The Challenge of Patient Notification and the Work of Follow-Up Generated by a 2-Step Testing Protocol for Group A Streptococcal Pharyngitis in the Pediatric Emergency Department.

OBJECTIVE: Current guidelines recommend confirmatory testing for negative rapid antigen detection tests (RADTs) for group A streptococcal pharyngitis in children. We sought to describe the work of follow-up generated by this process and frequency of our inability to notify patients of positive results. METHODS: We retrospectively reviewed laboratory and outreach nurse records of patients who had group A streptococcal pharyngitis testing performed in an academic pediatric emergency department during 2014. For patients with a negative RADT and subsequent positive backup direct nucleic acid probe test, we recorded whether the patient was successfully notified of the positive result, the number of contact attempts, and the time to antibiotic prescription. RESULTS: There were 6504 patients who had an RADT performed, of which 5474 (84.2%) were negative with a confirmatory test performed. There were 234 patients with positive confirmatory testing and not prescribed antibiotics at the time of the initial visit. Of these, 90.1% were ultimately contacted and prescribed appropriate antibiotics, whereas 7.3% were lost to follow-up and 2.6% had potentially unnecessary repeat visits. Of those contacted, 43.1% were reached only after multiple telephone calls or a letter. The median time from the negative RADT to the submission of an electronic prescription was 19.6 hours (interquartile range, 7.5-24.9 hours; range, 6-144 hours). CONCLUSIONS: Although confirmatory testing after a negative RADT in children is currently the standard of care, this practice requires a substantial amount of work. Furthermore, a significant fraction of patients are lost to follow-up or have unnecessary repeat visits.

Accurate PCR Detection of Influenza A/B and Respiratory Syncytial Viruses by Use of Cepheid Xpert Flu+RSV Xpress Assay in Point-of-Care Settings: Comparison to Prodesse ProFlu.

The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting.

Climate research priorities for policy-makers, practitioners, and scientists in Georgia, USA.

Climate change has far-reaching effects on human and ecological systems, requiring collaboration across sectors and disciplines to determine effective responses. To inform regional responses to climate change, decision-makers need credible and relevant information representing a wide swath of knowledge and perspectives. The southeastern U. S. State of Georgia is a valuable focal area for study because it contains multiple ecological zones that vary greatly in land use and economic activities, and it is vulnerable to diverse climate change impacts. We identified 40 important research questions that, if answered, could lay the groundwork for effective, science-based climate action in Georgia. Top research priorities were identified through a broad solicitation of candidate research questions (180 were received). A group of experts across sectors and disciplines gathered for a workshop to categorize, prioritize, and filter the candidate questions, identify missing topics, and rewrite questions. Participants then collectively chose the 40 most important questions. This cross-sectoral effort ensured the inclusion of a diversity of topics and questions (e.g., coastal hazards, agricultural production, ecosystem functioning, urban infrastructure, and human health) likely to be important to Georgia policy-makers, practitioners, and scientists. Several cross-cutting themes emerged, including the need for long-term data collection and consideration of at-risk Georgia citizens and communities. Workshop participants defined effective responses as those that take economic cost, environmental impacts, and social justice into consideration. Our research highlights the importance of collaborators across disciplines and sectors, and discussing challenges and opportunities that will require transdisciplinary solutions.

Outbreaks of Disease Associated with Food Imported into the United States, 1996-20141.

The proportion of US food that is imported is increasing; most seafood and half of fruits are imported. We identified a small but increasing number of foodborne disease outbreaks associated with imported foods, most commonly fish and produce. New outbreak investigation tools and federal regulatory authority are key to maintaining food safety.

Polymorphisms in α-Defensin-Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux.

The contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real-time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk.

Evaluation of novel urinary tract infection biomarkers in children.

BACKGROUND: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children. METHODS: We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1-3, and test combinations were compared. RESULTS: For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82-0.93), respectively. Compared to LE ≥ trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone. CONCLUSION: Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children.

Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic Acid Amplification Test.

Rapid detection of group A beta-hemolytic streptococcus (GAS) is used routinely to help diagnose and treat pharyngitis. However, available rapid antigen detection tests for GAS have relatively low sensitivity, and backup testing is recommended in children. Newer assays are more sensitive yet require excessive time for practical point-of-care use as well as laboratory personnel. The Alere i strep A test is an isothermal nucleic acid amplification test designed to offer highly sensitive results at the point of care within 8 min when performed by nonlaboratory personnel. The performance of the Alere i strep A test was evaluated in a multicenter prospective trial in a Clinical Laboratory Improvement Amendments (CLIA)-waived setting in comparison to bacterial culture in 481 children and adults. Compared to culture, the Aleri i strep A test had 96.0% sensitivity and 94.6% specificity. Discrepant results were adjudicated by PCR and found the Alere i strep A test to have 98.7% sensitivity and 98.5% specificity. Overall, the Alere i strep A test could provide a one-step, rapid, point-of-care testing method for GAS pharyngitis and obviate backup testing on negative results.

