The V gene repertoires of classical and atypical memory B cells in malaria-susceptible West African children.

Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19(+)/CD20(+)/CD21(+)/CD27(+)/CD10(-)) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19(+)/CD20(+)/CD21(-)/CD27(-)/CD10(-)). At present, the function of atypical MBCs in malaria is not known, nor are the factors that drive their differentiation. To gain insight into the relationship between classical and atypical IgG(+) MBCs, we compared the Ab H and L chain V gene repertoires of children living in a malaria-endemic region in Mali. We found that these repertoires were remarkably similar by a variety of criteria, including V gene usage, rate of somatic hypermutation, and CDR-H3 length and composition. The similarity in these repertoires suggests that classical MBCs and atypical MBCs differentiate in response to similar Ag-dependent selective pressures in malaria-exposed children and that atypical MBCs do not express a unique V gene repertoire.

Chronic rapamycin treatment causes diabetes in male mice.

Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice. We observed that treatment with rapamycin for 52 wk induced diabetes in male mice, characterized by hyperglycemia, significant urine glucose levels, and severe glucose and pyruvate intolerance. Glucose intolerance occurred in male mice by 4 wk on rapamycin and could be only partially reversed with cessation of rapamycin treatment. Female mice developed moderate glucose intolerance over 1 yr of rapamycin treatment, but not diabetes. The role of sex hormones in the differential development of diabetic symptoms in male and female mice was further explored. HET3 mice treated with rapamycin for 52 wk were gonadectomized and monitored over 10 wk. Castrated male mice remained glucose intolerant, while ovariectomized females developed significant glucose intolerance over the same time period. Subsequent replacement of 17ß-estradiol (E2) in ovariectomized females promoted a recovery of glucose tolerance over a 4-wk period, suggesting the protective role of E2 against rapamycin-induced diabetes. These results indicate that 1) oral rapamycin treatment causes diabetes in male mice, 2) the diabetes is partially reversible with cessation of treatment, and 3) E2 plays a protective role against the development of rapamycin-induced diabetes.

Integration of a Simulation Curriculum Across Semesters in an Acute Care Pediatric Nurse Practitioner Program.

INTRODUCTION: Simulation is a common strategy for health care education. Research regarding simulation for nurse practitioner education is sparse. This paper describes the integration of a nine simulation session curriculum into a nurse practitioner program, including motivating factors, process description, and lessons learned. RESULTS: Students report high satisfaction and improved perception of confidence and competence of knowledge, skills, and performance. DISCUSSION: Integrated learning experiences and outcomes that span an educational program are needed in thetransition to competency-based education. This description serves as a guide for other programs seeking to incorporate simulation-based education.

Nasogastric bridles are associated with improved tube-related outcomes in children.

OBJECTIVE: To compare tube-related outcomes in children with standard tape vs nasal bridle securement of nasogastric tubes (NGTs). STUDY DESIGN: This was a single-center, retrospective, correlational study of outcomes from the time of NGT placement until full oral feeds or durable-tube placement. Outcomes of interest included NGT dislodgments, length of stay, emergency department (ED) encounters, radiographic exposures, and adverse skin outcomes. Negative binomial regression and logistic regression were used to analyze differences between groups. RESULTS: Five hundred eighty-two children had NGTs secured traditionally (43% female; age at therapy initiation of 2.6 months [SD 8.1]), and 173 received nasal bridles (55.5% female; age at therapy initiation of 8.4 months [SD 11.8]). Children with bridled NGTs were 16.67 times less likely to experience one or more dislodgments (odds ratio [OR] = 0.06; 95% CI, 0.04-0.09); 2.5 times less likely to have one more ED visit (OR = 0.4; 95% CI, 0.19-0.82), and 4.76 times less likely to require one more radiographic exposure (OR = 0.21; 95% CI, 0.14-0.33) than unbridled children (all P values < 0.02). The mean initial hospital length of stay was 28 and 54 days in the bridled-NGT and standard-care groups, respectively (P < 0.001). Overall, 62.4% children with bridled NGTs and 77.1% children with unbridled NGTs progressed to full oral feedings and discontinued therapy (P < 0.001). Adverse skin outcomes were rare in both groups. CONCLUSION: Children with bridled NGTs experienced fewer dislodgments, hospital days, ED encounters, and radiographic exposures than unbridled NGTs. Most children in both groups progressed to full oral feedings.

Medical Device-related Pressure Injuries Associated With Electroencephalogram Leads in a Tertiary Care Children's Hospital: A Retrospective Chart Review.

