Use of multiple imputation method to improve estimation of missing baseline serum creatinine in acute kidney injury research.

BACKGROUND AND OBJECTIVES: Baseline creatinine (BCr) is frequently missing in AKI studies. Common surrogate estimates can misclassify AKI and adversely affect the study of related outcomes. This study examined whether multiple imputation improved accuracy of estimating missing BCr beyond current recommendations to apply assumed estimated GFR (eGFR) of 75 ml/min per 1.73 m(2) (eGFR 75). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 41,114 unique adult admissions (13,003 with and 28,111 without BCr data) at Vanderbilt University Hospital between 2006 and 2008, a propensity score model was developed to predict likelihood of missing BCr. Propensity scoring identified 6502 patients with highest likelihood of missing BCr among 13,003 patients with known BCr to simulate a "missing" data scenario while preserving actual reference BCr. Within this cohort (n=6502), the ability of various multiple-imputation approaches to estimate BCr and classify AKI were compared with that of eGFR 75. RESULTS: All multiple-imputation methods except the basic one more closely approximated actual BCr than did eGFR 75. Total AKI misclassification was lower with multiple imputation (full multiple imputation + serum creatinine) (9.0%) than with eGFR 75 (12.3%; P<0.001). Improvements in misclassification were greater in patients with impaired kidney function (full multiple imputation + serum creatinine) (15.3%) versus eGFR 75 (40.5%; P<0.001). Multiple imputation improved specificity and positive predictive value for detecting AKI at the expense of modestly decreasing sensitivity relative to eGFR 75. CONCLUSIONS: Multiple imputation can improve accuracy in estimating missing BCr and reduce misclassification of AKI beyond currently proposed methods.

Effect of a pharmacist intervention on clinically important medication errors after hospital discharge: a randomized trial.

BACKGROUND: Clinically important medication errors are common after hospital discharge. They include preventable or ameliorable adverse drug events (ADEs), as well as medication discrepancies or nonadherence with high potential for future harm (potential ADEs). OBJECTIVE: To determine the effect of a tailored intervention on the occurrence of clinically important medication errors after hospital discharge. DESIGN: Randomized, controlled trial with concealed allocation and blinded outcome assessors. (ClinicalTrials.gov registration number: NCT00632021) SETTING: Two tertiary care academic hospitals. PATIENTS: Adults hospitalized with acute coronary syndromes or acute decompensated heart failure. INTERVENTION: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge. MEASUREMENTS: The primary outcome was the number of clinically important medication errors per patient during the first 30 days after hospital discharge. Secondary outcomes included preventable or ameliorable ADEs, as well as potential ADEs. RESULTS: Among 851 participants, 432 (50.8%) had 1 or more clinically important medication errors; 22.9% of such errors were judged to be serious and 1.8% life-threatening. Adverse drug events occurred in 258 patients (30.3%) and potential ADEs in 253 patients (29.7%). The intervention did not significantly alter the per-patient number of clinically important medication errors (unadjusted incidence rate ratio, 0.92 [95% CI, 0.77 to 1.10]) or ADEs (unadjusted incidence rate ratio, 1.09 [CI, 0.86 to 1.39]). Patients in the intervention group tended to have fewer potential ADEs (unadjusted incidence rate ratio, 0.80 [CI, 0.61 to 1.04]). LIMITATION: The characteristics of the study hospitals and participants may limit generalizability. CONCLUSION: Clinically important medication errors were present among one half of patients after hospital discharge and were not significantly reduced by a health-literacy-sensitive, pharmacist-delivered intervention. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit.

OBJECTIVE: To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements. DESIGN AND SETTING: A prospective observational cohort study investigating the Pediatric Confusion Assessment Method for Intensive Care Unit (pCAM-ICU) patients in the pediatric medical, surgical, and cardiac intensive care unit of a university-based medical center. PATIENTS: A total of 68 pediatric critically ill patients, at least 5 years of age, were enrolled from July 1, 2008, to March 30, 2009. INTERVENTIONS: None. MEASUREMENTS: Criterion validity including sensitivity and specificity and interrater reliability were determined using daily delirium assessments with the pCAM-ICU by two critical care clinicians compared with delirium diagnosis by pediatric psychiatrists using Diagnostic and Statistical Manual, 4th Edition, Text Revision criteria. RESULTS: A total of 146 paired assessments were completed among 68 enrolled patients with a mean age of 12.2 yrs. Compared with the reference standard for diagnosing delirium, the pCAM-ICU demonstrated a sensitivity of 83% (95% confidence interval, 66-93%), a specificity of 99% (95% confidence interval, 95-100%), and a high interrater reliability (κ = 0.96; 95% confidence interval, 0.74-1.0). CONCLUSIONS: The pCAM-ICU is a highly valid reliable instrument for the diagnosis of pediatric delirium in critically ill children chronologically and developmentally at least 5 yrs of age. Use of the pCAM-ICU may expedite diagnosis and consultation with neuropsychiatry specialists for treatment of pediatric delirium. In addition, the pCAM-ICU may provide a means for delirium monitoring in future epidemiologic and interventional studies in critically ill children.

Rationale and design of the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study.

