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Three-dimensional (3D) printing is becoming an attractive technology for the design and development of personalized paediatric dosage forms with improved palatability. In this work micro-extrusion based printing was implemented for the fabrication of chewable paediatric ibuprofen (IBU) tablets by assessing a range of front runner polymers in taste masking. Due to the drug-polymer miscibility and the IBU plasticization effect, micro-extrusion was proved to be an ideal technology for processing the drug/polymer powder blends for the printing of paediatric dosage forms. The printed tablets presented high printing quality with reproducible layer thickness and a smooth surface. Due to the drug-polymer interactions induced during printing processing, IBU was found to form a glass solution confirmed by differential calorimetry (DSC) while H-bonding interactions were identified by confocal Raman mapping. IBU was also found to be uniformly distributed within the polymer matrices at molecular level. The tablet palatability was assessed by panellists and revealed excellent taste masking of the IBU's bitter taste. Overall micro-extrusion demonstrated promising processing capabilities of powder blends for rapid printing and development of personalised dosage forms.

Objectives Carbapenems are an important target for antimicrobial stewardship (AS) efforts. In this study, we sought to compare different hospital-based strategies for improving carbapenem use. Methods We analysed a cohort of all patients hospitalized at Veterans Health Administration (VHA) acute care hospitals during 2016 and a mandatory survey that characterized each hospital’s carbapenem-specific AS strategy into one of three types: no strategy (NS), prospective audit and feedback (PAF) or restrictive policies (RP). Carbapenem use was compared using risk-adjusted generalized estimating equations that accounted for clustering within hospitals. Two infectious disease (ID) physicians independently performed manual chart reviews in 425 randomly selected cases. Auditors assessed carbapenem appropriateness with an assessment score on Day 4 of therapy. Results There were 429 062 admissions in 90 sites (24 NS, 8 PAF, 58 RP). Carbapenem use was lower at PAF than NS sites [rate ratio (RR) 0.6 (95% CI 0.4–0.9); P = 0.01] but similar between RP and NS sites. Carbapenem prescribing was considered appropriate/acceptable in 215 (50.6%) of the reviewed cases. Assessment scores were lower (i.e. better) at RP than NS sites (mean 2.3 versus 2.7; P Conclusions In this VHA cohort, PAF strategies were associated with lower carbapenem use and ID consultation and RP strategies were associated with more appropriate carbapenem prescribing. AS and ID consultations may work complementarily and hospitals could leverage both to optimize carbapenem use.

Objectives Antimicrobial stewardship programmes have focused on reducing inappropriate inpatient antimicrobial prescribing, but several small studies have found a large portion of antimicrobial exposure occurs immediately after hospital discharge. In this study, we describe the prescribing of oral antimicrobials at hospital discharge across an integrated national healthcare system. At the hospital level, we also compare total inpatient antimicrobial use and post-discharge oral antimicrobial use. Methods This retrospective cross-sectional study used national administrative data to identify all acute-care admissions during 2014–2016 within the Veterans Health Administration (VHA). We evaluated inpatient days of therapy (DOT) and post-discharge DOT, defined as oral outpatient antimicrobials dispensed at the time of hospital discharge. At the hospital level, inpatient DOT/100 admissions were compared with post-discharge DOT/100 admissions using Spearman's rank-order correlation. Results There were 1 681 701 acute-care admissions across 122 hospitals, and 335 369 (19.9%) were prescribed an oral antimicrobial at discharge. Fluoroquinolones (38.3%) were the most common post-discharge antimicrobial. At the hospital level, median inpatient antimicrobial use was 331.3 (interquartile range (IQR) 284.9–367.9) DOT/100 admissions and median post-discharge use was 209.5 (IQR 181.5–239.6) DOT/100 admissions. Thirty-nine per cent of the total duration of antimicrobial exposure occurred after discharge. At the hospital-level, the metrics of inpatient DOT/100 admissions and post-discharge DOT/100 admissions were weakly positively correlated with rho=0.44 (p Conclusions A large proportion of antimicrobial exposure among hospitalized patients occurred immediately following discharge. Antimicrobial-prescribing at hospital discharge provides an opportunity for antimicrobial stewardship. Hospital-level stewardship metrics need to include both inpatient and post-discharge antimicrobial-prescribing to provide a comprehensive assessment of hospital-associated antimicrobial use.

Objective:To develop a fully automated algorithm using data from the Veterans’ Affairs (VA) electrical medical record (EMR) to identify deep-incisional surgical site infections (SSIs) after cardiac surgeries and total joint arthroplasties (TJAs) to be used for research studies.Design:Retrospective cohort study.Setting:This study was conducted in 11 VA hospitals.Participants:Patients who underwent coronary artery bypass grafting or valve replacement between January 1, 2010, and March 31, 2018 (cardiac cohort) and patients who underwent total hip arthroplasty or total knee arthroplasty between January 1, 2007, and March 31, 2018 (TJA cohort).Methods:Relevant clinical information and administrative code data were extracted from the EMR. The outcomes of interest were mediastinitis, endocarditis, or deep-incisional or organ-space SSI within 30 days after surgery. Multiple logistic regression analysis with a repeated regular bootstrap procedure was used to select variables and to assign points in the models. Sensitivities, specificities, positive predictive values (PPVs) and negative predictive values were calculated with comparison to outcomes collected by the Veterans’ Affairs Surgical Quality Improvement Program (VASQIP).Results:Overall, 49 (0.5%) of the 13,341 cardiac surgeries were classified as mediastinitis or endocarditis, and 83 (0.6%) of the 12,992 TJAs were classified as deep-incisional or organ-space SSIs. With at least 60% sensitivity, the PPVs of the SSI detection algorithms after cardiac surgeries and TJAs were 52.5% and 62.0%, respectively.Conclusions:Considering the low prevalence rate of SSIs, our algorithms were successful in identifying a majority of patients with a true SSI while simultaneously reducing false-positive cases. As a next step, validation of these algorithms in different hospital systems with EMR will be needed.

Objective:Assessments of antibiotic prescribing in ambulatory care have largely focused on viral acute respiratory infections (ARIs). It is unclear whether antibiotic prescribing for bacterial ARIs should also be a target for antibiotic stewardship efforts. In this study, we evaluated antibiotic prescribing for viral and potentially bacterial ARIs in patients seen at emergency departments (EDs) and urgent care centers (UCCs).Design:This retrospective cohort included all ED and UCC visits by patients who were not hospitalized and were seen during weekday, daytime hours during 2016–2018 in the Veterans Health Administration (VHA). Guideline concordance was evaluated for viral ARIs and for 3 potentially bacterial ARIs: acute exacerbation of COPD, pneumonia, and sinusitis.Results:There were 3,182,926 patient visits across 129 sites: 80.7% in EDs and 19.3% in UCCs. Mean patient age was 60.2 years, 89.4% were male, and 65.6% were white. Antibiotics were prescribed during 608,289 (19.1%) visits, including 42.7% with an inappropriate indication. For potentially bacterial ARIs, guideline-concordant management varied across clinicians (median, 36.2%; IQR, 26.0–52.7) and sites (median, 38.2%; IQR, 31.7–49.4). For viral ARIs, guideline-concordant management also varied across clinicians (median, 46.2%; IQR, 24.1–68.6) and sites (median, 40.0%; IQR, 30.4–59.3). At the clinician and site levels, we detected weak correlations between guideline-concordant management for viral ARIs and potentially bacterial ARIs: clinicians (r = 0.35; P = .0001) and sites (r = 0.44; P < .0001).Conclusions:Our findings suggest that, across EDs and UCCs within VHA, there are major opportunities to improve management of both viral and potentially bacterial ARIs. Some clinicians and sites are more frequently adhering to ARI guideline recommendations on antibiotic use.

