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Nursing education, along with higher education in general, is increasingly focusing on educational outcomes; critical thinking is one of these outcomes. This study examined the impact of a baccalaureate registered nurse programme on the critical thinking skills of students. Students were tested upon entry and exit of the programme and a significant (0.05) difference was found. Subtest gains were significant (0.05) on Recognition of Assumptions, and Deductions. A significant relationship (0.05) between the nursing grade point average (GPA) and the post-test total score existed, accounting for a variance of 4%. No relationship was found between the post-test total score and the general education GPA. The two GPA correlation coefficients were significantly different from one another (0.05). Since one goal of professional nursing education is to prepare nurses who engage in complex problem solving and critical thinking, both the curriculum and teaching strategies need to engance these skills. [ABSTRACT FROM AUTHOR]

Background: The goal of antibiotic stewardship programs (ASPs) is to ensure that patients receive effective therapy while minimizing adverse events. To overcome barriers commonly faced in implementing successful ASPs, the Agency for Healthcare Research and Quality (AHRQ) established a multifaceted, nationwide Safety Program for Improving Antibiotic Use in 2018. This report summarizes the lessons learned from the implementation of this initiative based on structured interviews of personnel from participating sites., Methods: At the completion of the one-year initiative, semistructured exit interviews were conducted with site leaders at 151 of the 402 hospitals that participated. These interviews consisted of open-ended questions about the perceived effectiveness of components of the Safety Program. Qualitative analyses incorporated both deductive coding themes (based on existing literature) and an iteratively developed inductive coding framework (based on salient themes that emerged from a subset of interviews)., Results: Several components of the Safety Program were identified as effective in expanding local stewardship activities, including techniques and strategies to implement sustainable ASPs, access to Implementation Advisors to keep sites engaged, provision of local benchmarked antibiotic use data to compare to similar hospitals, and Safety Program materials such as the antibiotic time-out tool to integrate stewardship techniques into daily work flows. The biggest challenges to greater effectiveness were suboptimal frontline staff engagement and difficulty changing antibiotic prescribing culture. Some approaches used to overcome these barriers (peer-to-peer communication and education through team huddles, identifying physician champions, informal rounds to enhance collegiality and buy-in, and engagement of hospital leadership) were identified., Conclusion: Lessons learned from the Safety Program can be applied by other teams looking to promote an effective ASP at their hospital or system. The themes that emerged in this study likely also have relevance across a wide range of large-scale quality improvement initiatives., (Copyright © 2024 The Joint Commission. All rights reserved.)

Importance: Unprecedented increases in hospital occupancy rates during COVID-19 surges in 2020 caused concern over hospital care quality for patients without COVID-19., Objective: To examine changes in hospital nonsurgical care quality for patients without COVID-19 during periods of high and low COVID-19 admissions., Design, Setting, and Participants: This cross-sectional study used data from the 2019 and 2020 Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases. Data were obtained for all nonfederal, acute care hospitals in 36 states with admissions in 2019 and 2020, and patients without a diagnosis of COVID-19 or pneumonia who were at risk for selected quality indicators were included. The data analysis was performed between January 1, 2023, and March 15, 2024., Exposure: Each hospital and week in 2020 was categorized based on the number of COVID-19 admissions per 100 beds: less than 1.0, 1.0 to 4.9, 5.0 to 9.9, 10.0 to 14.9, and 15.0 or greater., Main Outcomes and Measures: The main outcomes were rates of adverse outcomes for selected quality indicators, including pressure ulcers and in-hospital mortality for acute myocardial infarction, heart failure, acute stroke, gastrointestinal hemorrhage, hip fracture, and percutaneous coronary intervention. Changes in 2020 compared with 2019 were calculated for each level of the weekly COVID-19 admission rate, adjusting for case-mix and hospital-month fixed effects. Changes during weeks with high COVID-19 admissions (≥15 per 100 beds) were compared with changes during weeks with low COVID-19 admissions (<1 per 100 beds)., Results: The analysis included 19 111 629 discharges (50.3% female; mean [SD] age, 63.0 [18.0] years) from 3283 hospitals in 36 states. In weeks 18 to 48 of 2020, 35 851 hospital-weeks (36.7%) had low COVID-19 admission rates, and 8094 (8.3%) had high rates. Quality indicators for patients without COVID-19 significantly worsened in 2020 during weeks with high vs low COVID-19 admissions. Pressure ulcer rates increased by 0.09 per 1000 admissions (95% CI, 0.01-0.17 per 1000 admissions; relative change, 24.3%), heart failure mortality increased by 0.40 per 100 admissions (95% CI, 0.18-0.63 per 100 admissions; relative change, 21.1%), hip fracture mortality increased by 0.40 per 100 admissions (95% CI, 0.04-0.77 per 100 admissions; relative change, 29.4%), and a weighted mean of mortality for the selected indicators increased by 0.30 per 100 admissions (95% CI, 0.14-0.45 per 100 admissions; relative change, 10.6%)., Conclusions and Relevance: In this cross-sectional study, COVID-19 surges were associated with declines in hospital quality, highlighting the importance of identifying and implementing strategies to maintain care quality during periods of high hospital use.

