Yersinia pseudotuberculosis doxycycline tolerance strategies include modulating expression of genes involved in cell permeability and tRNA modifications.

Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that can contribute to treatment failure and recurrent infections. Although tolerant cells may emerge prior to treatment, the stress of prolonged antibiotic exposure can also promote tolerance. Here, we sought to determine how Yersinia pseudotuberculosis responds to doxycycline exposure, to then verify if these gene expression changes could promote doxycycline tolerance in culture and in our mouse model of infection. Only four genes were differentially regulated in response to a physiologically-relevant dose of doxycycline: osmB and ompF were upregulated, tusB and cnfy were downregulated; differential expression also occurred during doxycycline treatment in the mouse. ompF, tusB and cnfy were also differentially regulated in response to chloramphenicol, indicating these could be general responses to ribosomal inhibition. cnfy has previously been associated with persistence and was not a major focus here. We found deletion of the OmpF porin resulted in increased antibiotic accumulation, suggesting expression may promote diffusion of doxycycline out of the cell, while OsmB lipoprotein had a minor impact on antibiotic permeability. Overexpression of tusB significantly impaired bacterial survival in culture and in the mouse, suggesting that tRNA modification by tusB, and the resulting impacts on translational machinery, promotes survival during treatment with an antibiotic classically viewed as bacteriostatic. We believe this may be the first observation of bactericidal activity of doxycycline under physiological conditions, which was revealed by reversing tusB downregulation.

Satisfaction With and Adherence to Off-Label Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis: Results of a Web-Based Survey in the United States.

GOALS: We assessed satisfaction with and adherence to off-label corticosteroids in patients with eosinophilic esophagitis (EoE) in the United States. BACKGROUND: EoE is a chronic inflammatory disease for which there are currently no US Food and Drug Administration-approved swallowed topical corticosteroids. STUDY: This noninterventional, cross-sectional, web-based survey included caregivers of adolescents (aged 11 to 17 y) and adults (aged 18 years or older) with a self-reported [or caregiver-reported (adolescents)] physician diagnosis of EoE who were receiving corticosteroids. Participants were recruited through 2 nonprofit, patient advocacy groups. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used to assess satisfaction across effectiveness, convenience, and global satisfaction domains (scale: 1 to 100 per domain); higher scores indicated greater satisfaction. The 4-item Morisky Green Levine Medication Adherence Scale (MGL-4) was used to assess adherence; an MGL-4 score of <3 indicated adherence. Participants also reported reasons for nonadherence. RESULTS: Overall, 201 participants (caregivers of adolescents, n=98; adults, n=103) were included in this study. Mean TSQM-9 scores indicated low satisfaction with off-label corticosteroids across all 3 satisfaction domains in adolescents (≤61.1) and adults (≤55.7). Slightly fewer adolescents (37.1%) than adults (40.8%) were considered adherent. Forgetfulness was the most frequently reported reason for nonadherence; some patients chose not to take their medications, owing to poor palatability (adolescents), difficulty taking medications at specific times (adults), or feeling depressed/overwhelmed (adolescents and adults). CONCLUSIONS: Satisfaction with and adherence to off-label corticosteroids were low in this web-based survey of adolescents and adults with EoE in the United States.

Reassessing the July Effect: 30 Years of Evidence Show No Difference in Outcomes.

OBJECTIVE: The aim of this study was to critically evaluate whether admission at the beginning versus end of the academic year is associated with increased risk of major adverse outcomes. SUMMARY BACKGROUND DATA: The hypothesis that the arrival of new residents and fellows is associated with increases in adverse patient outcomes has been the subject of numerous research studies since 1989. Methods: We conducted a systematic review and random-effects meta-analysis of July Effect studies published before December 20, 2019, looking for differences in mortality, major morbidity, and readmission. Given a paucity of studies reporting readmission, we further analyzed 7 years of data from the Nationwide Readmissions Database to assess for differences in 30-day readmission for US patients admitted to urban teaching versus nonteach-ing hospitals with 3 common medical (acute myocardial infarction, acute ischemic stroke, and pneumonia) and 4 surgical (elective coronary artery bypass graft surgery, elective colectomy, craniotomy, and hip fracture) conditions using risk-adjusted logistic difference-in-difference regression. RESULTS: A total of 113 studies met inclusion criteria; 92 (81.4%) reported no evidence of a July Effect. Among the remaining studies, results were mixed and commonly pointed toward system-level discrepancies in efficiency. Metaanalyses of mortality [odds ratio (95% confidence interval): 1.01 (0.98-1.05)] and major morbidity [1.01 (0.99-1.04)] demonstrated no evidence of a July Effect, no differences between specialties or countries, and no change in the effect over time. A total of 5.98 million patient encounters were assessed for readmission. No evidence of a July Effect on readmission was found for any of the 7 conditions. CONCLUSION: The preponderance of negative results over the past 30 years suggests that it might be time to reconsider the need for similarly-themed studies and instead focus on system-level factors to improve hospital efficiency and optimize patient outcomes.