We evaluated the relationship between local MRSA prevalence rates and antibiotic use across 122 VHA hospitals in 2016. Higher hospital-level MRSA prevalence was associated with significantly higher rates of antibiotic use, even after adjusting for case mix and stewardship strategies. Benchmarking anti-MRSA antibiotic use may need to adjust for MRSA prevalence.

In this single-center study, the standardized antimicrobial administration ratio (SAAR) for total antimicrobial use decreased in response to a stewardship intervention. Antimicrobial prescribing and clinical outcomes were stable or improved during the period of lower SAARs. Our findings suggest that SAAR values of ~0.8 can be safely achieved.

OBJECTIVEThe optimal approach to auditing outpatient antimicrobial prescribing has not been established. We assessed how different types of electronic data—including prescriptions, patient-visits, and International Classification of Disease, Tenth Revision (ICD-10) codes—could inform automated antimicrobial audits.DESIGNOutpatient visits during 2016 were retrospectively reviewed, including chart abstraction, if an antimicrobial was prescribed (cohort 1) or if the visit was associated with an infection-related ICD-10 code (cohort 2). Findings from cohorts 1 and 2 were compared.SETTINGPrimary care clinics and the emergency department (ED) at the Iowa City Veterans Affairs Medical Center.RESULTSIn cohort 1, we reviewed 2,353 antimicrobial prescriptions across 52 providers. ICD-10 codes had limited sensitivity and positive predictive value (PPV) for validated cases of cystitis and pneumonia (sensitivity, 65.8%, 56.3%, respectively; PPV, 74.4%, 52.5%, respectively). The volume-adjusted antimicrobial prescribing rate was 13.6 per 100 ED visits and 7.5 per 100 primary care visits. In cohort 2, antimicrobials were not indicated in 474 of 851 visits (55.7%). The antimicrobial overtreatment rate was 48.8% for the ED and 59.7% for primary care. At the level of the individual prescriber, there was a positive correlation between a provider’s volume-adjusted antimicrobial prescribing rate and the individualized rates of overtreatment in both the ED (r=0.72; PP=0.03).CONCLUSIONSIn this single-center study, ICD-10 codes had limited sensitivity and PPV for 2 infections that typically require antimicrobials. Electronically extracted data on a provider’s rate of volume-adjusted antimicrobial prescribing correlated with the frequency at which unnecessary antimicrobials were prescribed, but this may have been driven by outlier prescribers.Infect Control Hosp Epidemiol 2018;39:64–70

Trimethoprim/sulfamethoxazole (TMP/SMX) and clindamycin are frequently prescribed to treat cellulitis. The primary objective was to determine if weight-based dosing of these antibiotics is associated with better outcomes in cellulitis. The secondary objective was to assess variables associated with clinical failure among hospitalized patients with cellulitis with or without cutaneous abscess.This multi-center retrospective cohort study was conducted from January 1, 2010 to September 4, 2014. Adult patients admitted for cellulitis who received a minimum of seven days of therapy and discharged on oral clindamycin or TMP/SMX were included. Binary univariate and multivariate logistic regression analyses were performed to identify risk factors for clinical failure, including the impact of dose adequacy of clindamycin and TMP/SMX on clinical outcomes.A total of 208 cases met inclusion criteria. Of these cases, 120 (57.7%) received inadequate dosing of clindamycin (10 mg/kg/day) or TMP/SMX (5 mg TMP/kg per day) while 88 (42.3%) received adequate dosing. Clinical failure occurred in 36/120 (30%) and 15/88 (17%) of patients receiving inadequate and adequate doses, respectively (p = 0.032). Upon univariate analysis length of stay ≥ 7 days (OR = 2.96, p = 0.046) and inadequate dosing (OR = 2.09, p = 0.034) were associated with clinical failure. Upon multivariate analysis, inadequate dosing was independently associated with clinical failure (OR = 2.01, p = 0.032).Inadequate dosing of clindamycin and TMP/SMX is independently associated with clinical failure in patients hospitalized with cellulitis. Further prospective studies evaluating weight-based dosing of clindamycin and TMP/SMX in the setting of cellulitis are warranted.

Staphylococcus aureus bacteremia (SAB) is common and associated with poor long-term outcomes. Previous studies have demonstrated an association between infectious diseases (ID) consultation and improved short-term (ie, within 90 days) outcomes for patients with SAB, but associations with long-term outcomes are unknown.To investigate the association of ID consultation with long-term (ie, 5 years) postdischarge outcomes among patients with SAB.This cohort study included all patients (N = 31 002) with a first episode of SAB who were discharged alive from 116 acute care units of the nationwide Veterans Health Administration where ID consultation was offered. Data were collected from January 2003 to December 2014, with follow-up through September 30, 2018. Data analysis was conducted from February to December 2019.Infectious diseases consultation during the index hospital stay.The primary outcome was time to development of a composite event of all-cause mortality or recurrence of SAB within 5 years of discharge. As secondary outcomes, SAB recurrence and all-cause mortality with and without recurrence were analyzed while accounting for semicompeting risks.The cohort included 31 002 patients (30 265 [97.6%] men; median [interquartile range] age at SAB onset, 64.0 [57.0-75.0] years). Among 31 002 patients, there were 18 794 (60.6%) deaths, 4772 (15.4%) SAB recurrences, and 20 414 (65.8%) composite events during 5 years of follow-up; 12 773 deaths (68.0%) and 2268 recurrences (47.5%) occurred more than 90 days after discharge. Approximately half of patients (15 360 [49.5%]) received ID consultation during the index hospital stay; ID consultation was associated with prolonged improvement in the composite outcome (adjusted hazard ratio at 5 years, 0.71; 95% CI, 0.68-0.74; P .001). Infectious diseases consultation was also associated with improved outcomes when all-cause mortality without recurrence and SAB recurrence were analyzed separately (all-cause mortality without recurrence: adjusted hazard ratio at 5 years, 0.77; 95% CI, 0.74-0.81; P .001; SAB recurrence: adjusted hazard ratio at 5 years, 0.68; 95% CI, 0.64-0.72; P .001).Having an ID consultation during the index hospital stay among patients with SAB was associated with improved postdischarge outcomes for at least 5 years, suggesting that contributions of ID specialists to management during acute infection may have a substantial influence on long-term outcomes. Further investigations of the association of ID consultation with outcomes after S aureus should include long-term follow-up.

