Association of HIV Infection and Incident Abdominal Aortic Aneurysm Among 143 001 Veterans.

BACKGROUND: People with HIV (PWH) have an increased risk of cardiovascular disease. Previous cross-sectional data suggest there is a higher prevalence of abdominal aortic aneurysm (AAA) in PWH than in those without HIV. Whether PWH have an increased risk of incident AAA compared with those without HIV is unknown. METHODS: We analyzed data among participants without prevalent AAA from the Veterans Aging Cohort Study, a prospective, observational, longitudinal cohort of veterans with HIV matched 1:2 with veterans without HIV infection. We calculated AAA rates by HIV status and assessed the association between HIV infection and incident AAA using Cox proportional hazards models. We defined AAA using the International Classification of Diseases, 9th or 10th revision, or Current Procedural Terminology codes and adjusted all models for demographic characteristics, cardiovascular disease risk factors, and substance use. Secondary analyses examined the association between time-varying CD4+ T-cell count or HIV viral load and incident AAA. RESULTS: Among 143 001 participants (43 766 with HIV), over a median follow-up of 8.7 years, there were 2431 incident AAA events (26.4% among PWH). Rates of incident AAA per 1000 person-years were similar among PWH (2.0 [95% CI, 1.9-2.2]) and people without HIV (2.2 [95% CI, 2.1-2.3]). There was no evidence that HIV infection increased the risk of incident AAA compared with no HIV infection (adjusted hazard ratio, 1.02 [95% CI, 0.92-1.13]). In adjusted analyses with time-varying CD4+ T-cell counts or HIV viral load, PWH with CD4+ T-cell counts <200 cells/mm3 (adjusted hazard ratio, 1.29 [95% CI, 1.02-1.65]) or HIV viral load ≥500 copies/mL (adjusted hazard ratio, 1.29 [95% CI, 1.09-1.52]) had an increased risk of AAA compared with those without HIV. CONCLUSIONS: HIV infection is associated with an increased risk of AAA among those with low CD4+ T-cell counts or elevated HIV viral load over time.

Capnography access and use in Kenya and Ethiopia.

PURPOSE: Lack of access to safe and affordable anesthesia and monitoring equipment may contribute to higher rates of morbidity and mortality in low- and middle-income countries (LMICs). While capnography is standard in high-income countries, use in LMICs is not well studied. We evaluated the association of capnography use with patient and procedure-related characteristics, as well as the association of capnography use and mortality in a cohort of patients from Kenya and Ethiopia. METHODS: For this retrospective observational study, we used historical cohort data from Kenya and Ethiopia from 2014 to 2020. Logistic regression was used to study the association of capnography use (primary outcome) with patient/procedure factors, and the adjusted association of intraoperative, 24-hr, and seven-day mortality (secondary outcomes) with capnography use. RESULTS: A total of 61,792 anesthetic cases were included in this study. Tertiary or secondary hospital type (compared with primary) was strongly associated with use of capnography (odds ratio [OR], 6.27; 95% confidence interval [CI], 5.67 to 6.93 and OR, 6.88; 95% CI, 6.40 to 7.40, respectively), as was general (vs regional) anesthesia (OR, 4.83; 95% CI, 4.41 to 5.28). Capnography use was significantly associated with lower odds of intraoperative mortality in patients who underwent general anesthesia (OR, 0.31; 95% CI, 0.17 to 0.48). Nevertheless, fully-adjusted models for 24-hr and seven-day mortality showed no evidence of association with capnography. CONCLUSION: Capnography use in LMICs is substantially lower compared with other standard anesthesia monitors. Capnography was used at higher rates in tertiary centres and with patients undergoing general anesthesia. While this study revealed decreased odds of intraoperative mortality with capnography use, further studies need to confirm these findings.