Modifying TIMER to generate a slow-folding DsRed derivative for optimal use in quickly-dividing bacteria.

It is now well appreciated that members of pathogenic bacterial populations exhibit heterogeneity in growth rates and metabolic activity, and it is known this can impact the ability to eliminate all members of the bacterial population during antibiotic treatment. It remains unclear which pathways promote slowed bacterial growth within host tissues, primarily because it has been difficult to identify and isolate slow growing bacteria from host tissues for downstream analyses. To overcome this limitation, we have developed a novel variant of TIMER, a slow-folding fluorescent protein, named DsRed42, to identify subsets of slowly dividing bacteria within host tissues. The original TIMER folds too slowly for fluorescence accumulation in quickly replicating bacterial species (Escherichia coli, Yersinia pseudotuberculosis), however DsRed42 accumulates red fluorescence in late stationary phase cultures of E. coli and Y. pseudotuberculosis. We show DsRed42 signal also accumulates during exposure to sources of nitric oxide (NO), suggesting DsRed42 signal detects growth-arrested bacterial cells. In a mouse model of Y. pseudotuberculosis deep tissue infection, DsRed42 signal was detected, and primarily accumulates in bacteria expressing markers of stationary phase growth. There was no significant overlap between DsRed42 signal and NO-exposed subpopulations of bacteria within host tissues, suggesting NO stress was transient, allowing bacteria to recover from this stress and resume replication. This novel DsRed42 variant represents a tool that will enable additional studies of slow-growing subpopulations of bacteria, specifically within bacterial species that quickly divide.

Plague's partners in crime.

The hallmark of bubonic plague is the presence of grotesquely swollen lymph nodes, called buboes. This frenzied inflammatory response to Yersinia pestis is poorly understood. In this issue of Immunity, St. John et al. (2014) explore the mechanism by which Y. pestis spreads and thus leads to this striking lymphadenopathy.

An interprofessional geriatrics faculty development program: exploration of the barriers and facilitators of capstone projects.

Faculty development programs (FDPs) are an effective, evidence-based method of promoting knowledge, skills and self-efficacy of faculty. However, implementation and sustainability of curricular capstone projects developed by faculty as part of these programs are rarely reported. Challenges to sustaining programmatic implementation of interprofessional FDP curricular content into academic and clinical settings over time were not found in peer-reviewed literature. To better understand the sustained impact of our geriatrics-focused FDP, we explored barriers and facilitators to implementation and sustainability of capstone projects designed by faculty Scholars in our FDP. Thematic analysis of virtual interviews with 17 Scholars revealed several key factors that impacted the implementation and Dynamic sustainability of curricular projects. Three major themes and sub-themes were identified: Project Implementation (Supportive Factors, Hindering Factors and Filling in Gaps in the Field); Pedagogical Development (Enhancement of Skills and Culture Change); and Sustainability Impact (Project Sustainability, Career Development and Passing the Torch). Results suggest it is important to ensure logistical support, dedicated time, and organizational or institutional support. Implementation of geriatrics-focused FDPs provides an evidence-based approach to sustainability. Further study of the ongoing barriers and facilitators to sustainability is encouraged.

NO-Stressed Y. pseudotuberculosis Has Decreased Cell Division Rates in the Mouse Spleen.

