Nicole Artz

Adult emergency department patients with sickle cell pain crisis: results from a quality improvement learning collaborative model to improve analgesic management.

OBJECTIVES The aims of this study were to 1) estimate differences in pain management process and patient-reported outcomes, pre- and postimplementation of analgesic protocols for adults with sickle cell disease (SCD), and 2) examine the effects of site and visit frequency on changes in pain scores and time to analgesic. METHODS A multicenter, prospective, longitudinal study enrolled patients from three academic medical centers between October 2007 and September 2009. All ED patients 18 years or older with a chief complaint of a sickle cell pain episode were enrolled. Sites formed a SCD quality improvement (QI) team and implemented standard nurse-initiated emergency department (ED) analgesic protocols; outcomes were compared between study periods defined as pre- and postimplementation of protocols. Medical record review was conducted to measure time to administration of initial analgesic, opioids used, route of opioid administration, the change in pain scores from arrival to discharge (negative numbers reflect a decrease in pain scores), and the number of ED visits per individual patient during the study period at each site. On day 7 after the ED visit, a follow-up phone interview was conducted. Patients were queried about their ED pain management using a scale from 1 to 10 (1 = outstanding, 10 = worst). Descriptive statistics are used to report the results. Ordinary least-squares regression models were constructed to measure the effect of time period, site, and number of visits per patient on change in pain score. RESULTS During the study period, 342 unique patients (57% female, mean ± SD age = 32 ± 11 years) were enrolled and had a total of 2,934 visits. There was no difference in time to administration of the initial analgesic between study periods. Overall, there was a significant decrease in pain scores from arrival to discharge between the pre- and postintervention study periods: the average difference in arrival to discharge pain scores (cm) was greater during the postimplementation period than during the preintervention period (-4.1 vs. -3.6, t = 2.6, p < 0.01). Site 1 had significant improvement between study periods (mean difference = -0.87, t = 2.63, p < 0.01; F = 14.3, p < 0.01). Patients with few ED visits (one to six annual visits, mean difference = -1.55, t = 2.1, p = 0.04) and those with frequent ED visits (7 to 19 annual visits, mean difference = -1.65, t = 3.52, p < 0.01) had a significant decrease in pain scores compared to patients with very frequent ED visits (>19 visits). There was an overall decrease in the use of morphine sulfate (MS) and increase in the use of hydromorphone (χ(2) = 105.67, p < 0.001) between study periods and a significant increase in the use of oral (PO) and subcutaneous (SC) routes, with a corresponding decrease in the intravenous (IV) route (χ(2) = 13.67, p < 0.001). There were no statistically significant differences in patient-reported satisfaction with the attempt to manage pain in the ED between study periods (p = 0.54). CONCLUSIONS While the use of a learning collaborative and implementation of nurse-initiated analgesic protocols was not associated with improvement in time to administration of the initial analgesic, improvements in the decrease in the arrival to discharge pain score and increased use of hydromorphone and the SC route were noted in adults with SCD in the ED.

Adult Emergency Department Patients with Sickle Cell Pain Crisis: A Learning Collaborative Model to Improve Analgesic Management

OBJECTIVES The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. METHODS A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. RESULTS A total of 155 patients met study criteria (median age = 32 years, IQR = 24-40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48-135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean +/- SD = 4.19 +/- 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean +/- SD = 5.77 +/- 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). CONCLUSIONS While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable.

A novel molecular signature for elevated tricuspid regurgitation velocity in sickle cell disease

RATIONALE An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD). OBJECTIVES We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD. METHODS Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms. MEASUREMENTS AND MAIN RESULTS Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B). CONCLUSIONS These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.

Prevalence of Vitamin D Deficiency in Adults With Sickle Cell Disease

Vitamin D deficiency has been linked to fracture risk and chronic musculoskeletal pain. Adults with sickle cell disease have a high prevalence of low bone density and chronic pain with poorly defined etiologies. We recognized that vitamin D deficiency may represent a treatable etiology and sought to determine the prevalence of vitamin D deficiency in adults with sickle cell. We measured 25-hydroxy vitamin D levels in adults at 2 university-based sickle cell disease-management programs. Regression was performed in 142 patients to identify predictors of low vitamin D. Mean vitamin D levels were 9.0 ng/mL at Eastern Virginia Medical School and 12.8 ng/mL at University of Chicago; 139 of 142 (98%) had suboptimal levels (<30 ng/mL) and 85/142 (60%) were severely deficient (<10 ng/mL). Vitamin D level was not related to age, sex, hydroxyurea use, sickle cell type, or date of lab draw. Vitamin D deficiency was, therefore, nearly ubiquitous in our patient population, with a majority being severely deficient. Further studies are warranted to evaluate the effects of vitamin D repletion on clinical outcomes such as bone density, chronic musculoskeletal pain, and functional status. Clinicians caring for patients with sickle cell disease should be aware of and screen for this important clinical state.

