bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Critical to Quality Elements for Intensive Care Rounds by Kano Analysis
Authors: Tripathi Sandeep , Henrekin Lamonica L. , Read Cynthia D. , Welke Karl F.
Published: June 2019

Background:

Pediatric cardiac intensive care unit rounds require high levels of efficiency in data transfer and decision making to achieve optimal performance. Traditional survey methods do not discriminate and prioritize effectively the elements of rounds essential to a provider. In this study, we describe our experience with a novel survey method (Kano analysis) to assess customers’ (surgeons, intensivists, cardiologists, advanced practice nurses, and nurses) requirements from rounds.

Methods:

A 26-point survey divided into 3 domains (presentation, decision, and process elements) was conducted among Pediatric Intensive Care Unit (PICU) providers. Based on the survey, attractive, must be, performance, indifferent, and reverse categories were identified using methods described in the literature. Average satisfaction and dissatisfaction coefficients and percentages of attractive and mandatory elements in subgroups were compared. Results from the quantitative analysis were charted on a categorization plane.

Results:

The survey was returned by all providers with 96% valid responses. The highest satisfaction coefficient in the presentation domain was for “one line statement about the patient” (0.76), in the decision domain “rhythm/anti-arrhythmics” (0.54), and in the process domain “reformatting presentation script” (0.77). The highest dissatisfaction gradients were for “overnight events” (-0.91), “rhythm/anti-arrhythmics” (-0.71), and “asking families to join rounds” (-0.49). Among the 5 subgroups, surgeons required the largest percentage of items as mandatory or attractive and had the highest dissatisfaction coefficients in all 3 categories.

Conclusion:

Kano survey can provide rapid and precise actionable data to restructure a new process. Further research potentially also involving patients and families in the Kano survey may provide insight on patient-centered care models.
Effects of Skin-to-Skin Care on Late Preterm and Term Infants At-Risk for Neonatal Hypoglycemia
Authors: Chiruvolu Arpitha , Miklis Kimberly K. , Stanzo Karen C. , Petrey Barbara , Groves Chelsey G. , McCord Kari , Qin Huanying , Desai Sujata , Tolia Veeral N.
Published: June 2019

Objective:

The objective of this study was to evaluate the effects of prolonged skin-to-skin care (SSC) during blood glucose monitoring (12–24 hours) in late preterm and term infants at-risk for neonatal hypoglycemia (NH).

Study design:

We conducted a retrospective pre- and postintervention study. We compared late preterm and term infants at-risk for NH born in a 1-year period before the SSC intervention, May 1, 2013, to April 30, 2014 (pre-SSC) to at-risk infants born in the year following the implementation of SSC intervention, May 1, 2014, to April 30, 2015 (post-SSC).

Results:

The number of hypoglycemia admissions to neonatal intensive care unit among at-risk infants for NH decreased significantly from 8.1% pre-SSC period to 3.5% post-SSC period (P = 0.018). The number of infants receiving intravenous dextrose bolus in the newborn nursery also decreased significantly from 5.9% to 2.1% (P = 0.02). Number of infants discharged exclusively breastfeeding increased from 36.4% to 45.7%, although not statistically significant (P = 0.074).

Conclusion:

This SSC intervention, as implemented in our hospital, was associated with a significant decrease in newborn hypoglycemia admissions to neonatal intensive care unit. The SSC intervention was safe and feasible with no adverse events.
Reducing Blood Testing in Pediatric Patients after Heart Surgery: Proving Sustainability
Authors: Bodily Stephanie A. , Delgado-Corcoran Claudia , Wolpert Katherine , Lucas Kathryn , Presson Angela P. , Bratton Susan L.
Published: June 2019

Introduction:

Frequent blood testing increases risk of iatrogenic anemia, infection, and blood transfusion. This study describes 3 years of sustained blood testing reduction from a quality improvement (QI) initiative which began in 2011.

Methods:

The cohort consisted of postop children whose surgery had a Risk Adjustment for Congenital Heart Surgery (RACHS) classification consecutively admitted to a tertiary Cardiac Intensive Care Unit. Data were collected for a 2010 preintervention, 2011 intervention, and 2012–13 postintervention periods, tabulating common laboratory studies per patient (labs/pt) and adjusted for length of stay (labs/pt/d). The QI initiative eliminated standing laboratory orders and changed to testing based on individualized patient condition. Adverse outcomes data were collected including reintubation, central line–associated bloodstream infections and hospital mortality. Safety was measured by the number of abnormal laboratory studies, electrolyte replacements, code blue events, and arrhythmias.

Results:

A total of 1169 patients were enrolled (303 preintervention, 315 intervention, and 551 postintervention periods). The number of labs/pt after the QI intervention was sustained (38 vs. 23 vs. 23) and labs/pt/d (15 vs. 11 vs. 10). The postintervention group had greater surgical complexity (P = 0.002), were significantly younger (P = 0.002) and smaller (P = 0.008). Children with RACHS 3–4 classification in the postintervention phase had significant increased risk of reintubation and arrhythmias.