Fluorescence dilution approaches can detect bacterial cell division events and can detect if there are differential rates of cell division across individual cells within a population. This approach typically involves inducing expression of a fluorescent protein and then tracking partitioning of fluorescence into daughter cells. However, fluorescence can be diluted very quickly within a rapidly replicating population, such as pathogenic bacterial populations replicating within host tissues. To overcome this limitation, we have generated two revTetR reporter constructs, where either mCherry or yellow fluorescent protein (YFP) is constitutively expressed and repressed by addition of tetracyclines, resulting in fluorescence dilution within defined time frames. We show that fluorescent signals are diluted in replicating populations and that signal accumulates in growth-inhibited populations, including during nitric oxide (NO) exposure. Furthermore, we show that tetracyclines can be delivered to the mouse spleen during Yersinia pseudotuberculosis infection and defined a drug concentration that results in even exposure of cells to tetracyclines. We then used this system to visualize bacterial cell division within defined time frames postinfection. revTetR-mCherry allowed us to detect slow-growing cells in response to NO in culture; however, this strain had a growth defect within mouse tissues, which complicated results. To address this issue, we constructed revTetR-YFP using the less toxic YFP and showed that heightened NO exposure correlated with heightened YFP signal, indicating decreased cell division rates within this subpopulation in vivo. This revTetR reporter will provide a critical tool for future studies to identify and isolate slowly replicating bacterial subpopulations from host tissues.

Geographic Variation in the Utilization of and Mortality After Emergency General Surgery Operations in the Northeastern and Southeastern United States.

OBJECTIVE: To define geographic variations in emergency general surgery (EGS) care, we sought to determine how much variability exists in the rates of EGS operations and subsequent mortality in the Northeastern and Southeastern United States (US). SUMMARY BACKGROUND DATA: While some geographic variations in healthcare are normal, unwarranted variations raise questions about the quality, appropriateness, and cost-effectiveness of care in different areas. METHODS: Patients ≥18 years who underwent 1 of 10 common EGS operations were identified using the State Inpatient Databases (2011-2012) for 6 states, representing Northeastern (New York) and Southeastern (Florida, Georgia, Kentucky, North Carolina, Mississippi) US. Geographic unit of analysis was the hospital service area (HSA). Age-standardized rates of operations and in-hospital mortality were calculated and mapped. Differences in rates across geographic areas were compared using the Kruskal-Wallis test, and variance quantified using linear random-effects models. Variation profiles were tabulated via standardized rates of utilization and mortality to compare geographically heterogenous areas. RESULTS: 227,109 EGS operations were geospatially analyzed across the 6 states. Age-standardized EGS operation rates varied significantly by region (Northeast rate of 22.7 EGS operations per 10,000 in population versus Southeast 21.9; P < 0.001), state (ranging from 9.9 to 29.1; P < 0.001), and HSA (1.9-56.7; P < 0.001). The geographic variability in age-standardized EGS mortality rates was also significant at the region level (Northeast mortality rate 7.2 per 1000 operations vs Southeast 7.4; P < 0.001), state-level (ranging from 5.9 to 9.0 deaths per 1000 EGS operations; P < 0.001), and HSA-level (0.0-77.3; P < 0.001). Maps and variation profiles visually exhibited widespread and substantial differences in EGS use and morality. CONCLUSIONS: Wide geographic variations exist across 6 Northeastern and Southeastern US states in the rates of EGS operations and subsequent mortality. More detailed geographic analyses are needed to determine the basis of these variations and how they can be minimized.

Learning From England's Best Practice Tariff: Process Measure Pay-for-Performance Can Improve Hip Fracture Outcomes.

