Pro-Coagulant Endothelial Dysfunction Results from EHEC Shiga Toxins and Host Damage-Associated Molecular Patterns

Hemolytic uremic syndrome (HUS) from enterohemorrhagic Escherichia coli infection is a leading cause of kidney failure in otherwise healthy U.S. children. The bacterial Shiga toxins (Stx) induce the characteristic coagulopathy of HUS, but the damage to toxin-receptor expressing cells and organ injury due to ischemia likely also releases inflammatory damage-associated molecular patterns (DAMPs), which may exacerbate injury along with the toxins. To examine this, human aortic and renal glomerular cell anti-coagulant and barrier functions were studied after in vitro challenge with Stx1, Stx2, and DAMPs. There was significant loss of surface anti-coagulant protein C pathway molecules, increased expression of pro-thrombotic PAR1 and reduced protein C activation capability by 15–27%. Histones nearly completely prevented the activated protein C protection of endothelial cells from thrombin-induced permeability. In mice, lethal Stx2 challenge elevated plasma HMGB1 (day 2, 321 ± 118%; p < 0.01) and extracellular histones (day 3, 158 ± 62%; p < 0.01). Mice colonized with Stx2-expressing Citrobacter rodentium developed increased HMGB1 (day 5, 155 ± 55%; p < 0.01) and histones (day 3, 378 ± 188%; p < 0.01). Anti-histone antibody reduced both DAMPs to baseline, but was not sufficient to improve survival outcome or kidney function. Together, these data suggest a potential role Stx to produce DAMPs, and DAMPs to produce endothelial injury and a pro-thrombotic environment

Shiga Toxin Therapeutics: Beyond Neutralization

Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells. The preclinical development of toxin-targeted HUS therapies has been hindered by the sporadic, geographically dispersed nature of STEC outbreaks with HUS cases and the limited financial incentive for the commercial development of therapies for an acute disease with an inconsistent patient population. The following review considers potential therapeutic targeting of the downstream cellular impacts of Shiga toxicity, which include the unfolded protein response (UPR) and the ribotoxic stress response (RSR). Outcomes of the UPR and RSR are relevant to other diseases with large global incidence and prevalence rates, thus reducing barriers to the development of commercial drugs that could improve STEC and HUS patient outcomes

Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals

toxin

Quality Improvement Study for Postpartum Hypertension Readmissions

Background: Hospital readmission rates are a focus of the Centers for Medicare and Medicaid Services. This was identified as a system opportunity to improve health care quality and patient education in order to reduce preventable readmissions. In 2009, 27% of obstetric readmissions were due to hypertensive disease, and preventable readmissions regarding hypertension are flagged as an area for quality improvement in our health care system. There is limited evidence on specific management of postpartum hypertension. Purpose: Identify risk factors in our community and reduce postpartum readmissions for hypertension within our hospital. Methods: We performed a retrospective chart review from November 2014 to November 2015. We collected demographic data, comorbidities and information regarding hospitalization and readmission. In this, we identified 28 readmissions for postpartum hypertension, representing 57% of obstetric readmissions and noted that discharge instructions and blood pressure monitoring postpartum were two areas for improvement. Only 18% had printed instructions regarding postpartum hypertension. Via multidisciplinary education sessions, we aimed to increased surveillance for postpartum vitals for at-risk patients and provide appropriate verbal and written precautions for signs and symptoms of de novo or worsening hypertensive disease. We also improved access to care by scheduling blood pressure checks within 72 hours of discharge and utilization of visiting nursing services for blood pressure checks. The same measures were then recollected for readmissions from June 2016 to December 2016. Results: After intervention, 61% of readmissions were related to hypertension, with 31 readmissions. Overall, there was a significant improvement in written discharge instructions regarding postpartum hypertension, with 94% receiving written instructions. At discharge, 33% had blood pressure checks and 13% had visiting nursing services arranged. Conclusion: Postpartum hypertension is more recognized, and readmissions are becoming more common. We increased efforts to optimize medical management of hypertension and reduce preventable readmissions. Improvement in discharge instructions for patients did not decrease overall admission for postpartum hypertension but may have improved overall patient care. Overall cost analysis would be beneficial to see further economic impact

Identifying and Targeting Age-Related Colorectal Cancer Screening Rate Disparities in Family Medicine Residency Clinics