Objective: Given the dearth of literature examining the link between trauma exposure and sleep among youth and young adults of color, the current study examined the association between individual types of trauma exposure, accumulation within subtypes of trauma exposure, and overall cumulative trauma exposure with sleep problems in a sample of Black students attending an alternative high school., Method: Participants were recruited from an alternative high school in a large, southeastern city in the United States, of which all students qualify for free/reduced lunch. The sample included 101 students (53% female) ages 16-24 ( M = 17.86 years, SD = 1.36) who identified as Black., Results: Participants reported a high rate of trauma exposure ( M = 6.03 unique traumatic experiences, SD = 2.63). Linear regression models showed that exposure to more overall cumulative trauma and to interpersonal loss was significantly associated with higher levels of insomnia symptoms. Threats to health were significantly related to daytime sleepiness. Other threats to safety were associated with restless legs syndrome symptoms., Conclusions: Adolescence and young adulthood are a time of complex sleep-related issues. Black youth and young adults have elevated risk of trauma exposure and sleep problems; therefore, targeted assessment and intervention are warranted. Clinicians and researchers addressing sleep in youth and young adults, and those working within alternative school settings, should also consider a trauma-informed lens to optimize outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Purpose: University of Kentucky developed a fully virtual course to educate global health learners about the COVID-19 pandemic and compare country responses to it., Educational Activity and Setting: Forty-three students participated in 13 weeks of synchronous interprofessional group meetings via Zoom (Zoom Video Communications, Inc) and asynchronous modules. Interprofessionality was intentional yet implicit, and a flipped classroom was utilized. Assessment was accomplished with one instrument measuring learning outcomes associated with select Consortium of Universities of Global Health Interprofessional Global Health Competencies, Association of American Colleges and Universities Global Learning Value Rubric competencies, and course satisfaction and effectiveness utilizing a retrospective pre-/post-methodology., Findings: Positive pre-/post-change was observed in 10 survey items. Evaluation results concerning course structure and experience were uniformly high, with the key informant interview rated most helpful. Items with significant improvement included a better understanding of the student's place in the world; improved interprofessional communication skills; population health data skills; and understanding of health systems and entities that influence global health and development. Learners appreciated the value of interprofessional teamwork and gained a deeper understanding of the roles and training of colleagues from other programs, leading to a deeper understanding of the actions those professions may take within health systems., Summary: The pivot to all online global health education was a viable solution to addressing the pause in global travel and study abroad experiences at University of Kentucky., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use aimed to improve antibiotic prescribing in ambulatory care practices by engaging clinicians and staff to incorporate antibiotic stewardship into practice culture, communication, and decision-making. Little is known about implementation of antibiotic stewardship in ambulatory care practices., Objective: To examine changes in visits and antibiotic prescribing during the AHRQ Safety Program., Design, Setting, and Participants: This cohort study evaluated a quality improvement intervention in ambulatory care throughout the US in 389 ambulatory care practices from December 1, 2019, to November 30, 2020., Exposures: The AHRQ Safety Program used webinars, audio presentations, educational tools, and office hours to engage stewardship leaders and clinical staff to address attitudes and cultures that challenge judicious antibiotic prescribing and incorporate best practices for the management of common infections., Main Outcomes and Measures: The primary outcome of the Safety Program was antibiotic prescriptions per 100 acute respiratory infection (ARI) visits. Data on total visits and ARI visits were also collected. The number of visits and prescribing rates from baseline (September 1, 2019) to completion of the program (November 30, 2020) were compared., Results: Of 467 practices enrolled, 389 (83%) completed the Safety Program; of these, 292 (75%) submitted complete data with 6 590 485 visits to 5483 clinicians. Participants included 82 (28%) primary care practices, 103 (35%) urgent care practices, 34 (12%) federally supported practices, 39 (13%) pediatric urgent care practices, 21 (7%) pediatric-only practices, and 14 (5%) other practice types. Visits per practice per month decreased from a mean of 1624 (95% CI, 1317-1931) at baseline to a nadir of 906 (95% CI, 702-1111) early in the COVID-19 pandemic (April 2020), and were 1797 (95% CI, 1510-2084) at the end of the program. Total antibiotic prescribing decreased from 18.2% of visits at baseline to 9.5% at completion of the program (-8.7%; 95% CI, -9.9% to -7.6%). Acute respiratory infection visits per practice per month decreased from baseline (n = 321) to a nadir of 76 early in the pandemic (May 2020) and gradually increased through completion of the program (n = 239). Antibiotic prescribing for ARIs decreased from 39.2% at baseline to 24.7% at completion of the program (-14.5%; 95% CI, -16.8% to -12.2%)., Conclusions and Relevance: In this study of US ambulatory practices that participated in the AHRQ Safety Program, significant reductions in the rates of overall and ARI-related antibiotic prescribing were noted, despite normalization of clinic visits by completion of the program. The forthcoming AHRQ Safety Program content may have utility in ambulatory practices across the US.

Introduction: Transvenous implantable cardioverter-defibrillators (TV-ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV-ICD infection in a large Medicare population with de novo TV-ICD implants., Methods: A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent de novo TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias., Results: Among 26,742 Medicare patients with de novo TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 (95% CI: 2.08-2.85) times in the mortality hazard ratio., Conclusion: The rate of TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections., (© 2022 Wiley Periodicals LLC.)

