A Survey of PICU Clinician Practices and Perceptions regarding Respiratory Cultures in the Evaluation of Ventilator-Associated Infections in the BrighT STAR Collaborative.

OBJECTIVES: To characterize respiratory culture practices for mechanically ventilated patients, and to identify drivers of culture use and potential barriers to changing practices across PICUs. DESIGN: Cross-sectional survey conducted May 2021-January 2022. SETTING: Sixteen academic pediatric hospitals across the United States participating in the BrighT STAR Collaborative. SUBJECTS: Pediatric critical care medicine physicians, advanced practice providers, respiratory therapists, and nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We summarized the proportion of positive responses for each question within a hospital and calculated the median proportion and IQR across hospitals. We correlated responses with culture rates and compared responses by role. Sixteen invited institutions participated (100%). Five hundred sixty-eight of 1,301 (44%) e-mailed individuals completed the survey (median hospital response rate 60%). Saline lavage was common, but no PICUs had a standardized approach. There was the highest variability in perceived likelihood (median, IQR) to obtain cultures for isolated fever (49%, 38-61%), isolated laboratory changes (49%, 38-57%), fever and laboratory changes without respiratory symptoms (68%, 54-79%), isolated change in secretion characteristics (67%, 54-78%), and isolated increased secretions (55%, 40-65%). Respiratory cultures were likely to be obtained as a "pan culture" (75%, 70-86%). There was a significant correlation between higher culture rates and likelihood to obtain cultures for isolated fever, persistent fever, isolated hypotension, fever, and laboratory changes without respiratory symptoms, and "pan cultures." Respondents across hospitals would find clinical decision support (CDS) helpful (79%) and thought that CDS would help align ICU and/or consulting teams (82%). Anticipated barriers to change included reluctance to change (70%), opinion of consultants (64%), and concern for missing a diagnosis of ventilator-associated infections (62%). CONCLUSIONS: Respiratory culture collection and ordering practices were inconsistent, revealing opportunities for diagnostic stewardship. CDS would be generally well received; however, anticipated conceptual and psychologic barriers to change must be considered.

Sustainability of the Bright STAR Diagnostic Stewardship Program to Reduce Blood Culture Rates Among Critically Ill Children.

This quality improvement study evaluates whether pediatric intensive care units sustained reduced blood culture rates after participation in the Bright STAR collaborative from 2017 to 2020.

Application of Participatory Ergonomics to the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use.

BACKGROUND: Blood cultures are overused in pediatric ICUs (PICUs), which may lead to unnecessary antibiotic use and antibiotic resistance. Using a participatory ergonomics (PE) approach, the authors disseminated a quality improvement (QI) program for optimizing blood culture use in PICUs to a national 14-hospital collaborative. The objective of this study was to evaluate the dissemination process and its impact on blood culture reduction. METHODS: The PE approach emphasized three key principles (stakeholder participation, application of human factors and ergonomics knowledge and tools, and cross-site collaboration) with a six-step dissemination process. Data on interactions between sites and the coordinating team and site experiences with the dissemination process were collected using site diaries and semiannual surveys with local QI teams, respectively, and correlated with the site-specific change in blood culture rates. RESULTS: Overall, participating sites were able to successfully implement the program and reduced their blood culture rates from 149.4 blood cultures per 1,000 patient-days/month before implementation to 100.5 blood cultures per 1,000 patient-days/month after implementation, corresponding to a 32.7% relative reduction (p < 0.001). Variations in the dissemination process, as well as in local interventions and implementation strategies, were observed across sites. Site-specific changes in blood culture rates were weakly negatively correlated with the number of preintervention interactions with the coordinating team (p = 0.057) but not correlated with their experiences with the six domains of the dissemination process or their interventions. CONCLUSIONS: The authors applied a PE approach to disseminate a QI program for optimizing PICU blood culture use to a multisite collaborative. Working with local stakeholders, participating sites tailored their interventions and implementation processes and achieved the goal of reducing blood culture use.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report.

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including 1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions; 2) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support; 3) developing and applying novel clinical trial designs; and 4) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Practices, Perceptions, and Attitudes in the Evaluation of Critically Ill Children for Bacteremia: A National Survey.