Background: Health care systems continuously seek to improve patient care through population-level analysis of clinical quality metrics and patient characteristics to identify disparities in care. Nationally, disparities in colorectal cancer (CRC) screening rates have been identified with lower screening rates reported for patients who are uninsured and/or lower socioeconomic status, African American/black, Asian, and non-English-speaking Hispanic patients. No age-related CRC screening rate disparities with associated interventions have been reported. Purpose: Determine and address CRC screening disparities in care provided to eligible patients \u3e 50 years old in two primary care residency clinics. Methods: Retrospective analysis using REAL-G (race, ethnicity, age, preferred language, gender) categories and insurance coverage was completed on a 12-month data set to identify presence of CRC screening disparities. Barriers to CRC screening for largest disparity gap were then identified by clinic staff at two family medicine residency clinics (a third primary care clinic in same zip code and service region were used for nonintervention comparison) using the Institute for Healthcare Improvement fishbone approach. The project team, informed by the literature, then identified and implemented targeted interventions, monitoring progress during a 6-month period. Interventions included provider education with periodic reminders regarding system-approved CRC screening options and a workflow-based intervention. Postintervention analysis was completed using same preintervention approach. Results: The largest CRC screening disparity for region and clinics was associated with age, with screening gaps ranging from 13% to 15% between populations aged 50–54 years versus \u3e 65 years. CRC screening rate disparities by race, ethnicity, and gender were less than 10%. Postintervention, one targeted clinic had a 6% increase in the CRC screening rates in the target population (age: 50–54) while a second targeted clinic had a 1% increase in screening rates during this period. The comparison primary care residency clinic had a 1% decline in CRC screening rates. Differences in insurance utilization types for CRC screening rates by clinic were noted. Differences between targeted clinic screening rates were attributed to successful workflow implementation and provider/staff champions. Conclusion: Analyzing population data at a micro/clinic level using REAL-G categories can inform targeted interventions that aim to reduce health disparity gaps

Identifying Disparities in Colorectal Cancer Screening Rates in Milwaukee-Based Academic and Nonacademic Clinics

Background: The Institute for Healthcare Improvement’s Triple Aim focuses on improving the patient’s experience of care, improving population health and reducing the per capita cost of health care. Health care systems and providers continuously seek to improve quality of care through understanding what percentage of their patients are achieving quality-of-care standards for various indicators, including immunizations, tobacco cessation, asthma and cancer screening. As health care moves toward reimbursing for value-based care, deepening our understanding of patient population characteristics within each of these conditions is vital to continuous quality improvement. Purpose: To determine if there are race/ethnicity/age/preferred language (REAL) disparities in care to patients 50 years old or older who are eligible for colorectal cancer (CRC) screening in family medicine residency clinics. Methods: A retrospective analysis of all patients eligible for CRC screening at two Milwaukee-based family medicine residency teaching clinics (referred to as FM1 and FM2) and nonacademic clinics in greater Milwaukee (NAC-MKE) during a 12-month period (December 2014 – November 2015) was undertaken in collaboration with health care system quality improvement specialists. Percentage of patients achieving CRC screening metric was reported by REAL and gender. As the ultimate goal was to identify subpopulations to target for improvement, categories with N \u3c 25 were omitted and criterion for disparity within a category was defined as \u3e 10%. Results: The largest CRC screening disparity was associated with age, with gaps ranging from 13% to 15% between populations \u3e 65 years old versus 50–54 years old: NAC-MKE (79% vs 66%), FM1 (81% vs 68%), and FM2 (80% vs 65%). CRC screening disparities varied by black/African-American race per location, 54% at NAC-MKE and 67% at FM2 (N ≤ 25 at FM1). Other race, ethnicity and gender were \u3c 10%. Conclusion: Per the Centers for Disease Control and Prevention, the African-American/black race has the highest CRC death, making early CRC screening an imperative. While the Wisconsin Collaborative for Healthcare Quality ranks Aurora Health Care as eighth out of 20 systems in Wisconsin (77.6% from 2014 Q3 to 2015 Q2), local data analysis identified age as the largest disparity gap. Analyzing local population REAL/gender data provides key insights to support initiatives to reduce health disparity gaps and further progress toward achieving the Triple Aim for health care

Addressing Barriers to Resident & Faculty

Incident reporting has been recognized as a critical strategy for improving patient safety (PS) as is the focus area/pathway ACGME’s Clinical Learning Environment Review (CLER). Yet despite its importance, physician incident reporting remains limited hindering efforts to learn and develop processes to prevent future occurrences. An often cited barrier to physician reporting is that submissions go into a “black hole” with no process for learning. Through collaboration with incident reporting leaders, we developed an approach whereby residency program directors review incidents related to their program from an educational perspective