OBJECTIVE: The objective of this study was to evaluate England's Best Practice Tariff (BPT) and consider potential implications for Medicare patients should the US adopt a similar plan. SUMMARY BACKGROUND DATA: Since the beginning of the Affordable Care Act, Medicare has renewed efforts to improve the outcomes of older adults through introduction of an expanding set of alternative-payment models. Among trauma patients, recommended arrangements met with mixed success given concerns about the heterogeneous nature of trauma patients and resulting outcome variation. A novel approach taken for hip fractures in England could offer a viable alternative. METHODS: Linear regression, interrupted time-series, difference-in-difference, and counterfactual models of 2000 to 2016 Medicare (US), HES-APC (England) death certificate-linked claims (≥65 years) were used to: track US hip fracture trends, look at changes in English hip fracture trends before-and-after BPT implementation, compare changes in US-versus-English mortality, and estimate total/theoretical lives saved. RESULTS: A total of 806,036 English and 3,221,109 US hospitalizations were included. After BPT implementation, England's 30-day mortality decreased by 2.6 percentage-points (95%CI: 1.7-3.5) from a baseline of 9.9% (relative reduction 26.3%). 90- and 365-day mortality decreased by 5.6 and 5.4 percentage-points. 30/90/365-day readmissions also declined with a concurrent shortening of hospital length-of-stay. From 2000 to 2016, US outcomes were stagnant (P > 0.05), resulting in an inversion of the countries' mortality and >38,000 potential annual US lives saved. CONCLUSIONS: Process measure pay-for-performance led to significant improvements in English hip fracture outcomes. As efforts to improve US older adult health continue to increase, there are important lessons to be learned from a successful initiative like the BPT.

Evaluation of Firearm-Related Reinjury in Connecticut: An Opportunity for Gun Violence Prevention.

BACKGROUND: The regional extent of the risk of repeat firearm-related injury (FRI) and homicide mortality for victims of firearm injury in Connecticut is unknown. In this study, we evaluate the risk of repeat firearm injury in survivors of firearm violence in Connecticut. METHODS: Using medical record data from the Yale New Haven Health (YNHH) system and data from the Connecticut Office of the Chief Medical Examiner, we conducted a cohort study of patients with an FRI in 2014 to determine their risk of a repeat firearm injury or mortality from homicide in the ensuing 5 years compared with nonviolence-related trauma patient controls. RESULTS: We identified 94 patients with an FRI in the YNHH system from 2014 who survived to discharge. Of these patients, 8.5% (8 of 94) had a repeat FRI and 2% (2 of 94) died from homicide within the next 5 years. Compared with nonviolence-related trauma patients from 2014 (n = 2001), those with an FRI had 12 times the odds of a repeat firearm injury (odds ratio: 12.0, P = 0.047) in the next 5 years after adjustment for relevant covariates. CONCLUSIONS: Of the patients presenting with an initial FRI in the YNHH system, one in twelve will experience another firearm injury within the next 5 years. These data indicate that firearm-related reinjury is common in Connecticut and suggest the need for further violence prevention efforts.

Defining Referral Regions for Inpatient Trauma Care: The Utility of a Novel Geographic Definition.

INTRODUCTION: Geographic variation is an inherent feature of the US health system. Despite efforts to account for geographic variation in trauma system strengthening, it remains unclear how trauma "regions" should be defined. The objective of this study is to evaluate the utility of a novel definition of Trauma Referral Regions (TRR) for assessing geographic variation in inpatient trauma across the age span of hospitalized trauma patients. METHODS: Using 2016-2017 State Inpatient Databases, we assessed the extent of geographic variability in three common metrics of hospital use (localization index, market share index, net patient flow) among TRRs and, as a comparison, trauma regions alternatively defined based on Hospital Referral Regions, Hospital Service Areas, and counties. RESULTS: A total of 860,593 admissions from 102 TRRs, 127 Hospital Referral Regions, 884 Hospital Service Areas, and 583 counties were included. Consistent with expectations for distinct trauma regions, TRR presented with high average localization indices (mean [standard deviation]: 83.4 [11.7%]), low market share indices (mean [standard deviation]: 11.9 [7.0%]), and net patient flows close to 1.00. Similar results were found among stratified pediatric, adult, and older adult patients. Associations between TRRs and variations in important demographic features (e.g., travel time by road to the nearest Level I or II Trauma Center) suggest that while indicative of standalone trauma regions, TRRs are also able to simultaneously capture critical variations in regional trauma care. CONCLUSIONS: TRRs offer a standalone set of geographic regions with minimal variation in common metrics of hospital use, minimal geographic clustering, and preserved associations with important demographic factors. They provide a needed, valid means of assessing geographic variation among trauma systems.

Assessing the Race, Ethnicity, and Gender Inequities in Blood Alcohol Testing After Trauma.