Conclusions:

After the implementation of a QI initiative, blood testing was reduced and sustained in young, complex children after heart surgery. This may or may not have contributed to greater reintubation and arrhythmias among patients with RACHS 3–4 category procedures.
A Quality Initiative for Optimal Therapeutic Hypothermia during Transport for Neonates with Neonatal Encephalopathy
Authors: Bourque Stephanie L. , Meier Stephanie A. , Palmer Claire , Melara Diane L. , Grover Theresa R. , Delaney Cassidy A.
Published: June 2019

Introduction:

Neuroprotection with therapeutic hypothermia (TH) is standard of care for neonatal encephalopathy (NE) and decreases death and neurodevelopmental disability. TH initiated shortly after birth insult results in greater neuroprotection compared with delayed initiation.

Methods:

Quality improvement methodology was used to improve temperature control during transport to a level IV neonatal intensive care unit. We included neonates with NE transported to a single institution for TH from 2010 to 2016. The quality improvement interventions were 2-fold. Review of the Transport Body Cooling Protocol revealed a suboptimal temperature goal of 34–35°C; this protocol was revised to 33–34°C. The second intervention was the implementation of an active cooling protocol. Clinical characteristics were compared using 2-sample t tests for continuous variables and Fisher’s exact tests for categorical variables; statistical process control chart was used to monitor admission temperatures.

Results:

We obtained baseline data for 78 neonates admitted from 2010 to 2014. These data were compared with postintervention data for 26 patients admitted between 2015 and 2016. Distance transported, NE severity, and seizures were similar between the 2 groups. The use of active cooling increased from 8% preimplementation to 31% postimplementation (P < 0.01). After implementation of the 2 interventions, more infants were admitted within the goal temperature of 33–34°C, 58% versus 22% (P < 0.01), and the average neonatal intensive care unit admission temperature improved from 34.4 ± 0.8°C to 33.8 ± 0.8°C (P < 0.01).

Conclusion:

Increased utilization of active cooling during transport for TH improves the percentage of neonates admitted within the target temperature range. However, 42% of neonates remained outside the target temperature range, supporting the need for additional tools to improve admission temperatures.
Decision Tree Model for Hematology/Oncology Patients with Severe and Nonsevere Sepsis
Authors: Munger Jessica A. , Lavin Stephanie M. , Hurt Clint J. , Bullock Erin K. , Gelvez Javier
Published: June 2019

Background:

Hematology/oncology (H/O) patients have been screened for sepsis since 2013 at a pediatric hospital. Using sepsis screening (Ss) tool, results, and addition of organ dysfunction screening (ODs), decision tree (DT) was designed (Fig. 1) for nurses to identify sepsis and intervene.

Objectives:

Positive Ss require multiple assessments by nurses and H/O physicians creating sepsis alert fatigue. By implementing DT, calls to H/O physicians for sepsis alerts could be reduced 24% without increasing misses of patients with sepsis.

Methods:

Patients with Ss < 4 considered negative; Ss > 4 positive. ODs < 2 considered negative, = 2 at risk, > 2 positive for sepsis. In 2016, Ss were performed on H/O patients upon admission, status change, or nurse concern. May 2017, DT was implemented on H/O. From 5/5/17 to 8/30/17 Ss and ODs were conducted every 12 hours or with status change (Fig. 2).

Results:

Design period: 1,457 Ss (n = 1,393); 200 Ss positive (n = 180); 8 Ss, ODs < 2 (n = 44); 152 Ss, ODs = 2 (n = 139); and 0 Ss, ODs > 2. Implementation period: 6,502 Ss (n = 512); 1,647 Ss positive (n = 292); 293 Ss, ODs < 2 (n = 72); 1,351 Ss, ODs = 2 (n = 265); and 30 Ss, ODs > 2 (n = 14). See Figure 3 for pediatric intensive care unit (PICU) transfers during design/implementation periods.

Conclusions/Implications:

During implementation, calls were reduced to H/O physicians by 17.5% (ODs < 2). Most patients were ODs = 2. Recommendations included calling physician only if nurse was concerned of patient’s status with OD = 2. DT with addition of ODs has increased awareness of sepsis and communication between transferring providers. We have not found an increase in sepsis misses requiring transfer to PICU.
Improving Wait Time for Patients in a Pediatric Echocardiography Laboratory - a Quality Improvement Project
Authors: Parthiban Anitha , Warta Ashley , Marshall Jennifer A. , Reid Kimberly J. , Mann Keith , Shirali Girish , Swanson Tara
Published: June 2019

Background:

Prolonged wait times for echocardiograms in the outpatient pediatric cardiology clinic led to patient and provider dissatisfaction at our institution. The aims of this project were to measure our baseline performance with regard to echocardiogram wait time (EWT), to implement a formal quality improvement (QI) program to improve EWT, and to measure the impact of QI on EWT.

Methods:

A QI team was formed comprising of cardiologists (A.P., T.S.), sonographer (A.W.), and QI mentor (J.M.). EWT was defined as time in minutes from initiation of the order in the electronic medical record to start of the echocardiogram. Goal EWT was set as ≤ 20 minutes for 90% patients. Flowcharts were created after process observation to identify sources of potential delay contributing to EWT. QI methodology such as driver diagrams were utilized to identify interventions, which were then implemented and studied as Plan-Do-Study-Act cycles.