Background Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. Methods This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals’ antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. Results Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85–.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54–.70) and higher narrow-spectrum β-lactam use (1.43; 1.22–1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86–.99). Conclusions Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health care–associated infections in long-term care facilities (LTCFs). The Centers for Disease Control and Prevention recommends contact precautions for the prevention of MRSA within acute care facilities, which are being used within the United States Department of Veterans Affairs (VA) for LTCFs in a modified fashion. The impact of contact precautions in long-term care is unknown. Methods To evaluate whether contact precautions decreased MRSA acquisition in LTCFs, compared to standard precautions, we performed a retrospective effectiveness study (pre-post, with concurrent controls) using data from the VA health-care system from 1 January 2011 until 31 December 2015, 2 years before and after a 2013 policy recommending a more aggressive form of contact precautions. Results Across 75 414 patient admissions from 74 long-term care facilities in the United States, the overall unadjusted rate of MRSA acquisition was 2.6/1000 patient days. Patients were no more likely to acquire MRSA if they were cared for using standard precautions versus contact precautions in a multivariable, discrete time survival analysis, controlling for patient demographics, risk factors, and year of admission (odds ratio, 0.97; 95% confidence interval, .85–1.12; P = .71). Conclusions MRSA acquisition and infections were not impacted by the use of active surveillance and contact precautions in LTCFs in the VA.

In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.

Background Despite increasing awareness of harms, fluoroquinolones are still frequently prescribed to inpatients and at hospital discharge. Our goal was to describe fluoroquinolone prescribing at hospital discharge across the Veterans Health Administration (VHA) and to contrast the volume and appropriateness of fluoroquinolone prescribing across 3 antimicrobial stewardship strategy types. Methods We analyzed a retrospective cohort of patients hospitalized at 122 VHA acute-care hospitals during 2014–2016. Data from a mandatory VHA survey were used to identify 9 hospitals that self-reported 1 of 3 strategies for optimizing fluoroquinolone prescribing: prospective audit and feedback (PAF), restrictive policies (RP), and no strategy. Manual chart reviews to assess fluoroquinolone appropriateness at hospital discharge (ie, postdischarge) were performed across the 9 hospitals (3 hospitals and 125 cases per strategy type). Results There were 1.7 million patient admissions. Overall, there were 1 727 478 fluoroquinolone days of therapy (DOTs), with 674 918 (39.1%) DOTs prescribed for inpatients and 1 052 560 (60.9%) DOTs prescribed postdischarge. Among the 9 reviewed hospitals, postdischarge fluoroquinolone exposure was lower at hospitals using RP, compared to no strategy (3.8% vs 9.3%, respectively; P = .012). Postdischarge fluoroquinolones were deemed inappropriate in 154 of 375 (41.1%) patients. Fluoroquinolones were more likely to be inappropriate at hospitals without a strategy (52.8%) versus those using either RP or PAF (35.2%; P = .001). Conclusions In this retrospective cohort, the majority of fluoroquinolone DOTs occurred after hospital discharge. A large proportion of postdischarge fluoroquinolone prescriptions were inappropriate, especially in hospitals without a strategy to manage fluoroquinolone prescribing. Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial prescribing at hospital discharge.

Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions, however, limited throughput, high-costs, and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. To address these challenges, we have utilized a novel high-throughput transcriptomics (HTT) platform, TempO-Seq, to apply the interpretive power of concentration-response modeling with exposures to 24 reference compounds in both differentiated and non-differentiated human HepaRG cell cultures. Our goals were to (1) explore transcriptomic characteristics distinguishing liver injury compounds, (2) assess impacts of differentiation state of HepaRG cells on baseline and compound-induced responses (eg, metabolically-activated), and (3) identify and resolve reference biological-response pathways through benchmark concentration (BMC) modeling. Study data revealed the predictive utility of this approach to identify human liver injury compounds by their respective BMCs in relation to human internal exposure plasma concentrations, and effectively distinguished drug analogs with varied associations of human liver injury (eg, withdrawn therapeutics trovafloxacin and troglitazone). Impacts of cellular differentiation state (proliferated vs differentiated) were revealed on baseline drug metabolizing enzyme expression, hepatic receptor signaling, and responsiveness to metabolically-activated toxicants (eg, cyclophosphamide, benzo(a)pyrene, and aflatoxin B1). Finally, concentration-response modeling enabled efficient identification and resolution of plausibly-relevant biological-response pathways through their respective pathway-level BMCs. Taken together, these findings revealed HTT paired with differentiated in vitro liver models as an effective tool to model, explore, and interpret toxicological and pharmacological interactions.

This cohort study assesses the association of remdesivir treatment with 30-day survival and length of hospital stay among US veterans hospitalized with COVID-19 between May and October 2020., Key Points Question Is remdesivir treatment associated with improved survival or shortened hospitalizations among people with COVID-19 in routine care settings? Findings In this cohort study of 2344 US veterans hospitalized with COVID-19, remdesivir therapy was not associated with improved 30-day survival but was associated with a significant increase in median time to hospital discharge. Meaning The findings suggest that routine use of remdesivir may be associated with increased use of hospital beds but not with improvements in survival., Importance Randomized clinical trials have yielded conflicting results about the effects of remdesivir therapy on survival and length of hospital stay among people with COVID-19. Objective To examine associations between remdesivir treatment and survival and length of hospital stay among people hospitalized with COVID-19 in routine care settings. Design, Setting, and Participants This retrospective cohort study used data from the Veterans Health Administration (VHA) to identify adult patients in 123 VHA hospitals who had a first hospitalization with laboratory-confirmed COVID-19 from May 1 to October 8, 2020. Propensity score matching of patients initiating remdesivir treatment to control patients who had not initiated remdesivir treatment by the same hospital day was used to create the analytic cohort. Exposures Remdesivir treatment. Main Outcomes and Measures Time to death within 30 days of remdesivir treatment initiation (or corresponding hospital day for matched control individuals) and time to hospital discharge with time to death as a competing event. Associations between remdesivir treatment and these outcomes were assessed using Cox proportional hazards regression in the matched cohort. Results The initial cohort included 5898 patients admitted to 123 hospitals, 2374 (40.3%) of whom received remdesivir treatment (2238 men [94.3%]; mean [SD] age, 67.8 [12.8] years) and 3524 (59.7%) of whom never received remdesivir treatment (3302 men [93.7%]; mean [SD] age, 67.0 [14.4] years). After propensity score matching, the analysis included 1172 remdesivir recipients and 1172 controls, for a final matched cohort of 2344 individuals. Remdesivir recipients and matched controls were similar with regard to age (mean [SD], 66.6 [14.2] years vs 67.5 [14.1] years), sex (1101 men [93.9%] vs 1101 men [93.9%]), dexamethasone use (559 [47.7%] vs 559 [47.7%]), admission to the intensive care unit (242 [20.7%] vs 234 [19.1%]), and mechanical ventilation use (69 [5.9%] vs 45 [3.8%]). Standardized differences were less than 10% for all measures. Remdesivir treatment was not associated with 30-day mortality (143 remdesivir recipients [12.2%] vs 124 controls [10.6%]; log rank P = .26; adjusted hazard ratio [HR], 1.06; 95% CI, 0.83-1.36). Results were similar for people receiving vs not receiving dexamethasone at remdesivir initiation (dexamethasone recipients: adjusted HR, 0.93; 95% CI, 0.64-1.35; nonrecipients: adjusted HR, 1.19; 95% CI, 0.84-1.69). Remdesivir recipients had a longer median time to hospital discharge compared with matched controls (6 days [interquartile range, 4-12 days] vs 3 days [interquartile range, 1-7 days]; P

Purpose The question of whether publication of selected clinical trials is temporally followed by changes in prescribing of adjunctive lipid-lowering medications was evaluated. Methods In this retrospective preanalysis and postanalysis, Veterans Health Administration (VHA) patients 18 years or older who received a new or renewed order for any lipid-lowering medication between April 2, 2004, and September 2, 2014, were included. This period was chosen based on the publication dates of three trials investigating the efficacy of nonstatin medications: Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia (ENHANCE, April 3, 2008), Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid, March 14, 2010), and Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy (AIM-HIGH, December 15, 2011). Annual prescribing rates for ezetimibe, fibrates, and niacin were analyzed for 4 years before and after the ENHANCE, ACCORD, and AIM-HIGH trial publication dates, respectively (3 years for niacin in AIM-HIGH) and reported as percent of patients in the cohort. Results Among patients receiving lipid-lowering medications, relatively low overall prescribing rates were observed for all three target medications. Prescribing rates for each medication decreased after its respective trial publication, with ezetimibe having the greatest change. Conclusion Prescribing of fibrates, niacin, and ezetimibe in the VHA system decreased after the publication of landmark trials assessing their addition to a statin, consistent with the recommendations in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, which did not encourage routine use of adjunctive therapies to lower the risk of cardiovascular disease.

