The Effect of Early Knowledge of Respiratory Syncytial Virus Positivity on Medical Decision Making and Throughput Time Within the Pediatric Emergency Department.

OBJECTIVE: The aim of this study was to evaluate whether early knowledge of respiratory syncytial virus (RSV) positivity by rapid triage-based testing protocol improved emergency department (ED) throughput time and decreased ED ancillary testing and antibiotic administration. METHODS: A retrospective cohort study was performed of ED patients aged 2 to 12 months, presenting November 1 to March 31 for the years 2008-2013. Included patients presented with fever and upper respiratory tract symptoms. Patients were excluded if they tested positive for influenza, had chronic underlying medical problems, or were admitted or transferred from an outside facility or if no RSV result was documented. The study group was compared with infants who tested negative for RSV by the triage-based protocol and were diagnosed as having (1) bronchiolitis and (2) a viral illness. RESULTS: Of 899 patients tested for RSV within triage, the study included 713 (79%); 231 (35.3%) tested positive for RSV. When comparing children diagnosed as having bronchiolitis, there was no statistically significant difference between RSV positive and negative in ED throughput time, ED administered antibiotics, or chest radiographs, urine analyses, blood cultures, or lumbar punctures obtained. When comparing children diagnosed as having a viral illness, RSV-positive patients had less chest radiographs, urine analysis, and blood cultures performed. CONCLUSIONS: Identifying the virus responsible for bronchiolitis through a triage-based protocol does not decrease ED throughput time, antibiotic administration, or chest radiographs, urine analysis, or blood cultures obtained. In infants presenting with upper respiratory tract symptoms and fever, knowing RSV infectivity through a triage-based protocol does significantly decrease chest radiographs, urine analysis, and blood cultures obtained.

Can a Septic Hip Decision Rule Aid in the Evaluation of Suspected Pediatric Musculoskeletal Infections?

BACKGROUND: Musculoskeletal (MSK) infections can be difficult to diagnose in acute care settings. The utility of clinical decision tools for pediatric MSK infections in an emergency department has not been well studied. OBJECTIVE: Our aim was to evaluate the performance of a septic hip clinical decision rule (CDR) in the evaluation of pediatric musculoskeletal infections. METHODS: We performed a retrospective study of children evaluated for an MSK infection in our emergency department from 2014 to 2016. Data collection included demographics, discharge diagnoses, and clinical/laboratory predictors from the CDR. A χ2 analysis and Wilcoxon rank-sum tests compared patients with and without MSK infections. Logistic regression analysis examined the predictors for MSK infections. A receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the predictors. RESULTS: Of 996 evaluations included in the final analysis, 109 (10.9%) had MSK infections. In a multivariable model, an adjusted odds ratio (OR) was significant for fever (OR 3.9, 95% confidence interval [CI] 2.4-6.4), refusal to bear weight/pseudoparalysis (OR 4.4, 95% CI 2.7-7.1), and C-reactive protein (CRP) > 2.0 mg/dL (OR 5.4, 95% CI 3.2-9.1). The probability of infection was 75.1% with five predictors present, 1.9% for zero predictors, and 5.1% if one predictor was present. An ROC curve showed an area under the curve of 0.82, indicating moderate accuracy. CONCLUSIONS: A septic hip CDR demonstrates a low predicted probability of an MSK infection with zero or one clinical predictor present and moderate predictability with all five predictors. Fever, refusal to bear weight/pseudoparalysis, and CRP > 2.0 mg/dL performed best and should alert providers to consider other MSK infections in addition to septic arthritis.

Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department.

OBJECTIVES: Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED). METHODS: A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate. RESULTS: Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM. CONCLUSIONS: The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.

A Quality Improvement Bundle Including Pay for Performance for the Standardization of Order Set Use in Moderate Asthma.