Results:

Sequential interventions included early start time, huddles involving clinic and echo laboratory staff, patient tracking system, and repurposing of a clinic room for echo. EWT was tracked for 840 patients. Mean EWT was 22.5 ± 17.5 minutes at baseline and decreased to 15.3 ± 7.8 minutes postintervention (P < 0.001). Postintervention, 81% of the patients waited < 20 minutes for their echo, and 98% patients waited < 30 minutes, compared with baseline numbers of 62% and 76%, respectively (P < 0.001).

Conclusions:

We were able to utilize QI methodology to derive interventions and track changes, resulting in quantifiable improvement in EWT in a busy pediatric echo laboratory.
A Saturated Approach to the Four-Phase, Brain-Based Simulation Framework for TeamSTEPPS® in a Pediatric Medicine Unit
Authors: Clapper Timothy C. , Ching Kevin , Mauer Elizabeth , Gerber Linda M. , Lee Joanna G. , Sobin Brittany , Ciraolo KerriAnn , Osorio Snezana Nena , DiPace Jennifer I.
Published: June 2019

Introduction:

Although many organizations have reported successful outcomes as a result of Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), implementation can be challenging, with its share of administrative obstacles and lack of research that shows observable change in practice.

Methods:

This quantitative, pretest/posttest design pilot research used a combination of classroom simulation-based instruction and in situ simulation in a Pediatrics department in an urban academic center. All personnel with direct patient care responsibilities (n = 547) were trained in TeamSTEPPS in an 8-week period. TeamSTEPPS course knowledge scores were compared pretraining to posttraining using the Wilcoxon rank-sum test. The performance of two-day and overnight shift teams, pre- and postintervention was assessed using the TeamSTEPPS Team Performance Observation Tool.

Results:

TeamSTEPPS course knowledge improved from the beginning of the course to completion with median scores of 16 and 19, respectively (P < 0.001). Both day and evening postintervention groups demonstrated greater team performance scores than their control counterparts. Specifically, postintervention day shift team showed the greatest improvement and demonstrated more TeamSTEPPS behaviors.

Conclusion:

This pilot study involving 1 department in an urban hospital showed that TeamSTEPPS knowledge and performance could be improved to increase patient safety and reduce medical errors. However, teams need to be trained within a shorter period so they can apply a shared-model of teamwork and communication. Leaders and educators throughout the department must also reinforce the behaviors and include them in every education intervention.
A Quality Improvement Initiative to Decrease Time to Antibiotics for Children with Intestinal Failure, Fever, and a Central Line
Authors: Hariharan Selena , Mezoff Ethan A. , Dandoy Christopher E. , Zhang Yue , Chiarenzelli Janis , Troutt Misty L. , Simpkins Jean , Dewald Mary , Klotz Kim , Mezoff Adam G. , Cole Conrad R.
Published: June 2019

Introduction:

Pediatric intestinal failure (IF) patients experience significant morbidity, including sepsis related to central line–associated bloodstream infections. Adult studies of sepsis demonstrate an association between time to antibiotic administration (TTA) and mortality. To overcome challenges in treating pediatric IF patients in an emergency department (ED), we appropriated an existing, reliable system for febrile immunocompromised oncology/bone marrow transplant children. We describe the translation of this process to febrile IF patients in the ED and steps toward sustained improvement.

Methods:

We formed a multidisciplinary team and used the Model for Improvement to define aims and identify key drivers. The goal was to use an existing improvement process to increase the percentage of patients with IF who receive antibiotics within 60 minutes of arrival to the ED from 46% to 90%. Key drivers included pre- and postarrival processes, staff and family engagement, and a preoccupation with failure. We performed Plan-Do-Study-Act cycles targeting family engagement, prearrival efficiency, and postarrival consistency.

Results:

Two hundred seventy-six encounters involving febrile IF patients between November 2012 and March 2017 were evaluated. There was a sustained reduction in the median time from arrival to antibiotic administration (71–45 minutes). We decreased TTA to less than 60 minutes for 77% of febrile IF patients.

Conclusions:

The basic tenets of process improvement for 1 high-risk population can be translated to another high-risk population but must be adjusted for variability in characteristics.
Reducing Time to Pain Medication Administration for Pediatric Patients with Long Bone Fractures in the Emergency Department
Authors: Schuman Sarah S. , Regen Rebecca B. , Stuart Lindsay H. , Harrell Camden , Jones Tamekia L. , Stewart Barbara M. , Berg Allyson M. , Longjohn Mindy , Kink Rudy J.
Published: June 2019

Introduction:

Pain management is a critical aspect of effective long bone fracture treatment. Pediatric patients frequently report suboptimal pain management, which is an area of growing public concern. The purpose of this quality improvement project was to develop a protocol with the goal to administer pain medication to children presenting with suspected long bone fractures ≤47 minutes of emergency department arrival.

Methods:

A multidisciplinary team developed a standardized protocol for pain management of patients presenting with musculoskeletal pain utilizing acetaminophen as the first-line agent under a nurse-initiated order. Following education and implementation, weekly reports generated using the International Classification of Diseases codes of fractures were reviewed to assess compliance with the protocol. This study evaluates the frequency of a second pain medication administration and reduction in vital signs and pain scores.