OBJECTIVES: Sending blood cultures in children at low risk of bacteremia can contribute to a cascade of unnecessary antibiotic exposure, adverse effects, and increased costs. We aimed to describe practice variation, clinician beliefs, and attitudes about blood culture testing in critically ill children. DESIGN: Cross-sectional electronic survey. SETTING: Fifteen PICUs enrolled in the Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children collaborative, an investigation of blood culture use in critically ill children in the United States. SUBJECTS: PICU clinicians (bedside nurses, resident physicians, fellow physicians, nurse practitioners, physician assistants, and attending physicians). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Survey items explored typical blood culture practices, attitudes and beliefs about cultures, and potential barriers to changing culture use in a PICU setting. Fifteen of 15 sites participated, with 347 total responses, 15-45 responses per site, and an overall median response rate of 57%. We summarized median proportions and interquartile ranges of respondents who reported certain practices or beliefs: 86% (73-91%) report that cultures are ordered reflexively; 71% (61-77%) do not examine patients before ordering cultures; 90% (86-94%) obtain cultures for any new fever in PICU patients; 33% (19-61%) do not obtain peripheral cultures when an indwelling catheter is in place; and 64% (36-81%) sample multiple (vs single) lumens of central venous catheters for new fever. When asked about barriers to reducing unnecessary cultures, 80% (73-90%) noted fear of missing sepsis. Certain practices (culture source and indication) varied by clinician type. Obtaining surveillance cultures and routinely culturing all possible sources (each lumen of indwelling catheters and peripheral specimens) are positively correlated with baseline blood culture rates. CONCLUSIONS: There is variation in blood culture practices in the PICU. Fear and reflexive habits are common drivers of cultures. These practices may contribute to over-testing for bacteremia. Further investigation of how to optimize blood culture use is warranted.

Shaping anesthetic techniques to reduce post-operative delirium (SHARP) study: a protocol for a prospective pragmatic randomized controlled trial to evaluate spinal anesthesia with targeted sedation compared with general anesthesia in older adults undergoing lumbar spine fusion surgery.

BACKGROUND: Postoperative delirium is common in older adults, especially in those patients undergoing spine surgery, in whom it is estimated to occur in > 30% of patients. Although previously thought to be transient, it is now recognized that delirium is associated with both short- and long-term complications. Optimizing the depth of anesthesia may represent a modifiable strategy for delirium prevention. However, previous studies have generally not focused on reducing the depth of anesthesia beyond levels consistent with general anesthesia. Additionally, the results of prior studies have been conflicting. The primary aim of this study is to determine whether reduced depth of anesthesia using spinal anesthesia reduces the incidence of delirium after lumbar fusion surgery compared with general anesthesia. METHODS: This single-center randomized controlled trial is enrolling 218 older adults undergoing lumbar fusion surgery. Patients are randomized to reduced depth of anesthesia in the context of spinal anesthesia with targeted sedation using processed electroencephalogram monitoring versus general anesthesia without processed electroencephalogram monitoring. All patients are evaluated for delirium using the Confusion Assessment Method for 3 days after surgery or until discharge and undergo assessments of cognition, function, health-related quality of life, and pain at 3- and 12-months after surgery. The primary outcome is any occurrence of delirium. The main secondary outcome is change in the Mini-Mental Status Examination (or telephone equivalent) at 3-months after surgery. DISCUSSION: Delirium is an important complication after surgery in older adults. The results of this study will examine whether reduced depth of anesthesia using spinal anesthesia with targeted depth of sedation represents a modifiable intervention to reduce the incidence of delirium and other long-term outcomes. The results of this study will be presented at national meetings and published in peer-reviewed journals with the goal of improving perioperative outcomes for older adults. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03133845. This study was submitted to Clinicaltrials.gov on October 23, 2015; however, it was not formally registered until April 28, 2017 due to formatting requirements from the registry, so the formal registration is retrospective.

Dissemination of a Novel Framework to Improve Blood Culture Use in Pediatric Critical Care.

INTRODUCTION: Single center work demonstrated a safe reduction in unnecessary blood culture use in critically ill children. Our objective was to develop and implement a customizable quality improvement framework to reduce unnecessary blood culture testing in critically ill children across diverse clinical settings and various institutions. METHODS: Three pediatric intensive care units (14 bed medical/cardiac; 28 bed medical; 22 bed cardiac) in 2 institutions adapted and implemented a 5-part Blood Culture Improvement Framework, supported by a coordinating multidisciplinary team. Blood culture rates were compared for 24 months preimplementation to 24 months postimplementation. RESULTS: Blood culture rates decreased from 13.3, 13.5, and 11.5 cultures per 100 patient-days preimplementation to 6.4, 9.1, and 8.3 cultures per 100 patient-days postimplementation for Unit A, B, and C, respectively; a decrease of 32% (95% confidence interval, 25-43%; P < 0.001) for the 3 units combined. Postimplementation, the proportion of total blood cultures drawn from central venous catheters decreased by 51% for the 3 units combined (95% confidence interval, 29-66%; P < 0.001). Notable difference between units included the identity and involvement of the project champion, adaptions of the clinical tools, and staff monitoring and communication of project progress. Qualitative data also revealed a core set of barriers and facilitators to behavior change around pediatric intensive care unit blood culture practices. CONCLUSIONS: Three pediatric intensive units adapted a novel 5-part improvement framework and successfully reduced blood culture use in critically ill children, demonstrating that different providers and practice environments can adapt diagnostic stewardship programs.

