Publications by authors named "James E Bost"

70 Publications

High Acuity Therapy Variation Across Pediatric Acute Care Cardiology Units: Results from the Pediatric Acute Care Cardiology Collaborative Hospital Surveys.

Pediatr Cardiol 2021 Apr 4. Epub 2021 Apr 4.

Division of Pediatric Cardiology, Department of Pediatrics, UCSF Benioff Children's Hospital, UCSF School of Medicine, San Francisco, CA, USA.

We utilized the multicenter Pediatric Acute Care Cardiology Collaborative (PAC) 2017 and 2019 surveys to describe practice variation in therapy availability and changes over a 2-year period. A high acuity therapies (ATs) score was derived (1 point per positive response) from 44 survey questions and scores were compared to center surgical volume. Of 31 centers that completed the 2017 survey, 26 also completed the 2019 survey. Scores ranged from 11 to 34 in 2017 and 11 to 35 in 2019. AT scores in 2019 were not statistically different from 2017 scores (29/44, IQR 27-32.5 vs. 29.5/44, IQR 27-31, p = 0.9). In 2019, more centers reported initiation of continuous positive airway pressure (CPAP) and Bi-level positive airway pressure (BiPAP) in Acute Care Cardiology Unit (ACCU) (19/26 vs. 4/26, p < 0.001) and permitting continuous CPAP/BiPAP (22/26 vs. 14/26, p = 0.034) compared to 2017. Scores in both survey years were significantly higher in the highest surgical volume group compared to the lowest, 33 ± 1.5 versus 25 ± 8.5, p = 0.046 and 32 ± 1.7 versus 23 ± 5.5, p = 0.009, respectively. Variation in therapy within the ACCUs participating in PAC presents an opportunity for shared learning across the collaborative. Experience with PAC was associated with increasing available respiratory therapies from 2017 to 2019. Whether AT scores impact the quality and outcomes of pediatric acute cardiac care will be the subject of further investigation using a comprehensive registry launched in early 2019.
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http://dx.doi.org/10.1007/s00246-021-02584-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019478PMC
April 2021

Ambulatory cardiology telemedicine: a large academic pediatric center experience.

J Investig Med 2021 Mar 12. Epub 2021 Mar 12.

Department of Pediatrics, George Washington University School of Medicine & Health Sciences, Washington, DC, USA

We performed a retrospective study of cardiology telemedicine visits at a large academic pediatric center between 2016 and 2019 (pre COVID-19). Telemedicine patient visits were matched to data from their previous in-person visits, to evaluate any significant differences in total charge, insurance compensation, patient payment, percent reimbursement and zero reimbursement. Miles were measured between patient's home and the address of previous visit. We found statistically significant differences in mean charges of telemedicine versus in-person visits (2019US$) (172.95 vs 218.27, p=0.0046), patient payment for telemedicine visits versus in-person visits (2019US$) (11.13 vs 62.83, p≤0.001), insurance reimbursement (2019US$) (65.18 vs 110.85, p≤0.001) and insurance reimbursement rate (43% vs 61%, p=0.0029). Rate of zero reimbursement was not different. Mean distance from cardiology clinic was 35 miles. No adverse outcomes were detected. This small retrospective study showed cost reduction and a decrease in travel time for families participating in telemedicine visits. Future work is needed to enhance compensation for telemedicine visits.
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http://dx.doi.org/10.1136/jim-2021-001800DOI Listing
March 2021

Promoting Judicious Primary Care Referral of Patients with Chest Pain to Cardiology: A Quality Improvement Initiative.

Med Decis Making 2021 Mar 3:272989X21991445. Epub 2021 Mar 3.

Department of Pediatrics, George Washington University School of Medicine & Health Sciences, Washington, DC, USA.

Objective: To decrease referrals to cardiology of patients ages 7 to 21 years with low-probability cardiac pathology who presented to primary care with chest pain by 50% within 24 months.

Study Design: A multidisciplinary team designed and implemented an initiative consisting of 1) a decision support tool (DST), 2) educational sessions, 3) routine feedback to improve use of referral criteria, and 4) patient family education. Four pediatric practices, comprising 34 pediatricians and 7 nurse practitioners, were included in this study. We tracked progress via statistical process control charts.

Results: A total of 421 patients ages 7 to 21 years presented with chest pain to their pediatrician. The utilization of the DST increased from baseline of 16% to 68%. Concurrently, the percentage of low-probability cardiology referrals in pediatric patients ages 7 to 21 years who presented with chest pain decreased from 17% to 5% after our interventions. At a median follow-up time of 0.9 years (interquartile range, 0.3-1.6 years), no patient had a life-threatening cardiac event.

Conclusion: Our health care improvement initiative to reduce low-probability cardiology referrals for children presenting to primary care practices with chest pain was feasible, effective, and safe.
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http://dx.doi.org/10.1177/0272989X21991445DOI Listing
March 2021

Early Inflammatory Markers are Associated With Inadequate Post-Induction Infliximab Trough in Pediatric Crohn's Disease.

J Pediatr Gastroenterol Nutr 2021 Mar;72(3):410-416

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's National Hospital, George Washington University, Washington, DC.