Results:

Implementation of a pain management protocol reduced median time to pain medication administration to 26 minutes. Overall, 63% (n = 638) of patients required a second pain medication. Of these, 66.5% (348/523) who initially received acetaminophen and 59.7% (286/479) who initially received an opioid required a second pain medication. No significant changes in pre and posttreatment vital signs were found between groups. Patients who initially received opioids experienced a greater reduction in posttreatment pain scores.

Conclusions:

Using a standardized pain management protocol in combination with comprehensive education effectively reduces median time to pain medication administration in pediatric patients with long bone fractures. Acetaminophen is a rapid and effective first-line agent for managing pain in this population.
Improving Low-acuity Patient Flow in a Pediatric Emergency Department: A System Redesign.
Authors: Berkowitz Deena A. , Brown Kathleen , Morrison Sephora , Payne Asha , Pettinichi Jeannie , Schultz Theresa Ryan , Thomas Anthony , Chamberlain James M.
Published: June 2019

Background:

Children’s National Health Systems pediatric emergency department (ED), is a level 1 trauma center in Washington, DC, which treats over 90 000 patients annually. Approximately 50% of arriving patients are triaged as low acuity, Emergency Severity Index level 4 or 5. With limited space and resources, these patients are treated inefficiently, with average delays from arrival to provider time of 1.3 hours and length of stays (LOS) close to 2.5 hours.

Objectives:

In July 2016, Children’s National Health Systems ED initiated a focused approach to improve both patient flow and experience for these low-acuity patients.

Methods:

We assembled a multidisciplinary ED-based task force. The quality improvement initiative began in January 2017 and consisted of 4 steps: (1) front-end space redesign; (2) implementation of a new front-end patient triage and assessment process; (3) increased doctor and nurse staffing; and (4) dissemination of data updates to reinforce awareness and adherence to workflow. Our process outcomes were arrival-to-provider time and LOS for low-acuity patients. Our balancing measures were the rate of return to the ED within 72 hours and arrival to provider times for high-acuity patients. We used statistical process control methodology to measure the effects of our interventions over time. We performed a secondary analysis to measure the response of wait times to total daily volume comparing preintervention to postintervention.

Results:

We decreased the LOS by 11 minutes (9%) and arrival to MD times 21 minutes (35%) for the same period 1 year apart.
Pediatric Surgeon Perceptions of Participation in External Patient Safety Programs: impact on Patient Safety
Authors: Berman Loren , Rangel Shawn , Tsao KuoJen ,   for the APSA Quality and Safety Committee
Published: June 2019

Introduction:

Surgeons play a crucial role in preventing harm and contributing to the safety culture of their institutions. External safety data programs are designed to review adverse events and provide performance benchmarks to ameliorate future adverse events. The extent to which pediatric surgeons are aware of these programs, utilize data from these programs, and believe that they improve patient safety, is unknown.

Methods:

A cross-sectional survey of the American Pediatric Surgical Association membership was conducted to evaluate participation in and attitudes toward national safety benchmark programs (eg, National Surgical Quality Improvement Program). Surgeons’ perceptions of these activities, including barriers to participation and utilization of safety data, were measured. We performed standard frequency analyses and tests of associations between surgeon characteristics and the likelihood of utilizing safety data.

Results:

The response rate was 38% (353/928). Seventy-two percentage of respondents reported institutional participation in external safety benchmark programs. Of those, only 68% utilized data to improve or monitor patient safety. Surgeon-reported barriers to this process included lack of knowledge, time, and institutional resources.

Conclusions:

Many pediatric surgeons are aware of institutional participation in external safety data programs, but only a portion are involved in the utilization of these data. We have identified several barriers to participation and data utilization. These findings can help direct educational efforts to optimize our ability to learn from adverse event benchmarking and improve pediatric surgical care.
Audit-and-Feedback and Workflow Changes Improve Emergency Department Care of Critically Ill Children
Authors: Spencer Sandra P. , Karsies Todd
Published: June 2019

Introduction:

Children with severe infection have improved outcomes when they received antibiotics promptly. Positive cultures help guide physicians in antibiotic selection. In 2011, 30% of children intubated in the emergency department received antibiotics and had respiratory culture collected within 60 minutes of intubation. Knowing the risk of delaying appropriate antibiotics, we charted a quality improvement team to improve compliance with 80% of intubated patients receiving both.

Methods:

The team evaluated all children intubated with concern for infection in the emergency department. Using a multidisciplinary team and employing quality improvement methods, we implemented multiple plan-do-study-act cycles to improve time to antibiotics and respiratory cultures. The team continued to implement successful interventions and restarted interventions directly affecting improvement.

Results:

While multiple interventions had small effects on the baseline of 30% compliance, 2 interventions appeared more influential than others. Workflow changes and audit-and-feedback created the largest, persistent positive changes. The importance of audit-and-feedback became very obvious when the project entered sustain mode. An abrupt decrease in compliance occurred when audit-and-feedback stopped. Complete recovery in compliance to greater than 80% occurred with the resumption of the audit-and-feedback intervention.

