David K. Hooper

The Influence of Context on Quality Improvement Success in Health Care: A Systematic Review of the Literature

CONTEXT The mixed results of success among QI initiatives may be due to differences in the context of these initiatives. METHODS The business and health care literature was systematically reviewed to identify contextual factors that might influence QI success; to categorize, summarize, and synthesize these factors; and to understand the current stage of development of this research field. FINDINGS Forty-seven articles were included in the final review. Consistent with current theories of implementation and organization change, leadership from top management, organizational culture, data infrastructure and information systems, and years involved in QI were suggested as important to QI success. Other potentially important factors identified in this review included: physician involvement in QI, microsystem motivation to change, resources for QI, and QI team leadership. Key limitations in the existing literature were the lack of a practical conceptual model, the lack of clear definitions of contextual factors, and the lack of well-specified measures. CONCLUSIONS Several contextual factors were shown to be important to QI success, although the current body of literature lacks adequate definitions and is characterized by considerable variability in how contextual factors are measured across studies. Future research should focus on identifying and developing measures of context tied to a conceptual model that examines context across all levels of the health care system and explores the relationships among various aspects of context.

Risk of tacrolimus toxicity in CYP3A5 nonexpressors treated with intravenous nicardipine after kidney transplantation.

Background. Tacrolimus is commonly prescribed for immunosuppression, yet it can cause acute and chronic kidney injury. Continuous intravenous nicardipine (CIVN), prescribed for posttransplant hypertension, inhibits tacrolimus metabolism by cytochrome P450 (CYP) 3A4 and could lead to tacrolimus overexposure in patients genetically lacking the alternative pathway for tacrolimus metabolism, CYP3A5. Methods. We compared maximum 12-hr tacrolimus trough levels (MaxC0) and dose-adjusted MaxC0 in 12 cases treated with CIVN immediately after kidney transplantation with 26 controls (no CIVN). CYP3A5 genotype was determined for all cases. Results. Eight cases not expressing CYP3A5 (CYP3A5*3/*3) had higher median MaxC0 (24.3 ng/mL) than four cases expressing CYP3A5 (CYP3A5*1/*1; 13.9 ng/mL, P=0.028) and controls (14.6 ng/mL, P=0.003). Compared with the other two groups combined, CYP3A5*3/*3 cases had higher median dose-adjusted MaxC0 (330 vs. 175, P=0.012), less time to MaxC0 (42 vs. 72 hr, P<0.001), and more scheduled tacrolimus doses held per patient (1.75 vs. 0.4, P=0.007). Six of eight (75%) CYP3A5*3/*3 cases had potentially toxic MaxC0 (>20 ng/mL) compared with none of four CYP3A5*1/*1 cases and 3 of 26 (11.5%) controls (P<0.001, CYP3A5*3/*3 cases vs. all others). Conclusion. CYP3A5 nonexpressors simultaneously treated with tacrolimus and CIVN may be at increased risk for tacrolimus toxicity.

Reliable individualized monitoring improves cholesterol control in kidney transplant recipients.

OBJECTIVE: To develop and evaluate a system for reliable and efficient individualized risk-based monitoring of cholesterol and 11 other tests after kidney transplantation in children. METHODS: We identified system components that drive reliable individualized monitoring and used quality improvement methods to develop and implement interventions, including (1) monitoring schedules individualized by dyslipidemia risk assigned to each patient, (2) automated previsit decision support from our electronic medical record, (3) standardized work flow and responsibility, and (4) automated forwarding of results to providers. We measured the proportion of patients due for cholesterol testing who had it performed within 1 week of their clinic visit and the proportion of patients in our population who achieved low-density lipoprotein (LDL) cholesterol control at baseline and for 2 years after improved monitoring. RESULTS: The proportion of visits in which cholesterol monitoring was completed when indicated improved from 80% to 98% within 8 months and was sustained for more than 1 year. The number of patients with controlled LDL (<130 mg/dL, 3.3 mmol/L) improved from 44 (71%) of 62 at the start of our project to 58 (94%) of 62 (P = .002) at an average follow-up of 24 months. CONCLUSIONS: Using quality improvement and health information technology, we achieved sustained, reliable and efficient personalized monitoring of cholesterol and 11 other tests. This approach enabled substantial improvement in LDL cholesterol control. Structured methods of system redesign that leverage information technology systems hold promise for rapidly achieving reliable individualized care in other settings.

Interaction between tacrolimus and intravenous nicardipine in the treatment of post‐kidney transplant hypertension at pediatric hospitals

Hooper DK, Carle AC, Schuchter J, Goebel J. Interaction between tacrolimus and intravenous nicardipine in the treatment of post‐kidney transplant hypertension at pediatric hospitals.
Pediatr Transplantation 2011: 15:88–95.

Masked hypertension and allograft function in pediatric and young adults kidney transplant recipients

Masked hypertension is a common complication of pediatric kidney transplantation. While office hypertension is known to be associated with worse short‐ and long‐term graft function, the role of masked hypertension in allograft dysfunction is not clear. We conducted a retrospective cross‐sectional analysis of 77 consecutive pediatric kidney transplant recipients who had routine 24‐h ambulatory blood pressure monitoring with the aims to estimate the prevalence of masked hypertension and examine its association with allograft function. Masked hypertension was defined as a 24‐h systolic or diastolic blood pressure load ≥25%. Twenty‐nine percent of patients had masked hypertension. Patients with masked hypertension had significantly lower allograft function estimated using the creatinine‐based Schwartz‐Lyon formula, a cystatin C‐based formula, and combined cystatin C and creatinine‐based formulas than patients with normal blood pressure (all p values <0.05). In a multivariable analysis, masked hypertension remained independently associated with worse allograft function after adjustment for age, sex, race, time post‐transplant, rejection history, antihypertensive treatment, and hemoglobin level. We conclude that in young kidney transplant recipients, masked hypertension is common and is associated with worse allograft function. These results support the case for routine ambulatory blood pressure monitoring as the standard of care in these patients to detect and treat masked hypertension.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients

Patient‐identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post‐transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient‐centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non‐judgmental discussion around adherence. We performed time‐series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient‐caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR‐integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient‐endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient‐caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss).