BACKGROUND: Medical device-related pressure injuries (MDRPIs) present a substantial safety risk for children who are hospitalized. PURPOSE: This study aimed to describe patient and clinical characteristics of children who develop MDRPIs related to electroencephalogram (EEG) leads, determine risk factors associated with their development, and determine if there are common risk factors that can lead to actionable strategies to reduce MDRPIs related to EEG leads. METHODS: A retrospective review was completed of the electronic health records of all 3136 children who had EEG lead placements between January 1, 2014, and April 16, 2018, at a large tertiary care children's hospital. Data abstracted included demographic variables, patient and pressure injury characteristics, as well as length of stay. RESULTS: Twenty-four (24) of the 3136 children (0.8%) developed an MDRPI. Most were stage 2 pressure injuries. Patients who developed a pressure injury were significantly younger than patients who did not (median age, 0.9 and 5.2 years, respectively; P = .005). Fifty percent (50%) of all patients who developed pressure injuries were younger than 1 year of age compared with 27% of patients who did not develop pressure injuries. The median length of stay for patients in whom MDRPI developed was 84.5 days (interquartile range, 45-137) versus 3.0 days (interquartile range, 2-8) for those who did not develop an MDRPI (P < .001). The mortality rate during the hospital stay was 21% (n = 5) for those who developed MDPRIs versus 4% (n = 19) for those who did not (P = .002). All patients received standard preventive strategies. CONCLUSION: The incidence of MDRPIs in this patient population was significantly higher in younger and longer-stay patients, and their mortality rate was significantly higher. This suggests that the patients who developed an MDRPI were more critically ill than those who did not. Vigilant assessment and more research are needed to determine if there are appropriate strategies to reduce MDRPIs related to EEG lead placement.

Acute Care Pediatric Nurse Practitioners as Leaders: Perceptions, Self-Identity, and Role Congruity.

INTRODUCTION: This study aimed to gain an understanding of practicing acute care pediatric nurse practitioners' (AC-PNPs') perceptions of themselves as leaders in both clinical and professional contexts. METHOD: This qualitative study was conducted at a midwestern quaternary care children's hospital. Cultural domain analysis, semistructured interviews, and free listing techniques were employed to identify areas of consensus and variation among a convenience sample of AC-PNPs. RESULTS: Findings demonstrated the AC-PNPs have a limited self-view of leadership. DISCUSSION: Nurse practitioners need additional leadership capacity and capability building during graduate education, the transition to practice, and throughout their careers.

Living the Manatt report: Advancing the future of nursing through joint academic appointments.

In 2016, the American Association of Colleges of Nursing published the Manatt Report which outlines recommendations to address the future of academic nursing. This report asserts that in order to influence the direction of healthcare, academic nursing needs to partner with academic health centers in leadership positions, embrace current clinical practice, and prioritize research. The following paper details the successful implementation of joint academic appointments between a college of nursing and a medical college. Joint appointments have formalized the role of clinician-educator, brought current clinical knowledge to academia, and allowed for protected academic time that is focused on enhancing the nursing curriculum. The development of joint appointments must be approached in a structured fashion ensuring a symbiotic relationship for all parties. This arrangement validates the commitment of both organizations to the education of future providers within the interdisciplinary team.

Creation and Implementation of a Pediatric Advanced Practice Nurse Critical Care Fellowship Program.

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Skin integrity in critically ill and injured children.

BACKGROUND: Skin breakdown increases the cost of care, may lead to increased morbidity, and has negative psychosocial implications because of secondary scarring or alopecia. The scope of this problem has not been widely studied in critically ill and injured children. OBJECTIVES: To determine the incidence of skin breakdown in critically ill and injured children and to compare the characteristics of patients who experience skin breakdown with those of patients who do not. METHODS: Admission and follow-up data for a 15-week period were collected retrospectively on children admitted to a large pediatric intensive care unit. The incidence of skin breakdown was calculated. The risk for skin breakdown associated with potential risk factors (relative risk) and 95% confidence intervals were determined. RESULTS: The sample consisted of 401 distinct stays in the intensive care unit for 373 patients. During the 401 stays, skin breakdown occurred in 34 (8.5%), redness in 25 (6.2%), and breakdown and redness in 13 (3.2%); the overall incidence was 18%. Patients who had skin breakdown or redness were younger, had longer stays, and were more likely to have respiratory illnesses and require mechanical ventilatory support than those who did not. Patients who had skin breakdown or redness had a higher risk of mortality than those who did not. CONCLUSIONS: Risk factors for skin breakdown were similar to those previously reported. Compared with children of other ages, children 2 years or younger are at higher risk for skin breakdown.