Context.—Previous studies suggest that training in pathology residency programs does not adequately prepare pathology residents to become competent in clinical chemistry.Objectives.—To define the beliefs of pathology residents in the United States regarding their preparation for practicing clinical chemistry in their career, their attitude toward the discipline, and the attractiveness of clinical chemistry as a career.Design.—The residents of all pathology residency programs in the United States were given the opportunity to participate in an online survey.Results.—Three hundred thirty-six pathology residents responded to the survey. Analysis of the survey results indicates that pathology residents are more likely to believe that their income may be lower if they select a career that has a clinical chemistry focus and that their faculty do not value clinical chemistry as much as the anatomic pathology part of the residency. Residents also report that clinical chemistry is not as enjoyable as anatomic pathology rotations during residency or preferable as a sole career path. A large proportion of residents also believe that they will be slightly prepared or not prepared to practice clinical chemistry by the end of their residency and that they do not have enough background and/or time to learn clinical chemistry during their residency programs to be able to practice this specialty effectively post graduation.Conclusions.—Our survey results suggest that many pathology residents do not have a positive attitude toward clinical chemistry and do not experience a supportive learning environment with an expectation that they will become competent in clinical chemistry with a residency alone.

BACKGROUND The Veterans Health Administration (VHA) introduced the Methicillin-Resistant Staphylococcus aureus (MRSA) Prevention Initiative in March 2007. Although the initiative has been perceived as a vertical intervention focusing on MRSA, it also expanded infection prevention and control programs and resources. We aimed to assess the horizontal effect of the initiative on hospital-onset (HO) gram-negative rod (GNR) bacteremia. METHODS This retrospective cohort included all patients who had HO bacteremia due to Escherichia coli, Klebsiella species, or Pseudomonas aeruginosa at 130 VHA facilities from January 2003 to December 2013. The effects were assessed using segmented linear regression with autoregressive error models, incorporating autocorrelation, immediate effect, and time before and after the initiative. Community-acquired (CA) bacteremia with same species was also analyzed as nonequivalent dependent controls. RESULTS A total of 11 196 patients experienced HO-GNR bacteremia during the study period. There was a significant change of slope in HO-GNR bacteremia incidence rates from before the initiative (+0.3%/month) to after (-0.4%/month) (P < .01), while CA GNR incidence rates did not significantly change (P = .08). Cumulative effect of the intervention on HO-GNR bacteremia incidence rates at the end of the study period was estimated to be -43.2% (95% confidence interval, -51.6% to -32.4%). Similar effects were observed in subgroup analyses of each species and antimicrobial susceptibility profile. CONCLUSIONS Within 130 VHA facilities, there was a sustained decline in HO-GNR bacteremia incidence rates after the implementation of the MRSA Prevention Initiative. As these organisms were not specifically targeted, it is likely that horizontal components of the initiative contributed to this decline.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with poor prognosis and limited therapeutic options. The 2011 ATS/ERS/JRS/ALAT consensus statement provided a number of recommendations for the management of IPF patients. The primary objective of this study was to determine if "bundling" these recommendations in the management of patients with IPF impacts clinical outcomes. Methods We conducted a single center, retrospective cohort study of 284 patients diagnosed with IPF. The proposed bundle of care (BOC) components were: (1) visits to a specialized interstitial lung diseases clinic with evaluation of pulmonary function tests at least twice yearly; (2) referral to pulmonary rehabilitation yearly; (3) timed walk test yearly; (4) echocardiogram yearly; and (5) gastroesophageal reflux therapy. Each component of the BOC was given a score of "1" per year of follow up, and the average sum of the scores (ranging from 0 to 5) was determined for the entire period of follow-up (BOC S ), as well as during the first year of follow-up (BOC Y1 ). The primary outcome measure was transplant-free survival. Results Age, gender, smoking status, BMI, %FVC, %D L CO did not differ between levels of BOC S and BOC Y1 . Lowest BOC S (≤1) was associated with a lower transplant-free survival independent of age and %FVC compared to patients with the highest BOC S (>4) (HR 2.274, CI 1.12–4.64, p = 0.024). Lower BOC Y1 was associated with a higher risk for transplant or death independent of age and %FVC in comparison to patients with highest BOC Y1 (≤1 vs. >4, HR 2.23, p = 0.014; >1 to 2 vs. >4, HR 1.87, p = 0.011; >2 to 3 vs. >4, HR 1.72, p = 0.019). Conclusion IPF patients with higher BOC scores had improved transplant-free survival. Prospective studies are needed to confirm these findings and determine the best strategies for the management of patients with IPF.

Background: Topiramate has been associated with metabolic acidosis secondary to decreased serum bicarbonate. Product labeling recommends serum bicarbonate monitoring at baseline and periodically thereafter. Objective: The study objective was to assess changes in serum bicarbonate within the first year of topiramate use in an outpatient veteran population. Methods: This was a single-center, retrospective study conducted at the Iowa City Veterans Affairs Health Care System. Inclusion criteria required a minimum of 1 topiramate outpatient prescription between October 1, 1999, and August 31, 2012, and at least 1 serum bicarbonate level within 12 months prior to topiramate initiation. Patients with topiramate nonadherence, concurrent use of sodium bicarbonate or oral carbonic anhydrase inhibitors, and individual serum bicarbonate values obtained during inpatient hospitalizations were excluded. Change in bicarbonate was evaluated using a paired t test. Decreases in bicarbonate of ≥5 mEq/L, values

Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the Veterans Health Administration (VHA), and dissemination patterns of innovative, efficacious therapies can inform areas for potential improvement of diffusion efforts and quality prescribing. In this study, we replicated a prior examination of the period prevalence of prazosin use as a function of distance from Puget Sound, Washington, where prazosin was first tested as an effective treatment for PTSD and where prazosin use was previously shown to be much greater than in other parts of the United States. We tested the following three hypotheses related to prazosin geographic diffusion: (1) a positive geographical correlation exists between the distance from Puget Sound and the proportion of users treated according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d), (2) an inverse geographic correlation exists between prazosin and benzodiazepine use, and (3) no geographical correlation exists between prazosin use and serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%, whereas utilization rates at locations a minimum of 2,500 miles away increased from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the Puget Sound location. In contrast, at distances of at least 2,500 miles from Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to 17.7%). No discernible association was demonstrated between SSRI/SNRI or benzodiazepine utilization and the geographic distance from Puget Sound. Minimal threshold dosing of prazosin correlated positively with increased diffusion of prazosin use, but there was still a distance diffusion gradient. Although prazosin adoption has improved, geographic differences persist in both prescribing rates and minimum target dosing. Importantly, these regional disparities appear to be limited to prazosin prescribing and are not meaningfully correlated with SSRI/SNRI and benzodiazepine use as indicators of PTSD prescribing quality.