BACKGROUND: Medication errors and adverse drug events are common after hospital discharge due to changes in medication regimens, suboptimal discharge instructions, and prolonged time to follow-up. Pharmacist-based interventions may be effective in promoting the safe and effective use of medications, especially among high-risk patients such as those with low health literacy. METHODS AND RESULTS: The Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study is a randomized controlled trial conducted at 2 academic centers-Vanderbilt University Hospital and Brigham and Women's Hospital. Patients admitted with acute coronary syndrome or acute decompensated heart failure were randomly assigned to usual care or intervention. The intervention consisted of pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and tailored telephone follow-up after discharge. The primary outcome is the occurrence of serious medication errors in the first 30 days after hospital discharge. Secondary outcomes are health care utilization, disease-specific quality of life, and cost-effectiveness. Enrollment was completed September 2009. A total of 862 patients were enrolled, and 430 patients were randomly assigned to receive the intervention. Analyses will determine whether the intervention was effective in reducing serious medication errors, particularly in patients with low health literacy. CONCLUSIONS: The PILL-CVD study was designed to reduce serious medication errors after hospitalization through a pharmacist-based intervention. The intervention, if effective, will inform health care facilities on the use of pharmacist-assisted medication reconciliation, inpatient counseling, low-literacy adherence aids, and patient follow-up after discharge. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00632021.

Immortal time bias in critical care research: application of time-varying Cox regression for observational cohort studies.

OBJECTIVES: To examine the bias introduced by using time-fixed methodology to analyze the effects of a time-varying exposure incurred in the intensive care unit. DESIGN: Prospective cohort and Monte Carlo simulation studies. SETTING: Medical and coronary intensive care units in a university hospital. PATIENTS: A total of 224 mechanically ventilated patients. METHODS: Part I was a case study analyzing the association between delirium in the intensive care unit (exposure variable) and outcomes (intensive care unit length of stay and 6-mo mortality) in a prospective cohort study. Part II was a Monte Carlo simulation generating 16,000 data sets wherein the true associations between delirium and outcomes were known before analysis. In both parts, we assessed associations between delirium in the intensive care unit and outcomes (intensive care unit length of stay and mortality), using time-fixed vs. time-varying Cox regression methodology. MEASUREMENTS AND MAIN RESULTS: In the case study, delirium analyzed as a time-fixed variable was associated with a delayed intensive care unit discharge (adjusted hazard ratio = 1.9, 95% confidence interval, 1.3-2.7, p < .001), but no association was noted using a time-varying method (adjusted hazard ratio = 1.1, 95% confidence interval = 0.7-1.6, p = .70). Alternatively, delirium analyzed as a time-fixed variable was not associated with 6-mo mortality (adjusted hazard ratio = 2.9, 95% confidence interval, 0.9-5.0, p = .09), whereas delirium analyzed as a time-varying variable was associated with increased mortality (adjusted hazard ratio = 3.2, 95% confidence interval, 1.4-7.7, p = .008). In the simulation study, time-fixed methods produced erroneous results in 97.1% of the data sets with no true association; time-varying methods produced erroneous results in only 3.7%. Similarly, time-fixed methods produced biased results when a true association was present, whereas time-varying methods produced accurate results. CONCLUSIONS: Studies using a time-fixed analytic approach to understand relationships between exposures and clinical outcomes can result in considerable bias when the variables overlap temporally in occurrence. Those conducting such studies, and clinicians reading them, should ensure that time-varying exposures are correctly analyzed to avoid biased conclusions.

Fluoroquinolone resistance in Mycobacterium tuberculosis: an assessment of MGIT 960, MODS and nitrate reductase assay and fluoroquinolone cross-resistance.

OBJECTIVES: The aim of this study was to assess the sensitivity, specificity and time to results of mycobacterial growth indicator tube (MGIT) 960, microscopic observation drug susceptibility (MODS) assay and nitrate reductase assay (NRA) compared with the gold standard agar proportion method (PM), and to determine whether there is cross-resistance between older-generation fluoroquinolones and moxifloxacin. METHODS: Mycobacterium tuberculosis isolates from culture-confirmed tuberculosis patients from 2002 to 2007 were tested for ofloxacin (2 mg/L) resistance by PM and MGIT 960. All isolates from 2005 and 2006 were also tested by MODS and NRA. Ofloxacin-resistant isolates by PM were further tested by all four methods using ciprofloxacin, levofloxacin and moxifloxacin. For each ofloxacin-resistant isolate, two ofloxacin-susceptible isolates were tested against all three fluoroquinolones using all four methods. RESULTS: Of the 797 M. tuberculosis isolates, 19 (2.4%) were ofloxacin-resistant by PM. MGIT 960 had 100% sensitivity (95% CI, 83%-100%) and specificity (95% CI, 99.5%-100%). Of the 797 isolates, 239 were from 2005 to 2006 and 6 of these (2.5%) were resistant by PM. MODS had 100% sensitivity (95% CI, 61%-100%) and specificity (95% CI, 98%-100%). NRA had 100% sensitivity (95% CI, 61%-100%) and 98.7% specificity (95% CI, 96%-99.6%). The median time to results was shorter using MGIT 960 (8 days), MODS (6 days) or NRA (9 days) compared with PM (21 days) (P < 0.001). All 19 ofloxacin-resistant isolates were resistant to ciprofloxacin, levofloxacin and moxifloxacin by PM. CONCLUSIONS: MGIT 960, MODS and NRA are sensitive and specific and more rapid than PM for identifying fluoroquinolone resistance in M. tuberculosis. Ofloxacin resistance was associated with cross-resistance to ciprofloxacin, levofloxacin and moxifloxacin.