Prevalence and predictors of aortic dilation as a novel cardiovascular complication in children with end-stage renal disease

Background: Cardiovascular disease is the leading cause of death in children with end-stage renal disease (ESRD). Isolated aortic dilation (AD) is rare in children. We aimed to determine the prevalence and the risk factors for AD in children with ESRD. Methods and study design: We reviewed records of all ESRD patients followed at our institution from January 2007 to October 2012. AD was defined as Z-score > 2 in the dimension of at least one of the following echocardiographic aortic parameters: annulus, root at the sinus, sino-tubular junction, ,or ascending aorta. Results: The records of 78 patients on dialysis and 19 kidney transplant recipients were available. 30 patients (30.9%) had AD. Multivariate analysis revealed independent associations of AD with body mass index (BMI) Z-score (OR = 0.52, 95% confidence interval (CI): 0.35 – 0.78) and ESRD secondary to glomerular disease (OR = 4.58, 95% CI: 1.45 – 14.46). We developed a classification and regression tree (CART) model to identify patients at low vs. high AD risk. Our model classified 62 patients of the cohort (64%) to be high- or low-risk, with a positive predictive value of 89% and a negative predictive value of 100%. Conclusion: Our data suggest that AD, as a possible marker of aortopathy and early aneurysm formation, is a novel and prevalent cardiovascular complication in ESRD children. Glomerular disease and low BMI Z-score appear to be potent predictors. CART modeling helps identify high-risk children, potentially guiding decisions regarding targeted echocardiographic evaluations.

Population pharmacokinetic−pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post‐transplant period

AIM The purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK-PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post-transplant period. METHODS A total of 214 MPA plasma concentrations-time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK-PD modelling. The PK-PD model was developed using non-linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK-PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co-medication and clinical laboratory data. Non-parametric bootstrapping and prediction-corrected visual predictive checks were performed to evaluate the final models. RESULTS A two compartment model with a transit compartment absorption best described MPA PK. A non-linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h(-1) 70 kg(-1) ; Vc /F, 45.4 (29.6, 55.6) l; Vp /F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h(-1) ; Ka , 2.5 (1.45, 4.93) h(-1) . Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK-PD parameter estimates (and their 95% confidence intervals) were: E0 , 3.45 (2.61, 4.56) nmol h(-1)  mg(-1) protein and EC50 , 1.73 (1.16, 3.01) mg l(-1) . Emax was fixed to 0. There were two African-American patients in our study cohorts and both had low IMPDH baseline activities (E0 ) compared with Caucasian patients (mean value 2.13 mg l(-1) vs. 3.86 mg l(-1) ). CONCLUSION An integrated population PK-PD model of MPA has been developed in paediatric renal transplant recipients. The current model provides information that will facilitate future studies and may be implemented in a Bayesian algorithm to allow a PK-PD guided therapeutic drug monitoring strategy.

Characteristics of Successful Recruitment in Prospective Pediatric Pharmacogenetic Studies

BACKGROUND There is a need to explore feasible means of accruing an appropriate study cohort to help fill the knowledge gap between pharmacogenetic contributions to drug response and clinical application in the pediatric population. OBJECTIVES The aim of this study was to identify factors affecting recruitment of eligible subjects in pharmacogenetic studies at a large Midwestern pediatric academic medical center. The objectives were to evaluate recruitment success of ongoing trials and ascertain contributors to differential recruitment rates. We hypothesized that studies with good recruitment of eligible subjects would share characteristics not present in studies with lower than anticipated recruitment. The goal was to better understand barriers to good recruitment in pharmacogenetic studies to help inform future trial and infrastructure design. METHODS Investigators designed a survey with proposed elements of success, which was then completed by lead and/or site investigators of all pharmacogenetics studies at the institution. Results were evaluated using an investigator-developed likelihood of success scoring system. RESULTS Two studies recruited >95% of the approached eligible patients; 4 studies were consistent with investigator-anticipated recruitment (>50%), and 1 study did not meet expected recruitment. A studys total score on the investigator-devised scoring tool correlated well with the proportion of approached patients recruited (Pearsons correlation, r = 0.82; P < 0.001). Multiple factors impacted successful recruitment into these pharmacogenetic studies. Features of studies with successful recruitment included standardized clinical care, an ongoing team-patient relationship, severe and/or life-threatening outcome measures, study coordinator with experience in clinical research, a study medication with few or no alternative treatment options, and active involvement of the research team in clinical care. CONCLUSIONS A scoring system for study characteristics may be useful to calculate the risk of failure for successful recruitment, allow discrimination among characteristics contributing to the risk, and permit study design alterations to improve likelihood of successful recruitment in pediatric pharmacogenetic studies.

A systems-based approach to managing blood pressure in children following kidney transplantation

Hypertension is one of the most common and well-known complications following kidney transplantation in children. Yet, despite numerous available therapies many pediatric kidney transplant recipients continue to have poorly controlled blood pressure, suggesting that traditional approaches to blood pressure management in this population might be inadequate. Over the last two decades, the Chronic Care Model has been developed to improve chronic illness outcomes through delivery system design and clinical information systems that support patient self-management and provider decision-making. In this educational review we discuss key elements of managing blood pressure following pediatric kidney transplantation and suggest ways that they may be reliably implemented into clinical practice using principles from the Chronic Care Model.