Objectives: In pediatric Crohn's disease, infliximab trough concentrations after standard weight-based induction therapy are commonly below 7 μg/mL. Clinical treatment outcomes are associated with post-induction infliximab trough concentration. Markers of inflammation are associated with low infliximab concentrations during maintenance dosing. We sought to determine if early markers of disease activity are associated with inadequate post-induction infliximab trough concentrations in pediatric Crohn's disease.

Methods: We performed a retrospective single-center case-control study of pediatric Crohn's disease patients to assess the association between baseline and week-2 biomarkers (albumin, C-reactive protein, and erythrocyte sedimentation rate) and inadequate post-induction infliximab trough concentration (<7 μg/mL) in patients treated with standard 5 mg/kg dosing. Baseline and week-2 biomarker values were coded as dichotomous variables at clinically useful thresholds. Univariable logistic regression was used to calculate odds ratios of developing an inadequate infliximab trough concentration for each threshold, as well as thresholds in combination.

Results: Fifty-five patients were evaluated. Early biomarker thresholds significantly associated with inadequate post-induction infliximab trough concentrations included baseline C-reactive protein >1 mg/dL (odds ratio [OR] 4.58; 95% confidence interval [CI] 1.24--17.01), both baseline C-reactive protein >0.5 mg/dL and albumin <3.5 g/dL (OR 8.31; 95% CI 1.99--34.63), and week-2 C-reactive protein >0.5 mg/dL or albumin <3.5 mg/dL or erythrocyte sedimentation rate >25 mm/hour (OR 11.08; 95% CI 2.14--57.22).

Conclusions: Routine baseline and week-2 markers of disease activity at clinically useful thresholds were associated with inadequate post-induction infliximab trough concentration in pediatric Crohn's disease patients receiving standard weight-based induction dosing.
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http://dx.doi.org/10.1097/MPG.0000000000002975DOI Listing
March 2021

The Association of Laboratory Test Abnormalities With Mortality Risk in Pediatric Intensive Care.

Pediatr Crit Care Med 2021 Feb;22(2):147-160

Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To determine the bivariable associations between abnormalities of 28 common laboratory tests and hospital mortality and determine how mortality risks changes when the ranges are evaluated in the context of commonly used laboratory test panels.

Design: A 2009-2016 cohort from the Health Facts (Cerner Corporation, Kansas City, MO) database.

Setting: Hospitals caring for children in ICUs.

Patients: Children cared for in ICUs with laboratory data.

Interventions: None.

Measurements And Main Results: There were 2,987,515 laboratory measurements in 71,563 children. The distribution of laboratory test values in 10 groups defined by population percentiles demonstrated the midrange of tests was within the normal range except for those measured predominantly when significant abnormalities are suspected. Logistic regression analysis at the patient level combined the population-based groups into ranges with nonoverlapping mortality odds ratios. The most deviant test ranges associated with increased mortality risk (mortality odds ratios > 5.0) included variables associated with acidosis, coagulation abnormalities and blood loss, immune function, liver function, nutritional status, and the basic metabolic profile. The test ranges most associated with survival included normal values for chloride, pH, and bicarbonate/total Co2. When the significant test ranges from bivariable analyses were combined in commonly used test panels, they generally remained significant but were reduced as risk was distributed among the tests.

Conclusions: The relative importance of laboratory test ranges vary widely, with some ranges strongly associated with mortality and others strongly associated with survival. When evaluated in the context of test panels rather than isolated tests, the mortality odds ratios for the test ranges decreased but generally remained significant as risk was distributed among the components of the test panels. These data are useful to develop critical values for children in ICUs, to identify risk factors previously underappreciated, for education and training, and for future risk score development.
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http://dx.doi.org/10.1097/PCC.0000000000002610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855885PMC
February 2021

Treadmill exercise testing improves diagnostic accuracy in children with concealed congenital long QT syndrome.

Pacing Clin Electrophysiol 2020 12 12;43(12):1521-1528. Epub 2020 Oct 12.

Division of Cardiology, Children's National Health System, Washington, District of Columbia.

Background: Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve to guide which children with borderline prolonged QT intervals may be gene positive for LQTS.

Methods: Pediatric patients (n = 139) were divided into three groups: Controls (n = 76), gene positive LQTS with borderline QTc (n = 21), and gene negative patients with borderline QTc (n = 42). Borderline QTc was defined between 440-470 (male) and 440-480 (female) ms. ECGs were recorded supine, sitting, and standing. Patients then underwent treadmill stress testing with Bruce protocol followed by a 9-minute recovery phase.

Results: Supine resting QTc, age, and Schwartz score for the three groups were: (a) gene positive: 446 ± 23 ms, 12.4 ± 3.4 years old, 3.2 ± 1.8; (b) gene negative: 445 ± 20 ms, 12.1 ± 2 years old, 2.0 ± 1.2; and (c) control: 400 ± 24 ms, 15.0 ± 3 years old. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at 6 minutes. Standing QTc ≥460 ms differentiated borderline prolonged QTc patients (gene positive and gene negative) from controls. Late recovery QTc ≥480 ms distinguished gene positive from gene negative patients.

Conclusion: Exercise stress testing can be useful to identify children who are gene positive borderline LQTS from a normal population and gene negative borderline QTc children, allowing for selective gene testing in a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.
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http://dx.doi.org/10.1111/pace.14085DOI Listing
December 2020

Criticality: A New Concept of Severity of Illness for Hospitalized Children.