OBJECTIVE: In order to standardize use of our hospital's computerized asthma order set, which was developed based on an asthma clinical practice guideline, for moderately ill children presenting for care of asthma, we developed a quality improvement bundle, including a time-limited pay-for-performance component, for pediatric emergency department and pediatric urgent care faculty members. METHODS: Following baseline measurement, we used a run-in period for education, feedback, and improvement of the asthma order set. Then, faculty members earned 0.1% of salary during each of 10 successive months (evaluation period) in which the asthma order set was used in managing 90% or more of eligible patients. RESULTS: At baseline, the asthma order set was used in managing 60.5% of eligible patients. Order set use rose sharply during the run-in period. During the 10-month evaluation period, use of the asthma order set was significantly above baseline, with a mean of 91.6%; faculty earned pay-for-performance bonuses during 8 of 10 possible months. Following completion of the evaluation period, asthma order set use remained high. CONCLUSIONS: A quality improvement bundle, including a time-limited pay-for-performance component, was associated with a sustained increase in the use of a computerized asthma order set for managing moderately ill asthmatic children.

System Stresses in 2 Pediatric Emergency Departments and 2 Pediatric Urgent Care Centers During the 2014 Enterovirus-D68 Outbreak.

OBJECTIVE: To describe the association of an unprecedented large-scale Enterovirus-D68 outbreak in 2014 with changes in patient volume and acuity and system stress in 2 pediatric emergency departments and 2 pediatric urgent care centers of a single children's hospital. METHODS: We compared measures of patient volume, acuity, and system stress during the 2014 Enterovirus-D68 outbreak and the corresponding dates of the previous year. RESULTS: Both settings experienced large census increases during the Enterovirus-D68 outbreak; patient census increased significantly more in the pediatric urgent care setting (20.3%) than in the pediatric emergency departments (14.3%). Both settings had significant increases in patient acuity. The proportion of pediatric emergency department patients requiring hospital admission increased; the proportion of patients who left the pediatric urgent care setting without being seen also increased. Although there was no emergency department inpatient boarding during the 2013 comparison period, 4.4% of admitted patients required emergency department boarding during the 2014 outbreak. There was no significant change in the mean length of stay or the probability that patient admission was to the pediatric intensive care unit. CONCLUSIONS: Both the pediatric emergency departments and the pediatric urgent care centers experienced increased patient volumes and acuity and significant system stress in association with the 2014 Enterovirus-D68 outbreak. These data will inform those planning resource allocation for future large-scale viral outbreaks.

Grueneberg Glomeruli in the Olfactory Bulb are Activated by Odorants and Cool Temperature.

Neurons of the Grueneberg ganglion respond to cool temperatures as well as to distinct odorants and extend axonal processes to the olfactory bulb of the brain. Analyses of transgenic mice, in which Grueneberg ganglion neurons and their axons are labeled, revealed that these axons innervated nine distinct glomeruli distributed in a characteristic topographical pattern in dorsal, lateral, ventral, and medial regions of rather posterior areas in the bulb. To assess activation of these glomeruli (hereinafter designated as Grueneberg glomeruli) upon stimulation of Grueneberg ganglion neurons, mice were exposed to the odorant 2,3-dimethylpyrazine (2,3-DMP) and the expression of the activity-dependent marker c-Fos in juxtaglomerular cells of the relevant glomeruli was monitored. It was found that all of these glomeruli were activated, irrespective of their localization in the bulb. To verify that the activation of juxtaglomerular cells in Grueneberg glomeruli was indeed based on stimulation of Grueneberg ganglion neurons, the 2,3-DMP-induced responses in these glomeruli were investigated in mice lacking the cyclic nucleotide-gated channel CNGA3 which is critical for chemo- and thermosensory signal transduction in Grueneberg ganglion neurons. This approach revealed that elimination of CNGA3 led to a reduction of the odorant-induced activity in Grueneberg glomeruli, indicating that the activation of these glomeruli is based on a preceding stimulation of the Grueneberg ganglion. Analyzing whether Grueneberg glomeruli in the bulb might also process thermosensory information, it was found that upon exposure to coolness, Grueneberg glomeruli were activated. Investigating mice lacking CNGA3, the activation of these glomeruli by cool temperatures was attenuated.

Assessing Structural Quality Elements of Pediatric Emergency Care.