An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract.

Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has a broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7, but regulation of its antimicrobial activity has not been well defined. Here, we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on the antimicrobial activity of RNase 7. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time polymerase chain reaction showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility.

Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract.

The mechanisms that maintain sterility in the urinary tract are incompletely understood; however, recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Ribonuclease 7 (RNase 7), a potent antimicrobial peptide contributing to urinary tract sterility, is expressed by intercalated cells in the renal collecting tubules and is present in the urine at levels sufficient to kill bacteria at baseline. Here, we characterize the expression and function of RNase 7 in the human urinary tract during infection. Both quantitative real-time PCR and enzyme-linked immunosorbant assays demonstrated increases in RNASE7 expression in the kidney along with kidney and urinary RNase 7 peptide concentrations with infection. While immunostaining localized RNase 7 production to the intercalated cells of the collecting tubule during sterility, its expression during pyelonephritis was found to increase throughout the nephron but not in glomeruli or the interstitium. Recombinant RNase 7 exhibited antimicrobial activity against uropathogens at low micromolar concentrations by disrupting the microbial membrane as determined by atomic force microscopy. Thus, RNase 7 expression is increased in the urinary tract with infection and has antibacterial activity against uropathogens at micromolar concentrations.

Contribution of structural domains to the activity of ribonuclease 7 against uropathogenic bacteria.

Ribonuclease 7 (RNase 7) is a 14.5-kDa peptide that possesses potent antimicrobial properties against Gram-negative and Gram-positive bacteria and is expressed in a variety of epithelial tissues. Little is known about its mechanisms of action and the determinants of its antimicrobial properties. The objective of this study was to identify the intrinsic functional domains of RNase 7 that influence its activity against uropathogenic bacteria. A series of RNase 7 fragments were generated that contained different components of its secondary motifs starting from both the N terminus and the C terminus of RNase 7. We determined the antimicrobial properties of each fragment against both Gram-positive Staphylococcus saprophyticus and Gram-negative Escherichia coli and Proteus mirabilis. RNase 7 fragments displayed significant differences in their antimicrobial activity profiles. Compared to N-terminal fragments, C-terminal fragments showed uniformly decreased activity against Gram-negative E. coli and P. mirabilis and Gram-positive S. saprophyticus. Fragments that lack ß-sheets 1, 3, and 4 also demonstrated significantly decreased activities. We have also identified one fragment with at least 4-fold increased potency against both E. coli and Staphylococcus compared to full-length peptide. We identified distinct regions of the peptide that are independently responsible for Gram-negative and Gram-positive activity. Our results suggest that distinct mechanisms are responsible for RNase 7's antimicrobial activity against various uropathogens.

Rising oceans, flooded towns: How Georgia coastline communities are readying to recover despite a changing climate.

Climate change is posing a significant threat to the coastal counties of Georgia. The Georgia Department of Natural Resources and Hagerty Consulting have recognised this threat and are facilitating a nine-year project aimed at developing a disaster recovery and redevelopment plan for the state's coastal communities, and providing state-wide technical assistance. This paper provides an overview of this planning initiative and summarises the many insights into the pre-disaster recovery and resilience planning process gained from this project.

Community-University Partnership Characteristics for Translation: Evidence From CDC's Prevention Research Centers.

Background: The Centers for Disease Control and Prevention's Prevention Research Centers (PRC) Program supports community engagement and partnerships to translate health evidence into practice. Translation is dependent on the quality of partnerships. However, questions remain about the necessary characteristics to develop and maintain translation partnerships. Aim: To identify the characteristics that influence community-university partnerships and examine alignment with the Knowledge to Action (K2A) Framework. Methods: Final Progress Reports (N = 37) from PRCs funded from September 2009 to September 2014 were reviewed in 2016-2017 to determine eligibility. Eligible PRCs included those that translated an innovation following the applied research phase (2009-2014) of the PRC award (n = 12). The PRCs and the adopters (i.e., community organizations) were recruited and participated in qualitative interviews in 2017. Results: Ten PRCs (83.3% response rate) and four adopters participated. Twelve codes (i.e., elements) were found that impacted partnerships along the translation continuum (e.g., adequate communication, technical assistance). Each element aligned with the K2A Framework at multiple steps within the translation phase. The intersection between the element and step in the translation phase is termed a "characteristic." Using interview data, fifty-two unique partnership characteristics for translation were found. Discussion and Conclusion: The results suggest multiple characteristics that impact translation partnerships. The inclusion of these partnership characteristics in policies and practices that seek to move practice-based or research-based evidence into widespread use may impact the receptivity by partners and evidence uptake by communities. Using the K2A Framework to assess translation partnerships was helpful and could be considered in process evaluations to inform translation partnership improvement.