Pediatr Crit Care Med 2021 Jan;22(1):e33-e43

Department of Pediatrics, Division of Critical Care Medicine, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To validate the conceptual framework of "criticality," a new pediatric inpatient severity measure based on physiology, therapy, and therapeutic intensity calibrated to care intensity, operationalized as ICU care.

Design: Deep neural network analysis of a pediatric cohort from the Health Facts (Cerner Corporation, Kansas City, MO) national database.

Setting: Hospitals with pediatric routine inpatient and ICU care.

Patients: Children cared for in the ICU (n = 20,014) and in routine care units without an ICU admission (n = 20,130) from 2009 to 2016. All patients had laboratory, vital sign, and medication data.

Interventions: None.

Measurements And Main Results: A calibrated, deep neural network used physiology (laboratory tests and vital signs), therapy (medications), and therapeutic intensity (number of physiology tests and medications) to model care intensity, operationalized as ICU (versus routine) care every 6 hours of a patient's hospital course. The probability of ICU care is termed the Criticality Index. First, the model demonstrated excellent separation of criticality distributions from a severity hierarchy of five patient groups: routine care, routine care for those who also received ICU care, transition from routine to ICU care, ICU care, and high-intensity ICU care. Second, model performance assessed with statistical metrics was excellent with an area under the curve for the receiver operating characteristic of 0.95 for 327,189 6-hour time periods, excellent calibration, sensitivity of 0.817, specificity of 0.892, accuracy of 0.866, and precision of 0.799. Third, the performance in individual patients with greater than one care designation indicated as 88.03% (95% CI, 87.72-88.34) of the Criticality Indices in the more intensive locations was higher than the less intense locations.

Conclusions: The Criticality Index is a quantification of severity of illness for hospitalized children using physiology, therapy, and care intensity. This new conceptual model is applicable to clinical investigations and predicting future care needs.
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http://dx.doi.org/10.1097/PCC.0000000000002560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790867PMC
January 2021

Severity Trajectories of Pediatric Inpatients Using the Criticality Index.

Pediatr Crit Care Med 2021 Jan;22(1):e19-e32

Department of Pediatrics, Division of Critical Care Medicine, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To assess severity of illness trajectories described by the Criticality Index for survivors and deaths in five patient groups defined by the sequence of patient care in ICU and routine patient care locations.

Design: The Criticality Index developed using a calibrated, deep neural network, measures severity of illness using physiology, therapies, and therapeutic intensity. Criticality Index values in sequential 6-hour time periods described severity trajectories.

Setting: Hospitals with pediatric inpatient and ICU care.

Patients: Pediatric patients never cared for in an ICU (n = 20,091), patients only cared for in the ICU (n = 2,096) and patients cared for in both ICU and non-ICU care locations (n = 17,023) from 2009 to 2016 Health Facts database (Cerner Corporation, Kansas City, MO).

Interventions: None.

Measurements And Main Results: Criticality Index values were consistent with clinical experience. The median (25-75th percentile) ICU Criticality Index values (0.878 [0.696-0.966]) were more than 80-fold higher than the non-ICU values (0.010 [0.002-0.099]). Non-ICU Criticality Index values for patients transferred to the ICU were 40-fold higher than those never transferred to the ICU (0.164 vs 0.004). The median for ICU deaths was higher than ICU survivors (0.983 vs 0.875) (p < 0.001). The severity trajectories for the five groups met expectations based on clinical experience. Survivors had increasing Criticality Index values in non-ICU locations prior to ICU admission, decreasing Criticality Index values in the ICU, and decreasing Criticality Index values until hospital discharge. Deaths had higher Criticality Index values than survivors, steeper increases prior to the ICU, and worsening values in the ICU. Deaths had a variable course, especially those who died in non-ICU care locations, consistent with deaths associated with both active therapies and withdrawals/limitations of care.

Conclusions: Severity trajectories measured by the Criticality Index showed strong validity, reflecting the expected clinical course for five diverse patient groups.
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http://dx.doi.org/10.1097/PCC.0000000000002561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790848PMC
January 2021

Reducing Vancomycin Use in a Level IV NICU.

Pediatrics 2020 08 1;146(2). Epub 2020 Jul 1.

Department of Pediatrics, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia; and.

Background And Objectives: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year.

Methods: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program.

Results: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days.

Conclusions: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.
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http://dx.doi.org/10.1542/peds.2019-2963DOI Listing
August 2020

Medications for Children Receiving Intensive Care: A National Sample.

Pediatr Crit Care Med 2020 09;21(9):e679-e685

Division of Critical Care Medicine, Department of Pediatrics, Children's National Health System and George Washington University School of Medicine and Health Sciences, Washington, DC.

Objective: To examine medication administration records through electronic health record data to provide a broad description of the pharmaceutical exposure of critically ill children.

Design: Retrospective cohort study using the Cerner Health Facts database.

Setting: United States.

Patients: A total of 43,374 children 7 days old to less than 22 years old receiving intensive care with available pharmacy data.

Interventions: None.

Measurements And Main Results: A total of 907,440 courses of 1,080 unique medications were prescribed with a median of nine medications (range, 1-99; 25-75th percentile, 5-16) per patient. The most common medications were acetaminophen, ondansetron, and morphine. Only 45 medications (4.2%) were prescribed to more than 5% of patients, and these accounted for 442,067 (48.7%) of the total courses of medications. Each additional medication was associated with increased univariate risk of mortality (odds ratio, 1.05; 95% CI, 1.05-1.06; p < 0.001).