RéSUMé: OBJECTIF: Le manque d'accès à des équipements d'anesthésie et de monitorage sécuritaires et abordables peut contribuer à des taux plus élevés de morbidité et de mortalité dans les pays à revenu faible et intermédiaire (PRFI). Alors que la capnographie est une modalité standard dans les pays à revenu élevé, son utilisation dans les PRFI n'est pas bien étudiée. Nous avons évalué l'association de l'utilisation de la capnographie avec les caractéristiques des patient·es et des interventions, ainsi que l'association de l'utilisation de la capnographie et de la mortalité dans une cohorte de patient·es du Kenya et d'Éthiopie. MéTHODE: Pour cette étude observationnelle rétrospective, nous avons utilisé des données de cohortes historiques du Kenya et de l'Éthiopie de 2014 à 2020. Une régression logistique a été utilisée pour étudier l'association entre l'utilisation de la capnographie (critère d'évaluation principal) et les facteurs patient·es/interventions, ainsi que pour étudier l'association ajustée entre la mortalité peropératoire, à 24 h et à sept jours (critères d'évaluation secondaires) et l'utilisation de la capnographie. RéSULTATS: Au total, 61 792 cas d'anesthésie ont été inclus dans cette étude. Le type d'hôpital tertiaire ou secondaire (par rapport à un établissement primaire) était fortement associé à l'utilisation de la capnographie (rapport de cotes [RC], 6,27; intervalle de confiance [IC] à 95 %, 5,67 à 6,93 et RC, 6,88; IC 95 %, 6,40 à 7,40, respectivement), tout comme l'était l'anesthésie générale (vs régionale) (RC, 4,83; IC 95 %, 4,41 à 5,28). L'utilisation de la capnographie était significativement associée à une probabilité plus faible de mortalité peropératoire chez les patient·es ayant reçu une anesthésie générale (RC, 0,31; IC 95 %, 0,17 à 0,48). Néanmoins, les modèles entièrement ajustés pour la mortalité à 24 heures et à sept jours n'ont montré aucune donnée probante d'association avec la capnographie. CONCLUSION: L'utilisation de la capnographie dans les PRFI est considérablement moins répandue que celle d'autres moniteurs d'anesthésie standard. La capnographie a été utilisée à des taux plus élevés dans les centres tertiaires et chez des patient·es sous anesthésie générale. Bien que cette étude ait révélé une diminution de la probabilité de mortalité peropératoire avec l'utilisation de la capnographie, d'autres études doivent confirmer ces résultats.

Spearman-like correlation measure adjusting for covariates in bivariate survival data.

We propose an extension of Spearman's correlation for censored continuous and discrete data that permits covariate adjustment. Previously proposed nonparametric and semiparametric Spearman's correlation estimators require either nonparametric estimation of the bivariate survival surface or parametric assumptions about the dependence structure. In practice, nonparametric estimation of the bivariate survival surface is difficult, and parametric assumptions about the correlation structure may not be satisfied. Therefore, we propose a method that requires neither and uses only the marginal survival distributions. Our method estimates the correlation of probability-scale residuals, which has been shown to equal Spearman's correlation when there is no censoring. Because this method relies only on marginal distributions, it tends to be less variable than the previously suggested nonparametric estimators, and the confidence intervals are easily constructed. Although under censoring, it is biased for Spearman's correlation as our simulations show, it performs well under moderate censoring, with a smaller mean squared error than nonparametric approaches. We also extend it to partial (adjusted), conditional, and partial-conditional correlation, which makes it particularly relevant for practical applications. We apply our method to estimate the correlation between time to viral failure and time to regimen change in a multisite cohort of persons living with HIV in Latin America.

Nonparametric estimation of Spearman's rank correlation with bivariate survival data.

We study rank-based approaches to estimate the correlation between two right-censored variables. With end-of-study censoring, it is often impossible to nonparametrically identify the complete bivariate survival distribution, and therefore it is impossible to nonparametrically compute Spearman's rank correlation. As a solution, we propose two measures that can be nonparametrically estimated. The first measure is Spearman's correlation in a restricted region. The second measure is Spearman's correlation for an altered but estimable joint distribution. We describe population parameters for these measures and illustrate how they are similar to and different from the overall Spearman's correlation. We propose consistent estimators of these measures and study their performance through simulations. We illustrate our methods with a study assessing the correlation between the time to viral failure and the time to regimen change among persons living with HIV in Latin America who start antiretroviral therapy.

