Quantifying Mast Cell and Eosinophil Cellular Density in Skin Biopsy Tissue From Adults With Maculopapular Cutaneous Mastocytosis as Compared With Urticaria and Normal Skin: A Retrospective Histopathologic Study.

BACKGROUND: Maculopapular cutaneous mastocytosis (MPCM) is a rare disorder characterized by a pathologic accumulation of mast cells in the skin, which may or may not be accompanied by systemic mastocytosis. Diagnosis of MPCM on skin biopsy can be challenging because the findings may be subtle. Although mast cell density in MPCM has been reported, data informing a proposed cutoff for diagnosis and diagnostic criteria are limited. METHODS: We identified adult patients diagnosed with MPCM and urticarial tissue reaction/chronic urticaria on skin biopsy and compared the mast cell and eosinophil counts per 1 mm2 in 10 cases each of MPCM, chronic urticaria, and normal skin from routine biopsies. All slides were stained with CD117, and CD117-positive mast cells were counted per 1 mm2 using digital microscopy. Eosinophils were counted on hematoxylin and eosin-stained slides per 1 mm2 using digital microscopy. RESULTS: The median number of mast cells per 1 mm2 was significantly higher in MPCM than in cases of urticaria and normal skin/control tissue (177.3 vs. 26.8 vs. 47.8 mast cell per mm2, respectively; P ≤ 0.001). The calculated "cut point" for mastocytosis versus chronic urticaria and normal skin was 66 mast cells per 1 mm2, whereas the value for controls versus urticaria was 37 mast cells per 1 mm2. Eosinophils had similar density in MPCM and urticaria, and their presence was significant in the differentiation of MPCM and urticaria from normal tissue. CONCLUSIONS: This study adds to the literature by providing objective mast cell density data to distinguish challenging cases of cutaneous mastocytosis from urticarial reactions and normal skin. Future studies could explore the development of computer-aided estimations of cellular density with more extensive comparison with other inflammatory conditions to translate our findings more readily into clinical practice.

Patients' Willingness to Accept Social Needs Navigation After In-Person versus Remote Screening.

BACKGROUND: Social needs screening and referral interventions are increasingly common in health care settings. Although remote screening offers a potentially more practical alternative to traditional in-person screening, there is concern that screening patients remotely could adversely affect patient engagement, including interest in accepting social needs navigation. METHODS: We conducted a cross-sectional study using a multivariable logistic regression analysis and data from the Accountable Health Communities (AHC) model in Oregon. Participants were Medicare and Medicaid beneficiaries in the AHC model from October 2018 through December 2020. The outcome variable was patients' willingness to accept social needs navigation assistance. We included an interaction term (total number of social needs + screening mode) to test whether in-person versus remote screening was an effect modifier. RESULTS: The study included participants who screened positive for ≥1 social need(s); 43% were screened in person and 57% remotely. Overall, 71% of participants were willing to accept help with social needs. Neither screening mode nor interaction term were significantly associated with willingness to accept navigation assistance. CONCLUSIONS: Among patients presenting with similar numbers of social needs, results indicate that type of screening mode may not adversely affect patients' willingness to accept health care-based navigation for social needs.

Carer preparedness improved by providing a supportive educational intervention for carers of patients with high-grade glioma: RCT results.

BACKGROUND: High-grade glioma (HGG) is a rapidly progressing and debilitating disease. Family carers take on multiple responsibilities and experience high levels of distress. We aimed to deliver a nurse-led intervention (Care-IS) to carers to improve their preparedness to care and reduce distress. METHODS: We conducted a randomised controlled trial (ACTRN:12612001147875). Carers of HGG patients were recruited during patients' combined chemoradiation treatment. The complex intervention comprised four components: (1) initial telephone assessment of carer unmet needs; (2) tailored hard-copy resource folder; (3) home visit; and, (4) monthly telephone support for up to 12 months. Primary outcomes included preparedness for caregiving and distress at 2, 4, 6 and 12 months. Intervention effects were estimated using linear mixed models which included a time by group interaction. Secondary outcomes included anxiety, depression, quality of life, carer competence and strain. RESULTS: We randomised 188 carers (n = 98 intervention, n = 90 control). The intervention group reported significantly higher preparedness for caregiving at 4 months (model ß = 2.85, 95% CI 0.76-4.93) and all follow-up timepoints including 12 months (model ß = 4.35, 95% CI 2.08-6.62), compared to the control group. However, there was no difference between groups in carer distress or any secondary outcomes. CONCLUSIONS: This intervention was effective in improving carer preparedness. However, carer distress was not reduced, potentially due to the debilitating/progressive nature of HGG and ongoing caring responsibilities. Future research must explore whether carer interventions can improve carer adjustment, self-efficacy and coping and how we support carers after bereavement. Additionally, research is needed to determine how to implement carer support into practice.

Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes.

With the development of novel prognostic tools derived from omics technologies, transplant medicine is entering the era of precision medicine. Currently, there are no established predictive biomarkers for posttransplant kidney function. A total of 270 deceased donor pretransplant kidney biopsies were collected and posttransplant function was prospectively monitored. This study first assessed the utility of pretransplant gene expression profiles in predicting 24-month outcomes in a training set (n = 174). Nearly 600 differentially expressed genes were associated with 24-month graft function. Grafts that progressed to low function at 24 months exhibited upregulated immune responses and downregulated metabolic processes at pretransplantation. Using penalized logistic regression modeling, a 55 gene model area under the receiver operating curve (AUROC) for 24-month graft function was 0.994. Gene expression for a subset of candidate genes was then measured in an independent set of pretransplant biopsies (n = 96) using quantitative polymerase chain reaction. The AUROC when using 13 genes with three donor characteristics (age, race, body mass index) was 0.821. Subsequently, a risk score was calculated using this combination for each patient in the validation cohort, demonstrating the translational feasibility of using gene markers as prognostic tools. These findings support the potential of pretransplant transcriptomic biomarkers as novel instruments for improving posttransplant outcome predictions and associated management.

Trainee-led Engagement of the Care Team Improves Application of an Institutional Blood Culture Clinical Decision Algorithm to Pediatric Oncology Inpatients: A Single-institution Quality Improvement Project.

Meaningful engagement in quality improvement (QI) projects by trainees is often challenging. A fellow-led QI project aimed to improve adherence to a blood culture clinical decision algorithm and reduce unnecessary cultures in pediatric oncology inpatients. Methods: We visualized preintervention rates of blood cultures drawn on pediatric oncology inpatients using a control chart. Following the introduction of the algorithm to our division, an Ishikawa fishbone diagram of cause-and-effect identified two areas for improvement: prescriber education on the algorithm and targeted feedback on its use. We developed two interventions to support algorithm awareness and use: (1) bundled educational interventions and (2) targeted chart review and feedback. Fellows reviewed >750 blood culture episodes and adjudicated each as "adherent" or "nonadherent" to the algorithm. In addition, fellows provided direct feedback to prescribers regarding nonadherent episodes and discussed strategies for algorithm adherence. Results: Blood culture rates in preintervention, intervention, and follow-up periods were 33.35, 25.24, and 22.67 cultures/100 patient-days, respectively. The proportion of nonadherent culture episodes decreased from 47.14% to 11.11%. The use of the algorithm did not prolong the time to cultures drawn on patients with new fever. Seventy-five percent of fellows provided feedback to inpatient teams on algorithm use. Following this project, trainees reported feeling more qualified to apply QI principles to patient care. Conclusions: Implementation of a clinical decision algorithm reduced the rate of cultures drawn on pediatric oncology inpatients. Fellow-led education of the care team decreased the proportion of nonadherent culture episodes and provided active engagement in QI.

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

BACKGROUND: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology. METHODS: In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection. RESULTS: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology: 27 (13%) versus MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI: 0.74-0.86) versus histology (AUC = 0.75; 95% CI: 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies. CONCLUSIONS: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D-/R- transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R- compared with D-/R- (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Impact of Belatacept Conversion on Renal Function, Histology, and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection.