BACKGROUND AND OBJECTIVE: Emergency departments must have appropriate resources and equipment available to meet the unique needs of children. We assessed the availability of stakeholder-endorsed quality structure performance measures for pediatric emergency department patients. METHODS: A survey of Child Health Corporation of America member hospitals was conducted. Six broad equipment groups were queried: general, monitoring, respiratory, vascular access, fracture-management, and specialized pediatric trays. Equipment availability was determined at the level of the individual item, 6 broad groups, and 44 equipment subgroups. The survey queried the availability of 8 protocol/procedure elements: method to identify age-based abnormal vital signs, patient-centered care advisory council, bronchiolitis evidence-based guideline, pediatric radiation dosing standards, suspected child abuse protocols, use of validated pediatric triage tool, and presence of nurse and physician pediatric coordinators. RESULTS: Fifty-two percent (22/42) of sites completed the survey. Forty-one percent reported availability of all 113 recommended equipment items. Every hospital reported complete availability of equipment in 77% of the subgroups. The most common missing items were adult-sized lumbar puncture needles, hypothermia thermometers, and various sizes of laryngeal mask airways. Regarding the protocol/procedure elements, a method to identify age-based abnormal vital signs, pediatric radiation dosing standard, and nurse and physician pediatric coordinators were present in 100%. Ninety-five percent used a validated triage tool and had suspected child abuse protocols. CONCLUSIONS: Presence of necessary pediatric emergency equipment is better in the surveyed hospitals than in prior reports. Most responding hospitals have important protocol/procedures in place. These data may provide benchmarks for optimal care.

Glucocorticoid use is associated with increase in HDL and no change in other lipids in rheumatoid arthritis patients.

The aim of this article was to examine the association of glucocorticoid use and dose and changes in the lipid profile in rheumatoid arthritis (RA) patients. RA patients between January 1, 2001, and November 30, 2011, who received oral or intravenous glucocorticoids and who had lipid levels within 1 year before and 1 year after ongoing (at least 3 months) glucocorticoids use along with RA patients who did not take glucocorticoids (controls) were included. Glucocorticoid exposure was calculated as a weighted daily dose in prednisone equivalents and analyzed using as cutoff dose prednisone equivalent of 7.5 mg/day. Outcomes were changes in high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), triglycerides, and TC/HDL ratio and were calculated in linear regression models adjusting for relevant confounders. In total, 202 subjects on glucocorticoids and 436 controls were included. The glucocorticoid group of ≥7.5 mg/day had the greatest increase in HDL of 6.0 mg/dL (p = 0.003 compared to controls) with lower increases of 3.1 and 2.4 mg/dL in the glucocorticoid group of <7.5 mg/day and controls, respectively. There were no significant differences in other parameters of the lipid profile between the two glucocorticoid groups and controls. In this RA cohort, glucocorticoid dose equivalent of prednisone ≥7.5 mg/day was associated with increased HDL and no change in LDL or TC/HDL ratio compared to no glucocorticoid use These results suggest that this glucocorticoid dose is not associated with an atherogenic lipid profile in RA, a finding that is important in this patient population at high risk for cardiovascular disease.

Proteomic and pathway analyses reveal a network of inflammatory genes associated with differences in skin tumor promotion susceptibility in DBA/2 and C57BL/6 mice.