Importance: Antibiotic overuse in long-term care (LTC) is common, prompting calls for antibiotic stewardship programs (ASPs) designed for specific use in these settings. The optimal approach to establish robust, sustainable ASPs in LTC facilities is unknown., Objectives: To determine if the Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use, an educational initiative to establish ASPs focusing on patient safety, is associated with reductions in antibiotic use in LTC settings., Design, Setting, and Participants: This quality improvement study including 439 LTC facilities in the US assessed antibiotic therapy data following a pragmatic quality-improvement program, which was implemented to assist facilities in establishing ASPs and with antibiotic decision-making. Training was conducted between December 2018 and November 2019. Data were analyzed from January 2019 to December 2019., Interventions: Fifteen webinars occurred over 12 months (December 2018 to November 2019), accompanied by additional tools, activities, posters, and pocket cards. All clinical staff were encouraged to participate., Main Outcomes and Measures: The primary outcome was antibiotic starts per 1000 resident-days. Secondary outcomes included days of antibiotic therapy (DOT) per 1000 resident-days, the number of urine cultures per 1000 resident-days, and Clostridioides difficile laboratory-identified events per 10 000 resident-days. All outcomes compared data from the baseline (January-February 2019) to the completion of the program (November-December 2019). Generalized linear mixed models with random intercepts at the site level assessed changes over time., Results: Of a total 523 eligible LTC facilities, 439 (83.9%) completed the safety program. The mean difference for antibiotic starts from baseline to study completion per 1000 resident-days was -0.41 (95% CI, -0.76 to -0.07; P = .02), with fluoroquinolones showing the greatest decrease at -0.21 starts per 1000 resident-days (95% CI, -0.35 to -0.08; P = .002). The mean difference for antibiotic DOT per 1000 resident-days was not significant (-3.05; 95% CI, -6.34 to 0.23; P = .07). Reductions in antibiotic starts and use were greater in facilities with greater program engagement (as measured by webinar attendance). While antibiotic starts and DOT in these facilities decreased by 1.12 per 1000 resident-days (95% CI, -1.75 to -0.49; P < .001) and 9.97 per 1000 resident-days (95% CI, -15.4 to -4.6; P < .001), respectively, no significant reductions occurred in low engagement facilities. Urine cultures per 1000 resident-days decreased by 0.38 (95% CI, -0.61 to -0.15; P = .001). There was no significant change in facility-onset C difficile laboratory-identified events., Conclusions and Relevance: Participation in the AHRQ safety program was associated with the development of ASPs that actively engaged clinical staff in the decision-making processes around antibiotic prescriptions in participating LTC facilities. The reduction in antibiotic DOT and starts, which was more pronounced in more engaged facilities, indicates that implementation of this multifaceted program may support successful ASPs in LTC settings.

Gertrude Gerrard is a relatively unknown but important early nurse anesthetist in the United Sates in the early part of the 20th century. She was in the first class to graduate from the Peter Bent Brigham Hospital (PBBH) School of Nursing in Boston, Massachusetts. After graduating from nursing school, she participated in anesthesia training with Walter Boothby and became the first nurse anesthetist at the PBBH. In 1917 she was included in a group of medical professionals from the Harvard hospital system to serve in the medical corps in France during World War I. While there she worked with surgeon Harvey Cushing and this professional relationship continued back in Boston. She also was the first nurse anesthetist at Strong Memorial Hospital in Rochester, New York from 1925-1927. She returned to Boston in 1928 and continued as the chief anesthetist at PBBH until leaving in 1946 during a departmental staffing transition after WWII., Competing Interests: Name: Michael A. Miller, MSN, CRNA; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. Name: Sukumar P. Desai, MD; Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: None. The authors did not discuss off-label use within the article. Disclosure statements are available for viewing upon request., (Copyright © by the American Association of Nurse Anesthetists.)

Background: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection., Objective: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population., Methods: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted., Results: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus., Conclusion: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Importance: Regulatory agencies and professional organizations recommend antibiotic stewardship programs (ASPs) in US hospitals. The optimal approach to establish robust, sustainable ASPs across diverse hospitals is unknown., Objective: To assess whether the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use is associated with reductions in antibiotic use across US hospitals., Design, Setting, and Participants: A pragmatic quality improvement program was conducted and evaluated over a 1-year period in US hospitals. A total of 437 hospitals were enrolled. The study was conducted from December 1, 2017, to November 30, 2018. Data analysis was performed from March 1 to October 31, 2019., Interventions: The Safety Program assisted hospitals with establishing ASPs and worked with frontline clinicians to improve their antibiotic decision-making. All clinical staff (eg, clinicians, pharmacists, and nurses) were encouraged to participate. Seventeen webinars occurred over 12 months, accompanied by additional durable educational content. Topics focused on establishing ASPs, the science of safety, improving teamwork and communication, and best practices for the diagnosis and management of infectious processes., Main Outcomes and Measures: The primary outcome was overall antibiotic use (days of antibiotic therapy [DOT] per 1000 patient days [PD]) comparing the beginning (January-February 2018) and end (November-December 2018) of the Safety Program. Data analysis occurred using linear mixed models with random hospital unit effects. Antibiotic use from 614 hospitals in the Premier Healthcare Database from the same period was analyzed to evaluate contemporary US antibiotic trends. Quarterly hospital-onset Clostridioides difficile laboratory-identified events per 10 000 PD were a secondary outcome., Results: Of the 437 hospitals enrolled, 402 (92%) remained in the program until its completion, including 28 (7%) academic medical centers, 122 (30%) midlevel teaching hospitals, 167 (42%) community hospitals, and 85 (21%) critical access hospitals. Adherence to key components of ASPs (ie, interventions before and after prescription of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% over the 1-year period (P < .01). Antibiotic use decreased by 30.3 DOT per 1000 PD (95% CI, -52.6 to -8.0 DOT; P = .008). Similar changes in antibiotic use were not observed in the Premier Healthcare Database. The incidence rate of hospital-onset C difficile laboratory-identified events decreased by 19.5% (95% CI, -33.5% to -2.4%; P = .03)., Conclusions and Relevance: The Agency for Healthcare Research and Quality Safety Program appeared to enable diverse hospitals to establish ASPs and teach frontline clinicians to self-steward their antibiotic use. Safety Program content is publicly available.