A Comparison of National Pediatric Procedures Training Guidelines With Actual Clinical Practice in Ohio.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) and Pediatrics Review Committee (RC) recommends the clinical procedures residents should master during their training. These guidelines may be partially based on consensus opinion or tradition rather than actual need. The literature defining which procedures general pediatricians actually perform in practice is limited. OBJECTIVE: Our objective was to determine how often general pediatricians perform procedures recommended by accreditation bodies, how well prepared they feel to perform them, and how important the procedures are to their practice. METHODS: We categorized recommended procedures as emergent, urgent, or office-based, then developed and administered a survey in 2017 based on these classes. We randomly sampled and polled 439 general pediatricians from urban, suburban, or rural regions across central Ohio. Responses were compared using the Welch ANOVA, Mann Whitney U, and post-hoc tests. RESULTS: The response rate was 60% (265 of 439). Pediatricians almost never performed 11 of 13 recommended procedures, yet felt well prepared to perform them all and believed that all were important. Rural pediatricians performed significantly more emergent and office-based procedures and rated them as more important. Commonly performed non-ACGME/RC procedures were circumcision, wart removal, cerumen removal, umbilical cauterization, and suture removal. CONCLUSIONS: Findings suggest that pediatricians rarely perform most of the recommended procedures, but think they are important. There are several office-based non-ACGME recommended procedures that pediatricians commonly perform. Regional differences suggest the need for customized training based on future practice plans.

Pediatric Emergency Medicine Physicians' Use of Point-of-care Ultrasound and Barriers to Implementation: A Regional Pilot Study.

OBJECTIVES: Point-of-care ultrasound (POCUS) has been identified as a critical skill for pediatric emergency medicine (PEM) physicians. The purpose of this study was to profile the current status of PEM POCUS in pediatric emergency departments (EDs). METHODS: An electronic survey was distributed to PEM fellows and attending physicians at four major pediatric academic health centers. The 24-item questionnaire covered professional demographics, POCUS experience and proficiency, and barriers to the use of POCUS in pediatric EDs. We used descriptive and inferential statistics to profile respondent's PEM POCUS experience and proficiency and Rasch analysis to evaluate barriers to implementation. RESULTS: Our return rate was 92.8% (128/138). Respondents were attending physicians (68%) and fellows (28%). Most completed pediatric residencies prior to PEM fellowship (83.6%). Almost all had some form of ultrasound education (113/128, 88.3%). Approximately half (46.9%) completed a formal ultrasound curriculum. More than half (53.2%) said their ultrasound education was pediatric-specific. Most participants (67%) rated their POCUS proficiency low (Levels 1-2), while rating proficiency in other professional competencies (procedures 52%, emergency stabilization 70%) high (Levels 4-5). There were statistically significant differences in POCUS proficiency between those with formal versus informal ultrasound education (p < 0.001) and those from pediatric versus emergency medicine residencies (p < 0.05). Participants identified both personal barriers discomfort with POCUS skills (76.7%), insufficient educational time to learn POCUS (65%), and negative impact of POCUS on efficiency (58.5%)-and institutional barriers to the use of ultrasound-consultants will not use ultrasound findings from the ED (60%); insufficient mentoring (64.7%), and POCUS not being a departmental priority (57%). CONCLUSIONS: While POCUS utilization continues to grow in PEM, significant barriers to full implementation still persist. One significant barrier relates to the need for dedicated time to learn and practice POCUS to achieve sufficient levels of proficiency for use in practice.

Barriers to Seizure Management in Schools: Perceptions of School Nurses.

The purpose of this study was to assess school nurses' perceptions of barriers to optimal management of seizures in schools. Eighty-three school nurses completed an electronic survey. Most agreed they felt confident they could identify a seizure (97.6%), give rectal diazepam (83.8%), and handle cluster seizures (67.1%), but fewer were confident they could give intranasal midazolam (63.3%), had specific information about a student's seizures (56.6%), or could swipe a vagus nerve stimulator magnet (47.4%). Nurses were more likely to be available at the time of a seizure in rural (17/20) (85%) versus suburban (21/34) (62%) or urban (8/25) (32%) schools (P = .001). School nurses are comfortable managing seizures in the school setting. However, a specific seizure plan for each child and education on intranasal midazolam and vagus nerve stimulator magnet use are needed. A barrier in urban schools is decreased availability of a nurse to identify seizures and administer treatment.

Expression and antimicrobial function of beta-defensin 1 in the lower urinary tract.

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1(-/-)) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1(-/-) and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.