The diagnostic accuracy of community spine radiology for adolescent idiopathic scoliosis brace candidates.

PURPOSE: The study aims to establish the diagnostic accuracy of community spine x-rays for brace candidates. METHODS: A review of adolescent idiopathic scoliosis patients seen for initial visit at a tertiary care pediatric hospital was conducted (n = 170). The index test was the pre-referral community spine x-ray interpreted by a community radiologist. Measures of diagnostic accuracy for the index test were determined against the reference standard if images were obtained within 90 days (n = 111). The reference standard was the 3-foot standing EOS spine x-ray evaluated by spine specialists. Diagnostic criterion for a brace candidate was dichotomized by Cobb angle range (25-40°) according to Scoliosis Research Society criteria. Risser stage was not included given significant missing data in index reports. To mitigate the uncertainty around true progression, sensitivity analyses were conducted on a sub-sample of data when index test was within 60 days of the reference standard (n = 67). RESULTS: Accuracy of the community spine x-ray to detect a brace candidate was 65.8% (95% CI 56.2-74.5). Sensitivity of the index test was 65.4% with a false negative rate of 34.6%. Specificity was 66.1% with a false positive rate of 33.9%. Positive and negative predictive values were 63.0% and 68.4%, respectively. Of the total number of brace candidates (n = 52), 32.7% were missed because of underestimation in Cobb angle (95% CI 21.5-46.2). The proportion of missed brace candidates because of underestimation was unchanged with 60-day data (p = 0.37). CONCLUSIONS: Inaccuracies in community spine radiology may lead to missed opportunities for non-operative treatment.

Psychological Distress After Inpatient Noncardiac Surgery: A Secondary Analysis of the Measurement of Exercise Tolerance Before Surgery Prospective Cohort Study.

OBJECTIVE: To describe the incidence and natural progression of psychological distress after major surgery. BACKGROUND: The recovery process after surgery imposes physical and mental burdens that put patients at risk of psychological distress. Understanding the natural course of psychological distress after surgery is critical to supporting the timely and tailored management of high-risk individuals. METHODS: We conducted a secondary analysis of the "Measurement of Exercise Tolerance before Surgery" multicentre cohort study (Canada, Australia, New Zealand, and the UK). Measurement of Exercise Tolerance before Surgery recruited adult participants (≥40 years) undergoing elective inpatient noncardiac surgery and followed them for 1 year. The primary outcome was the severity of psychological distress measured using the anxiety-depression item of EQ-5D-3L. We used cumulative link mixed models to characterize the time trajectory of psychological distress among relevant patient subgroups. We also explored potential predictors of severe and/or worsened psychological distress at 1 year using multivariable logistic regression models. RESULTS: Of 1546 participants, moderate-to-severe psychological distress was reported by 32.6% of participants before surgery, 27.3% at 30 days after surgery, and 26.2% at 1 year after surgery. Psychological distress appeared to improve over time among females [odds ratio (OR): 0.80, 95% CI: 0.65-0.95] and patients undergoing orthopedic procedures (OR: 0.73, 95% CI: 0.55-0.91), but not among males (OR: 0.87, 95% CI: 0.87-1.07) or patients undergoing nonorthopedic procedures (OR: 0.95, 95% CI: 0.87-1.04). Among the average middle-aged adult, there were no time-related changes (OR: 0.94, 97% CI: 0.75-1.13), whereas the young-old (OR: 0.89, 95% CI: 0.79-0.99) and middle-old (OR: 0.87, 95% CI: 0.73-1.01) had small improvements. Predictors of severe and/or worsened psychological distress at 1 year were younger age, poor self-reported functional capacity, smoking history, and undergoing open surgery. CONCLUSIONS: One-third of adults experience moderate to severe psychological distress before major elective noncardiac surgery. This distress tends to persist or worsen over time among select patient subgroups.

Modelling time-varying risk factors of tooth loss: Results from joint model compared with extended Cox regression model.