INTRODUCTION: Alcohol use remains a significant contributing factor in traumatic injuries in the United States, resulting in substantial patient morbidity and societal cost. Because of this, the American College of Surgeons Verification, Review, and Consultation Program requires the screening of 80% of trauma admissions. Multiple studies suggest that patients who use alcohol are subject to stigma by health care providers and may ultimately face legal and financial ramifications of a positive alcohol screening test. There is also evidence that sociodemographic factors may dictate drug and alcohol screening patterns among patients. Because this screening target is often not uniformly achieved among all patients presenting with injury, we sought to investigate whether there are any discrepancies in screening across sociodemographic groups. METHODS: We investigated the Trauma Quality Program Participant User File for all trauma cases admitted during 2017 and compared the rates of the serum alcohol screening test across different demographic factors, including race and ethnicity. We then performed an adjusted multivariable logistic regression to determine the odds ratio (OR) for receiving a test based on these demographic factors adjusted for hospital and clinical factors. RESULTS: There were 729,174 traumas included in the study. Of this group, 345,315 (47.4%) were screened with a serum alcohol test. Screening rates varied by injury mechanism and were highest among motorcycle crashes (66.0% of patients screened) and lowest among falls (32.8% of patients screened). Overall, Asian and Pacific Islander (52.5% screened), Black (57.7% screened), and other race (58.4% screened) had higher rates of alcohol screening than White patients (43.7% screened, P < 0.001). Similarly, Hispanic patients were screened at higher rates than non-Hispanic patients (56.4% screening versus 46.2% screening, P < 0.001). These differences persisted across nearly all injury categories. In multivariable logistic regression, Asian and Pacific Islanders were associated with the highest odds of being screened (OR 1.34, P < 0.001) followed by other race (OR 1.25, P < 0.001) in comparison to White patients. CONCLUSIONS: There are consistent and significant differences in alcohol screening rates across race and ethnicity, despite accounting for injury mechanism and comorbidities.

Infusing geriatrics expertise in health professions education through interprofessional faculty development.

As the population of older adults continues to grow, the need for health care professionals trained in the delivery of interprofessional care for older adult patients is critical. The purpose of this paper is to detail the outcomes of an interprofessional, geriatrics training program for healthcare professionals with a faculty appointment. Specifically, we gathered outcomes at four levels: reactions/satisfaction, learning, behavioral, and organizational. Our findings suggest that programs structured like the Faculty Development Program (FDP) have the potential to increase the amount of geriatrics content introduced in already existing health professions curricula, as well as to offer faculty needed training in how to provide their students with interprofessional learning experiences.

Learning by Doing: Student & Faculty Reflections on a Collaborative Model for Conducting and Publishing Mixed Methods Research in a Graduate Course.

Due to time constraints and faculty resources, one-semester research methods courses, especially mixed methods, often do not result in meaningful student-produced work that contributes to scholarly literature. As publishing increasingly becomes expected for graduate students, instructors may seek ways to incorporate publishing opportunities into course curriculum. This case study presents one instructor's collaborative teaching and publishing model along with graduate student feedback and recommendations for reproducibility of the course model. The model described in the course-based research model vignette was designed to give students practical experience working with raw data, presenting preliminary findings, navigating the IRB process, drafting a manuscript, determining authorship, and identifying and submitting the manuscript to a journal. Acknowledging the importance of and the challenges to graduate student publishing, the instructor in this case study sought to reduce some of the barriers for students. Post-course, the researchers employed a single-case study methodology that includes elements of participatory action research to answer research questions about student participants' learning experiences related to conducting a collaborative mixed methods study and the research and publishing process. The interview protocol included questions about the participants' perceptions about the success of the collaborative teaching methods to teach mixed methods research, their prior experience with research projects, and their interest and engagement with the publishing process during and after the course. The discussion includes practical information for instructors interested in implementing a similar model.

Anticoagulation is Associated with Increased Mortality in Splenic Injuries.