Conclusions: Children receiving intensive care receive a median of nine medications per patient and one quarter are prescribed at least than 16 medications. Only 45 medications were prescribed to more than 5% of patients, but these accounted for almost half of all medication courses.
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http://dx.doi.org/10.1097/PCC.0000000000002391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483286PMC
September 2020

Sedation, Analgesia, and Neuromuscular Blockade: An Assessment of Practices From 2009 to 2016 in a National Sample of 66,443 Pediatric Patients Cared for in the ICU.

Pediatr Crit Care Med 2020 09;21(9):e599-e609

Division of Critical Care Medicine, Department of Pediatrics, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs.

Design: A retrospective analysis using data extracted from the national database Health Facts.

Setting: One hundred sixty-one ICUs in the United States with pediatric admissions.

Patients: Children in ICUs receiving medications from 2009 to 2016.

Exposure/intervention: Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications.

Measurements And Main Results: Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes.

Conclusions: Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.
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http://dx.doi.org/10.1097/PCC.0000000000002351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483172PMC
September 2020

Acupuncture for pain management in children with sickle cell disease.

Complement Ther Med 2020 Mar 11;49:102287. Epub 2020 Jan 11.

Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, District of Columbia, Washington, United States; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, District of Columbia, United States. Electronic address:

Pain associated with sickle cell disease (SCD) is frequently treated with opioids which have many side effects. There is a need for adjuvant non-opioid therapies that can improve pain control. Acupuncture, an integrative approach, has been shown to be useful in non-SCD pain conditions but has been used to a very limited extent in SCD. In this report we present a single academic pediatric center experience showing acceptability, feasibility and improved pain experience with adjuvant acupuncture therapy in children with SCD and suggest that acupuncture should be explored as a treatment option for managing pain in SCD.
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http://dx.doi.org/10.1016/j.ctim.2019.102287DOI Listing
March 2020

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis.

Sci Rep 2019 02 22;9(1):2534. Epub 2019 Feb 22.

Computational Biology Institute, GWU, 45085 University Drive, Ashburn, VA, 20147, USA.

In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.
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http://dx.doi.org/10.1038/s41598-019-38984-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385179PMC
February 2019

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients.

J Pediatr Pharmacol Ther 2018 Sep-Oct;23(5):379-389

Objectives: To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function.

Methods: Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values.

Results: The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests.

Conclusions: We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.
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http://dx.doi.org/10.5863/1551-6776-23.5.379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213626PMC
November 2018

A Quality Initiative: A System-Wide Reduction in Serious Medication Events Through Targeted Simulation Training.

Simul Healthc 2018 Oct;13(5):324-330

From the Children's Healthcare of Atlanta (K.B.H., L.W., J.P. L.D., H.J., G.F.); Division of Pediatric Critical Care (K.B.H., N.C.), and Department of Pediatrics (K.B.H., N.C.), Emory University School of Medicine, Atlanta, GA; and Children's National Medical Center (J.B.), Washington, DC.

Introduction: Medication administration events (MAEs) are a great concern to the healthcare industry, because they are both common and costly. Pediatric patients pose unique challenges to healthcare systems, particularly regarding the safety of medication administration. Our objectives were to improve adherence to best practices, decrease MAEs, and decrease cost related to error reduction rates by implementing a scenario-based simulation training program for frontline nursing staff in the general care units, emergency departments, and intensive care units within our institution.

Methods: Children's simulation center in conjunction with the medication safety workgroup developed a 2-hour target-specific simulation-based training. This quality initiative focused on implementation of a MAE bundle that included the following three elements: The Five Rights, MedZone, and Independent Double Check. Adherence to the use of bundle elements was monitored via bedside auditing for 18 months after the intervention. This audit was accomplished using an institution-wide MAE reporting system. The 2012 Healthcare Cost and Utilization Project Kids' Inpatient Database and 2014 Children's Hospital Association, Pediatric Health Information System databases were used to estimate cost impact.

Results: A total of 1434 nurses from our intensive care units, emergency departments, and general care inpatient units participated in simulation training. Nursing adherence to the MAE bundle in the 18-month period after simulation increased by 33%, from January 2014 to June 2015. Medication administration event monitoring during the preintervention, intervention, and postintervention periods demonstrated a decrease in error rate from 2.5 events per month to 0.86 events per month This error reduction correlated to an estimated charge savings of $165,000 to $255,000 and a cost impact of $90,000 to $130,000 per year.

Conclusions: Target-specific simulation-based training on a large scale has improved adherence with best practice guidelines and has led to a significant reduction in MAEs.
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http://dx.doi.org/10.1097/SIH.0000000000000321DOI Listing
October 2018

Characteristics of Correctly Identified Pediatric Obesity and Overweight Status and Management in an Academic General Pediatric Clinic.

Clin Pediatr (Phila) 2018 09 7;57(10):1168-1175. Epub 2018 Mar 7.