Acute Kidney Injury and Risk of Incident Heart Failure Among US Veterans.

BACKGROUND: Acute kidney injury (AKI) is common and associated with poor outcomes. Heart failure is a leading cause of cardiovascular disease among patients with chronic kidney disease. The relationship between AKI and heart failure remains unknown and may identify a novel mechanistic link between kidney and cardiovascular disease. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied a national cohort of 300,868 hospitalized US veterans (2004-2011) without a history of heart failure. PREDICTOR: AKI was the predictor and was defined as a 0.3-mg/dL or 50% increase in serum creatinine concentration from baseline to the peak hospital value. Patients with and without AKI were matched (1:1) on 28 in- and outpatient covariates using optimal Mahalanobis distance matching. OUTCOMES: Incident heart failure was defined as 1 or more hospitalization or 2 or more outpatient visits with a diagnosis of heart failure within 2 years through 2013. RESULTS: There were 150,434 matched pairs in the study. Patients with and without AKI during the index hospitalization were well matched, with a median preadmission estimated glomerular filtration rate of 69mL/min/1.73m2. The overall incidence rate of heart failure was 27.8 (95% CI, 19.3-39.9) per 1,000 person-years. The incidence rate was higher in those with compared with those without AKI: 30.8 (95% CI, 21.8-43.5) and 24.9 (95% CI, 16.9-36.5) per 1,000 person-years, respectively. In multivariable models, AKI was associated with 23% increased risk for incident heart failure (HR, 1.23; 95% CI, 1.19-1.27). LIMITATIONS: Study population was primarily men, reflecting patients seen at Veterans Affairs hospitals. CONCLUSIONS: AKI is an independent risk factor for incident heart failure. Future studies to identify underlying mechanisms and modifiable risk factors are needed.

Predictors of Recurrent AKI.

Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19-167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.

Parent health literacy and "obesogenic" feeding and physical activity-related infant care behaviors.

OBJECTIVE: To examine the relationship between parent health literacy and "obesogenic" infant care behaviors. STUDY DESIGN: Cross-sectional analysis of baseline data from a cluster randomized controlled trial of a primary care-based early childhood obesity prevention program (Greenlight). English- and Spanish-speaking parents of 2-month-old children were enrolled (n = 844). The primary predictor variable was parent health literacy (Short Test of Functional Health Literacy in Adults; adequate ≥ 23; low <23). Primary outcome variables involving self-reported obesogenic behaviors were: (1) feeding content (more formula than breast milk, sweet drinks, early solid food introduction), and feeding style-related behaviors (pressuring to finish, laissez-faire bottle propping/television [TV] watching while feeding, nonresponsiveness in letting child decide amount to eat); and (2) physical activity (tummy time, TV). Multivariate logistic regression analyses (binary, proportional odds models) performed adjusting for child sex, out-of-home care, Women, Infants, and Children program status, parent age, race/ethnicity, language, number of adults/children in home, income, and site. RESULTS: Eleven percent of parents were categorized as having low health literacy. Low health literacy significantly increased the odds of a parent reporting that they feed more formula than breast milk, (aOR = 2.0 [95% CI: 1.2-3.5]), immediately feed when their child cries (aOR = 1.8 [1.1-2.8]), bottle prop (aOR = 1.8 [1.002-3.1]), any infant TV watching (aOR = 1.8 [1.1-3.0]), and inadequate tummy time (<30 min/d), (aOR = 3.0 [1.5-5.8]). CONCLUSIONS: Low parent health literacy is associated with certain obesogenic infant care behaviors. These behaviors may be modifiable targets for low health literacy-focused interventions to help reduce childhood obesity.

Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function.