Conclusions:

Workflow changes and audit-and-feedback interventions resulted in large improvements. Loss of compliance with cessation of the audit-and-feedback and resumption demonstrated the importance of this intervention. Recovery to >80% compliance with the renewal of the audit-and-feedback program indicates its strength as a positive intervention.
Strengthening the Chain of Survival: Cardiopulmonary Resuscitation Workshop for Caregivers of Children at Risk
Authors: Tomatis Souverbielle Cristina , González-Martínez Felipe , González-Sánchez Maria I. , Carrón Marta , Guerra Miguez Luis , Butragueño Laura , Gonzalo Henar , Villalba Tomas , Perez Moreno Jimena , Toledo Blanca , Rodríguez-Fernández Rosa
Published: June 2019

Background:

Parents and caregivers should receive training regarding pediatric cardiopulmonary resuscitation (CPR) because this knowledge improves survival. We conducted a study as part of a Patient Safety Project to improve caregivers’ CPR knowledge and skills. We also aimed to improve the quality of patient care.

Methods:

We performed a prospective, longitudinal study in 2013–2014 in a pediatric hospital. We enrolled the caregivers of all patients admitted with a diagnosis of an acute life-threatening event, apnea, or choking. We provided a 45-minute CPR workshop for parents at discharge and evaluated the results using a test before, immediately after, and at 1 and 3 months after the workshop. Participants also completed an evaluation survey about the CPR workshop.

Results:

We admitted 62 patients [median age, 1 mo (0.5–2 mo)]. We provided 62 pediatric CPR workshops to 106 enrolled relatives. The median score was 5 (CI, 3–6) out of 10 at baseline, which increased to 8 (CI, 7–10) immediately after the workshop (P < 0.01). After 1 and 3 months, the median score was 8 (CI, 6–9; P < 0.01). The severity of the acute life-threatening event episode correlated with a better score (P = 0.02). The utility of the workshop scored 9.9 out of 10.

Conclusions:

This CPR workshop significantly increased CPR knowledge and confidence, and this was maintained up to 3 months post-training. Caregiver satisfaction was high.
Co-designed PICU Family Stress Screening and Response System to Improve Experience, Quality, and Safety
Authors: Liaw K. Ron-Li , Cho Jeanne , Devins Lea , Daly Jennifer , Sklenar Dennis , Al-Qaqaa Yasir
Published: June 2019

Objective:

Evidence for successful and sustainable models that systematically identify and address family stress in the pediatric intensive care unit (PICU) remains scarce. Using an integrated improvement science and family engagement framework, we implemented a standardized family stress screening tool and response protocol to improve family experience and reduce family crises through the timely coordination of parent support interventions.

Methods:

We conducted this improvement initiative in the 12-bed PICU of a children’s hospital within a large, urban academic medical center. Our team, which included 2 family advisors, adapted a validated Distress Thermometer for use in pediatric intensive care. A co-designed family stress screening tool and response protocol were iteratively tested, refined, and implemented in 2015–2017. Process and outcome measures included screening and response reliability, parent satisfaction, and security calls for distressed families.

Results:

Over the 18 months, the percentage of families screened for stress increased from 0% to 100%. Among families who rated stress levels ≥5, 100% received the recommended response protocol, including family support referrals made and completed within 24 hours of an elevated stress rating. From 2015 to 2017, PICU parent satisfaction scores regarding emotional support increased from a mean score of 81.7–87.0 (P < 0.01; 95% CI). The number of security calls for distressed families decreased by 50%.

Conclusions:

The successful implementation of a co-designed family stress screening tool and response protocol led to the timely coordination of parent support interventions, the improved family perception of emotional support, and reduced family crises in the PICU.
Standardized Implementation of Evidence-based Guidelines to Decrease Blood Transfusions in Pediatric Intensive Care Units
Authors: Hanson Sheila J. , Owen Erin B. , McDonald Mark J. , Woods Katherine J. , Montgomery Vicki L.
Published: June 2019

Introduction:

Despite evidence that red blood cell (RBC) transfusions may be associated with more harm than benefit, current transfusion practices vary significantly. This multicenter, quality improvement study aimed to sustainably decrease the rate of RBC transfusions in pediatric intensive care units (PICUs).

Methods:

This 16-month prospective study included 5 PICUs. We implemented a standardized project plan including education, bedside tools, real-time reminders, and email feedback. We collected data from consecutive transfusions during pre-implementation (Phase I), postimplementation (Phase II), and post-stabilization phases (Phase III).

Results:

Of the 2,064 RBC transfusions, we excluded 35% (N = 729) from analysis in patients undergoing extracorporeal membrane oxygenation. Transfusion/1,000 admissions improved throughout the study periods from a baseline 209.6 -199.8 in Phase II and 195.8 in Phase III (P value < 0.05). There were fewer transfusions outside of the hemoglobin threshold guideline, decreasing from 81% of transfusions outside of guidelines in Phase I to 74% in Phases II and III, P < 0.05. Study phase, site, co-management status, service of requesting provider, admit reason, previous transfusion status, and age were associated with transfusion above guideline threshold.

