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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.

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.

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., (© 2013 Society for Public Health Education.)

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., (Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.)

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.

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60 ml/min per 1.73 m(2). Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25-60 ml/min per 1.73 m(2). We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log-transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log-transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity.

Background: Despite the surge of recent research on the association between perceived discrimination and health-related outcomes, few studies have focused on race-based discrimination encountered in health care settings. This study examined the prevalence of such discrimination, and its association with health status, for the 3 largest race/ethnic groups in the United States., Methods: Data were drawn from the 2004 Behavioral Risk Factor Surveillance System survey. The primary variables were perceived racial discrimination in health care and self-reported health status. Multivariable logistic regression was used to compare the prevalence of perceived discrimination for whites, African Americans, and Hispanics, and to examine the association between perceived discrimination and health status, controlling for sex, age, income, education, health care coverage, affordability of medical care, racial salience, and state., Results: Perceived discrimination was reported by 2%, 5.2%, and 10.9% of whites, Hispanics, and African Americans, respectively. Only the difference between African Americans and whites remained significant in adjusted analyses [odds ratio (OR) = 3.22, 95% confidence interval (CI) = 2.46-4.21]. Racial/ethnic differences in perceived discrimination depended on income, education, health care coverage, and affordability of medical care. Perceived discrimination was associated with worse health status for the overall sample (OR = 1.71, 95% CI = 1.35-2.16). Stratified analyses revealed that this relationship was significant for whites (OR = 2.00, 95% CI = 1.45-2.77) and African Americans (OR = 1.95, 95% CI = 1.39-2.73), but not for Hispanics (OR = 0.55, 95% CI = 0.24-1.22)., Conclusions: Perceived racial discrimination in health care is much more prevalent for African Americans than for whites or Hispanics. Furthermore, such discrimination is associated with worse health both for African Americans and for whites.

Objective: We sought to assess whether health maintenance organizations (HMOs) operating in competitive markets, or markets with substantial HMO penetration, perform better on the standardized Health Plan Employer Data and Information Set (HEDIS) and Consumer Assessment of Health Plans Survey (CAHPS) measures., Study Design: We performed a secondary analysis of nonexperimental, cross-sectional data., Data Sources: Data were obtained from a variety of sources, including the National Committee for Quality Assurance (NCQA), Interstudy, the Area Resource File, the U.S. Office of Personnel Management, and the U.S. Department of Labor., Methods: Multiple Indicator Multiple Cause models were used to simultaneously estimate 6 latent quality variables from 35 HEDIS and CAHPS measures and to relate these latent variables to HMO competition and HMO penetration while controlling for other health plan and market characteristics., Principal Findings: Greater competition, as measured by the Herfindahl index, was associated with inferior health plan performance on 3 of 6 quality dimensions. Plans in markets with greater HMO penetration perform better on HEDIS- but not CAHPS-based dimensions of performance. Plans that make their data available publicly perform significantly better on both the HEDIS and CAHPS domains, performing one third to three quarters of a standard deviation better than plans that don't make their results available publicly., Conclusions: Plans in more competitive markets in 1999 did not achieve better quality after controlling for other important covariates, although plans in markets with a high degree of HMO penetration are performing better on the HEDIS quality dimensions. Although our study design cannot determine causality, the results suggest reason to revisit the belief that competition among HMOs will inherently improve quality.