Genetic susceptibility to two-stage skin carcinogenesis is known to vary significantly among different stocks and strains of mice. In an effort to identify specific protein changes or altered signaling pathways associated with skin tumor promotion susceptibility, a proteomic approach was used to examine and identify proteins that were differentially expressed in epidermis between promotion-sensitive DBA/2 and promotion-resistant C57BL/6 mice following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We identified 19 differentially expressed proteins of which 5 were the calcium-binding proteins annexin A1, parvalbumin α, S100A8, S100A9, and S100A11. Further analyses revealed that S100A8 and S100A9 protein levels were also similarly differentially upregulated in epidermis of DBA/2 versus C57BL/6 mice following topical treatment with two other skin tumor promoters, okadaic acid and chrysarobin. Pathway analysis of all 19 identified proteins from the present study suggested that these proteins were components of several networks that included inflammation-associated proteins known to be involved in skin tumor promotion (e.g. TNF-α, NFκB). Follow-up studies revealed that Tnf, Nfkb1, Il22, Il1b, Cxcl1, Cxcl2 and Cxcl5 mRNAs were highly expressed in epidermis of DBA/2 compared with C57BL/6 mice at 24h following treatment with TPA. Furthermore, NFκB (p65) was also highly activated at the same time point (as measured by phosphorylation at ser276) in epidermis of DBA/2 mice compared with C57BL/6 mice. Taken together, the present data suggest that differential expression of genes involved in inflammatory pathways in epidermis may play a key role in genetic differences in susceptibility to skin tumor promotion in DBA/2 and C57BL/6 mice.

Use of a Novel Electronic Auto-Notification Process to Manage Transitions of Care in Patients With Rheumatic Disease Receiving Disease-Modifying Antirheumatic Drug Therapy.

OBJECTIVE: To integrate an auto-notification system into clinical workflow, so timely communication of sentinel events (elective surgery, hospital admission, or emergency room [ER] visit) in immunosuppressed patients with rheumatic disease happened by design. METHODS: We developed an algorithm that triggered auto-notification within the electronic medical record to rheumatology when a patient experienced a sentinel event. A telephone encounter was created that included event type, baseline therapy, and event date. This was forwarded to the rheumatologist, who recorded guideline-driven recommendations and returned it to nursing. Instructions were included to communicate recommendations to the patient, inpatient rheumatology team, or other clinician. This was studied over 4 months at a multispecialty medical practice in Central Pennsylvania. Primary outcomes were percentage of total notifications, notifications by sentinel event type where a change in care plan was recommended, as well as percentage of time where rheumatologists were notified of sentinel events compared to prior to the intervention. The secondary outcome was staff work effort. RESULTS: Two hundred forty notifications were received (57% for elective surgeries, 39% for ER visits, and 4% for admissions). The need for change in care plan was only 17% for ER visits but was 25% for hospital admissions and 44% for elective surgeries. The percentage of time that rheumatologists were notified of events increased from 57.6% to 100%. The average number of messages received per week was 2.2, requiring a weekly average of 13 minutes of work per physician. CONCLUSION: We developed an easy, well-received process that hardwires rheumatologist notification sentinel events to facilitate timely care.

Use of protocol-driven medication refills by pharmacists decreases rheumatologist in-basket work and improves rheumatologist satisfaction.

Burn-out among US physicians has been on the rise in the past few decades. Similarly, rheumatologists in the Geisinger Health System have experienced professional dissatisfaction through significant administrative burden and in-basket work. We embedded pharmacists into our rheumatology team in 2019 with the aim of reallocating medication refills to pharmacists, trained professionals in this domain, to help reduce physician workload and burn-out and increase satisfaction. Protocol-driven medication refill parameters per the American College of Rheumatology guidelines and new refill workflows for disease-modifying antirheumatic drugs (DMARDs) and non-DMARDs were created for use by our rheumatology pharmacists. Monthly data on medication refill volume and time saved for rheumatologists were collected from 1 January 2019 to 31 March 2021. Statistical analysis was completed via Shewhart p-charts. The volume of refills by rheumatologists decreased by 73% and the time saved per month for all the rheumatologists increased to 41.5 hours within 6 months. Physicians' feedback was obtained via anonymous electronic surveys preintervention and postintervention. The statistical difference between the presurveys and postsurveys was calculated via two-tailed unpaired t-testing. It demonstrated reduced burn-out and improved workplace satisfaction. This study showed that the integration of rheumatology pharmacists into our practice can help improve the work life of the rheumatologists. It is important for physicians' well-being to practice at the top of their scope and achieve work-life balance.

Patterns of preventive health services in rheumatoid arthritis patients compared to a primary care patient population.