Conclusions:

Multicenter collaboration can successfully deploy a standardized plan that adheres to implementation science principles to sustainably decrease the rate of RBC transfusion outside of guideline thresholds. However, we did not decrease the total number of transfusions in our study. The complexity of multiple specialties co-managing patients is common in the contemporary PICU. Educational initiatives aimed at one specialty may have limited effectiveness in a multifaceted system of care.
Multifaceted Quality Improvement Initiative Improves Retention in Treatment for Youth with Opioid Use Disorder
Authors: Cottrill Casey B. , Lemle Stephanie , Matson Steven C. , Bonny Andrea E. , McKnight Erin R.
Published: June 2019

Introduction:

There is a critical need to develop interventions that help adolescents and young adults with opioid use disorders (OUDs) connect with, engage in, and remain consistent with the treatment given that patients who develop long-term OUDs experience long-term medical and mental health sequelae.

Methods:

We implemented quality improvement (QI) processes to increase early engagement and 6-month retention within a medication-assisted treatment clinic for youth with OUDs. QI interventions included motivational interviewing (MI) staff training, implementation of reduced initial treatment requirements, reduction of access barriers to treatment, and enhancement of patient treatment motivation. We monitored the impact of the interventions via a p-chart.

Results:

A statistically significant shift was seen in the 6-month retention rate following both MI staff training and the use of reduced initial treatment requirements. Second visit return rate also experienced a statistically significant shift following transportation support and an incentive program.

Discussion:

Our data demonstrate that following MI staff training, reduced initial clinic requirements, transportation support, and utilization of an incentive program, the second visit return rate, and 6-month retention rate improved within an outpatient medication-assisted treatment clinic for youth with OUDs.
Fostering Quality Improvement Capacity in a Network of Primary Care Practices Affiliated With a Pediatric Accountable Care Organization
Authors: Gowda Charitha , Toth Christina , Hoholik Suzanne , Brilli Richard J. , Gleeson Sean , Cardamone Stephen
Published: June 2019

Objectives:

Quality improvement (QI) methodologies are not widely implemented in primary care practices. As an accountable care organization serving pediatric Medicaid recipients in Ohio, Partners For Kids (PFK) sought to build QI capacity in affiliated primary care practices to improve organizational performance on key quality measures.

Methods:

A team of QI specialists developed a comprehensive training program focused on pediatric QI initiatives. From 2014 to 2017, community-based, primary care practices affiliated with PFK were recruited to participate in QI. The primary outcome, assessed yearly, was the proportion of eligible PFK patients accessing care at a practice with ≥1 active QI project. The proportion of QI projects that demonstrated moderate improvement, defined as the implementation of ≥1 intervention and observed improvement in process measures, within 12 months of initiation was also calculated for 2017.

Results:

Over the study period, the PFK QI team supported 72 projects in 33 primary care practices throughout central and southeast Ohio. In 2017, 26 practices were engaged in ≥1 active QI project, reaching 26% of all eligible PFK patients. Of the 21 projects active as of January 2017, 11 (52%) showed moderate improvement within 12 months.

Conclusions:

The PFK QI team successfully supported QI capacity building in primary care practices throughout Ohio using a systematic approach to recruitment, training, and QI resource support. New, multilevel interventions are needed to promote the uptake of preventive services among patients.
A Multifaceted Quality Improvement Intervention to Improve Watchful Waiting in Acute Otitis Media Management
Authors: Sun Di , Rivas-Lopez Vanessa , Liberman Danica B.
Published: June 2019

Introduction:

Despite the American Academy of Pediatrics (AAP) guidelines for acute otitis media (AOM) describing a watchful waiting (WW) approach in qualifying patients, immediate antibiotics are consistently overutilized. The study team developed a multifaceted quality improvement intervention that educated providers and families about WW and included a behavioral component to modify physician prescribing patterns.

Methods:

We used data from a prior study of 250 patients 18 years old and younger with AOM in a tertiary care children’s hospital emergency department (ED) to characterize baseline AOM management before interventions. In this study, interventions took place from September to December 2016. Following the interventions, 65 patients were randomly selected, which would allow for the detection of a 20% increase in adherence to AAP guidelines for management of AOM.

Results:

In the preintervention cohort of 250 patients, 247 had documented AOM. Two hundred thirty-one (93.5%) received immediate antibiotics, 7 (2.8%) underwent WW, and 9 (3.6%) were sent home without antibiotics. Overall management agreed with AAP guidelines at a rate of 44.1%. In the postintervention cohort of 65 patients, 63 met age and diagnostic criteria for AOM; 56 (88.9%) patients received immediate antibiotics; and 7 (11.1%) underwent WW. Postintervention, which the ED management of AOM agreed with AAP guidelines 60.3% of the time, was significantly increased from preintervention adherence (P = 0.02).

Conclusions:

A multipronged quality improvement intervention for AOM management in a single pediatric ED significantly improved adherence to AAP guidelines by increasing WW and reducing immediate antibiotic prescriptions.
Leptospira yasudae sp. nov. and Leptospira stimsonii sp. nov., two new species of the pathogenic group isolated from environmental sources
Authors: Casanovas-Massana Arnau , Hamond Camila , Santos Luciane A. , de Oliveira Daiana , Hacker Kathryn P. , Balassiano Ilana , Costa Federico , Medeiros Marco A. , Reis Mitermayer G. , Ko Albert I. , Wunder Elsio A.
Published: June 2019