BACKGROUND: Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with chronic active antibody-mediated rejection (caAMR) and a high degree of chronicity at the time of diagnosis. METHODS: We converted 19 patients (mean age, 45 ± 12 y) with biopsy-proven caAMR from tacrolimus to belatacept at a median of 44 months post-kidney transplant. RESULTS: At a median of 29 months (interquartile range, 16-46 mo) postconversion, death-censored graft and patient survivals were 89% and 95%, respectively. When compared to a 1:2 propensity-matched control cohort from the INSERM U970 registry maintained on calcineurin inhibitor, the belatacept group had progressive improvement (P = 0.02) in estimated glomerular filtration rate from a mean of 33.9 ± 10 at baseline to 37.8 ± 13 at 6 months and 38.5 ± 12 mL/min/1.73 m2 at 12 months postconversion, as compared to a steady decline noted in the controls (36.2 [baseline] → 33.1 [6 mo] → 32.7 mL/min/1.73 m2 [12 mo] of follow-up). A paired histologic comparison of preconversion and postconversion (performed at median 9.5 mo postconversion) biopsies showed no worsening in microvascular inflammation or chronicity. The paired tissue gene expression analysis showed improved mean total rejection score (0.68 ± 0.26-0.56 ± 0.33; P = 0.02) and a trend toward improved antibody-mediated rejection score (0.64 ± 0.34-0.56 ± 0.39; P = 0.06). CONCLUSIONS: Here, we report that in patients diagnosed with caAMR who were not subjected to intensive salvage immunosuppressive therapies, isolated belatacept conversion alone was associated with stabilization in renal function. These results are bolstered by molecular evidence of improved inflammation.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.3 years) post transplant. Five (of 6) patients required inpatient admission, 2 patients (mortality = 33%) died. Among those with mortality, an increased concentration of inflammatory biomarkers (interleukin-6 and C-reactive protein) was noted with a lack of response to interleukin-6 blockade, remdesivir, and/or convalescent plasma. None of the kidney-only transplants (4/6; 67%) had elevation in plasma donor-derived cell-free DNA above the previously published cut-off of 1%, suggesting absence of significant allo-immune injury. Four (of 5) admitted patients had detectable SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) in blood on samples obtained at/during hospitalization. Of the 4 discharged patients, 2 patients with undetectable virus on repeat nasopharyngeal swabs had seroconversion with positive SARS-CoV-2 IgG formation at 30 to 48 days post infection. One patient had prolonged shedding of virus on nasopharyngeal swab at 28 days post discharge despite lack of symptoms. In this preliminary report, we find that immunocompromised transplant patients had higher rates of RNAemia (67%) than reported in the general population (15%), seeming absence of allo-immune injury despite systemic inflammation, and formation of IgG overtime after recovery from infection.

Impact of belatacept conversion on kidney transplant function, histology, and gene expression - a single-center study.

Prior studies on belatacept conversion from calcineurin inhibitor (CNI) have been limited by an absence of postconversion surveillance biopsies that could underestimate subclinical rejection, or a case-controlled design. A total of 53 adult patients with allograft dysfunction underwent belatacept conversion (median: 6 months) post-transplant. At a median follow-up = 2.5 years, patient survival was 94% with a death-censored graft survival of 85%. Seven (13%) patients had acute rejection (including 3 subclinical) at median 6 months postconversion. Overall, eGFR improved (P = <0.001) from baseline = 31±15 to 40.2 ± 17.6 ml/min/1.73m2 by 6 months postconversion, but then stayed stable. This improvement was also observed (P < 0.001) in comparison with a propensity matched control cohort on CNI, where eGFR stayed stable (mean ~ 32ml/min/1.72m2 ) over 2-year follow-up. Patients converted < 6 months post-transplant were more likely to have a long-term improvement in kidney function. Paired gene expression analysis of 30 (of 53) consecutive pre- and postconversion surveillance biopsies did not reveal changes in inflammation/acute injury; although atrophy-fibrosis score worsened (mean = 0.28 to 0.44; P = 0.005). Thus, improvement in renal function with belatacept conversion occurred early and then sustained in comparison with controls where renal function remained unchanged overtime. We were unable to show molecular signals that could be related to CNI administration and regressed after withdrawal.

How good is our diagnostic intuition? Clinician prediction of bacteremia in critically ill children.

BACKGROUND: Clinical intuition and nonanalytic reasoning play a major role in clinical hypothesis generation; however, clinicians' intuition about whether a critically ill child is bacteremic has not been explored. We endeavored to assess pediatric critical care clinicians' ability to predict bacteremia and to evaluate what affected the accuracy of those predictions. METHODS: We conducted a retrospective review of clinicians' responses to a sepsis screening tool ("Early Sepsis Detection Tool" or "ESDT") over 6 months. The ESDT was completed during the initial evaluation of a possible sepsis episode. If a culture was ordered, they were asked to predict if the culture would be positive or negative. Culture results were compared to predictions for each episode as well as vital signs and laboratory data from the preceding 24 h. RESULTS: From January to July 2017, 266 ESDTs were completed. Of the 135 blood culture episodes, 15% of cultures were positive. Clinicians correctly predicted patients with bacteremia in 82% of cases, but the positive predictive value was just 28% as there was a tendency to overestimate the presence of bacteremia. The negative predictive value was 96%. The presence of bandemia, thrombocytopenia, and abnormal CRP were associated with increased likelihood of correct positive prediction. CONCLUSIONS: Clinicians are accurate in predicting critically ill children whose blood cultures, obtained for symptoms of sepsis, will be negative. Clinicians frequently overestimate the presence of bacteremia. The combination of evidence-based practice guidelines and bedside judgment should be leveraged to optimize diagnosis of bacteremia.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

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.