INTRODUCTION: Anticoagulation (AC) is associated with worse outcomes after trauma in some but not all studies. To further investigate the effect of AC on outcomes in patients with splenic injury, we analyzed the Trauma Quality Programs Participant Use File (PUF) METHODS: The 2017 PUF was used to identify adult (18+ y) with all mechanisms and grades of splenic injury. Demographics, comorbidities, hospital course and outcomes were compared between AC and non-AC patients. RESULTS: A total of 18,749 patients were included, 622 were on AC. The AC patients were older but had comparable gender composition to non-AC patients. Injury Severity Score (18.2 versus 22.5) and rates of serious (AIS ≥ 3) injury were all lower in the AC group (P = 0.001). AC patients received fewer units of RBC (5.7 versus 8.0 units, P < 0.001) and FFP (3.9 versus 5.4 units, P < 0.001) in the first 24 h but underwent angiography at similar rates (23.6 versus 24.5%, P = 0.8). Among those who underwent angiography, patients were more likely to undergo embolization if they were on AC (89.7 versus 73.9%, P = 0.04). Rates of splenic surgery were comparable (19.3 versus 21.5%, P = 0.2) between AC versus non-AC patients. Median LOS was longer in AC patients (6.3 versus 5.6 d, P = 0.002). AC patients had a higher mortality (13.3 versus 7.0%, P = 0.001). In a multivariable binary logistic regression, AC was an independent risk factor for mortality with OR 1.4 (95% CI: 1.1-1.9) CONCLUSIONS: Anticoagulation is associated with increased mortality in patients with splenic injury.

Choosing the Best Approach to Warfarin Reversal After Traumatic Intracranial Hemorrhage.

BACKGROUND: Patients on warfarin with traumatic intracranial hemorrhage often have the warfarin effects pharmacologically reversed. We compared outcomes among patients who received 4-factor prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), or no reversal to assess the real-world impact of PCC on elderly patients with traumatic intracranial hemorrhage (ICH). MATERIALS AND METHODS: This was a retrospective analysis of 150 patients on preinjury warfarin. Data were manually abstracted from the electronic medical record of an academic level 1 trauma center for patients admitted between January 2013 and December 2018. Outcomes were ICH progression on follow-up computed tomography scan, mortality, need for surgical intervention, and trends in the use of reversal agents. RESULTS: Of 150 patients eligible for analysis, 41 received FFP, 60 PCC, and 49 were not reversed. On multivariable analysis, patients not reversed [OR 0.25 95% CI (0.31-0.85)] and women [OR 0.38 95% CI (0.17-0.88)] were less likely to experience progression of their initial bleed on follow-up computed tomography while subdural hemorrhage increased the risk [OR 3.69 95% CI (1.27-10.73)]. There was no difference between groups in terms of mortality or need for surgery. Over time use of reversal with PCC increased while use of FFP and not reversing warfarin declined (P < 0.001). CONCLUSIONS: Male gender and using a reversal agent were associated with progression of ICH. Choice of reversal did not impact the need for surgery, hospital length of stay, or mortality. Some ICH patients may not require warfarin reversal and may bias studies, especially retrospective studies of warfarin reversal.

Very Long-Term Outcomes in Children Admitted in a Disorder of Consciousness After Severe Traumatic Brain Injury.

OBJECTIVES: To investigate functional outcomes and state of consciousness at 1 year and ≥2 years postinjury in children who sustained a traumatic brain injury and were in a disorder of consciousness (DOC), either vegetative state (VS) or minimally conscious state (MCS), upon admission to inpatient rehabilitation. DESIGN: Retrospective chart review. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Children aged 2-18 years (N=37) who were admitted to inpatient rehabilitation with admission scores <30 on the Cognitive and Linguistic Scale (CALS). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale- Extended, Pediatric Revision (GOS-E Peds), and state of consciousness based on previously established guidelines. RESULTS: At admission, 16 children were in VS (43.2%) and 21 (56.8%) were in MCS. Children admitted in VS had a significantly longer time from injury to inpatient rehabilitation admission, lower CALS admission scores, were more likely to be in a DOC ≥28 days, and had greater disability at both follow-up time points. At the 1-year follow-up, 3 patients were in VS, 7 were in MCS, and 27 had emerged from MCS. By the time of the most recent follow-up (≥2y), 2 more patients had emerged from MCS. Across the cohort, GOS-E Peds scores at 1 year ranged from VS (GOS-E Peds, 7) to upper moderate disability (GOS-E Peds, 3). Most patients were functioning in the lower severe disability category (GOS-E Peds, 6) at 1 year (43.2%) and at the time of the most recent follow-up (43.2%). Twenty-seven patients (73.0%) showed stable GOS-E Peds scores between the 2 time points, 6 (16.2%) improved, and 4 (10.8%) were deceased. CONCLUSIONS: Although a majority of patients emerged from a DOC by 1 year postinjury, most continued to demonstrate notable functional impairment at the 1-year follow-up that persisted to the most recent follow-up. A small subset demonstrated important improvements between 1 year and the most recent follow-up (2 patients emerged, 6 patients showed improvement in GOS-E Peds scores).