Bacteremia caused by gram-negative bacteria is associated with serious illness and death, and emergence of antimicrobial drug resistance in these bacteria is a major concern. Using national microbiology and patient data for 2003–2013 from the US Veterans Health Administration, we characterized nonsusceptibility trends of community-acquired, community-onset; healthcare-associated, community-onset; and hospital-onset bacteremia for selected gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter spp.). For 47,746 episodes of bacteremia, the incidence rate was 6.37 episodes/10,000 person-years for community-onset bacteremia and 4.53 episodes/10,000 patient-days for hospital-onset bacteremia. For Klebsiella spp., P. aeruginosa, and Acinetobacter spp., we observed a decreasing proportion of nonsusceptibility across nearly all antimicrobial drug classes for patients with healthcare exposure; trends for community-acquired, community-onset isolates were stable or increasing. The role of infection control and antimicrobial stewardship efforts in inpatient settings in the decrease in drug resistance rates for hospital-onset isolates needs to be determined.

We investigated the frequency and determinants of guideline-discordant antibiotic prescribing in outpatients with respiratory infections or cystitis. Antibiotic prescribing was guideline discordant in 60% of patients. The most common reason for discordance was prescribing an antibiotic when not indicated. In a multivariate analysis, physicians in training had the highest likelihood of guideline-concordant antibiotic prescribing. Infect Control Hosp Epidemiol 2017;38:724–728

Pluripotent stem cells offer unprecedented potential not only for human medicine but also for veterinary medicine, particularly in relation to the horse. Induced pluripotent stem cells (iPSCs) are particularly promising, as they are functionally similar to embryonic stem cells and can be generated in vitro in a patient-specific manner. In this study, we report the generation of equine iPSCs from skin fibroblasts obtained from a foal and reprogrammed using viral vectors coding for murine Oct4, Sox2, c-Myc, and Klf4 sequences. The reprogrammed cell lines were morphologically similar to iPSCs reported from other species and could be stably maintained over more than 30 passages. Immunostaining and polymerase chain reaction analyses revealed that these cell lines expressed an array of endogenous markers associated with pluripotency, including OCT4, SOX2, NANOG, REX1, LIN28, SSEA1, SSEA4, and TRA1-60. Furthermore, under the appropriate conditions, the equine iPSCs readily formed embryoid bodies and differentiated in vitro into cells expressing markers of ectoderm, mesoderm, and endoderm, and when injected into immunodeficient mice, gave raise to tumors containing differentiated derivatives of the 3 germ layers. Finally, we also reprogrammed fibroblasts from a 2-year-old horse. The reprogrammed cells were similar to iPSCs derived from neonatal fibroblasts in terms of morphology, expression of pluripotency markers, and differentiation ability. The generation of these novel cell lines constitutes an important step toward the understanding of pluripotency in the horse, and paves the way for iPSC technology to potentially become a powerful research and clinical tool in veterinary biomedicine.

Approximately 8 million health care workers are unnecessarily exposed to highly toxic drugs used to treat cancer; antineoplastic drugs can contribute to negative health effects for these workers. The drugs have been detected in the urine of workers and on the floors and counters of worksites. Safety precautions that could reduce the risk of exposure are underutilized. This cross-sectional study of 163 oncology health care workers used a survey to measure workplace and individual factors, and environmental sampling to measure surface contamination. The study objective was to identify potential exposures to antineoplastic drugs and factors influencing safety behavior. Personal protective equipment (PPE) use was lower than recommended; unit of employment was significantly associated with PPE use. Chemical residue from antineoplastic drugs was found, revealing potential exposures. Workplace safety must be a higher organizational priority. The contamination of common work areas where PPE use is not expected was of utmost concern.

Nine classes of glucose-lowering agents (GLAs) are available for patients with type 2 diabetes prior to starting insulin. This study's aim was to determine if the number of GLAs is associated with a difference in glycated hemoglobin (A1C) at insulin initiation in the US Department of Veterans Affairs Health Care System (VAHCS).Retrospective cohort study.A retrospective cohort with national Veterans Health Administration data was created. Veterans with type 2 diabetes and first insulin prescription filled in the VAHCS between January 1, 2009, and August 28, 2013, were identified. Included veterans refilled insulin within the first year, had an A1C7% (53 mmol/mol) at least 60 days prior to insulin initiation, and received a GLA within 6 months prior to insulin. Veterans were grouped into 4 cohorts according to the number of GLAs used.A total of 90,497 veterans with type 2 diabetes met inclusion criteria. Insulin was initiated at a mean A1C of 9.9% (85 mmol/mol). The mean A1Cs prior to insulin for 1, 2, 3, or3 GLAs were 10.3% (89 mmol/mol), 9.9% (85 mmol/mol), 9.6% (81 mmol/mol), and 9.6% (81 mmol/mol), respectively. Months to insulin increased with the number of GLA trials and prolonged the time veterans were exposed to A1C8% (64 mmol/mol).Multiple glucose-lowering drug classes are associated with a numerical, but not a clinical, difference in A1C at insulin initiation in the closed formulary of the VAHCS.

Summary Graduate medical education of pathologists has undergone considerable changes since 2006. The “Outcome Project” and reduction of basic anatomic pathology/clinical pathology training to 4 years are major changes. With implementation of the 80-hour week, it now takes 16 000 hours to train a pathologist who is competent to sit for the American Board of Pathology examination and practice independently. Reduction of the training time from 5 to 4 years has produced a perception (or reality) of mandatory fellowships. Changes are discussed, and trends are updated. Recent data is compared with data reported by the author in 2001 and 2006, and is updated through 2010.

Changes in atmospheric pressure may influence hepatic blood flow and drug metabolism. Anecdotal experience suggests international normalized ratio (INR) variability may be temporally related to significant atmospheric pressure changes. We investigated this potential association in a large sample of patients with multiple INRs. This is a retrospective review of outpatient anticoagulation records from the Iowa City Veteran's Affairs Medical Center and affiliated outpatient clinics from October 1999 to July 2007. All patients, receiving at least one prescription for warfarin and INR at least 30 days or more from the date of the first warfarin prescription, were identified. INRs during periods of hospitalization and vitamin K use were excluded. Proximity analysis using geocoding of ZIP codes of identified patients to the nearest National Oceanic and Atmospheric Administration station was performed to assign atmospheric pressure with INR. Spearman's Rho and Pearson's correlation were used to evaluate atmospheric pressure and INR. Unique patients (1441) with 45 187 INRs were analyzed. When limited to nontherapeutic INRs following a previously therapeutic INR (1121 unique patients/5256 INRs), a small but clinically insignificant association between delta INR and delta atmospheric pressure was observed (r = -0.025; P = 0.038), but not for actual INR and atmospheric pressure (P = 0.06). Delta atmospheric pressure demonstrated greater variation during fall/winter months compared with spring/summer (0.23 vs. 0.15 inHg; P < 0.001); however, variability in INRs for the corresponding seasons was not significant (P = 0.136). No significant difference was detected in the proportions of nontherapeutic INRs among the different seasons (P = 0.371). No correlation was observed between atmospheric pressure changes and INR variability. These findings refute the anecdotal experience seen in our anticoagulation clinic.