Impact of Induction Immunosuppression Strategies in Simultaneous Liver/Kidney Transplantation.

BACKGROUND: There is scant data on the use of induction immunosuppression for simultaneous liver/kidney transplantation (SLKT). METHODS: We analyzed the Organ Procurement and Transplant Network registry from 1996 to 2016 to compare outcomes of SLKT, based on induction immunosuppression. RESULTS: Of 5172 patients, 941 (18%) received T-cell depletion induction, 1635 (32%) received interleukin 2 receptor antagonist (IL2-RA), and 2596 (50%) received no induction (NI). At 5 years, patient survivals were 68% in the T-cell group, 74% in the IL2-RA group, and 71% in the NI group (P = 0.0006). Five-year liver and kidney allograft survivals were 67% and 64% in the T-cell group, 73% and 70% in the IL2-RA group, and 70% and 68% in the NI group (P = 0.001 and 0.003), respectively. On multivariate analysis, the type of induction had no impact on patient or allograft survival. Maintenance steroids and calcineurin inhibitors (CNIs) at discharge were associated with improved patient and graft survival (steroids: patient survival hazard ratio [HR] 0.37 [0.27-0.52], liver survival HR 0.43 [0.31-0.59], kidney survival HR 0.46 [0.34-0.63]; P < 0.0001, CNI: patient survival HR 0.3 [0.21-0.43], liver survival HR 0.3 [0.2-0.44], kidney survival HR 0.4 [0.26-0.59]; P < 0.0001). CNI maintenance in patients who received T-cell induction was associated with decreased patient, liver, and kidney allograft survivals (respective HR: 1.4 [1.1, 1.8]; 1.5 [1.1, 1.9]; 1.3 [1.08, 1.7]; P < 0.05) CONCLUSION.: Induction immunosuppression had no impact on patient and allograft survival in SLKT, while maintenance steroids and CNI were associated with improved patient and graft survivals. Given the inherent limitations of a registry analysis, these findings should be interpreted with caution.

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Background: Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR. Methods: Ten adult recipients of KTs with biopsy-proven caAbMR were treated with TCZ at 8 mg/kg per month. Patients were monitored for adverse events, and therapy was interrupted in the setting of serious infections. Six patients (60%) underwent post-treatment biopsies. Results: Patients (mean age of 43 years) were initiated on TCZ at a median of 36 months post-KT. A majority of patients were black (70%), underwent regrafts (40%), and were sensitized (mean cPRA=41%). Patients received a median of six doses of TCZ (range=3-10). At a median follow-up of 12 months (range=8-24 months), renal function did not show improvement (mean eGFR, 42±18 ml/min per 1.73 m2 to 37±24 ml/min per 1.73 m2; P=0.27). The slope of decline in eGFR remained unchanged (-0.14±0.9 to -0.33±1.1; P=0.25). There was no improvement in mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; P=0.39) scores or Molecular Microscope Diagnostic System (MMDx) AbMR scores (0.79±0.17 to 0.78±0.26; P=0.86). There was a numeric worsening of chronicity (ci+ct) scores (2.5±0.8 to 3.3±1.7; P=0.38) and MMDx atrophy fibrosis scores (0.36±0.24 to 0.58±0.15; P=0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses in patients who had recurrent infections requiring hospitalization. Conclusions: In this early experience, we report a lack of efficacy and toxicity with the use of TCZ for caAbMR. Prospective clinical trials are needed to clarify the role of IL-6 blockade and the possibility of increased incidence of infections in patients with caAbMR who are treated with TCZ.

Work System Assessment to Facilitate the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use: A Case Study Using a Human Factors Engineering Approach.