The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type fatty acid-binding protein (L-FABP), and cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min per 1.73 m(2). One-hundred thirty AKI cases were identified following biomarker measurement and were compared with 250 controls without AKI. Areas under the receiver-operator characteristic curves (AUC-ROCs) for discriminating incident AKI from non-AKI were 0.58 (95% CI: 0.52-0.64), 0.59 (0.52-0.65), and 0.50 (0.48-0.57) for urine NGAL, L-FABP, and cystatin C, respectively. The combined AUC-ROC for NGAL and L-FABP was 0.59 (56-0.69). Both urine NGAL and L-FABP independently predicted AKI during multivariate regression; however, risk reclassification indices were mixed. Neither urine biomarker was independently associated with death or acute dialysis (NGAL hazard ratio 1.35 (95% CI: 0.93-1.96), L-FABP 1.15 (0.82-1.61)), although both independently predicted the need for acute dialysis alone (NGAL 3.44 (1.73-6.83), L-FABP 2.36 (1.30-4.25)). Thus, urine NGAL and L-FABP independently associated with the development of incident AKI and receipt of dialysis but exhibited poor discrimination for incident AKI using conventional definitions.

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.

Outpatient nephrology referral rates after acute kidney injury.

AKI associates with an increased risk for the development and progression of CKD and mortality. Processes of care after an episode of AKI are not well described. Here, we examined the likelihood of nephrology referral among survivors of AKI at risk for subsequent decline in kidney function in a US Department of Veterans Affairs database. We identified 3929 survivors of AKI hospitalized between January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per 1.73 m(2) 30 days after peak injury. We analyzed time to referral considering improvement in kidney function (eGFR ≥60 ml/min per 1.73 m(2)), dialysis initiation, and death as competing risks over a 12-month surveillance period. Median age was 73 years (interquartile range, 62-79 years) and the prevalence of preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m(2)) was 60%. Overall mortality during the surveillance period was 22%. The cumulative incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (95% confidence interval, 7.6-9.4). Severity of AKI did not affect referral rates. These data demonstrate that a minority of at-risk survivors are referred for nephrology care after an episode of AKI. Determining how to best identify survivors of AKI who are at highest risk for complications and progression of CKD could facilitate early nephrology-based interventions.

The Association of Prescribed Opioids and Incident Cardiovascular Disease.

Opioid prescribing remains common despite known overdose-related harms. Less is known about links to nonoverdose morbidity. We determined the association between prescribed opioid receipt with incident cardiovascular disease (CVD) using data from the Veterans Aging Cohort Study, a national prospective cohort of Veterans with/without Human Immunodeficiency Virus (HIV) receiving Veterans Health Administration care. Selected participants had no/minimal prior exposure to prescription opioids, no opioid use disorder, and no severe illness 1 year after the study start date (baseline period). We ascertained prescription opioid exposure over 3 years after the baseline period using outpatient pharmacy fill/refill data. Incident CVD ascertainment began at the end of the prescribed opioid exposure ascertainment period until the first incident CVD event, death, or September 30, 2015. We used adjusted Cox proportional hazards regression models with matching weights using propensity scores for opioid receipt to estimate CVD risk. Among 49,077 patients, 30% received opioids; the median age was 49 years, 97% were male, 49% were Black, and 47% were currently smoking. Prevalence of hypertension, diabetes, current smoking, alcohol and cocaine use disorder, and depression was higher in patients receiving opioids versus those not but were well-balanced by matching weights. Unadjusted CVD incidence rates per 1,000-person-years were higher among those receiving opioids versus those not: 17.4 (95% confidence interval [CI], 16.5-18.3) versus 14.7 (95% CI, 14.2-15.3). In adjusted analyses, those receiving opioids versus those not had an increased hazard of incident CVD (adjusted hazard ratio 1.16 [95% CI, 1.08-1.24]). Prescribed opioids were associated with increased CVD incidence, making opioids a potential modifiable CVD risk factor. PERSPECTIVE: In a propensity score weighted analysis of Veterans Administration data, prescribed opioids compared to no opioids were associated with an increased hazard of incident CVD. Higher opioid doses compared with lower doses were associated with increased hazard of incident CVD. Opioids are a potentially modifiable CVD risk factor.

Associations among perceived and objective disease knowledge and satisfaction with physician communication in patients with chronic kidney disease.