The phlebotomine sand fly Lutzomyia longipalpis takes blood from a variety of wild and domestic animals and transmits Leishmania (Leishmania) infantum chagasi, etiological agent of American visceral leishmaniasis. Blood meal identification in sand flies has depended largely on serological methods but a new protocol described here uses filter-based technology to stabilise and store blood meal DNA, allowing subsequent PCR identification of blood meal sources, as well as parasite detection, in blood-fed sand flies. This technique revealed that 53.6% of field-collected sand flies captured in the back yards of houses in Teresina (Brazil) had fed on chickens. The potential applications of this technique in epidemiological studies and strategic planning for leishmaniasis control programmes are discussed.

Purpose Extension for Community Health Outcomes (ECHO) is a provider-level telemedicine model successfully applied to hepatitis C care, but little is known about its application to Human Immunodeficiency Virus (HIV) care. We performed a mixed-methods evaluation of 3 HIV ECHO programs in the Veterans Health Administration, focusing on uptake by primary care clinics and veterans. Methods Administrative data were used to assess program uptake, including adoption (ie, proportion of primary care clinics participating) and reach (ie, proportion of eligible veterans participating). Veterans were considered eligible if they had an HIV diagnosis and lived nearer to a primary care clinic than to the HIV specialty clinic. We interviewed 31 HIV specialists, primary care providers (PCPs), and administrators engaged in HIV ECHO, and we analyzed interview transcripts to identify factors that influenced program adoption and reach. Findings Nine (43%) of 21 primary care clinics adopted HIV ECHO (range 33%-67% across sites). Program reach was limited, with 47 (6.1%) of 776 eligible veterans participating. Reach was similar among rural and urban veterans (5.3% vs 6.3%). In interviews, limited adoption and reach were attributed partly to: (1) a sense of “HIV exceptionalism” that complicated shifting ownership of care from HIV specialists to PCPs, and (2) low HIV prevalence and long treatment cycles that prevented rapid learning loops for PCPs. Conclusions There was limited uptake of HIV ECHO telemedicine programs in settings where veterans historically traveled to distant specialty clinics. Other telemedicine models should be considered for HIV care.

SummaryConsumer-mediated health information exchange (HIE) is one of the three types of HIE designated by the Office of the National Coordinator. HIE is intended to improve the quality of care while reducing cost, yet empirical support for this claim is mixed. Future research should identify the contexts whereby HIE is most effective.This study was conducted as a pilot two-arm randomized controlled trial. In the intervention arm, 27 veterans were taught how to generate a Continuity of Care Document (CCD) within the Blue Button feature of their VA patient portal and were then asked to share it with their community non-VA provider. In the attention control condition, 25 Veterans were taught how to look up health information on the Internet. The impact of this training on the next non-VA medical visit was examined.Nineteen (90%) veterans in the intervention arm shared their CCD with their non-VA provider as compared with 2 (17%) in the attention control arm (pIn this pilot randomized controlled trial, training 52 veterans to share their CCD was feasible and accepted by both patients and providers. Sharing this document appeared to reduce duplicate laboratory draws, but did not have an impact on documented medication list concordance. Citation: Turvey CL, Klein DM, Witry M, Klutts JS, Hill EL, Alexander B, Nazi KM. Patient education for consumer-mediated HIE: A pilot randomized controlled trial of the Department of Veterans Affairs Blue Button.

It is expected that the role of the clinical pathologist will evolve from the more passive role of managing testing facilities to one of active service provider, using powerful molecular, cell biologic, and biochemical tools. The scope of knowledge required to be an effective physician scientist or an accomplished practicing clinical pathologist, however, cannot be acquired through clinical training alone and requires dedicated, structured research learning time. The goal of this article is to consider mechanisms that effectively integrate research training and scholarly activity into residency education in laboratory medicine/clinical pathology. The proposed curricula are purposely unstructured to allow maximum flexibility for training programs to meet the needs and career goals of individual residents.

Routine monitoring of an 81-year-old man receiving treatment with nortriptyline for generalized anxiety disorder and depression revealed plasma concentrations of both amitriptyline and nortriptyline. In humans, the tricyclic antidepressant (TCA) tertiary amines imipramine and amitriptyline are typically metabolized by demethylation to the secondary active metabolites desipramine and nortriptyline, respectively. However, to our knowledge, methylation of secondary amine TCAs has been reported in only one case report of nortriptyline overdose and in two studies involving desipramine. In a retrospective analysis of patients from five Veterans Affairs medical centers, the rate of methylation of desipramine and nortriptyline was 8.9 % (five of 56 patients) and 14.6% (36 of 247), respectively. Possible explanations for methylation include genetic polymorphisms in cytochrome P450 metabolizing enzymes, polymorphism of amine N-methyltransferase enzyme, drug-drug interactions, smoking, and alcohol consumption. However, the mechanism by which methylation occurs is unclear and warrants further investigation. Awareness of the phenomenon could help in discouraging repeated laboratory tests and unnecessary adjustments of drug therapies, resulting in cost savings and better patient outcomes.

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.

Study Objective. As patients with a major psychiatric disorder such as schizophrenia generally are less likely to have their medical illnesses diagnosed and medically managed, we investigated whether osteoporosis screening, prevention management, and/or drug therapy (i.e., clinical services for osteoporosis) are provided consistently to both women with schizophrenia and those without the disease. Design. Retrospective medical record review. Setting. Three Midwest Veterans Affairs medical centers and clinics. Patients. Forty-six women aged 45 years or older who had schizophrenia and 46 female control subjects who were frequency matched on age. Measurements and Main Results. Twelve months of progress notes were reviewed for osteoporosis clinical services. In addition, smoking status, smoking cessation counseling, alcohol consumption, and fracture rates were compared between the groups. Overall, significantly fewer patients with schizophrenia (28 patients [61%]) received a clinical service for osteoporosis compared with the control group (37 patients [80%]). This difference was due to a significantly fewer number of patients with schizophrenia who received any osteoporosis agent (22 patients [48%]) compared with the control group (36 patients [78%]). Only 13 patients (28%) with schizophrenia received hormone replacement therapy compared with 25 control patients (54%). Conclusion. Women with schizophrenia in three Midwest Veterans Affairs medical centers did not receive the same level of osteoporosis care as that of age-matched control patients. This was primarily due to a lower utilization of osteoporosis agents, specifically hormone replacement therapy. Further research is necessary to determine the reason for this difference. Clinicians should be aware of medical management issues in patients with major psychiatric diagnoses and, specifically, osteoporosis care of women with schizophrenia.

In a zoonotic visceral leishmaniasis (ZVL)-endemic area in Brazil, deltamethrin-impregnated collars (DMC) were fitted to 136 dogs for 5 months and significantly reduced the odds of increasing their anti-Leishmania antibody titer during this period by 50% (95% confidence interval 29-87%, P=0.01), as compared with a population of 97 uncollared dogs with pre-intervention prevalence within the same town. Mathematical modeling suggests that under typical Brazilian ZVL-endemic conditions, the epidemiological impact of community-wide DMC application should be greater than the currently practiced dog culling strategy, but that its impact will be dependent on collar coverage and loss rate. Both interventions should have a higher proportional impact in regions of lower endemicity, but the relative advantage of DMC over culling increases with transmission rate. Sensitivity analyses indicate that the impact of either intervention is not significantly affected by variation in the biology of the sandfly vector, but is greatly influenced by variation in dog mortality and serorecovery rates.