Morbidity and mortality of rheumatic heart disease and acute rheumatic fever in the inpatient setting in Timor-Leste.

AIM: To describe the clinical features, treatment and outcomes of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children admitted to the national referral hospital in Dili, Timor-Leste. METHODS: This prospective study documented cases of ARF and RHD in children aged 14 years and under who were admitted between June 2017 and May 2019. ARF was diagnosed using an adapted version of the 2015 Jones criteria and presumed (rather than proven) exposure to group A Streptococcus. Clinical and echocardiographic findings, comorbidities and discharge outcomes are reported. RESULTS: A total of 63 patients were admitted with ARF or RHD; 54 were diagnosed with RHD for the first time. Median age was 11 years (range 3-14); 48% were female. Of those with echocardiograms, 56/58 had RHD, 55/56 (98%) had mitral regurgitation (37/55 (67%) severe), 11/56 (20%) had mitral stenosis and 43/56 (77%) had aortic regurgitation. Left ventricular dysfunction (55%), pulmonary hypertension (64%) and cardiac failure (78%) were common. Four (6%) patients died in hospital, and 30/59 (51%) of surviving patients were lost to follow up. CONCLUSIONS: Community echocardiography screening has reported a high prevalence of undetected mild to moderate cases of RHD in Timor-Leste, whereas this hospital study documents mostly severe disease among hospitalised patients with a high case fatality rate and loss to follow up. RHD is a significant health problem in Timor-Leste and improved recognition and diagnosis, as well as effective delivery of treatment and follow-up are imperative.

Evaluation of an interprofessional, evidence-based falls training.

Fall-related injuries and mortality are increasing in older adults. Evidence suggests a need for a multifactorial, interprofessional approach to reducing falls. The Program for All-Inclusive Care for the Elderly (PACE) utilizes an interprofessional approach to care and serves a high-risk population. The purpose of this study was to investigate the effectiveness of an EBP falls prevention training program conducted at a PACE. The program was a revision of an established program and was led by an interprofessional team. The evaluation used a mixed-methods approach to assess program quality, learning and self-efficacy gains, and intended behavioral changes. Quantitative evaluation demonstrated program satisfaction and qualitative responses identified the depth and interprofessional delivery as favorable. Qualitative data identified opportunities to enhance content and learning design. Overall knowledge gains were statistically significant (mean difference 5%), with the greatest gains related to the evidence base (mean difference 2.67%). Self-efficacy ratings increased significantly after each session. Participants noted changes to team function and a willingness to consider practice changes as a result of the training. The findings support the effectiveness of this interprofessional, EBP training program on falls prevention practices in a PACE and highlight the value of a multifaceted assessment and iterative development.

For the Greater (Bacterial) Good: Heterogeneous Expression of Energetically Costly Virulence Factors.

Bacterial populations are phenotypically heterogeneous, which allows subsets of cells to survive and thrive following changes in environmental conditions. For bacterial pathogens, changes within the host environment occur over the course of the immune response to infection and can result in exposure to host-derived, secreted antimicrobials or force direct interactions with immune cells. Many recent studies have shown host cell interactions promote virulence factor expression, forcing subsets of bacterial cells to battle the host response, while other bacteria reap the benefits of this pacification. It still remains unclear whether virulence factor expression is truly energetically costly within host tissues and whether expression is sufficient to impact the growth kinetics of virulence factor-expressing cells. However, it is clear that slow-growing subsets of bacteria emerge during infection and that these subsets are particularly difficult to eliminate with antibiotics. This minireview will focus on our current understanding of heterogenous virulence factor expression and discuss the evidence that supports or refutes the hypothesis that virulence factor expression is linked to slowed growth and antibiotic tolerance.