Purpose: The purpose of this study was to determine whether ostomy patients are receiving ostomy care pre- and postoperatively in accordance with the United Ostomy Associations of America Ostomy and Continent Diversion Patient Bill of Rights., Design: Descriptive, quantitative study., Subjects and Setting: The sample comprised 325 participants with an ostomy living in the United States. All participants underwent ostomy surgery in the United States., Methods: Participants were recruited through a purposive, nonprobability sampling method based on the presence of an ostomy and the ability to read and understand English. Data were collected between summer 2017 and fall 2018 from ostomy support groups (online and in-person support groups). Respondents completed a self-administered online questionnaire, which included closed-ended and open-ended questions., Results: Forty percent (n = 127) of participants reported not being supervised changing their pouch before discharge. Forty-two percent (n = 137) reported receiving only hands-on instruction on how to care for their ostomy after surgery (no reading materials, nor video tutorial). Slightly more than half (52%; n = 170) reported not receiving support group information, and only 14% (n = 46) indicated participating in a discussion on intimacy concerns., Conclusions: The study demonstrates that ostomy care at the hospital can improve. Receiving an ostomy is a life-changing operation, and the first line of support for ostomy patients is their provider. Future research should examine ostomy care from providers' perspectives and, prospectively, in order to test care measures on patient health outcomes.

Limitations in workforce size and access to resources remain perennial challenges to greater progress in academic veterinary medicine and engagement between human and veterinary medicine (One Health). Ongoing resource constraints occur in part due to limited public understanding of the role veterinarians play in improving human health. One Health interactions, particularly through interdisciplinary collaborations in biomedical research, present constructive opportunities to inform resource policies and advance health care. To this end, inter-institutional partnerships between individual veterinary medical education programs (VMEPs) and several National Institutes of Health (NIH) intramural research programs have created synergies beyond those provided by individual programs. In the NIH Comparative Biomedical Scientist Training Program (CBSTP), interdisciplinary cross-training of veterinarians consisting of specialty veterinary medicine coupled with training in human disease research leading to a PhD, occurs collaboratively on both VMEP and NIH campuses. Pre-doctoral veterinary student research opportunities have also been made available. Through the CBSTP, NIH investigators and national biomedical science policy makers gain access to veterinary perspective and expertise, while veterinarians obtain additional opportunities for NIH-funded research training. CBSTP Fellows serve as de facto ambassadors enhancing visibility for the profession while in residence at NIH, and subsequently through a variety of university, industry, and government research appointments, as graduates. Thus, the CBSTP represents an inter-institutional opportunity that not only addresses critical needs for veterinarian-scientists in the biomedical workforce, but also simultaneously exposes national policy makers to veterinarian-scientists' specialized training, leading to more effective realization of One Health goals to benefit human and animal health.

Importance: Given the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant., Objective: To determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure., Design, Setting, and Participants: This retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019., Main Outcomes and Measures: Survival at 5 years was analyzed using Cox proportional hazards models., Results: In total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P < .001), but there was no significant difference in sex (2701 men [79.2%] vs 2648 men [77.6%]; P = .13). After propensity score matching for age, sex, body mass index, renal function, and albumin level, 3411 patients were wait-listed for heart transplant. This included 1607 patients with bridge to transplant LVAD therapy and 1804 patients without LVAD. The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32)., Conclusions and Relevance: The present analysis suggests that heart transplant with or without bridge to transplant LVAD therapy was associated with superior 5-year survival compared with LVAD destination therapy among patients matched on several relevant clinical factors. Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy.

Sarcocystis neurona was recognised as an important cause of mortality in southern sea otters (Enhydra lutris nereis) after an outbreak in April 2004 and has since been detected in many marine mammal species in the Northeast Pacific Ocean. Risk of S. neurona exposure in sea otters is associated with consumption of clams and soft-sediment prey and is temporally associated with runoff events. We examined the spatial distribution of S. neurona exposure risk based on serum antibody testing and assessed risk factors for exposure in animals from California, Washington, British Columbia and Alaska. Significant spatial clustering of seropositive animals was observed in California and Washington, compared with British Columbia and Alaska. Adult males were at greatest risk for exposure to S. neurona, and there were strong associations with terrestrial features (wetlands, cropland, high human housing-unit density). In California, habitats containing soft sediment exhibited greater risk than hard substrate or kelp beds. Consuming a diet rich in clams was also associated with increased exposure risk. These findings suggest a transmission pathway analogous to that described for Toxoplasma gondii, with infectious stages traveling in freshwater runoff and being concentrated in particular locations by marine habitat features, ocean physical processes, and invertebrate bioconcentration.

Krysko et al. (2016a) used analyses of DNA sequence data to reveal two genetic lineages of Drymarchon couperi. The Atlantic lineage contained specimens from southeastern Georgia and eastern peninsular Florida, and the Gulf Coast lineage contained specimens from western and southern peninsular Florida as well as western Florida, southern Alabama, and southern Mississippi. In a second paper Krysko et al. (2016b) analyzed morphological variation of the two lineages, which allowed them to restrict D. couperi to the Atlantic lineage and to describe the Gulf Coast lineage as a new species, Drymarchon kolpobasileus. This taxonomic discovery was remarkable for such a large, wide-ranging species and was notable for its impact on conservation. Because of population declines, particularly in western Florida, southern Alabama, and southern Mississippi, D. couperi (sensu lato) was listed as Threatened under the Endangered Species Act (United States Fish and Wildlife Service 1978, 2008) and repatriation of the species to areas where it had been extirpated was listed as a priority conservation goal (United States Fish and Wildlife Service 1982, 2008). Such repatriation efforts were attempted in Alabama, Florida, Georgia, and South Carolina, starting in 1977 (Speake et al. 1987), but failed to create viable populations, likely because too few snakes were released at too many sites (Guyer et al. 2019; Folt et al. 2019a). A second attempt at repatriation was started in 2010 and concentrated on release of snakes at a single site in Alabama (Stiles et al. 2013). However, Krysko et al. (2016a) criticized this repatriation effort because it appeared to involve release of D. couperi (sensu stricto) into the geographic region occupied by D. kolpobasileus (as diagnosed in Krysko et al. 2016b).