Background: No effective therapy is currently available for the diffuse stage of bronchioloalveolar carcinoma. Objective: We tested the hypothesis that total lung replacement with standard lung transplantation techniques would provide curative therapy. Methods: Nine patients aged 31 to 58 years with bronchioloalveolar carcinoma were entered in the study. Five patients initially had bilateral diffuse tumor. Four patients had recurrence in the contralateral lung after pulmonary resection. Results: Between 1993 and 1998, all 9 patients underwent transplantation (2 single-lung and 7 bilateral transplants, 1 reoperative single-lung transplant, and 1 reoperative bilateral transplant). Two patients had mediastinal node metastasis (level 7) at the time of transplantation, and 1 of these had a frankly invasive adenocarcinoma. Of the 8 patients with pure bronchioloalveolar carcinoma, 6 had recurrent pulmonary tumor after transplantation. In 2 of these patients the tumor was localized and could be resected with left lower lobectomy in one case and left pneumonectomy in the other. One is alive 89 months after transplantation; the other died 82 months after transplantation. Four other patients had a diffuse pattern of pulmonary recurrence. Two died of progressive pulmonary failure; 1 of these had retransplantation with recurrence. A third patient died of cerebral edema shortly after bilateral retransplantation. The other patient is alive with recurrence 39 months after transplantation and has bronchiolitis obliterans. Two patients without recurrence are well with unrestricted performance levels 87 and 76 months after transplantation. Conclusions: Transplantation produces a powerful palliative outcome in patients with advanced bronchioloalveolar carcinoma, but the recurrence rate is high. Transplantation for this indication remains controversial. J Thorac Cardiovasc Surg 2003;125:45-8

OBJECTIVETo identify important risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) to assist clinicians in identifying high-risk patients for continued surveillance and follow-up.METHODSIn this retrospective cohort study, we examined patients with MRSA bacteremia at 122 Veterans Affairs medical facilities from January 1, 2003, through December 31, 2010. Recurrent MRSA bacteremia was identified by a positive blood culture result from 2 to 180 days after index hospitalization discharge. Subset analyses were performed to evaluate risk factors for early-onset (2–60 days after discharge) and late-onset (61–180 days after discharge) recurrence. Risk factors were evaluated using Cox proportional hazards regression.RESULTSOf 18,425 patients, 1,159 (6.3%) had recurrent MRSA bacteremia. The median time to recurrence was 63 days. Longer duration of index bacteremia, increased severity of illness, receipt of only vancomycin, community-acquired infection, and several comorbidities were risk factors for recurrence. Congestive heart failure, hypertension, and rheumatoid arthritis/collagen disease were risk factors for early-onset but not late-onset recurrence. Geographic region and cardiac arrhythmias were risk factors for late-onset but not early-onset recurrence.CONCLUSIONSRisk factors for recurrent MRSA bacteremia included comorbidities, severity of illness, duration of bacteremia, and receipt of only vancomycin. Awareness of risk factors may be important at patient discharge for implementation of quality improvement initiatives including surveillance, follow-up, and education for high-risk patients.Infect Control Hosp Epidemiol 2015;00(0): 1–7

To the Editor.—Long QT syndrome (LQTS) is one of several inherited genetically heterogeneous cardiac channelopathies (CCs) that are the cause for as many as 35% of sudden unexplained cardiac death (SUD) cases 1 and 7% of cases of sudden infant death syndrome. 2 Postmortem genetic testing in SUD can identify a CC mutation in 35% of cases. While this makes no difference to the patient, it has major significance to biologic relatives, as each first-degree relative is at increased risk for carrying a mutation, and therefore for SUD. Genetic testing is the only definitive method to determine if they are at risk. 3 In practice, genetic testing in SUD has been shown to have substantial benefit in 1 study 1 in which 28% of asymptomatic first-degree relatives tested were found to have the LQTS mutation. It has been suggested that genetic testing for CCs become standard of care. 4 However, barriers exist. One is cost, but just as significant is the ability of the medical examiner (ME) to order the right test and communicate the results to the family of the deceased person. To explore this we surveyed the ME community by using the National Medical Examiners’ listserv through the National Association of Medical Examiners to determine their knowledge of LQTS and other CCs, their perceived utility and availability of genetic testing, and their protocol for counseling of families. The study was approved by the Institutional Review Board of the University of Alabama at Birmingham. Of the 48 respondents to the 23question survey, 79% identified themselves as MEs and 46% as MDs. Most (87%) had no additional training in genetics and those that did report genetics training received this during residency rotations. The vast majority knew of genetic testing for CCs (97%) from a variety of sources: journals (85%), conferences (83%), colleagues (62%), medical school education (17%), and other sources (24%) including advertisements from commercial genetic testing companies. Almost all (98%) consider LQTS and other genetic CCs in SUD. Many reported that they investigated this possibility further by eliciting a family history (73%), genetic testing (29%), or through other methods such as referring patient’s families to geneticists or cardiologists, saving pathology specimens, consulting local geneticists, or reviewing past medical records. However, 60% reported never ordering the genetic test, with cost being the barrier (98%). Most (72%) reported personally counseling families about LQTS, but only 18% knew that these conditions are overwhelmingly inherited (as opposed to de novo mutations), and only 29% knew that they are autosomal dominant. More importantly, only 9% knew that a mutation will be identified in 35% of SUD cases; 55% believed it was less than 5%. Only 39% knew the risk to first-degree family members. This study has obvious limitations, with a small number of respondents.

To examine the impact of rural residence and primary care site on use of clinical pharmacy services (CPS) and to describe the use of clinical telepharmacy within the Veterans Health Administration (VHA) health care system.Using 2011 national VHA data, the frequency of patients with CPS encounters was compared across patient residence (urban or rural) and principal site of primary care (medical center, urban clinic, or rural clinic). The likelihood of CPS utilization was estimated with random effects logistic regression. Individual service types (e.g., anticoagulation clinics) and delivery modes (e.g., telehealth) were also examined.Of 3,040,635 patients, 711,348 (23.4%) received CPS. Service use varied by patient residence (urban: 24.9%; rural: 19.7%) and principal site of primary care (medical center: 25.9%; urban clinic: 22.5%; rural clinic: 17.6%). However, in adjusted analyses, urban-rural differences were explained primarily by primary care site and less so by patient residence. Similar findings were observed for individual CPS types. Telehealth encounters were common, accounting for nearly one-half of patients receiving CPS. Video telehealth was infrequent (0.2%), but more common among patients of rural clinics than those receiving CPS at medical centers (odds ratio [OR] = 9.7; 95% CI 9.0-10.5).We identified a potential disparity between rural and urban patients' access to CPS, which was largely explained by greater reliance on community clinics for primary care than on medical centers. Future research is needed to determine if this disparity will be alleviated by emerging organizational changes, including expanding telehealth capacity and integrating pharmacists into primary care teams, and whether lessons learned at VHA translate to other settings.