It is likely that patients with chronic kidney disease (CKD) have a limited understanding of their illness. Here we studied the relationships between objective and perceived knowledge in CKD using the Kidney Disease Knowledge Survey and the Perceived Kidney Disease Knowledge Survey. We quantified perceived and objective knowledge in 399 patients at all stages of non-dialysis-dependent CKD. Demographically, the patient median age was 58 years, 47% were women, 77% had stages 3-5 CKD, and 83% were Caucasians. The overall median score of the perceived knowledge survey was 2.56 (range: 1-4), and this new measure exhibited excellent reliability and construct validity. In unadjusted analysis, perceived knowledge was associated with patient characteristics defined a priori, including objective knowledge and patient satisfaction with physician communication. In adjusted analysis, older age, male gender, and limited health literacy were associated with lower perceived knowledge. Additional analysis revealed that perceived knowledge was associated with significantly higher odds (2.13), and objective knowledge with lower odds (0.91), of patient satisfaction with physician communication. Thus, our results present a mechanism to evaluate distinct forms of patient kidney knowledge and identify specific opportunities for education tailored to patients with CKD.

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.

Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort.

Objectives: This research describes the prevalence and covariates associated with opioid-induced constipation (OIC) in an observational cohort study utilizing a national veteran cohort and integrated data from the Center for Medicare and Medicaid Services (CMS). Methods: A cohort of 152,904 veterans with encounters between 1 January 2008 and 30 November 2010, an exposure to opioids of 30 days or more, and no exposure in the prior year was developed to establish existing conditions and medications at the start of the opioid exposure and determining outcomes through the end of exposure. OIC was identified through additions/changes in laxative prescriptions, all-cause constipation identification through diagnosis, or constipation related procedures in the presence of opioid exposure. The association of time to constipation with opioid use was analyzed using Cox proportional hazard regression adjusted for patient characteristics, concomitant medications, laboratory tests, and comorbidities. Results: The prevalence of OIC was 12.6%. Twelve positively associated covariates were identified with the largest associations for prior constipation and prevalent laxative (any laxative that continued into the first day of opioid exposure). Among the 17 negatively associated covariates, the largest associations were for erythromycins, androgens/anabolics, and unknown race. Conclusions: There were several novel covariates found that are seen in the all-cause chronic constipation literature but have not been reported for opioid-induced constipation. Some are modifiable covariates, particularly medication coadministration, which may assist clinicians and researchers in risk stratification efforts when initiating opioid medications. The integration of CMS data supports the robustness of the analysis and may be of interest in the elderly population warranting future examination.

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.

National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury.

OBJECTIVE: Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. MATERIALS AND METHODS: A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. RESULTS: The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. CONCLUSIONS: This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant.

Racial and ethnic differences associated with feeding- and activity-related behaviors in infants.

OBJECTIVE: To examine parental reports of feeding and activity behaviors in a cohort of parents of 2-month-olds and how they differ by race/ethnicity. METHODS: Parents participating in Greenlight, a cluster, randomized trial of obesity prevention at 4 health centers, were queried at enrollment about feeding and activity behaviors thought to increase obesity risk. Unadjusted associations between race/ethnicity and the outcomes of interest were performed by using Pearson χ(2) and Kruskal-Wallis tests. Adjusted analyses were performed by using proportional odds logistic regressions. RESULTS: Eight hundred sixty-three parents (50% Hispanic, 27% black, 18% white; 86% Medicaid) were enrolled. Exclusive formula feeding was more than twice as common (45%) as exclusive breastfeeding (19%); 12% had already introduced solid food; 43% put infants to bed with bottles; 23% propped bottles; 20% always fed when the infant cried; 38% always tried to get children to finish milk; 90% were exposed to television (mean, 346 minutes/day); 50% reported active television watching (mean, 25 minutes/day); and 66% did not meet "tummy time" recommendations. Compared with white parents, black parents were more likely to put children to bed with a bottle (adjusted odds ratio [aOR] = 1.97, P < .004; bottle propping, aOR = 3.1, P < .001), and report more television watching (aOR = 1.6, P = .034). Hispanic parents were more likely than white parents to encourage children to finish feeding (aOR = 1.9, P = .007), bottle propping (aOR = 2.5, P = .009), and report less tummy time (aOR = 0.6, P = .037). CONCLUSIONS: Behaviors thought to relate to later obesity were highly prevalent in this large, diverse sample and varied by race/ethnicity, suggesting the importance of early and culturally-adapted interventions.