Background: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed., Methods and Results: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −7784–21 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 253–17 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve., Conclusions: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040., Competing Interests: Dr Acker: consultant/advisory board for Thoratec (modest). Dr Gillinov: otherresearch support from St. Jude Medical, Abbott (modest); consultant/advisoryboard for St. Jude Medical, Edwards Lifesciences (modest); consultant/advisoryboard for Abbott, Medtronic, CryoLife, AtriCure (significant). Dr Thourani: researchgrants from Edwards Lifesciences, Medtronic Corp, and Abbott Medical(modest); consultant/advisory board for Edwards Lifesciences, Abbott Medical(modest). Dr Robert L. Smith: research grant from Edwards Lifesciences (significant);speakers bureau for Abbott Medical (significant); consultant/advisoryboard for Abbott Medical, Edwards Lifesciences (significant); other from AbbottMedical, Edwards Lifesciences (significant). The other authors report noconflicts. This work was supported by a cooperative agreement (U01 HL088942) fundedby the National Heart, Lung, and Blood Institute and the National Institute ofNeurological Disorders and Stroke of the National Institute of Health and theCanadian Institutes of Health Research. Dr Ferket was supported by AmericanHeart Association grant number 16MCPRP31030016. The views expressed inthis article are those of the authors and do not necessarily represent the viewsof the National Heart, Lung, and Blood Institute; National Institutes of Health;or the United States Department of Health and Human Services., (2018 American Heart Association, Inc.)

Introduction: In the United States, most antibiotics are prescribed in ambulatory settings. Human factors engineering, which explores interactions between people and the place where they work, has successfully improved quality of care. However, human factors engineering models have not been explored to frame what is known about ambulatory antibiotic stewardship (AS) interventions and barriers and facilitators to their implementation., Methods: We conducted a systematic review and searched OVID MEDLINE, Embase, Scopus, Web of Science, and CINAHL to identify controlled interventions and qualitative studies of ambulatory AS and determine whether and how they incorporated principles from a human factors engineering model, the Systems Engineering Initiative for Patient Safety 2.0 model. This model describes how a work system (ambulatory clinic) contributes to a process (antibiotic prescribing) that leads to outcomes. The work system consists of 5 components, tools and technology, organization, person, tasks, and environment, within an external environment., Results: Of 1,288 abstracts initially identified, 42 quantitative studies and 17 qualitative studies met inclusion criteria. Effective interventions focused on tools and technology (eg, clinical decision support and point-of-care testing), the person (eg, clinician education), organization (eg, audit and feedback and academic detailing), tasks (eg, delayed antibiotic prescribing), the environment (eg, commitment posters), and the external environment (media campaigns). Studies have not focused on clinic-wide approaches to AS., Conclusions: A human factors engineering approach suggests that investigating the role of the clinic's processes or physical layout or external pressures' role in antibiotic prescribing may be a promising way to improve ambulatory AS., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Background: Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population., Methods: Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs., Results: Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high., Conclusions: Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease., (Copyright © 2018 International Society for the Heart and Lung Transplantation. All rights reserved.)

Rationale: Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures., Objectives: To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes., Methods: A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model., Measurements and Main Results: The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio [HR], 2.83; 95% confidence interval [95% CI], 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58)., Conclusions: Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research., (Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.)

Background: Infections are the most common noncardiac complication after cardiac surgery, but their incidence across a broad range of operations, as well as the management factors that shape infection risk, remain unknown., Objectives: This study sought to prospectively examine the frequency of post-operative infections and associated mortality, and modifiable management practices predictive of infections within 65 days from cardiac surgery., Methods: This study enrolled 5,158 patients and analyzed independently adjudicated infections using a competing risk model (with death as the competing event)., Results: Nearly 5% of patients experienced major infections. Baseline characteristics associated with increased infection risk included chronic lung disease (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.21 to 2.26), heart failure (HR: 1.47; 95% CI: 1.11 to 1.95), and longer surgery (HR: 1.31; 95% CI: 1.21 to 1.41). Practices associated with reduced infection risk included prophylaxis with second-generation cephalosporins (HR: 0.70; 95% CI: 0.52 to 0.94), whereas post-operative antibiotic duration >48 h (HR: 1.92; 95% CI: 1.28 to 2.88), stress hyperglycemia (HR: 1.32; 95% CI: 1.01 to 1.73); intubation time of 24 to 48 h (HR: 1.49; 95% CI: 1.04 to 2.14); and ventilation >48 h (HR: 2.45; 95% CI: 1.66 to 3.63) were associated with increased risk. HRs for infection were similar with either <24 h or <48 h of antibiotic prophylaxis. There was a significant but differential effect of transfusion by surgery type (excluding left ventricular assist device procedures/transplant) (HR: 1.13; 95% CI: 1.07 to 1.20). Major infections substantially increased mortality (HR: 10.02; 95% CI: 6.12 to 16.39)., Conclusions: Major infections dramatically affect survival and readmissions. Second-generation cephalosporins were strongly associated with reduced major infection risk, but optimal duration of antibiotic prophylaxis requires further study. Given practice variations, considerable opportunities exist for improving outcomes and preventing readmissions. (Management Practices and Risk of Infection Following Cardiac Surgery; NCT01089712)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life., (Copyright © 2014 International Society for Heart and Lung Transplantation. All rights reserved.)