To determine the proportion of rheumatoid arthritis (RA) patients receiving preventive health care according to US Preventive Services Task Force recommendations compared with a community-based population sample, with emphasis on dyslipidemia testing, given the increased risk of cardiovascular disease (CVD) in RA patients. Patients with RA (ICD-9 code 714.0 at ≥2 office visits with a rheumatologist) and a primary care physician (PCP) at the Geisinger Health System (GHS) were identified through electronic health records. The records were searched back from 3/31/08 for the length of time required to satisfy each outcome measure. Percentages were compared with population testing rates using the Pearson Chi-square test. Eight hundred and thirty-one RA patients were compared to 169,476 subjects with a PCP at GHS, stratified by gender and age. Patients with RA were more likely to have had dyslipidemia and osteoporosis testing compared with the general population (86 vs. 75 and 75 vs. 55%, respectively, P < 0.0001 for both). The proportion of RA patients receiving breast and cervical cancer testing was similar to the general population. The majority (79%) of lipid testing was ordered by PCPs. Those RA patients with recommended lipid testing had more traditional CVD factors (hypertension, diabetes, coronary artery disease). RA patients are screened more than the general population for two RA-related co-morbidities, i.e. dyslipidemia and osteoporosis. The RA patients with traditional cardiovascular risk factors are more likely to be tested for dyslipidemia. Further work is warranted to improve testing for modifiable CVD risk factors in this group with multiple co-morbidities.

Unusual Stroke-Like Symptoms in a Patient With Generalized Osteoarthritis.

A usual presenting symptom for osteoarthritis (OA) is pain. However, OA of the spine can present as isolated nerve palsy. We present a case of isolated hypoglossal nerve palsy secondary to chronic OA of the cervical spine. A 68-year-old female presented to the emergency department with stroke-like symptoms of three-day duration. History revealed heaviness of the tongue with dysphagia to solid foods, tongue deviation to the right, and slurred speech over the past year. On examination, she had severe OA of the distal and proximal interphalangeal joints. Various imaging modalities revealed isolated right unilateral hypoglossal nerve paralysis secondary to craniocervical junction degenerative disease from C1-occipital osteophyte and juxta-articular atlantooccipital (AO) synovial cyst. This case is unique as evidenced by various imaging modalities which consistently revealed advanced OA of our patient's AO joint leading to osteophytic and juxta-articular cyst development causing unilateral hypoglossal nerve palsy.

Impact of an institution-designed algorithm for the management of dislodged gastrostomy tubes.

BACKGROUND: Gastrostomy tube (GT) dislodgement is a common reason for emergency department (ED) visits. We aim to assess the efficacy of our institution's algorithm in reducing surgical consultation and GT contrast studies for replacement of dislodged GT and to examine the need for operation before and after algorithm implementation. METHODS: A retrospective review was performed between March 2017-February 2018 (prealgorithm) and March 2018-December 2018 (postalgorithm) for patients <18 years presenting to the ED with GT dislodgement. Demographics and outcomes were analyzed. RESULTS: A total of 433 visits among 279 patients were included, 200 (46.2%) pre and 233 (53.8%) postalgorithm implementation. Median ED LOS was 2.1 h (IQR 1.4, 3.0). Surgery was consulted in 92 visits (21.3%) and a contrast study obtained in 287 (66.3%). The GT was replaced by ED providers in 363 visits (83.8%) and by surgery in 70 (16.2%). Surgical consultation increased postalgorithm (16.5% vs. 25.3%; p = 0.03). Six (1.4%) patients required reoperation, with 5 occurring postalgorithm, p = 0.22. For GTs placed < 8 weeks prior to the dislodgment, there were no differences in surgical consultations, contrast studies performed, or need for reoperation pre and postalgorithm. CONCLUSION: An algorithm for replacement of dislodged GT is usable, effective, and increased surgical team involvement without significant changes in patient outcomes. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

The -11A of promoter DNA and two conserved amino acids in the melting region of sigma70 both directly affect the rate limiting step in formation of the stable RNA polymerase-promoter complex, but they do not necessarily interact.