AIM: To illustrate the use of joint models (JMs) for longitudinal and survival data in estimating risk factors of tooth loss as a function of time-varying endogenous periodontal biomarkers (probing pocket depth [PPD], alveolar bone loss [ABL] and mobility [MOB]). MATERIALS AND METHODS: We used data from the Veterans Affairs Dental Longitudinal Study, a longitudinal cohort study of over 30 years of follow-up. We compared the results from the JM with those from the extended Cox regression model which assumes that the time-varying covariates are exogenous. RESULTS: Our results showed that PPD is an important risk factor of tooth loss, but each model produced different estimates of the hazard. In the tooth-level analysis, based on the JM, the hazard of tooth loss increased by 4.57 (95% confidence interval [CI]: 2.13-8.50) times for a 1-mm increase in maximum PPD, whereas based on the extended Cox model, the hazard of tooth loss increased by 1.60 (95% CI: 1.37-1.87) times. CONCLUSIONS: JMs can incorporate time-varying periodontal biomarkers to estimate the hazard of tooth loss. As JMs are not commonly used in oral health research, we provide a comprehensive set of R codes and an example dataset to implement the method.

Multiple imputation methods for missing multilevel ordinal outcomes.

BACKGROUND: Multiple imputation (MI) is an established technique for handling missing data in observational studies. Joint modelling (JM) and fully conditional specification (FCS) are commonly used methods for imputing multilevel data. However, MI methods for multilevel ordinal outcome variables have not been well studied, especially when cluster size is informative on the outcome. The purpose of this study is to describe and compare different MI strategies for dealing with multilevel ordinal outcomes when informative cluster size (ICS) exists. METHODS: We conducted comprehensive Monte Carlo simulation studies to compare the performance of five strategies: complete case analysis (CCA), FCS, FCS+CS (including cluster size (CS) in the imputation model), JM, and JM+CS under various scenarios. We evaluated their performance using a proportional odds logistic regression model estimated with cluster weighted generalized estimating equations (CWGEE). RESULTS: The simulation results showed that including CS in the imputation model can significantly improve estimation accuracy when ICS exists. FCS provided more accurate and robust estimation than JM, followed by CCA for multilevel ordinal outcomes. We further applied these strategies to a real dental study to assess the association between metabolic syndrome and clinical attachment loss scores. The results based on FCS + CS indicated that the power of the analysis would increase after carrying out the appropriate MI strategy. CONCLUSIONS: MI is an effective tool to increase the accuracy and power of the downstream statistical analysis for missing ordinal outcomes. FCS slightly outperforms JM when imputing multilevel ordinal outcomes. When there is plausible ICS, we recommend including CS in the imputation phase.

Survey design and analysis considerations when utilizing misclassified sampling strata.

BACKGROUND: A large multi-center survey was conducted to understand patients' perspectives on biobank study participation with particular focus on racial and ethnic minorities. In order to enrich the study sample with racial and ethnic minorities, disproportionate stratified sampling was implemented with strata defined by electronic health records (EHR) that are known to be inaccurate. We investigate the effect of sampling strata misclassification in complex survey design. METHODS: Under non-differential and differential misclassification in the sampling strata, we compare the validity and precision of three simple and common analysis approaches for settings in which the primary exposure is used to define the sampling strata. We also compare the precision gains/losses observed from using a disproportionate stratified sampling scheme compared to using a simple random sample under varying degrees of strata misclassification. RESULTS: Disproportionate stratified sampling can result in more efficient parameter estimates of the rare subgroups (race/ethnic minorities) in the sampling strata compared to simple random sampling. When sampling strata misclassification is non-differential with respect to the outcome, a design-agnostic analysis was preferred over model-based and design-based analyses. All methods yielded unbiased parameter estimates but standard error estimates were lowest from the design-agnostic analysis. However, when misclassification is differential, only the design-based method produced valid parameter estimates of the variables included in the sampling strata. CONCLUSIONS: In complex survey design, when the interest is in making inference on rare subgroups, we recommend implementing disproportionate stratified sampling over simple random sampling even if the sampling strata are misclassified. If the misclassification is non-differential, we recommend a design-agnostic analysis. However, if the misclassification is differential, we recommend using design-based analyses.

Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study.