Background: Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database., Methods: Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis., Results: Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant., Conclusions: Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis., (© 2013 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.)

Background: Post-traumatic depression (PTD) may be a result of several factors like secondary injury chemical cascades as well as psycho-social factors following traumatic brain injury (TBI). While the role of serotonin in the pathology and treatment of idiopathic major depression may be somewhat controversial, it is unclear what role serotonin may play in PTD following a TBI., Objective: To assess serotonergic function and genetic risk for PTD development over 1 year following TBI., Research Design: Examination of variation in the serotonin transporter gene [SLC6A4 (5-HTTLPR, rs25331, and a variable number of tandem repeats variant in Intron 2)] in 109 subjects with moderate-severe injury. Depression was assessed using the Patient Health Questionnaire (PHQ-9) at 6 and/or 12 months post-injury., Main Outcomes and Results: At 6 months post-injury, subjects with a history of pre-morbid mood disorders and 5-HTTLPR L-homozygotes were at greater risk for PTD. Contrary to major depression, subjects without pre-morbid mood disorders (n = 80) and S-carriers were 2.803-times less likely to be depressed compared to L-homozygotes. At 12 months post-injury, LG-carriers were also less likely to experience PTD. Temporal analysis also showed 5-HTTLPR associations in PTD development across recovery., Conclusions: This study suggests a unique injury- and temporally-specific interaction between TBI and genetic risk for depression.

Aims: The aim of the study was to assess the impact of isthmus location of atypical atrial flutters/atrial tachycardias (ATs) on outcomes of catheter ablation. Atrial tachycardias are clinically challenging arrhythmias that can occur in the presence of atrial scar--often due to either cardiac surgery or prior ablation for atrial fibrillation. We previously demonstrated a catheter ablation approach employing rapid multielectrode activation mapping with targeted entrainment manoeuvrs. However, the role that AT isthmus location plays in acute and long-term success of ablation remains uncertain., Methods and Results: Retrospective multicenter analysis of 91 consecutive AT patients undergoing ablation using a systematic four-step approach: (i) high-density activation mapping; (ii) analysis of atrial activation to identify wavefronts of electrical propagation; (iii) targeted entrainment of putative channels; and (iv) irrigated radiofrequency ablation of constrained regions of the circuit. Clinical outcomes, procedural details, and clinical profiles were determined. A total of 171 ATs (1.9 ± 1.0 per patient, 26% septal ATs) were targeted for ablation. The acute success rates were 97 and 77% for patients with either non-septal ATs or septal ATs, respectively (P = 0.0023). Similarly, the long-term success rates were 82 and 67% for patients with either no septal ATs or at least one septal AT, respectively (P = 0.1057). The long-term success rates were 75, 88, and 57% for patients with ATs associated with prior catheter ablation, cardiac surgery or MAZE, and idiopathic atrial scar, respectively., Conclusion: Catheter ablation of AT can be successfully performed employing a strategy of combined high-density activation and entrainment mapping. Septal ATs are associated with higher rates of acute and long-term recurrences.

The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps, actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Recurrence of Clostridium difficile infection (CDI) occurs in approximately 25% of successfully treated patients. Two phase 3 randomized, double-blind trials were conducted at 154 sites in the United States, Canada, and Europe to compare fidaxomicin vs vancomycin in treating CDI. Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days. The primary end point was clinical cure of CDI at end of treatment, and a secondary end point was recurrence during the 28 days following clinical cure. In all, 1164 subjects were enrolled, of which a subgroup of 128 in the per-protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment. In the analysis of this subgroup, initial response to therapy was similar for both drugs (>90% cure). However, recurrence within 28 days occurred in 35.5% of patients treated with vancomycin and 19.7% of patients treated with fidaxomicin (-15.8% difference; 95% confidence interval, -30.4% to -0.3%; P = .045). Early recurrence (within 14 days) was reported in 27% of patients treated with vancomycin and 8% of patients treated with fidaxomicin (P = .003). In patients with a first recurrence of CDI, fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days.

Fidaxomicin causes less disruption of anaerobic microbiota during treatment of Clostridium difficile infection (CDI) than vancomycin and has activity against many vancomycin-resistant enterococci (VRE). In conjunction with a multicenter randomized trial of fidaxomicin versus vancomycin for CDI treatment, we tested the hypothesis that fidaxomicin promotes VRE and Candida species colonization less than vancomycin. Stool was cultured for VRE and Candida species before and after therapy. For patients with negative pretreatment cultures, the incidence of VRE and Candida species acquisition was compared. For those with preexisting VRE, the change in concentration during treatment was compared. The susceptibility of VRE isolates to fidaxomicin was assessed. Of 301 patients, 247 (82%) had negative VRE cultures and 252 (84%) had negative Candida species cultures before treatment. In comparison with vancomycin-treated patients, fidaxomicin-treated patients had reduced acquisition of VRE (7% vs 31%, respectively; P < .001) and Candida species (19% vs 29%, respectively; P = .03). For patients with preexisting VRE, the mean concentration decreased significantly in the fidaxomicin group (5.9 vs 3.8 log(10) VRE/g stool; P = .01) but not the vancomycin group (5.3 vs 4.2 log(10) VRE/g stool; P = .20). Most VRE isolates recovered after fidaxomicin treatment had elevated fidaxomicin minimum inhibitory concentrations (MICs; MIC(90), 256 µg/mL), and subpopulations of VRE with elevated fidaxomicin MICs were common before therapy. Fidaxomicin was less likely than vancomycin to promote acquisition of VRE and Candida species during CDI treatment. However, selection of preexisting subpopulations of VRE with elevated fidaxomicin MICs was common during fidaxomicin therapy.