2 Children's National Health System, Washington, DC, USA.

This study identified and characterized the rates of documentation and guideline-based management of overweight and obese children within an academic pediatric clinic through a retrospective electronic medical record review of 7422 well-child visits in 2016. Diagnosis and treatment were analyzed by patient's weight diagnosis, sex, age, and provider training level. The percentages of correctly identified severely obese (90.2%), obese (77.0%), and overweight (42.0%) children were much higher than in previous retrospective chart reviews; however, less than 30% of children were referred for more intensive weight management to a dietitian or pediatric obesity weight management program. Increased provider training level was associated with a lower adherence to pediatric obesity guidelines. Strategic modifications to electronic medical records that automatically offer body mass index-associated weight diagnoses with a link to treatment pathways and resources are needed to facilitate improved compliance with current pediatric obesity guidelines in the primary care setting.
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http://dx.doi.org/10.1177/0009922818761891DOI Listing
September 2018

Variation in Preoperative Testing and Antireflux Surgery in Infants.

Pediatrics 2017 08;140(2)

Division of Pediatric Surgery, Department of Surgery, School of Medicine, Emory University, Atlanta, Georgia; and

Background: Despite the availability of objective tests, gastroesophageal reflux disease (GERD) diagnosis and management in infants remains controversial and highly variable. Our purpose was to characterize national variation in diagnostic testing and surgical utilization for infants with GERD.

Methods: Using the Pediatric Health Information System, we identified infants <1 year old diagnosed with GERD between January 2011 and March 2015. Outcomes included progression to antireflux surgery (ARS) and use of relevant diagnostic testing. By using adjusted generalized linear mixed models, we compared facility-level ARS utilization.

Results: Of 5 299 943 infants, 149 190 had GERD (2.9%), and 4518 (3.0%) of those patients underwent ARS. Although annual rates of GERD and ARS decreased, there was a wide range of GERD diagnoses (1.8%-6.2%) and utilization of ARS (0.2%-11.2%). Facilities varied in the use of laparoscopic versus open ARS (mean: 66%, range: 23%-97%). Variation in facility-level ARS rates persisted after adjustment. Overall 3.8% of patients underwent diagnostic testing, whereas 22.8% of ARS patients underwent diagnostic testing. The proportion of surgeries done laparoscopically was independently associated with ARS utilization (odds ratio: 1.57; 95% confidence interval: 1.21-2.02). Facility-level utilization of diagnostics ( > .1) and prevalence of GERD ( > .1) were not associated with utilization of ARS.

Conclusions: There is notable variation in the overall utilization of ARS and in the surgical and diagnostic approach in infants with GERD. Fewer than 4% of infants with GERD undergo diagnostic testing. This variation in care merits development of consensus guidelines and further research.
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http://dx.doi.org/10.1542/peds.2017-0536DOI Listing
August 2017

The ability of preoperative factors to predict patient-reported disability following surgery for rotator cuff pathology.

Disabil Rehabil 2017 10 22;39(20):2087-2096. Epub 2016 Aug 22.

c Department of Physical Therapy , University of Pittsburgh , Pittsburgh , PA , USA.

Purpose: Minimal research has examined the prognostic ability of shoulder examination data or psychosocial factors in predicting patient-reported disability following surgery for rotator cuff pathology. The purpose of this study was to examine these factors for prognostic value in order to help clinicians and patients understand preoperative factors that impact disability following surgery.

Methods: Sixty-two patients scheduled for subacromial decompression with or without supraspinatus repair were recruited. Six-month follow-up data were available for 46 patients. Patient characteristics, history of the condition, shoulder impairments, psychosocial factors, and patient-reported disability questionnaires were collected preoperatively. Six months following surgery, the Western Ontario Rotator Cuff Index (WORC) and global rating of change dichotomized subjects into responders versus nonresponders. Logistic regression quantified prognostic ability and created the most parsimonious model to predict outcome.

Results: Being on modified job duty (OR = .17, 95%CI: 0.03-0.94), and having a worker's compensation claim (OR = 0.08, 95%CI: 0.01-0.74) decreased probability of a positive outcome, while surgery on the dominant shoulder (OR = 11.96, 95%CI: 2.91-49.18) increased probability. From the examination, only impaired internal rotation strength was a significant univariate predictor. The Fear-avoidance Beliefs Questionnaire (FABQ) score (OR = 0.95, 95%CI: 0.91-0.98) and the FABQ_work subscale (OR = 0.92, 95%CI: 0.87-0.97) were univariate predictors. In the final model, surgery on the dominant shoulder (OR = 8.9, 95%CI 1.75-45.7) and FABQ_work subscale score ≤25 (OR = 15.3, 95%CI 2.3-101.9) remained significant.

Discussion: Surgery on the dominant arm resulted in greater improvement in patient-reported disability, thereby increasing the odds of a successful surgery. The predictive ability of the FABQ_work subscale highlights the potential impact of psychosocial factors on patient-reported disability. Implications for Rehabilitation Impairment-based shoulder measurements were not strong predictors of patient-reported outcome. Having high fear-avoidance behavior scores on the FABQ, especially the work subscale, resulted in a much lower chance of responding well to rotator cuff surgery as measured by self-reported disability. Having surgery on the dominant shoulder, as compared to the nondominant side, resulted in larger improvements in disability levels.
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http://dx.doi.org/10.1080/09638288.2016.1219396DOI Listing
October 2017

Diagnostic accuracy of behavioral, activity, ferritin, and clinical indicators of restless legs syndrome.

Sleep 2015 Mar 1;38(3):371-80. Epub 2015 Mar 1.

Johns Hopkins University, Baltimore, MD.