Formation of the stable, strand separated, 'open' complex between RNA polymerase and a promoter involves DNA melting of approximately 14 base pairs. The likely nucleation site is the highly conserved -11A base in the non-template strand of the -10 promoter region. Amino acid residues Y430 and W433 on the sigma70 subunit of the RNA polymerase participate in the strand separation. The roles of -11A and of the Y430 and W433 were addressed by employing synthetic consensus promoters containing base analog and other substitutions at -11 in the non-template strand, and sigma70 variants bearing amino acid substitutions at positions 430 and 433. Substitutions for -11A and for Y430 and W433 in sigma70 have small or no effects on formation of the initial RNA polymerase-promoter complex, but exert their effects on subsequent steps on the way to formation of the open complex. As substitutions for Y430 and W433 also affect open complex formation on promoter DNA lacking the -11A base, it is concluded that these amino acid residues have other (or additional) roles, not involving the -11A. The effects of the substitutions at -11A of the promoter and Y430 and W433 of sigma70 are cumulative.

Emergency department discharge following successful radiologic reduction of ileocolic intussusception in children: A protocol based prospective observational study.

PURPOSE: Pediatric intussusception's first line treatment consists of fluoroscopic guided air enema reduction. Postprocedure, these patients are usually admitted overnight for observation. The purpose of our study was to document the results of emergency department (ED) observation and discharge protocol after successful reduction of ileocolic intussusception. METHODS: A prospective observational study was conducted after implementation of an ED protocol for ileocolic intussusception from 10/2014 to 7/2017 and compared these patients to a historical cohort immediately prior to protocol initiation (10/2011-9/2014). Data collected included demographics, total time in the ED and hospital, enema reduction, recurrence, and requirement for operative intervention. Results reported as means with standard deviation and medians reported with interquartile ranges (IQR). RESULTS: 115 patients were treated with the prospective protocol and were compared to a 90 patient historical cohort. Reduction was successful in 84%-89% of cases. Median hospital time after enema was shorter in the protocol group [4.8 h (4.25, 14.97) versus 19.7 h (13.9, 33.45), p < 0.01]. Only 33% of patients were admitted following the protocol; the most common admission reason was persistent abdominal discomfort. CONCLUSION: ED observation and discharge after successful air enema reduction in children with ileocolic intussusception are safe, facilitate early discharge, and reduce hospital resource utilization. LEVEL OF EVIDENCE: III.

Failure mode and effects analysis to reduce risk of heparin use.

PURPOSE: Failure mode and effects analysis (FMEA) was used to identify safety risks of unfractionated heparin (UFH) use and to develop and implement countermeasures to improve safety. METHODS: FMEA was used to analyze the transportation, preparation, dispensation, administration, therapeutic monitoring, and disposal of UFH in a tertiary care, freestanding pediatric hospital. The FMEA was conducted in a stepwise fashion. First, frontline staff mapped the different steps within the UFH use process. Next, key stakeholders identified potential failures of each process step. Finally, using calibrated scales, the stakeholders ranked the likelihood of occurrence, severity, and detectability for each potential failure's cause. The rankings were used to prioritize high-risk areas on which to focus efforts for improvement countermeasures. RESULTS: The analysis revealed 233 potential failures and 737 unique potential causes. After ranking of all identified potential causes, 45 were deemed high scoring. Those 45 causes were further refined into 13 underlying contributing causes. To address the contributing causes, selected team members developed 22 countermeasures. The FMEA showed that implementation of the countermeasures reduced the level of mathematical risk. CONCLUSION: FMEA was helpful in identifying, ranking, and prioritizing medication risks in the UFH use process. Twenty-two countermeasures were developed to reduce potential for error in the riskiest steps of the process.

Reducing Variability in the Infant Sepsis Evaluation (REVISE): A National Quality Initiative.