BACKGROUND: Work system assessments can facilitate successful implementation of quality improvement programs. Using a human factors engineering approach, we conducted a work system assessment to facilitate the dissemination of a quality improvement program for optimizing blood culture use in pediatric intensive care units at 2 hospitals. METHODS: Semistructured face-to-face interviews were conducted with clinicians from Johns Hopkins All Children's Hospital and University of Virginia Medical Center. Interview data were analyzed using qualitative content analysis. RESULTS: Blood culture-ordering practices are influenced by various work system factors, including people, tasks, tools and technologies, the physical environment, organizational conditions, and the external environment. A clinical decision-support tool could facilitate implementation by (1) standardizing blood culture-ordering practices, (2) ensuring that prescribing clinicians review the patient's condition before ordering a blood culture, (3) facilitating critical thinking, and (4) empowering nurses to communicate with physicians and advocate for adherence to blood culture-ordering guidelines. CONCLUSION: The success of interventions for optimizing blood culture use relies heavily on the local context. A work system analysis using a human factors engineering approach can identify key areas to be addressed for the successful dissemination of quality improvement interventions.

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.

A Novel Role for Lymphotactin (XCL1) Signaling in the Nervous System: XCL1 Acts via its Receptor XCR1 to Increase Trigeminal Neuronal Excitability.

Chemokines are known to have a role in the nervous system, influencing a range of processes including the development of chronic pain. To date there are very few studies describing the functions of the chemokine lymphotactin (XCL1) or its receptor (XCR1) in the nervous system. We investigated the role of the XCL1-XCR1 axis in nociceptive processing, using a combination of immunohistochemical, pharmacological and electrophysiological techniques. Expression of XCR1 in the rat mental nerve was elevated 3 days following chronic constriction injury (CCI), compared with 11 days post-CCI and sham controls. XCR1 co-existed with neuronal marker PGP9.5, leukocyte common antigen CD45 and Schwann cell marker S-100. In the trigeminal root and white matter of the brainstem, XCR1-positive cells co-expressed the oligodendrocyte marker Olig2. In trigeminal subnucleus caudalis (Vc), XCR1 immunoreactivity was present in the outer laminae and was colocalized with vesicular glutamate transporter 2 (VGlut2), but not calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4). Incubation of brainstem slices with XCL1 induced activation of c-Fos, ERK and p38 in the superficial layers of Vc, and enhanced levels of intrinsic excitability. These effects were blocked by the XCR1 antagonist viral CC chemokine macrophage inhibitory protein-II (vMIP-II). This study has identified for the first time a role for XCL1-XCR1 in nociceptive processing, demonstrating upregulation of XCR1 at nerve injury sites and identifying XCL1 as a modulator of central excitability and signaling via XCR1 in Vc, a key area for modulation of orofacial pain, thus indicating XCR1 as a potential target for novel analgesics.

Antibody mediated rejection due to de-novo DSA causing venous thrombosis of pancreas allograft - A case report.

This case describes a 34year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection. She later received a pancreas allograft, again with a weakly positive FCXM, without DSA. After good initial graft function, she developed hyperglycemia six weeks posttransplant. Cross-sectional imaging demonstrated non-enhancing pancreas allograft with new vein thrombosis. She underwent transplant pancreatectomy, the explant pathology demonstrated changes consistent with severe acute antibody mediated rejection (AMR) causing thrombosis of the pancreas allograft. She had also developed several de-novo class-I DSAs at this time. Despite extensive testing, we could not identify a causative antibody for the initial positive FCXMs or its role in the eventual rejection of the pancreas allograft.

Feasibility Testing and Refinement of a Supportive Educational Intervention for Carers of Patients with High-Grade Glioma - a Pilot Study.

The aim of this pilot study was to test the feasibility and acceptability of a family carer intervention for carers of patients with high-grade glioma (HGG). The intervention consisted of: (1) an initial telephone assessment of carer needs; (2) a personalised tabbed resource file; (3) nurse-led home visit; and (4) ongoing telephone support. Two consumer representatives reviewed the intervention resources. The intervention was then piloted with participants who were the primary carer for patients undergoing treatment for HGG in Western Australia. Two consumers provided feedback on the resource, and 10 carers participated in the pilot. Positive feedback was received about the resource manual and intervention. Suggestions were also made for changes which were implemented into the trial. The surveys were shortened based on feedback. Participants identified a large range of issues during nursing assessments which would not otherwise be identified or addressed for carers receiving routine care. As a result of providing the intervention, the nurse was able to make referrals to address needs that were identified. This pilot study enabled us to refine and test the Care-IS intervention and test the feasibility and acceptability of proposed survey instruments. We were also able to estimate recruitment and retention and the overall study timeline required for the randomised controlled trial we are now conducting. It has also demonstrated the role of the nurse who delivered the intervention and allowed us to refine communication and referral pathways.