Study Objectives: Lack of a valid diagnostic measure of restless legs syndrome (RLS) for persons with dementia, who do not have the cognitive ability to report complex symptoms, impedes RLS treatment and research in this population. The aim of this study was to determine the sensitivity and specificity of a combination of indicators for identifying RLS that could eventually be used to diagnose RLS in persons with dementia.

Design: 3-day, prospective instrument validation.

Setting: Sleep laboratory.

Participants: Cognitively intact, 107 with RLS, 105 without RLS.

Interventions: N/A.

Measurements: Serial 20-min observations with a new measure, the Behavioral Indicators Test-Restless Legs (BIT-RL); leg movements with 3 nights of the Periodic Activity Monitor-Restless Legs (PAM-RL); ferritin; sleep history; clinical data; polysomnography; Hopkins Telephone Diagnostic Interview of RLS Symptoms.

Results: The best-fitting diagnostic model for identifying RLS included previous history of iron deficiency (odds ratio [OR] 7.30), leg discomfort (OR 6.47), daytime fatigue (OR 6.15), difficulty falling asleep (OR 3.25), RLS family history (OR 2.60), BIT-RL (OR 1.49), and absence of diabetes (OR 0.27), with sensitivity 78%, specificity 79%, and 77% correctly classified. This model retained its predictive accuracy even with co-morbid sleep apnea.

Conclusions: When compared to those without RLS, persons with RLS have observable behaviors, such as rubbing the legs, that differentiate them, but the behaviors have no circadian and activity-related variability. The final model of clinical and sleep historical data and observation for RLS behaviors using the BIT-RL had good diagnostic accuracy.
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http://dx.doi.org/10.5665/sleep.4492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335520PMC
March 2015

Impact of a rapid respiratory panel test on patient outcomes.

Arch Pathol Lab Med 2015 May 25;139(5):636-41. Epub 2014 Aug 25.

From the Departments of Pathology (Drs Rogers and Jerris and Ms Uwindatwa), Pediatrics (Drs Kotzbauer and Anderson), Infection Control (Ms Watson), and Statistics (Drs O'Brien and Bost and Ms McNamara), Children's Healthcare of Atlanta; and Departments of Pathology (Drs Rogers and Jerris), Medicine (Dr Shankar), and Pediatrics (Dr Anderson), Emory University School of Medicine, Atlanta, Georgia.

Context: Evolution of polymerase chain reaction testing for infectious pathogens has occurred concurrent with a focus on value-based medicine.

Objective: To determine if implementation of the FilmArray rapid respiratory panel (BioFire Diagnostics, Salt Lake City, Utah) (hereafter RRP), with a shorter time to the test result and expanded panel, results in different outcomes for children admitted to the hospital with an acute respiratory tract illness.

Design: Patient outcomes were compared before implementation of the RRP (November 1, 2011, to January 31, 2012) versus after implementation of the RRP (November 1, 2012, to January 31, 2013). The study included inpatients 3 months or older with an acute respiratory tract illness, most admitted through the emergency department. Testing before RRP implementation used batched polymerase chain reaction analysis for respiratory syncytial virus and influenza A and B, with additional testing for parainfluenza 1 through 3 in approximately 11% of patients and for human metapneumovirus in less than 1% of patients. The RRP tested for respiratory syncytial virus, influenza A and B, parainfluenza 1 through 4, human metapneumovirus, adenovirus, rhinovirus/enterovirus, and coronavirus NL62.

Results: The pre-RRP group had 365 patients, and the post-RRP group had 771 patients. After RRP implementation, the mean time to the test result was shorter (383 minutes versus 1119 minutes, P < .001), and the percentage of patients with a result in the emergency department was greater (51.6% versus 13.4%, P < .001). There was no difference in whether antibiotics were prescribed, but the duration of antibiotic use was shorter after RRP implementation (P = .003) and was dependent on receiving test results within 4 hours. If the test result was positive, the inpatient length of stay (P = .03) and the time in isolation (P = .03) were decreased after RRP implementation compared with before RRP implementation.

Conclusions: The RRP decreases the duration of antibiotic use, the length of inpatient stay, and the time in isolation.
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http://dx.doi.org/10.5858/arpa.2014-0257-OADOI Listing
May 2015

Development of a Patient-Centered Antipsychotic Medication Adherence Intervention.

Health Educ Behav 2014 Jun 25;41(3):315-24. Epub 2013 Dec 25.

VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.

Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to develop an intervention to bridge this gap with the goal of improving antipsychotic medication adherence.

Methods: IM is a stepwise method for developing and implementing health interventions. A previous study conducted in-depth qualitative interviews with patients diagnosed with schizophrenia and identified 477 BFMs associated with antipsychotic medication adherence. This article reports the results of using a variety of qualitative and quantitative item reduction and intervention development methods to transform the qualitative BFM data into a viable checklist and intervention.

Results: The final BFM checklist included 76 items (28 barriers, 30 facilitators, and 18 motivators). An electronic and hard copy of the adherence progress note included a summary of current adherence, top three patient-identified barriers and top three facilitators and motivators, clarifying questions, and actionable adherence tips to address barriers during a typical clinical encounter.