BACKGROUND: Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population. METHODS: The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source. Twelve months of baseline and 12 months of implementation data were collected from emergency departments and inpatient units. Ill-appearing infants and those with comorbid conditions were excluded. Participating sites received change tools, run charts, a mobile application, live webinars, coaching, and a LISTSERV. Analyses were performed via statistical process control charts and interrupted time series regression. The 2 outcome measures were the percentage of hospitalized infants who were evaluated and hospitalized appropriately and the percentage of hospitalized infants who were discharged with an appropriate LOS. RESULTS: In total, 124 hospitals from 38 states provided data on 20 570 infants. The median site improvement in percentages of infants who were evaluated and hospitalized appropriately and in those with appropriate LOS was 5.3% (interquartile range = -2.5% to 13.7%) and 15.5% (interquartile range = 2.9 to 31.3), respectively. Special cause variation toward the target was identified for both measures. There was no change in delayed treatment or missed bacterial infections (slope difference 0.1; 95% confidence interval, -8.3 to 9.1). CONCLUSIONS: Reducing Variability in the Infant Sepsis Evaluation noted improvement in key aspects of febrile infant management. Similar projects may be used to improve care in other clinical conditions.

Evidence that senescent human prostate epithelial cells enhance tumorigenicity: cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT.

Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo but the potential role of senescent NHP cells in prostate tumorigenesis remain unclear. Here we show that senescent NHP cells enhance the in vivo tumorigenicity of low-tumorigenic LNCaP prostate cancer and low/non-tumorigenic subset of cells (called L cells) isolated from multiple bulk-cultured prostate (and other) cancer cell lines. Subsequent studies suggest cell-cell fusion as a potential mechanism for senescent NHP cell-enhanced tumor development. Using fluorescently tagged tumor cells and/or NHP cells, we find that NHP cells, like fibroblasts, can undergo fusion with unfractionated tumor cells or the L cells. Using 293T-L cells as the model cell system, we verify NHP and 293T-L cell fusion by using differential RT-PCR, karyotyping, and gene expression analyses. Further experiments demonstrate that senescent NHP cells that have lost progenitor markers, accumulated p16INK4a (p16) protein expression, and acquired the AR mRNA expression, appear to be the preferential fusion targets. Strikingly, the tumorigenicity of the NHP/293T-L hybrid cells was inhibited by exogenous p16 as well as hTERT. Chromosomal analyses revealed that hTERT probably inhibited the in vivo tumorigenicity by maintaining genomic stability. These results suggest that senescent NHP cells, like senescent fibroblasts, may promote tumor development and that one of the mechanisms underlying the senescent NHP cell-enhanced tumorigenicity could be through cell fusion.

Synaptic Activity Protects Neurons Against Calcium-Mediated Oxidation and Contraction of Mitochondria During Excitotoxicity.

AIMS: Excitotoxicity triggered by extrasynaptic N-methyl-d-aspartate-type glutamate receptors has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction represents an early event in excitotoxicity. Neurons are rendered resistant to excitotoxicity by previous periods of synaptic activity that activates a nuclear calcium-driven neuroprotective gene program. This process, termed acquired neuroprotection, involves transcriptional repression of the mitochondrial calcium uniporter leading to a reduction in excitotoxcity-associated mitochondrial calcium load. As mitochondrial calcium and the production of reactive oxygen species may be linked, we monitored excitotoxicity-associated changes in the mitochondrial redox status using the ratiometric glutathione redox potential indicator, glutaredoxin 1 (GRX1)-redox-sensitive green fluorescent protein (roGFP)2, targeted to the mitochondrial matrix. Aim of this study was to investigate if suppression of oxidative stress underlies mitoprotection afforded by synaptic activity. RESULTS: We found that synaptic activity protects primary rat hippocampal neurons against acute excitotoxicity-induced mitochondrial oxidative stress and mitochondrial contraction associated with it. Downregulation of the mitochondrial uniporter by genetic means mimics the protective effect of synaptic activity on mitochondrial redox status. These findings indicate that oxidative stress acts downstream of mitochondrial calcium overload in excitotoxicity. Innovation and Conclusion: We established mito-GRX1-roGFP2 as a reliable and sensitive tool to monitor rapid redox changes in mitochondria during excitotoxicity. Our results highlight the importance of developing means of blocking mitochondrial calcium overload for therapeutic targeting of oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Antioxid. Redox. Signal. 29, 1109-1124.