In December 2011, the first delegation of oncology nurses from the United States visited Havana, Cuba. The delegation included oncology nurses, educators, and leaders from across America and provided opportunities to learn about the healthcare system, cancer, and oncology nursing in Cuba. Delegation members attended lectures, toured facilities, and enjoyed Cuban culture. This exchange highlighted the similarities in cancer care and oncology nursing between countries and opened doors for future collaborations.

Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies., (Copyright © 2012. Published by Elsevier B.V.)

Background: Ischemic mitral regurgitation, a complication of myocardial infarction and coronary artery disease more generally, is associated with a high mortality rate and is estimated to affect 2.8 million Americans. With 1-year mortality rates as high as 40%, recent practice guidelines of professional societies recommend repair or replacement, but there remains a lack of conclusive evidence supporting either intervention. The choice between therapeutic options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus a better long-term correction of mitral insufficiency with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to significant variation in surgical practice., Methods and Results: This article describes the design of a prospective randomized clinical trial to evaluate the safety and effectiveness of mitral valve repair and replacement in patients with severe ischemic mitral regurgitation. This trial is being conducted as part of the Cardiothoracic Surgical Trials Network. This article addresses challenges in selecting a feasible primary end point, characterizing the target population (including the degree of mitral regurgitation) and analytical challenges in this high mortality disease., Conclusions: The article concludes by discussing the importance of information on functional status, survival, neurocognition, quality of life, and cardiac physiology in therapeutic decision making., (Copyright © 2012. Published by Mosby, Inc.)

Objective: Daily interruption of sedation (DIS) has multiple proven benefits, but implementation is erratic. Past research on sedative interruption utilisation focused on individual clinicians, ignoring the role of organisations in shaping practice. The authors test the hypothesis that specific hospital organisational characteristics are associated with routine use of DIS., Design and Setting: National, mailed survey to a stratified random sample of US hospitals in 2009. Respondents were the lead infection control professionals at each institution., Methods: Survey items enquired about DIS use, institutional structure, and organisational culture. Multivariable analysis was used to evaluate the independent association of these factors with DIS use., Results: A total of 386 hospitals formed our final analytic sample; the response rate was 69.4%. Hospitals ranged in size from 25 to 1359 beds. 26% of hospitals were associated with a medical school. Almost 80% reported regular use of DIS for ventilated patients. While 75.4% of hospitals reported having leadership focus on safety culture, only 42.7% reported that their staff were receptive to changes in practice. In a multivariable logistic regression model, structural characteristics such as size and academic affiliation were not associated with use of DIS. However, leadership emphasis on safety culture (p=0.04), staff receptivity to change (p=0.02) and involvement in an infection prevention collaborative (p=0.04) were significantly associated with regular DIS use., Conclusions: Several elements of hospital organisational culture were associated with regular use of DIS in US hospitals. These findings emphasise the importance of combining specific administrative approaches with strategies to encourage receptivity to change among bedside clinicians in order to successfully implement complex evidence-based practices in the intensive care setting.

Background: Although pregnancy is a recognized risk factor for severe influenza infection, the effect of influenza on miscarriages and births remains unclear. We examined the relationship between influenza and birth rates during the 1918 pandemic in the United States, Denmark, Sweden, and Norway., Methods: We compiled monthly birth rates from 1911 through 1930 in 3 Scandinavian countries and the United States, identified periods of unusually low or high birth rates, and quantified births as "missing" or "in excess" of the normal expectation. Using monthly influenza data, we correlated the timing of peak pandemic exposure and depressions in birth rates, and identified pregnancy stages at risk of influenza-related miscarriage., Results: Birth rates declined in all study populations in spring 1919 by a mean of 2.2 births per 1000 persons, representing a 5%-15% drop below baseline levels (P < .05). The 1919 natality depression reached its trough 6.1-6.8 months after the autumn pandemic peak, suggesting that missing births were attributable to excess first trimester miscarriages in ∼1 in 10 women who were pregnant during the peak of the pandemic. Pandemic-related mortality was insufficient to explain observed patterns., Conclusions: The observed birth depressions were consistent with pandemic influenza causing first trimester miscarriages in ∼1 in 10 pregnant women. Causality is suggested by temporal synchrony across geographical areas.

Background: The epidemiology of traumatic, nonbattle, Combat Zone hand injuries has not been well explored., Methods: This was a retrospective chart review of Emergency Department visits occurring at the Ibn Sina Hospital in Baghdad Iraq., Results: During the 24-month period from May 2007 to June 2009, 7,520 patients were seen at the Ibn Sina Hospital Emergency Department. Three hundred thirty-one cases met the inclusion criteria. Seventy-four cases were found to have required near-term evacuation from area of operation., Conclusions: Traumatic, nonbattle hand injuries are common and appear to be a significant problem in the Combat Zone. Injuries occurring because of the closure of vehicle doors, hatches, and turrets make up a large portion of these injuries and represent an optimal area of intervention for possible injury mitigation.

Pregnancy is an example of Virchow's triad predisposing to the development of venous thromboembolism (VTE). Specific risk factors for antepartum and postpartum VTE have been identified. The diagnosis of pulmonary embolism in pregnancy is complicated by the physiologic changes of pregnancy as well as physicians' apprehension about ordering radiologic studies during pregnancy because of concerns with fetal well-being. Therapy for VTE is complicated by pregnancy physiology affecting medication pharmacokinetics and bioavailability, and the unpredictable occurrence of labor during therapeutic anticoagulation., (Copyright © 2011. Published by Elsevier Inc.)