Discussion: The IM approach supplemented with qualitative and quantitative methods provided a useful framework for developing a practical and potentially sustainable antipsychotic medication adherence intervention. A similar approach to intervention development may be useful in other clinical situations where a substantial gap exists between patients and providers regarding medication adherence or other health behaviors.
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http://dx.doi.org/10.1177/1090198113515241DOI Listing
June 2014

Predicting cancer mortality: Developing a new cancer care variable using mixed methods and the quasi-statistical approach.

Health Serv Res 2013 Dec 21;48(6 Pt 2):2208-23. Epub 2013 Oct 21.

Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA; Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: To demonstrate the value of using a variable derived from qualitative analysis in subsequent quantitative analyses.

Data Sources/study Setting: Mixed methods data were combined with 10-year mortality outcomes. Participants with cancer were recruited from services at a large teaching hospital, and mortality data were from the Social Security Death Index.

Study Design: An observational concurrent or convergent mixed methods design was used to collect demographics and structured ratings along with qualitative data from 909 cancer patients at baseline.

Data Collection/extraction Methods: Coding rules for qualitative data were defined for open-ended responses from cancer participants speaking about their view of self, and a variable was numerically coded for each case. Mortality outcomes were matched to baseline data, including the view of self variable.

Principal Findings: Individuals with an improved view of self had a significantly lower mortality rate than those for whom it was worse or unchanged, even when adjusting for age, gender, and cancer stage.

Conclusions: Statistical analysis of qualitative data is feasible and can identify new predictors with health services' implications associated with cancer mortality. Future studies should consider the value of testing coded qualitative variables in relation with key health care outcomes.
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http://dx.doi.org/10.1111/1475-6773.12116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097837PMC
December 2013

Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study.

PLoS One 2013 10;8(1):e53016. Epub 2013 Jan 10.

Division of Nephrology, University Hospital, Zürich, Switzerland.

Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI). The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV) based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001) with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053016PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542378PMC
July 2013

Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort.

Am J Kidney Dis 2013 Mar 22;61(3):420-9. Epub 2012 Oct 22.

Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB, Groningen, the Netherlands.

Background: Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, the significance of AVP in human ADPKD is unclear.

Study Design: Longitudinal observational study with 8.5 (IQR, 7.7-9.0) years' follow-up (CRISP [Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease]).

Setting & Participants: 241 patients with ADPKD with creatinine clearance >70 mL/min.

Predictor: Plasma copeptin concentration, a surrogate marker for AVP.

Outcomes: Change in measured glomerular filtration rate (mGFR, assessed by iothalamate clearance) and total kidney volume (measured by magnetic resonance imaging).

Measurements: Baseline copeptin level, plasma and urinary osmolality, and measurements of total kidney volume and mGFR during follow-up.

Results: In these patients (median age, 34 [IQR, 25-40] years; 38% men; median mGFR, 94 [IQR, 79-145] mL/min/1.73 m(2); median total kidney volume, 859 [IQR, 577-1,299] mL), median copeptin level was 2.9 (IQR, 1.8-5.1) pmol/L. Copeptin was not associated with plasma osmolality (P = 0.3), the physiologic stimulus for AVP release, but was associated significantly with change in total kidney volume during follow-up (P < 0.001). This association remained significant after adjusting for sex, age, cardiovascular risk factors, and diuretic use (P = 0.03). Copeptin level was associated borderline significantly with change in mGFR after adjusting for these variables (P = 0.09).

Limitations: No standardization of hydration status at time of copeptin measurement.

Conclusions: These data show that in ADPKD, copeptin level, as a marker for AVP, is not correlated with plasma osmolality. Most importantly, high copeptin levels are associated independently with disease progression in early ADPKD. This is in line with experimental studies that indicate a disease-promoting role for AVP.
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http://dx.doi.org/10.1053/j.ajkd.2012.08.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574620PMC
March 2013

Giving residents tools to talk about behavior change: a motivational interviewing curriculum description and evaluation.

Patient Educ Couns 2012 Nov 19;89(2):281-7. Epub 2012 Aug 19.

Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

Objective: To determine whether a motivational interviewing (MI) curriculum is effective in teaching internal medicine residents core MI skills and the empathic, nonjudgmental MI style.

Methods: Nineteen third-year residents met for 12 h with a faculty instructor. Teaching methods included lecture, written exercises, a simulated patient exercise, and discussion of residents' behavior change issues.

Results: Residents' adoption of MI skills was evaluated before and after the course with the Helpful Responses Questionnaire. Residents decreased use of closed-ended questions (from a score of 1.13 to 0.37, p=0.036) and MI roadblocks (4.00-1.08, p<0.001), and increased the use of reflections (1.87-4.87, p<0.001), and use of MI strategies (0.45-0.97, p=0.017). Residents' use of open-ended questions decreased from 1.97 to a mean of 1.05, p=0.023. Residents' ratings of the course on a 5-point scale varied from 3.7 for written exercises to 4.6/5 for the simulated patient exercise. After the course, residents rated behavior change counseling skills as more important.

Discussion And Conclusion: A 12-h course increased residents' use of core MI communication skills in a written measure, and was highly rated.

Practice Implications: Future work should examine whether teaching of the empathic, collaborative MI stance impacts patient outcomes.
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http://dx.doi.org/10.1016/j.pec.2012.08.001DOI Listing
November 2012

Implementing faculty evaluation of written sign-out.

Teach Learn Med 2012 ;24(3):231-7

Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213-2582, USA.