BACKGROUND: Global increases in colorectal cancer risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of colorectal cancer screening tailored to predicted colorectal cancer risk. METHODS: We compared screening tailored to predicted risk versus uniform screening in a validated decision analytic model, considering the average risk population's actual colorectal cancer risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as colorectal cancer risk after age 50 years of ≤3%, >3 to <12%, and ≥12%, respectively, based on threshold analyses with willingness-to-pay <$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at age 60 years for low risk, every 10 years for moderate risk, and every 5 years for high risk) was compared with colonoscopy every 10 years for all. Tailored fecal immunochemical testing (FIT)/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared with annual FIT for all. RESULTS: Assuming no colorectal cancer risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200-$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600-$60,000/QALY gained. Relatively modest colorectal cancer risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach. CONCLUSIONS: Current risk-prediction tools may not yet be accurate enough to optimize colorectal cancer screening. IMPACT: Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.

Marginal analysis of ordinal clustered longitudinal data with informative cluster size.

The issue of informative cluster size (ICS) often arises in the analysis of dental data. ICS describes a situation where the outcome of interest is related to cluster size. Much of the work on modeling marginal inference in longitudinal studies with potential ICS has focused on continuous outcomes. However, periodontal disease outcomes, including clinical attachment loss, are often assessed using ordinal scoring systems. In addition, participants may lose teeth over the course of the study due to advancing disease status. Here we develop longitudinal cluster-weighted generalized estimating equations (CWGEE) to model the association of ordinal clustered longitudinal outcomes with participant-level health-related covariates, including metabolic syndrome and smoking status, and potentially decreasing cluster size due to tooth-loss, by fitting a proportional odds logistic regression model. The within-teeth correlation coefficient over time is estimated using the two-stage quasi-least squares method. The motivation for our work stems from the Department of Veterans Affairs Dental Longitudinal Study in which participants regularly received general and oral health examinations. In an extensive simulation study, we compare results obtained from CWGEE with various working correlation structures to those obtained from conventional GEE which does not account for ICS. Our proposed method yields results with very low bias and excellent coverage probability in contrast to a conventional generalized estimating equations approach.

Evaluating the effects of rater and subject factors on measures of association.

Large-scale agreement studies are becoming increasingly common in medical settings to gain better insight into discrepancies often observed between experts' classifications. Ordered categorical scales are routinely used to classify subjects' disease and health conditions. Summary measures such as Cohen's weighted kappa are popular approaches for reporting levels of association for pairs of raters' ordinal classifications. However, in large-scale studies with many raters, assessing levels of association can be challenging due to dependencies between many raters each grading the same sample of subjects' results and the ordinal nature of the ratings. Further complexities arise when the focus of a study is to examine the impact of rater and subject characteristics on levels of association. In this paper, we describe a flexible approach based upon the class of generalized linear mixed models to assess the influence of rater and subject factors on association between many raters' ordinal classifications. We propose novel model-based measures for large-scale studies to provide simple summaries of association similar to Cohen's weighted kappa while avoiding prevalence and marginal distribution issues that Cohen's weighted kappa is susceptible to. The proposed summary measures can be used to compare association between subgroups of subjects or raters. We demonstrate the use of hypothesis tests to formally determine if rater and subject factors have a significant influence on association, and describe approaches for evaluating the goodness-of-fit of the proposed model. The performance of the proposed approach is explored through extensive simulation studies and is applied to a recent large-scale cancer breast cancer screening study.

Summary measures of agreement and association between many raters' ordinal classifications.

PURPOSE: Interpretation of screening tests such as mammograms usually require a radiologist's subjective visual assessment of images, often resulting in substantial discrepancies between radiologists' classifications of subjects' test results. In clinical screening studies to assess the strength of agreement between experts, multiple raters are often recruited to assess subjects' test results using an ordinal classification scale. However, using traditional measures of agreement in some studies is challenging because of the presence of many raters, the use of an ordinal classification scale, and unbalanced data. METHODS: We assess and compare the performances of existing measures of agreement and association as well as a newly developed model-based measure of agreement to three large-scale clinical screening studies involving many raters' ordinal classifications. We also conduct a simulation study to demonstrate the key properties of the summary measures. RESULTS: The assessment of agreement and association varied according to the choice of summary measure. Some measures were influenced by the underlying prevalence of disease and raters' marginal distributions and/or were limited in use to balanced data sets where every rater classifies every subject. Our simulation study indicated that popular measures of agreement and association are prone to underlying disease prevalence. CONCLUSIONS: Model-based measures provide a flexible approach for calculating agreement and association and are robust to missing and unbalanced data as well as the underlying disease prevalence.