Preventing CLABSIs among pediatric hematology/oncology inpatients: national collaborative results.

OBJECTIVES: Central lines (CLs) are essential for the delivery of modern cancer care to children. Nonetheless, CLs are subject to potentially life-threatening complications, including central line-associated bloodstream infections (CLABSIs). The objective of this study was to assess the feasibility of a multicenter effort to standardize CL care and CLABSI tracking, and to quantify the impact of standardizing these processes on CLABSI rates among pediatric hematology/oncology inpatients. METHODS: We conducted a multicenter quality improvement collaborative starting in November 2009. Multidisciplinary teams at participating sites implemented a standardized bundle of CL care practices and adopted a common approach to CLABSI surveillance. RESULTS: Thirty-two units participated in the collaborative and reported a mean, precollaborative CLABSI rate of 2.85 CLABSIs per 1000 CL-days. Self-reported adoption of the CL care bundle was brisk, with average compliance approaching 80% by the end of the first year of the collaborative and exceeding 80% thereafter. As of August 2012, the mean CLABSI rate during the collaborative was 2.04 CLABSIs per 1000 CL-days, a reduction of 28% (relative risk: 0.71 [95% confidence interval: 0.55-0.92]). Changes in self-reported CL care bundle compliance were not statistically associated with changes in CLABSI rates, although there was little variability in bundle compliance rates after the first year of the collaborative. CONCLUSIONS: A multicenter quality improvement collaborative found significant reductions in observed CLABSI rates in pediatric hematology/oncology inpatients. Additional interventions will likely be required to bring and sustain CLABSI rates closer to zero for this high-risk population.

Temporal dynamics and genetic control of transcription in the human prefrontal cortex.

Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud).

The epidemiology of Candida colonization and invasive candidiasis in a surgical intensive care unit where fluconazole prophylaxis is utilized: follow-up to a randomized clinical trial.

OBJECTIVE: To determine whether Candida glabrata colonization and invasive candidiasis (IC) increased among critically ill surgical patients 3 years after the introduction of fluconazole prophylaxis to a surgical intensive care unit (SICU). SUMMARY BACKGROUND DATA: Fluconazole prophylaxis has been shown in randomized clinical trials to reduce the occurrence of candidiasis in some patient populations, including high-risk SICU patients. One such trial was performed in The Johns Hopkins Hospital SICU in 1998. Whether the epidemiology of Candida colonization and IC has changed in SICUs where fluconazole prophylaxis is routinely utilized has not been adequately studied. METHODS: We conducted a prospective, observational study of subjects admitted for > or = 3 days to the SICU of a large, urban, academic medical center, where fluconazole prophylaxis had been utilized for approximately 3 years. Surveillance fungal cultures of rectal/fecal swabs, urine, and endotracheal aspirates were performed on admission to the SICU, once weekly, and upon discharge from the SICU. Demographic and clinical data were collected. C. glabrata colonization and IC prevalence among patients in the prospective cohort were compared with the prevalence among SICU patients enrolled in the 1998 clinical trial of fluconazole for the prevention of candidiasis that was performed at the same institution. RESULTS: C. glabrata colonization was not significantly more common among patients in the 2003 cohort as compared with patients in the 1998 trial (adjusted odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.57-1.41). Patients with IC in the 2003 cohort were not more likely than those in the 1998 trial to have IC due to C. glabrata (adjusted OR: 1.93, 95% CI: 0.20-18.98), while patients with IC in the 2003 cohort were less likely than patients in the 1998 trial to have acquired IC in the ICU (adjusted OR: 0.08, 95% CI: 0.009-0.82). CONCLUSIONS: There was no increase in C. glabrata colonization or in the proportion of IC due to C. glabrata after a 3-year period of routine fluconazole prophylaxis for selected SICU patients.