Purpose: Recently the Accreditation Council for Graduate Medical Education mandated decreased shift duration for intern physicians to no more than 16 hours. Such work-hour restrictions are likely to increase patient care hand-offs. It is well accepted that sign-out (i.e., hand-off) processes are error prone and lack standardization. Moreover, many residency programs do not evaluate sign-out. We designed and tested whether a sign-out evaluation process could be implemented to improve written sign-out.

Method: Based on observed sign-out deficiencies at our institution we adapted a simple curriculum incorporating the SIGNOUT mnemonic, which we paired with weekly faculty member evaluation and feedback on sign-out using a structured sign-out evaluation tool. Later in the week, written sign-out was independently scored by 2-blinded senior resident reviewers who compared the inclusion of sign-out content, organization, and readability.

Results: Compared to baseline data in 128 written sign-outs, the pairing of a 1-page curriculum with weekly faculty member evaluation of written sign-out improved the inclusion of advanced directives from 38% to 69% (p < .001) and anticipatory guidance from a mean score of 1.8 (SD = 1.2) to 2.3 (SD = 1.5) on a 5-point scale (p = .01) in 177 written sign-outs. Readability and organization were unchanged.

Conclusions: A simple curriculum paired with structured faculty evaluation and feedback can improve some parameters of sign-out. Structured evaluative sign-out tools may be useful to improve and teach sign-out skills.
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http://dx.doi.org/10.1080/10401334.2012.692271DOI Listing
December 2012

Faculty member review and feedback using a sign-out checklist: improving intern written sign-out.

Acad Med 2012 Aug;87(8):1125-31

Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA.

Purpose: Although residents commonly perform patient care sign-out during training, faculty do not frequently supervise or evaluate sign-out. The authors designed a sign-out checklist, and they investigated whether use of the checklist, paired with faculty member review and feedback, would improve interns' written sign-out.

Method: In a randomized, controlled design in 2011, the authors compared the sign-out content and the overall sign-out summary scores of interns who received twice-monthly faculty member sign-out evaluation with those of interns who received the standard sign-out instruction. A sign-out checklist, which the authors developed on the basis of internal needs assessment and published sign-out recommendations, guided the evaluation of written sign-out content and sign-out organization as well as the twice-monthly, face-to-face evaluation that the interns in the intervention group received.

Results: Using the sign-out checklist and receiving feedback from a faculty member led to statistically significant improvements in interns' sign-out. Through regression analysis, the authors calculated a 23% difference in the sign-out content (P = .005) and a 2.2-point difference in the overall summary score (on a 9-point scale, P = .009) between the interns who received sign-out feedback and those who did not. The content and quality of the intervention group's sign-outs improved, whereas the content and quality of the control group's worsened.

Conclusions: A sign-out checklist paired with twice-monthly, face-to-face feedback from a faculty member led to improvements in the content and quality of interns' written sign-out.
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http://dx.doi.org/10.1097/ACM.0b013e31825d1215DOI Listing
August 2012

Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease.

Clin J Am Soc Nephrol 2012 Mar 16;7(3):479-86. Epub 2012 Feb 16.

Emory University School of Medicine, Atlanta, GA 30322, USA.

Background And Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency.

Design, Setting, Participants, & Measurements: This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR <60 ml/min per 1.73 m(2)) during follow-up was determined.

Results: After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from -0.22 at baseline to -0.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKV was a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P<0.05).

Conclusions: Baseline htTKV ≥600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progression within 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD.
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http://dx.doi.org/10.2215/CJN.09500911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302672PMC
March 2012

Office-based patient education decreases non-emergent emergency department visits.

J Med Pract Manage 2011 Nov-Dec;27(3):131-5

Heartland Healthcare of Collinsville, Collinsville, Illinois, USA.

Emergency department (ED) utilization for non-emergent conditions is costly and inefficient. We evaluated whether a simple office-based intervention could encourage patients with non-emergent conditions to be seen in the office instead of in the ED. The study compared ED utilization of patients of the intervention family medicine clinic to those of the nearby internal medicine clinic. The intervention consisted of educational posters in the family medicine clinic and follow-up letters after non-emergent ED visits. We measured ED use for the two clinics before, during, and after the intervention. We found a statistically significant decrease in ED utilization for the patients of the intervention clinic. For the intervention office with approximately 1100 patient encounters per month, this resulted in a reduction of approximately 40 ED visits per month. If these results are replicated, this simple intervention could result in cost savings and more efficient patient care.
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March 2012

Evaluation of urine biomarkers of kidney injury in polycystic kidney disease.

Kidney Int 2012 Apr 18;81(8):784-90. Epub 2012 Jan 18.

Department of Medicine (Nephrology), Yale University School of Medicine, New Haven, Connecticut 06516, USA.

Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of autosomal dominant polycystic kidney disease (ADPKD). Here we evaluated the effect of these processes on the expression of Lcn2 (NGAL) and interleukin (IL)-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated, which resulted in early- or adult-onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples collected from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4/year and the mean decline in eGFR 2.4 ml/min/year. The trend of increased mean urine NGAL and IL-18 over 3 years was statistically significant; however, there was no association between tertiles of IL-18 or quartiles of NGAL and change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion is mildly and stably elevated in ADPKD, but does not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder.
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http://dx.doi.org/10.1038/ki.2011.465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319327PMC
April 2012