In the late 1990s, the Accreditation Council for Graduate Medical Education developed the Outcomes Project and the 6 general competencies with the intent to improve the outcome of graduate medical education in the United States. The competencies were used as the basis for developing learning goals and objectives and tools to evaluate residents' performance. By the mid-2000s the stakeholders in resident education and the general public felt that the Outcomes Project had fallen short of expectations.To develop a new evaluation method to track trainee progress throughout residency using benchmarks called milestones. A change in leadership at the Accreditation Council for Graduate Medical Education brought a new vision for the accreditation of training programs and a radically different approach to the evaluation of residents.The Pathology Milestones Working Group reviewed examples of developing milestones in other specialties, the literature, and the Accreditation Council for Graduate Medical Education program requirements for pathology to develop pathology milestones. The pathology milestones are a set of objective descriptors for measuring progress in the development of competency in patient care, procedural skill sets, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice.The milestones provide a national standard for evaluation that will be used for the assessment of all residents in Accreditation Council for Graduate Medical Education-accredited pathology training programs.

Eleven populations of Lutzomyia longipalpis (Lutz & Neiva), the sand fly vector of Leishmania chagasi, from different areas of Brazil were analyzed for genetic variation at 16 enzyme loci. In this region, the prevalence of visceral leishmaniasis (VL) caused by L. chagasi is spotty and reproductive isolation among populations of Lu. longipalpis has been reported. It is thought that morphologically similar cryptic species with varying vectorial capacity may be responsible for the discontinuous distribution of VL. The aim was to study the genetic structure of populations within this region and to identify demes that may represent sibling species. Genotypic frequencies within populations were in close compliance to Hardy-Weinberg expectations, suggesting there are no sympatric species among these 11 populations. Levels of genetic distance between pairs of populations were very low (< 0.03), consistent with local populations within a single sand fly species. When genotypic frequency data for all populations were pooled, 9 of the 13 polymorphic loci deviated from Hardy-Weinberg expectations, indicating some degree of genetic substructuring. Estimates of effective migration rates (N(e)m) among all populations were low, 2.73, suggesting that gene flow is restricted among populations, which is probably the reason for the observed genetic substructuring.

Posttraumatic stress disorder (PTSD) treatment is often complicated in veterans by co-occurring conditions including pain, insomnia, brain injury, and other mental disorders. Pharmacologic approaches to these conditions can produce an accumulation of sedating medications with potential for safety concerns.The objective of this study was to characterize polysedative prescribing among veterans with PTSD over an 8-year period.National Department of Veterans Affairs (VA) data were used to identify veterans with PTSD using International Classification of Diseases, Ninth Revision codes among regular medication users. Prescribing of benzodiazepines, hypnotics, atypical antipsychotics, opioids, and muscle relaxants was determined annually. Prevalence and incidence rates were determined for each medication class from 2004 through 2011. Polysedative use was determined from longitudinal refill patterns that indicated concurrent use across sedative classes.In 2004, 9.8% of veterans with PTSD concurrently received medications from three or more sedative classes. By 2011, the prevalence of concurrent use involving three or more classes increased to 12.1%. Polysedative use varied across demographic subgroups, with higher rates observed among women, rural residents, younger adults, Native Americans and Whites. The most common combination was an opioid plus a benzodiazepine, taken concurrently by 15.9% of veterans with PTSD.Important trends in polysedative use among veterans with PTSD illustrate the complexity of treating an intersecting cluster of symptoms managed by sedative medications. As the VA seeks to improve care by focusing on non-pharmacologic options, our findings emphasize the need for a comprehensive approach that encompasses overlapping conditions of relevance to veterans with PTSD.

Results of prior pathology workforce surveys have varied between a state of equilibrium and predictions of shortage.To assess the current and future supply of pathologists, and apply a dynamic modeling tool for assessing the effects of changing market forces and emerging technologies on the supply of pathologists' services through 2030.Data came from various sources, including the literature, College of American Pathologists' internal data, and primary research through custom-developed surveys for the membership and for pathology practice managersThrough 2010, there were approximately 18 000 actively practicing pathologists in the United States (5.7 per 100 000 population), approximately 93% of whom were board certified. Our model projects that the absolute and per capita numbers of practicing pathologists will decrease to approximately 14 000 full-time equivalent (FTE) pathologists or 3.7 per 100 000 in the coming 2 decades. This projection reflects that beginning in 2015, the numbers of pathologists retiring will increase precipitously, and is anticipated to peak by 2021. Including all types of separation, the net pathologist strength will begin falling by year 2015. Unless workforce entry or exit rates change, this trend will continue at least through 2030. These changes reflect the closure of many training programs 2 to 4 decades ago and the substantially decreased number of graduating residents.This comprehensive analysis predicts that pathologist numbers will decline steadily beginning in 2015. Anticipated population growth in general and increases in disease incidence owing to the aging population, to be presented in a companion article on demand, will lead to a net deficit in excess of more than 5700 FTE pathologists. To reach the projected need in pathologist numbers of nearly 20 000 FTE by 2030 will require an increase from today of approximately 8.1% more residency positions. We believe a pathologist shortage will negatively impact both patient access to laboratory services and health care providers' abilities to deliver more effective health care to their patient populations.

The daily man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia) neivai was determined in four ecologically distinct settlements of the Naya River, Department of Valle, Colombia. Differences were found among the settlements with respect to the mosquito species present, intradomiciliary and extradomiciliary biting activity and population densities.

Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species. When conjugated to the expression of a dominant mutant protein, this technology offers an attractive approach to generate new large animal models in a heterogeneous background. We adopted this strategy to mimic the phenotype diversity encounter in humans and generate a cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic, with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional impairment of vision was observed among the transgenic pigs at 3 months of age, with a follow-up at 1 year indicating a subsequent slower progression of phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell population, was observed exclusively amongst the transgenic animals. Of particular note, these transgenic animals were characterized by a range in the severity of the phenotype, reflecting the human clinical situation. We demonstrate that a transgenic approach using lentiviral vectors offers a powerful tool for large animal model development. Not only is the efficiency of transgenesis higher than conventional transgenic methodology but this technique also produces a heterogeneous cohort of transgenic animals that mimics the genetic variation encountered in human patients.

The effectiveness of bednets and curtains (nylon mesh 64 per cm2) impregnated with deltamethrin at 26 mg a.i./m2 in reducing the biting nuisance caused by three phlebotomine sandfly species: Lutzomyia columbiana, Lu.lichyi and the predominant Lu.youngi (Diptera: Psychodidae), was evaluated at La Guaira, a rural settlement in Valle de Cauca near Cali, Colombia. Pairs of volunteers collected sandflies under impregnated bednets, in rooms protected by impregnated curtains or in unprotected rooms in a randomized matched design. Collections were made in three houses per night on three consecutive nights, so that each house was sampled under each of the three treatments. This routine was repeated at 2-week intervals for 6 months. There was no significant difference between the overall numbers of sandflies collected in rooms with or without impregnated curtains. Only 0.14 sandflies/man-hour were caught on human bait under impregnated bednets, significantly fewer than the numbers collected on human bait outside the nets in the same room (1.91) or in unprotected rooms (3.29). In a second set of experiments carried out in La Guaira and the neighbouring community of Jiguales, the effect of deltamethrin impregnation was evaluated by comparing numbers of sandflies collected on human bait under treated and untreated nets. Significantly fewer were collected under the impregnated nets (0.25 v. 0.69/man-hour). Wild-caught female Lu.youngi exposed to treated netting for 2 min in the laboratory all died with 24 h. The impact of deltamethrin-impregnated bednets was considered to be useful against Lu.youngi and other potential vectors of leishmaniasis in such communities.