Assessing the influence of rater and subject characteristics on measures of agreement for ordinal ratings.

Widespread inconsistencies are commonly observed between physicians' ordinal classifications in screening tests results such as mammography. These discrepancies have motivated large-scale agreement studies where many raters contribute ratings. The primary goal of these studies is to identify factors related to physicians and patients' test results, which may lead to stronger consistency between raters' classifications. While ordered categorical scales are frequently used to classify screening test results, very few statistical approaches exist to model agreement between multiple raters. Here we develop a flexible and comprehensive approach to assess the influence of rater and subject characteristics on agreement between multiple raters' ordinal classifications in large-scale agreement studies. Our approach is based upon the class of generalized linear mixed models. Novel summary model-based measures are proposed to assess agreement between all, or a subgroup of raters, such as experienced physicians. Hypothesis tests are described to formally identify factors such as physicians' level of experience that play an important role in improving consistency of ratings between raters. We demonstrate how unique characteristics of individual raters can be assessed via conditional modes generated during the modeling process. Simulation studies are presented to demonstrate the performance of the proposed methods and summary measure of agreement. The methods are applied to a large-scale mammography agreement study to investigate the effects of rater and patient characteristics on the strength of agreement between radiologists. Copyright © 2017 John Wiley & Sons, Ltd.

Safety of Intravenous Iron in Hemodialysis: Longer-term Comparisons of Iron Sucrose Versus Sodium Ferric Gluconate Complex.

BACKGROUND: Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex. STUDY DESIGN: Retrospective cohort study of incident HD patients. SETTING & PARTICIPANTS: Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure. INTERVENTION: Facility-level use of iron sucrose versus ferric gluconate. OUTCOMES: Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths. MEASUREMENTS: HRs. RESULTS: We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96). LIMITATIONS: Unobserved selection bias from nonrandom treatment assignment. CONCLUSIONS: Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.

Use of Gene Expression Profiling and Chemotherapy in Early-Stage Breast Cancer: A Study of Linked Electronic Medical Records, Cancer Registry Data, and Genomic Data Across Two Health Care Systems.

PURPOSE: The 21-gene recurrence score (RS) identifies patients with breast cancer who derive little benefit from chemotherapy; it may reduce unwarranted variability in the use of chemotherapy. We tested whether the use of RS seems to guide chemotherapy receipt across different cancer care settings. METHODS: We developed a retrospective cohort of patients with breast cancer by using electronic medical record data from Stanford University (hereafter University) and Palo Alto Medical Foundation (hereafter Community) linked with demographic and staging data from the California Cancer Registry and RS results from the testing laboratory (Genomic Health Inc., Redwood City, CA). Multivariable analysis was performed to identify predictors of RS and chemotherapy use. RESULTS: In all, 10,125 patients with breast cancer were diagnosed in the University or Community systems from 2005 to 2011; 2,418 (23.9%) met RS guidelines criteria, of whom 15.6% received RS. RS was less often used for patients with involved lymph nodes, higher tumor grade, and age < 40 or ≥ 65 years. Among RS recipients, chemotherapy receipt was associated with a higher score (intermediate v low: odds ratio, 3.66; 95% CI, 1.94 to 6.91). A total of 293 patients (10.6%) received care in both health care systems (hereafter dual use); although receipt of RS was associated with dual use (v University: odds ratio, 1.73; 95% CI, 1.18 to 2.55), there was no difference in use of chemotherapy after RS by health care setting. CONCLUSION: Although there was greater use of RS for patients who sought care in more than one health care setting, use of chemotherapy followed RS guidance in University and Community health care systems. These results suggest that precision medicine may help optimize cancer treatment across health care settings.

Predicting advanced neoplasia at colonoscopy in a diverse population with the National Cancer Institute colorectal cancer risk-assessment tool.