Background: Eligibility for rosuvastatin treatment for cardiovascular disease prevention includes a C-reactive protein (CRP) concentration >2 mg/L. Most observational studies of CRP and cardiovascular disease have been in Europeans. We evaluated the influence of ancestry on population CRP concentration to assess the implications for statin targeting in non-Europeans., Methods and Results: In a systematic review and meta-analysis among 221 287 people from 89 studies, geometric mean CRP was 2.6 mg/L (95% credible interval, 2.27 to 2.96) in blacks resident in the United States (n=18 585); 2.51 mg/L (95% CI, 1.18 to 2.86) in Hispanics (n=5049); 2.34 mg/L (95% CI, 1.99 to 2.8) in South Asians (n=1053); 2.03 mg/L (95% CI, 1.77 to 2.3) in whites (n=104 949); and 1.01 mg/L (95% CI, 0.88 to 1.18) in East Asians (n=39 521). Differences were not explained by study design or CRP assay and were preserved after adjustment for age and body mass index. At age 60 years, fewer than half of East Asians but more than two thirds of Hispanics were estimated to have CRP values exceeding 2 mg/L. HapMap frequencies of CRP polymorphisms known to associate with CRP concentration but not coronary heart disease events differed by ancestry. In participant data from the Wandsworth Heart and Stroke Study including European, South Asian and African, and Caribbean-descent subjects, body mass index, systolic blood pressure, and smoking contributed to between-group differences in CRP, but the majority of the difference in CRP was unexplained., Conclusions: Differences in CRP concentration in populations of diverse ancestry are sufficiently large to affect statin eligibility, based on a single CRP threshold of 2 mg/L, and only partially influenced by differences in variables related to cardiovascular risk. A single threshold value of CRP for cardiovascular risk prediction could lead to inequalities in statin eligibility that may not accurately reflect underlying levels of cardiovascular risk.

Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination.

To determine the spatial and temporal dynamics of influenza A virus during a single epidemic, we examined whole-genome sequences of 284 A/H1N1 and 69 A/H3N2 viruses collected across the continental United States during the 2006-2007 influenza season, representing the largest study of its kind undertaken to date. A phylogenetic analysis revealed that multiple clades of both A/H1N1 and A/H3N2 entered and co-circulated in the United States during this season, even in localities that are distant from major metropolitan areas, and with no clear pattern of spatial spread. In addition, co-circulating clades of the same subtype exchanged genome segments through reassortment, producing both a minor clade of A/H3N2 viruses that appears to have re-acquired sensitivity to the adamantane class of antiviral drugs, as well as a likely antigenically distinct A/H1N1 clade that became globally dominant following this season. Overall, the co-circulation of multiple viral clades during the 2006-2007 epidemic season revealed patterns of spatial spread that are far more complex than observed previously, and suggests a major role for both migration and reassortment in shaping the epidemiological dynamics of human influenza A virus.

Background: How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age., Methods: We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure., Results: For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those >or=65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45-64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario., Conclusions: Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.

Recurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia. We found similar distributions of reproduction number estimates in the three countries, with mean value 1.3 and important year-to-year variability (range 0.9-2.1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation=0.61, P60%) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.

A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2% to approximately 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.

Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints.

Influenza poses a continuing public health threat in epidemic and pandemic seasons. The 1951 influenza epidemic (A/H1N1) caused an unusually high death toll in England; in particular, weekly deaths in Liverpool even surpassed those of the 1918 pandemic. We further quantified the death rate of the 1951 epidemic in 3 countries. In England and Canada, we found that excess death rates from pneumonia and influenza and all causes were substantially higher for the 1951 epidemic than for the 1957 and 1968 pandemics (by > or =50%). The age-specific pattern of deaths in 1951 was consistent with that of other interpandemic seasons; no age shift to younger age groups, reminiscent of pandemics, occurred in the death rate. In contrast to England and Canada, the 1951 epidemic was not particularly severe in the United States. Why this epidemic was so severe in some areas but not others remains unknown and highlights major gaps in our understanding of interpandemic influenza.

This anonymous survey sent to every battalion and brigade commander at Fort Hood, Texas assessed the new concept of residency-trained operational physicians that had completed military unique curriculum series training. Commanders provided anonymous professional information about themselves and their assigned physicians and evaluated their physicians in 22 areas of medical and military competence using a linear scoring method from 2 (indicating poor) to 6 (indicating outstanding). Main effects and interaction effects were analyzed using multiple analysis of variance. The commanders' overall confidence in their physicians was 5.4, suggesting general satisfaction. Prior-service physicians were rated higher on several factors if the commander had combat experience. Non-prior-service physicians were rated the same on nearly all variables regardless of the commander's experience. Commanders with combat experience rated their assigned physicians significantly higher than did commanders without combat experience. Despite high ratings, several candid remarks suggest there is still room for improvement.

Treatment of adolescent substance abusers is difficult. Treatment programs at multiple levels, from inpatient facilities to outpatient support groups, usually are available. Some of the most encouraging results have come from programs that involve family therapy in addition to individual treatment. 22 Knowing what resources are available, as well as the referral processes based on a particular patient's healthcare plans, facilitates access and makes dealing with these issues in a busy outpatient setting much easier. Frequent follow-up with an adolescent after a treatment program has been initiated to monitor for compliance and relapse can ensure a better drug-free outcome. Knowing the extent of the adolescent drug abuse problem should encourage providers to incorporate some type of screening into their routine care of adolescents. None of these methods is 100% sensitive, and incorporating each component into the process where appropriate likely is the best approach. Knowing risk and protective factors for drug use is helpful for both recognition of candidates for screening and counseling of parents regarding drug use prevention.