Four spirochetes (F1T, B21, YaleT and AMB6-RJ) were isolated from environmental sources: F1T and B21 from soils of an urban slum community in Salvador (Brazil), YaleT from river water in New Haven, Connecticut (USA) and AMB6-RJ from a pond in a horse farm in Rio de Janeiro (Brazil). Isolates were helix-shaped, aerobic, highly motile and non-virulent in a hamster model of infection. Draft genomes of the strains were obtained and analysed to determine the relatedness to other species of the genus

Leptospira

. The analysis of 498 core genes showed that strains F1T/B21 and YaleT/AMB6-RJ formed two distinct phylogenetic clades within the ‘Pathogens’ group (group I). The average nucleotide identity (ANI) values of strains F1T/B21 and YaleT/AMB6-RJ to other previously described Leptospira species were below <84 % and <82 %, respectively, which confirmed that these isolates should be classified as representatives of two novel species. Therefore, we propose

Leptospira
yasudae sp. nov. and

Leptospira
stimsonii sp. nov. as new species in the genus

Leptospira

. The type strains are F1T (=ATCC-TSD-163=KIT0259=CLEP00287) and YaleT (=ATCC-TDS-162=KIT0258=CLEP00288), respectively.
Effects of germline and somatic events in candidate BRCAness genes on breast-tumor signatures
Authors: Bodily Weston R. , Shirts Brian H. , Walsh Tom , Gulsuner Suleyman , King Mary-Claire , Parker Alyssa , Roosan Moom , Piccolo Stephen R.
Published: June 2019

Background

Mutations inBRCA1andBRCA2cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCAness” describes tumors that harbor an HR defect but have no detectable germline mutation inBRCA1orBRCA2. A better understanding of the genes and molecular events associated with BRCAness could provide mechanistic insights and guide development of targeted treatments.

Methods

Using data from The Cancer Genome Atlas (TCGA) for 1101 breast-cancer patients, we identified individuals with a germline mutation, somatic mutation, homozygous deletion, and/or hypermethylation event inBRCA1,BRCA2, and 59 other cancer-predisposition genes. Based on the assumption that BRCAness events would have similar downstream effects on tumor biology asBRCA1/BRCA2germline mutations, we quantified these effects based on somatic-mutation signatures and gene-expression profiles. We reduced the dimensionality of the somatic-mutation signatures and expression data and used a statistical resampling approach to quantify similarities between patients who had aBRCA1/BRCA2germline mutation, another type of aberration inBRCA1orBRCA2, or any type of aberration in one of the other genes.

Results

Somatic-mutation signatures of tumors having a somatic mutation, homozygous deletion, or hypermethylation event inBRCA1/BRCA2(n = 80) were generally similar to each other and to tumors fromBRCA1/BRCA2germline carriers (n = 44). Additionally, somatic-mutation signatures of tumors with germline or somatic events inATR(n = 16) andBARD1(n = 8) showed high similarity to tumors fromBRCA1/BRCA2carriers. Other genes also showed high similarity but only for a small number of events or for a single event type. Tumors with germline mutations or hypermethylation ofBRCA1had relatively similar gene-expression profiles and overlapped considerably with the Basal-like subtype; but the transcriptional effects of the other events lacked consistency.

Conclusions

Our findings confirm previously known relationships between molecular signatures and germline or somatic events inBRCA1/BRCA2and suggest additional genes that may be considered for inclusion in the definition of BRCAness.
Transcription factor LSF facilitiates lysine methylation of α-tubulin by microtubule-associated SET8
Authors: Chin Hang Gyeong , Estève Pierre Olivier , Ruse Cristian , Lee Jiyoung , Schaus Scott E. , Pradhan Sriharsa , Hansen Ulla
Published: June 2019

Microtubules are critical for mitosis, cell motility, and protein and organelle transport, and are a validated target for anticancer drugs. However, tubulin regulation and recruitment in these cellular processes is less understood. Post-translational modifications of tubulin are proposed to regulate microtubule functions and dynamics. Although many such modifications have been investigated, tubulin methylations and enzymes responsible for methylation have only recently begun to be described. Here we report that N-lysine methyl transferase KMT5A (SET8/PR-Set7), which methylates histone H4K20, also methylates α-tubulin. Furthermore, the transcription factor LSF binds both tubulin and SET8, and enhances α-tubulin methylationin vitro, countered by FQI1, a specific small molecule inhibitor of LSF. Thus, the three proteins SET8, LSF, and tubulin, all essential for mitotic progression, interact with each other. Overall, these results point to dual functions for both SET8 and LSF not only in chromatin regulation, but also for cytoskeletal modification.
Fraction and Spatial Organization of Tumor-Infiltrating Lymphocytes Correlating with Bladder Cancer Patient Survival
Authors: Xu Hongming , Park Sunho , Hwang Tae Hyun
Published: June 2019