BACKGROUND: Tailoring screening to colorectal cancer (CRC) risk could improve screening effectiveness. Most CRCs arise from advanced neoplasia (AN) that dwells for years. To date, no available colorectal neoplasia risk score has been validated externally in a diverse population. The authors explored whether the National Cancer Institute (NCI) CRC risk-assessment tool, which was developed to predict future CRC risk, could predict current AN prevalence in a diverse population, thereby allowing its use in risk stratification for screening. METHODS: This was a prospective examination of the relation between predicted 10-year CRC risk and the prevalence of AN, defined as advanced or multiple (≥3 adenomatous, ≥5 serrated) adenomatous or sessile serrated polyps, in individuals undergoing screening colonoscopy. RESULTS: Among 509 screenees (50% women; median age, 58 years; 61% white, 5% black, 10% Hispanic, and 24% Asian), 58 (11%) had AN. The prevalence of AN increased progressively from 6% in the lowest risk-score quintile to 17% in the highest risk-score quintile (P = .002). Risk-score distributions in individuals with versus without AN differed significantly (median, 1.38 [0.90-1.87] vs 1.02 [0.62-1.57], respectively; P = .003), with substantial overlap. The discriminatory accuracy of the tool was modest, with areas under the curve of 0.61 (95% confidence interval [CI], 0.54-0.69) overall, 0.59 (95% CI, 0.49-0.70) for women, and 0.63 (95% CI, 0.53-0.73) for men. The results did not change substantively when the analysis was restricted to adenomatous lesions or to screening procedures without any additional incidental indication. CONCLUSIONS: The NCI CRC risk-assessment tool displays modest discriminatory accuracy in predicting AN at screening colonoscopy in a diverse population. This tool may aid shared decision-making in clinical practice. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2663-2670. © 2016 American Cancer Society.

Multiple Imputation When Rate of Change is the Outcome of Interest.

Little research has been devoted to multiple imputation (MI) of derived variables. This study investigates various MI approaches for the outcome, rate of change, when the analysis model is a two-stage linear regression. Simulations showed that competitive approaches depended on the missing data mechanism and presence of auxiliary terms.

Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer.

INTRODUCTION: Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment. METHODS: We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS. RESULTS: We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013). CONCLUSIONS: CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross-sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS.

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients.

BACKGROUND: Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD). METHODS: Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)]. RESULTS: In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups. CONCLUSIONS: In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.

Longer-term outcomes of darbepoetin alfa versus epoetin alfa in patients with ESRD initiating hemodialysis: a quasi-experimental cohort study.

BACKGROUND: Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. STUDY DESIGN: Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO. SETTING & PARTICIPANTS: Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure. INTERVENTION: DPO versus EPO. OUTCOMES: All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. MEASUREMENTS: Unadjusted and adjusted HRs from Cox proportional hazards regression models. RESULTS: Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25). LIMITATIONS: Nonrandom treatment assignment, potential residual confounding. CONCLUSIONS: In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

Improving Antibiotic De-Escalation in Suspected Ventilator-Associated Pneumonia: An Observational Study With a Pharmacist-Driven Intervention.

BACKGROUND: Recommendations for treatment of ventilator-associated pneumonia (VAP) emphasize early empiric broad-spectrum antibiotics. However, appropriate antibiotic de-escalation is also critical for optimal patient care. MATERIALS AND METHODS: We examined how often intensivists in our institution appropriately de-escalated antibiotics in cases of suspected VAP, and whether decision support by intensive care unit pharmacists could improve rates of antibiotic targeting and early antibiotic discontinuation in low-risk patients. MAIN RESULTS: A total of 92 (observation phase = 50; intervention phase = 42) patients with suspected VAP were identified. During the observation phase, 39 cases yielded positive sputum cultures, but in only 23 (59%) were antibiotics targeted to culture results. This rate improved during the intervention phase when 29 (91%) of 32 cases with positive cultures were targeted (P value .003). There were 48 cases in which the risk of pneumonia was considered low. Of the 26 low-risk cases in the observation phase, 5 (19%) had antibiotics discontinued early versus 5 (23%) of the 22 cases in the intervention phase. CONCLUSIONS: Decision support by clinical pharmacists significantly improved rates of appropriate antibiotic targeting in cases of culture-positive suspected VAP but did not have a significant effect on early antibiotic discontinuation in patients at low risk of true pneumonia.

Heparin use in hemodialysis patients following gastrointestinal bleeding.

BACKGROUND: Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB. METHODS: We identified patients aged ≥ 67 who, from 2004-2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB. RESULTS: Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: -214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69-1.48; for recurrent GIB: 0.78; 0.39-1.57). CONCLUSIONS: The vast majority of these high-risk patients received heparin on the very first day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD.