to clinical laboratories to foster sharing of data and clinical specimens for public health surveillance and outbreak response.

Conference Proceedings: Aurora Scientific Day 2019.

s published within this journal supplement were presented at the 45th annual Aurora Scientific Day research symposium, held May 22, 2019, in Milwaukee, Wisconsin. This symposium provides a forum for research projects conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, which is part of Advocate Aurora Health, an integrated health system with hospitals and clinics in Wisconsin and Illinois.

School sessions are correlated with seasonal outbreaks of medically attended respiratory infections: electronic health record time series analysis, Wisconsin 2004-2011.

Increased social contact within school settings is thought to be an important factor in seasonal outbreaks of acute respiratory infection (ARI). To better understand the degree of impact, we analysed electronic health records and compared risks of respiratory infections within communities while schools were in session and out-of-session. A time series analysis of weekly respiratory infection diagnoses from 28 family medicine clinics in Wisconsin showed that people under the age of 65 experienced an increased risk of ARI when schools were in session. For children aged 5-17 years, the risk ratio for the first week of a school session was 1.12 (95% confidence interval (CI) 0.93-1.34), the second week of a session was 1.39 (95% CI 1.15-1.68) and more than 2 weeks into a session was 1.43 (95% CI 1.20-1.71). Less significant increased risk ratios were also observed in young children (0-4 years) and adults (18-64 years). These results were obtained after modelling for baseline seasonal variations in disease prevalence and controlling for short-term changes in ambient temperature and relative humidity. Understanding the mechanisms of seasonality make it easier to predict outbreaks and launch timely public health interventions.

695. Regional and Longitudinal Mapping of Escherichia coli Antibiotic Susceptibility

BackgroundAntimicrobial resistance (AMR) is a serious threat to global health with local implications. AMR varies regionally; however, limited tools are available to aid practitioners in appropriate antibiotic selection based on statewide antimicrobial susceptibilities. The objective of this study was to map E. coli antibiotic susceptibility regionally and longitudinally in Wisconsin. Methods. Antibiograms from 2009, 2013, and 2015 were collected from health systems, hospitals, and clinics in Wisconsin, resulting in 218 antibiograms representing 201,091 Gram-negative isolates. E. coli antibiotic susceptibility percentages were weighted by number of isolates and aggregated by county per year. Results. Spatial interpolation methods (inverse distance weighted, Kriging) were tested by both county center points and facility geocode where available. Susceptibility data for clinically relevant urinary tract infection antibiotics were interpolated to create geographic visualizations of AMR in Wisconsin. Antibiotics included amoxicillin, trimethoprim/sulfamethoxazole, ciprofloxacin, nitrofurantoin, ampicillin, ampicillin/sulbactam, levofloxacin. The interpolation extends to the furthest health system point in each direction and is presented within state boundaries. Facility geocodes were masked from public display for confidentiality. City names were added for orientation. The mapping depicts regional differences, such as 2015 ampicillin susceptibilities ranging 55–64% (Figure 1). The maps provide a preliminary susceptibility prediction in areas where no AMR data were available. Average susceptibilities were compared across 2009, 2013, and 2015 to map areas with the highest rates of AMR change. Conclusion. The described mapping provides a novel visualization of AMR across Wisconsin. The maps created will be utilized in continued efforts to improve the functionality of AMR data in clinical practice to optimize antimicrobial choice. Disclosures All authors: No reported disclosures.

Bayesian estimation of sensitivity and specificity of systematic thoracic ultrasound exam for diagnosis of bovine respiratory disease in pre-weaned calves

Among the different clinical presentations of bovine respiratory disease, active pneumonia, defined as an infection of the lower airway with signs of inflammation, is the most important to diagnose correctly so appropriate treatment can be initiated. Diagnostic tests that accurately identify cases of active pneumonia are lacking; however, thoracic ultrasonography (TUS) seems promising. The primary objective of this study was to estimate the accuracy of TUS compared to reference tests for the diagnosis of active pneumonia in pre-weaned calves, using a latent-class model method (LCM). The tests used for comparison were the Wisconsin Clinical Respiratory Scoring Chart (CRSC, positive if ≥5) and serum haptoglobin concentration (Hap, positive if ≥15 mg/dL). Secondary objectives were to assess the incremental value on TUS accuracy of combining TUS of the right cranial part and caudal parts, and to determine the accuracy of various thresholds for depth of consolidation (≥0 cm, ≥1 cm, or ≥3 cm) for diagnosis of active pneumonia. One population of veal calves (n = 209) and one of dairy calves (n = 301) were enrolled. TUS, CRSC and Hap were all performed on each calf on the same day. TUS was performed by screening the mid to ventral portion of the lung caudal of the heart (the caudal sites), as well as the right parenchyma cranial to the heart (the cranial site). The maximal depth of consolidation (DEPTH) on TUS was recorded and noted separately for caudal and cranial sites. Different TUS cases were defined according to site and DEPTH. The accuracy of TUS was estimated by LCM for three tests conducted in two populations. Prevalence of active pneumonia was low (0.05) in both populations. In general, higher minimal consolidation depth thresholds led to increased TUS specificity (Sp) estimates, with minimal effects on TUS sensitivity (Se). With a TUS DEPTH threshold of ≥3 cm, adding TUS of the cranial site had little effect on accuracy. Using the ≥3 cm threshold with caudal sites only, posterior Se and Sp median estimates of 0.89 (95%BCI: 0.55, 1.0) and 0.95 (95%BCI: 0.92, 0.98), respectively, were obtained. In conclusion, in populations with low active pneumonia prevalence, adding TUS of the cranial site did not enhance the performance of the test. We suggest using a DEPTH threshold of ≥3 cm solely on caudal sites to detect active pneumonia.

Adults born preterm exhibit bi‐ventricular hypercontractility and inefficiency

IntroductionIn the US, prematurity accounts for approximately 10% of all live births. Infants born preterm are at an increased risk of cardiopulmonary disease. Until recently, little was known about the long‐term sequelae in the myocardium in adult survivors of prematurity. One study demonstrated that adults born preterm had larger left (LV) and right ventricular (RV) masses, and lower RV ejection fraction compared to term born controls. To date, there is a paucity of information on the potential mechanism of altered ventricular mechanics in adult survivors of prematurity. Therefore, we hypothesized that preterm subjects would display reduced RV and LV strain.MethodsPreterm subjects were recruited from a prospectively followed cohort at UW‐Madison. Gestational ages for the preterm subjects were 28.2 ± 0.84 weeks and they weighed &lt; 1500 grams. Term‐born subjects were recruited from the general public. Cardiac magnetic resonance imaging (MRI) was used to determine myocardial strain and stroke volume (SV) in adults born preterm (n = 10, age = 26.9 ± 0.3 years) and age‐matched term born controls (n = 12, age = 25.8 ± 0.2 years). Three slices from the RV and LV (apex, mid and base) short‐axis cine MR images were used to analyze RV and LV circumferential and LV radial dimensions (mean peak strain, systolic and diastolic strain rate). SV was obtained from the main pulmonary artery (MPA) and aorta (Ao) 2‐D phase contrast images. SV was normalized to body surface area (SVI) and was divided by peak RV and LV circumferential strain to obtain RV and LV efficiency. All MRI analysis was performed using Segment (http://segment.heiberg.se). A Mann‐Whitney test was performed to test differences between groups (p &lt; 0.05).ResultsPreterm subjects demonstrated increased peak RV circumferential (−11.36 % ± 1.90 vs. −8.83 % ± 1.95; p = 0.003) and LV circumferential (−20.15 % ± 2.29 vs. −17.96 % ± 1.96; p = 0.025) strain compared to controls, respectively. Additionally, RV circumferential systolic strain rate, LV circumferential systolic and diastolic strain rate, and LV radial diastolic strain rate were greater (p &lt; 0.05) in preterm adults as compared to controls. SVI as measured from the MPA and Ao flow was not different between groups. Preterm subjects exhibited reduced (p &lt; 0.05) RV and LV (p = 0.06) efficiency as compared to controls.DiscussionWe used MRI to measure RV and LV strain, which is a measure of ventricular displacement during the cardiac cycle. Contrary to our hypothesis, these results demonstrate that adults born preterm exhibit a hypercontractile myocardium (increased strain) under resting conditions. The increased bi‐ventricular strain in the circumferential dimension in preterm born adults occurred despite no differences in SVI between groups. This results in reduced RV and LV efficiency in preterm subjects compared to controls, suggesting increased cardiac work may be required in adults born preterm for the same SVI. The implications for life‐time cardiovascular risk merit further study.Support or Funding InformationProject supported by funding from the National Institutes of Health: 1RO1 HL086897 (MWE) and RO1 HL38149 (MWE). Kara Goss is supported by the University of Wisconsin Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant NIH UL1TR000427 (PI Drezner; 4KL2TR000428‐‐10).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Knowledge, Confidence, and Practice Patterns of Speech-Language Pathologists Working With Adults With Traumatic Brain Injury.

Although speech-language pathologists (SLPs) are important members of the health care team serving adults with traumatic brain injury (TBI) with cognitive-communication disorders, little is known about services SLPs deliver and how they rate their own knowledge and skills. The aims of this study were to identify practice patterns, knowledge, and confidence levels of SLPs working with adults with TBI with cognitive-communication disorders. We surveyed 100 SLPs from rural and urban hospitals, skilled nursing facilities, and outpatient clinics in Wisconsin and analyzed data descriptively. SLPs in this sample had a combination of accurate and inaccurate knowledge related to TBI. Although all participants reported working with individuals with TBI, many participants rated themselves as lacking confidence or knowledge in this practice area. SLPs reported variable use of evidence-based procedures and training related to TBI. Results confirmed the high prevalence of TBI-related practice among SLPs in medical settings, but there was variable knowledge, confidence, and use of current evidence in practice. SLP graduate training programs, individual providers, health care administrators, and the American Speech-Language-Hearing Association can use results from this study to advance and improve SLP clinical services for adults with TBI.

Chaos in the Clinic: Characteristics and Consequences of Practices Perceived as Chaotic.

The Minimizing Error, Maximizing Outcome (MEMO) study of clinics in New York City, Chicago, and Wisconsin linked primary care work experiences to physician stress. We analyzed MEMO data to determine how chaos in the clinic was associated with work conditions and quality of care measures. Surveys and medical record audits determined practice characteristics and medical errors, respectively. Physicians rated clinic atmosphere on a scale of 1 (calm) to 5 (chaotic). Chaotic clinics were defined as practices rated either 4 or 5 by greater than 50% of clinic physicians. Forty of 112 MEMO clinics (36%) were chaotic. Compared with nonchaotic practices, these clinics served more minority and Medicaid patients and had a greater likelihood of clinic bottlenecks such as phone access (both p < .01). Physicians in chaotic clinics reported lower work control and job satisfaction, less emphasis on teamwork and professionalism, more stress and burnout, and a higher likelihood of leaving the practice within 2 years (all p < .05). Chaotic clinics had higher rates of medical errors and more missed opportunities to provide preventative services (both p < .05). More research should examine the effectiveness of organizational interventions to decrease chaos in the clinic and to mitigate its effects on patient safety.

Substance Use Screening, Brief Intervention, and Referral to Treatment Among Medicaid Patients in Wisconsin: Impacts on Healthcare Utilization and Costs.

Unhealthy substance use in the USA results in significant mortality and morbidity. This study measured the effectiveness of paraprofessional-administered substance use screening, brief intervention, and referral to treatment (SBIRT) services on subsequent healthcare utilization and costs. The pre-post with comparison group study design used a population-based sample of Medicaid patients 18-64years receiving healthcare services from 33 clinics in Wisconsin. Substance use screens were completed by 7367 Medicaid beneficiaries, who were compared to 6751 randomly selected treatment-as-usual Medicaid patients. Compared to unscreened patients, those screened changed their utilization over the 24-month follow-up periodby 0.143 outpatient days per member per month (PMPM) (p < 0.001), -0.036 inpatient days PMPM (p < 0.05), -0.001 inpatient admissions PMPM (non-significant), and -0.004 emergency department days PMPM (non-significant). The best estimate of net annual savings is $391 per Medicaid adult beneficiary (2014 dollars). SBIRT was associated with significantly greater outpatient visits and significant reductions in inpatient days among working-age Medicaid beneficiaries in Wisconsin.

A Retrospective: On Clinical Studies with 5-Fluorouracil.

See related article by Curreri et al., [Cancer Res 1958:18:478–484][1] . Visit the Cancer Research 75th Anniversary [timeline][2]. The 1950s saw the rise of rational drug design to target DNA synthesis in cancer cells. The concept was simple; cancer was replicating uncontrolled compared with

Can the sequence of chemotherapy regimens influence outcome in patients with metastatic pancreatic adenocarcinoma (MPAC)?

428 Background: FOLFIRINOX(FFX)/FOLFOX(FX) and Nab-paclitaxel plus Gemcitabine (NabG) represent standard first line (FL) treatment options for MPAC, but there is no prospective data to ascertain the ideal sequence of these regimens when used off protocol for patients with MPAC. We reviewed our single institution experience to evaluate whether the sequence of these regimens influenced clinical outcome. Methods: All MPAC patients treated with FFX/FX or NabG, in either sequence, from 1/1/11 to 12/31/14 at the Froedtert and Medical College of Wisconsin (MCW) Clinical Cancer Center were identified and their charts reviewed. This study was approved by the Froedtert &amp; MCW Institutional Review Board. Results: Among 64 patients reviewed, the median age at diagnosis was 62. 64.1% were male and 95.3% were Caucasian. Median Ca19-9 and CEA at diagnosis were 855 and 10.4 respectively. 37/64 (57.8%) patients received SL therapy. Details of treatment and disease control rate (DCR) are summarized in the Table. Of patients who were refractory to FL FFX/FX, 4/7 (57.1%) demonstrated disease control (DCR) with SL NabG; numbers were too small for reverse analysis. Median overall survival (OS) of patients who received 2 lines of therapy was 12.1 months, while median OS of patients who received one line was 4.1 months. Median OS associated with sequential therapy is summarized in the Table. Conclusions: Both FFX/FX and NabG are active in the SL setting. Outcomes appear to be fairly similar regardless of sequence. The numerically superior median OS associated with FL NabG followed by SL FFX should be interpreted with caution in the context of small number of patients in this subset. A substantial minority of patients do not receive second line chemotherapy due to deteriorating clinical status and/or patient preference suggesting unfavorable tumor biology. [Table: see text]