Recent studies based on deep learning on pathology images have shown the potential prognostic role of Tumor-infiltrating lymphocytes (TILs) in many cancer types. In general, most of these studies focused on detecting, quantifying and identifying TILs and spatial organization in entire whole slide images (WSIs) including both non-cancer and cancer regions. In this work, we hypothesize that TILs present in cancer regions not entire WSIs could have prognostic values. Here we present an automatic technique based on convolutional neural networks (CNN) that detects both cancer and TILs regions, and explores fraction and spatial organization of TILs in the detected cancer region from WSIs. A novel set of quantitative histological image features reflecting TILs fraction and spatial organization is extracted and used to stratify patients with distinct survival outcomes. In experiments using 277 different patient pathology slides selected from The Cancer Genome Atlas (TCGA) bladder cancer cohort, we show that bladder cancer patient survival is significantly correlated with our designed TIL-related image features, with a log-rank test p value below 0.05. Our method is extensible to histopathology images of other organs for predicting patient survival via TIL analysis.
Interkinetic nuclear movements promote apical expansion in pseudostratified epithelia at the expense of apicobasal elongation
Authors: Ferreira Marina A. , Despin-Guitard Evangeline , Duarte Fernando , Degond Pierre , Theveneau Eric
Published: June 2019

Pseudostratified epithelia (PSE) are a common type of columnar epithelia found in a wealth of embryonic and adult tissues such as ectodermal placodes, the trachea, the ureter, the gut and the neuroepithelium. PSE are characterized by the choreographed displacement of cells’ nuclei along the apicobasal axis according to phases of their cell cycle. Such movements, called interkinetic movements (INM) have been proposed to influence tissue expansion and shape and suggested as culprit in several congenital diseases such as CAKUT and esophageal atresia. INM rely on cytoskeleton dynamics just as adhesion, contractility and mitosis do. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. Here we bypassed this hurdle by generating a 2D agent-based model of a proliferating PSE and compared its output to the growth of the chick neuroepithelium to assess the interplay between INM and these other important cell processes during growth of a PSE. We found that INM directly generates apical expansion and apical nuclear crowding. In addition, our data strongly suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but rather requires a specific elongation program. We then discuss how such program might functionally link INM, tissue growth and differentiation.

Authors Summary

Pseudostratified epithelia (PSE) are a common type of epithelia characterized by the choreographed displacement of cells’ nuclei along the apicobasal axis during proliferation. These so-called interkinetic movements (INM) were proposed to influence tissue expansion and suggested as culprit in several congenital diseases. INM rely on cytoskeleton dynamics. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. We bypassed this hurdle by generating a mathematical model of PSE and compared it to the growth of an epithelium of reference. Our data show that INM drive expansion of the apical domain of the epithelium and suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but might rather requires a specific elongation program.
Detecting weak signals by combining small P-values in genetic association studies
Authors: Vsevolozhskaya Olga A. , Hu Fengjiao , Zaykin Dmitri V.
Published: June 2019

We approach the problem of combining top-ranking association statistics or P-values from a new perspective which leads to a remarkably simple and powerful method. Statistical methods, such as the Rank Truncated Product (RTP), have been developed for combining top-ranking associations and this general strategy proved to be useful in applications for detecting combined effects of multiple disease components. To increase power, these methods aggregate signals across top ranking SNPs, while adjusting for their total number assessed in a study. Analytic expressions for combined top statistics or P-values tend to be unwieldy, which complicates interpretation, practical implementation, and hinders further developments. Here, we propose the Augmented Rank Truncation (ART) method that retains main characteristics of the RTP but is substantially simpler to implement. ART leads to an efficient form of the adaptive algorithm, an approach where the number of top ranking SNPs is varied to optimize power. We illustrate our methods by strengthening previously reported associations ofµ-opioid receptor variants with sensitivity to pain.
Identification of TMEM206 proteins as pore of ASOR acid-sensitive chloride channels
Authors: Ullrich Florian , Blin Sandy , Lazarow Katina , Daubitz Tony , Kries Jens-Peter von , Jentsch Thomas J.
Published: June 2019

Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated anion channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying ASOR chloride channel. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.
Selective role of Nck1 in atherogenic inflammation and plaque formation
Authors: Alfaidi Mabruka , Acosta Christina H. , Wang Dongdong , Traylor James G. , Orr A. Wayne
Published: June 2019

While CANTOS established the role of treating inflammation in atherosclerosis, our understanding of endothelial activation at atherosclerosis-prone sites remains limited. Disturbed flow at atheroprone regions primes plaque inflammation by enhancing endothelial NF-κB signaling. Herein, we demonstrate a novel role for the Nck adaptor proteins in disturbed flow-induced endothelial activation. Although highly similar, only Nck1 deletion, but not Nck2 deletion, limits flow-induced NF-κB activation and proinflammatory gene expression. Nck1 knockout mice show reduced endothelial activation and inflammation in both models of disturbed flow and high fat diet-induced atherosclerosis. Bone marrow chimeras confirm that vascular Nck1, but not hematopoietic Nck1, mediates this effect. In contrast, endothelial Nck2 depletion does not affect endothelial activation or atherosclerosis. Domain swap experiments and point mutations identify the Nck1 SH2 domain and the first SH3 domain as critical for flow-induced endothelial activation. We further characterize Nck1’s proinflammatory role by identifying interleukin-1 type I receptor kinase-1 (IRAK-1) as a Nck1-selective binding partner, demonstrating IRAK-1 activation by disturbed flow requires Nck1 in vitro and in vivo, showing endothelial Nck1 and IRAK-1 staining in early human atherosclerosis, and demonstrating that disturbed flow-induced endothelial activation requires IRAK-1. Taken together, our data reveal a hitherto unknown link between Nck1 and IRAK-1 in atherogenic inflammation.