Mechanistic Insights and Characterization of Sickle Cell Disease Associated Cardiomyopathy

Background—Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Methods and Results—Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m2), right ventricle (127±28 vs 83±14 mL/m2), left atrium (65±16 vs 41±9 mL/m2), and right atrium (78±17 vs 56±17 mL/m2; P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e′, 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Conclusions—Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01044901.

Caring for the adult with sickle cell disease: results of a multidisciplinary pilot program.

BACKGROUND Care for adults with sickle cell disease (SCD) is often fragmented and costly. The chronic care model is recommended as a best practice approach to providing care for patients with chronic disease. However, no published reports exist examining the effectiveness of this approach in adults with SCD. PURPOSE To examine selected quality and utilization measures at baseline and following implementation of a new multidisciplinary program for adults with SCD at one academic institution. METHODS Administrative data were obtained for all adults with SCD admitted to the adult emergency department or hospital or seen in the adult outpatient clinic during calendar years 2000-2009. Charts of all patients seen in the adult multidisciplinary sickle cell clinic were abstracted using prespecified criteria. RESULTS Prescribing of hydroxyurea increased from 13% at baseline to 44%. An additional 53% of patients had a documented reason for no prescription. Decreases in admissions, 30-day readmissions, and lengths of stay resulted in an average savings of 458 bed days per year. CONCLUSION Multidisciplinary care for the adult with SCD provided in the context of the chronic care model can result in significant improvements in important quality targets and may reduce acute resource use.

Evaluation of a train-the-trainer workshop on sickle cell disease for ED providers.

OBJECTIVE (1) Determine the difference in pre-test and post-test knowledge scores for attendees of a train-the-trainer workshop and (2) determine the number of attendees who disseminated the content within 6 months of attending the workshop. METHODS A 1-day, train-the-trainer workshop focusing on sickle cell disease (SCD) was developed. ED nurses and physicians from the emergency departments with the highest number of patients with SCD were invited to participate at no cost. A panel consisting of 6 SCD and ED experts planned the workshop and developed 20 items for pre-test and post-test knowledge evaluation. The pre-test and post-test were administered at the beginning and end of the workshop, respectively. All attendees received a flash drive with all conference materials and were asked to disseminate workshop content to other ED colleagues. After 6 months, a brief survey was sent to the participants using Survey Monkey asking the number and type of providers trained. RESULTS Fifty-five participants attended the workshop. The mean (SD) pre-test score for the entire cohort was 13 (2) and the post-test score was 16 (2); mean difference (95% CI) 2.96 (2.36, 3.57). Items that scored low included questions dealing with pathophysiologic complications, addiction, or ED utilization. Eighteen participants completed the 6-month follow-up survey. Seven participants reported disseminating workshop content to a total of 99 providers. CONCLUSION A train-the-trainer workshop specifically designed for emergency physicians and nurses that discussed the broad spectrum of SCD was well attended, and 6 months later, 99 additional providers received training.

Physical and Mental Health in Adults Hospitalized with Sickle Cell Disease: Impact on Resource Use

BACKGROUND It is commonly perceived that patients with sickle cell disease have increased hospital length of stay (LOS) because of mental health issues, including depression and drug-seeking behavior. However, the effect of mental and physical functional status on acute care resource use is unknown. OBJECTIVE To assess Short Form (SF)-12 physical and mental health scores in adults with sickle cell disease and their impact on hospital LOS and costs. DESIGN We identified 145 adults with sickle cell disease admitted to the general medicine ward at the University of Chicago Medical Center between July 1997 and June 2003. Seventy-nine patients (54%), with a total of 103 admissions, completed the SF-12 for at least one admission. Administrative data were used to obtain demographic information, LOS, and costs. Multivariate regression was used to measure the association between SF-12 physical and mental composite scores (by quartile), and LOS and costs. RESULTS Twenty-five percent of patients accounted for nearly 80% of total hospital days and costs. The mean SF-12 physical score was 40 (SD, 12), and mental score 49 (SD, 12). Adjusted for age, gender, race, and comorbidities, admissions in the lowest quartile of the SF-12 physical composite score had an average LOS of 7.11 days and costs of

Mechanistic insights and characterization of cardiomyopathy due to Sickle Cell Disease

9060, compared to 4.6 days and

Left ventricular function, morphology, and myocardial tissue characterization in Sickle Cell Disease: a multi-modality imaging study

5520 in the highest quartile (p < .03, < .05). The SF-12 mental compositive score was not significantly associated with LOS or costs. CONCLUSIONS Poor physical function rather than poor mental function independently predicts greater use of acute health care resources in adults with sickle cell disease.