Laboratory test surveillance following acute kidney injury.

BACKGROUND: Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. METHODS: We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥ 60 L/min/1.73 m(2). Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. RESULTS: A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. CONCLUSIONS: Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease.

Health literacy and injury prevention behaviors among caregivers of infants.

BACKGROUND: Unintentional injury is a leading cause of infant mortality. PURPOSE: To examine the role of caregiver health literacy in infant injury prevention behaviors. METHODS: A cross-sectional analysis of data collected in 2010-2012 from a randomized trial at four pediatric clinics was performed in 2012-2013. Caregiver health literacy was assessed with the Short Test of Functional Health Literacy in Adults. Caregiver-reported adherence to American Academy of Pediatrics-recommended injury prevention behaviors was assessed across seven domains: (1) car seat position; (2) car seat use; (3) sleeping safety; (4) fire safety; (5) hot water safety; (6) fall prevention; and (7) firearm safety. RESULTS: Data were analyzed from 844 English- and Spanish-speaking caregivers of 2-month-old children. Many caregivers were non-adherent with injury prevention guidelines, regardless of health literacy. Notably, 42.6% inappropriately placed their children in the prone position to sleep, and 88.6% did not have their hot water heater set <120°F. Eleven percent of caregivers were categorized as having low health literacy. Low caregiver health literacy, compared to adequate health literacy, was significantly associated with increased odds of caregiver non-adherence with recommended behaviors for car seat position (AOR=3.4, 95% CI=1.6, 7.1) and fire safety (AOR=2.0, 95% CI=1.02, 4.1) recommendations. Caregivers with low health literacy were less likely to be non-adherent to fall prevention recommendations (AOR=0.5, 95% CI=0.2, 0.9). CONCLUSIONS: Non-adherence to injury prevention guidelines was common. Low caregiver health literacy was significantly associated with some injury prevention behaviors. Future interventions should consider the role of health literacy in promoting injury prevention.

Exploring the utility of ultra-brief delirium assessments in a nonintensive care geriatric population: the GEM study.

OBJECTIVE: To determine how an ultra-brief structured tool that would require usually less than a minute for delirium assessment compares with a clinical assessment based on Diagnostic and Statistical Manual-IV (DSM-IV) in a geriatric postacute care (PAC) rehabilitation unit. DESIGN: Prospective observational cohort study. SETTING: Postacute geriatric hospital ward of a Veteran's Affairs hospital. PARTICIPANTS: Consecutively admitted patients between 50 and 100 years old for inpatient postacute medical care. MEASUREMENTS: Two teams, blinded to one another's evaluations, performed daily delirium assessments using either the Confusion Assessment Method for the intensive care unit (CAM-ICU) or clinical assessment based on DSM-IV. RESULTS: There were 61 patients enrolled (median 73 years old, range: 52-94), who underwent 521 paired observations. Delirium was detected in 18 patients (29.5%) by one of the two screening methods over the course of the study, most of whom (14 patients, 23%) were delirious on the first day of enrollment. Delirium was identified by the CAM-ICU on 12.6% of the observations and by the clinical assessment on 6% of the observations (κ = 0.25, 95% confidence interval [CI]: 0.09, 0.40). Examination of disagreement between the 2 evaluations revealed that patients with dementia (κ = 0.11, 95% CI: -0.14, 0.27) had 10.7 times higher odds (95% CI: [3.1, 36.8], p value < .001) of having discordance than patients without dementia. CONCLUSIONS: Different delirium assessments may disagree depending on the study population. Dementia patients are especially challenging to evaluate for delirium.