Pediatric Skin Failure.

BACKGROUND: The phenomenon of skin failure as distinct from pressure ulcers has been documented in the adult literature. However, in the pediatric population, skin injury continues to be grouped indiscriminately as various types of pressure ulcers. OBJECTIVE: To identify and describe the phenomenon of skin failure in critically ill children. METHODS: Retrospective chart review of 19 patients who had serious skin injuries develop. Organ dysfunction scores, medications, pressure ulcer prevention techniques used, and laboratory values in the 7 days leading up to the development of a skin lesion were evaluated. RESULTS: At the start of the evaluation period, all patients (N = 19) had pressure ulcer prevention measures in place before the development of a serious skin injury. All of the skin lesions were full-thickness injuries on the day they were identified (as opposed to the more gradual progression from simple to complex skin injuries typically seen in pressure ulcers). As predicted, 18 of 19 patients had multiple organ dysfunction syndrome (MODS) in the week leading up to the skin injury. All patients with MODS had at least 2 dysfunctional systems, and 12 patients had 4 or more dysfunctional systems. Of the 19 patients, 8 (42%) progressed to death, compared with 1.8% in our general pediatric intensive care unit population. CONCLUSION: Although the traditional paradigm is that pressure ulcers are preventable, a subset of pressure ulcers in critically ill children may actually represent acute skin failure as a consequence of MODS.

A Quantitative Diffuse Reflectance Imaging (QDRI) System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins.

In an ongoing effort to address the clear clinical unmet needs surrounding breast conserving surgery (BCS), our group has developed a next-generation multiplexed optical-fiber-based tool to assess breast tumor margin status during initial surgeries. Specifically detailed in this work is the performance and clinical validation of a research-grade intra-operative tool for margin assessment based on diffuse optical spectroscopy. Previous work published by our group has illustrated the proof-of-concept generations of this device; here we incorporate a highly optimized quantitative diffuse reflectance imaging (QDRI) system utilizing a wide-field (imaging area = 17 cm(2)) 49-channel multiplexed fiber optic probe, a custom raster-scanning imaging platform, a custom dual-channel white LED source, and an astronomy grade imaging CCD and spectrograph. The system signal to noise ratio (SNR) was found to be greater than 40 dB for all channels. Optical property estimation error was found to be less than 10%, on average, over a wide range of absorption (µa = 0-8.9 cm(-1)) and scattering (µs' = 7.0-9.7 cm(-1)) coefficients. Very low inter-channel and CCD crosstalk was observed (2% max) when used on turbid media (including breast tissue). A raster-scanning mechanism was developed to achieve sub-pixel resolution and was found to be optimally performed at an upsample factor of 8, affording 0.75 mm spatially resolved diffuse reflectance images (λ = 450-600 nm) of an entire margin (area = 17 cm(2)) in 13.8 minutes (1.23 cm(2)/min). Moreover, controlled pressure application at the probe-tissue interface afforded by the imaging platform reduces repeated scan variability, providing <1% variation across repeated scans of clinical specimens. We demonstrate the clinical utility of this device through a pilot 20-patient study of high-resolution optical parameter maps of the ratio of the ß-carotene concentration to the reduced scattering coefficient. An empirical cumulative distribution function (eCDF) analysis is used to reduce optical property maps to quantitative distributions representing the morphological landscape of breast tumor margins. The optimizations presented in this work provide an avenue to rapidly survey large tissue areas on intra-operative time scales with improved sensitivity to regions of focal disease that may otherwise be overlooked.

Under pressure: preventing pressure ulcers in critically ill infants.

PURPOSE: To determine whether a pressure ulcer prevention bundle was associated with a significant reduction in pressure ulcer development in infants in the pediatric intensive care unit. DESIGN AND METHODS: Quasi-experimental design involving 399 infants 0 to 3 months of age at a large tertiary care medical center. RESULTS: The implementation of the care bundle was associated with a significant drop in pressure ulcer incidence from 18.8 to 6.8%. PRACTICE IMPLICATIONS: Pressure ulcers can be prevented in the most vulnerable patients with the consistent implementation of evidence-based interventions and system supports to assist nurses with the change in practice.

A survey of NAPNAP members' clinical and professional research priorities.

INTRODUCTION: The purpose of this methodological article is to describe the development, implementation, and analysis of the survey used to determine NAPNAP members' ranking of research priorities, to describe the top priorities ranked by participants, and to determine if priorities differed by area of practice (primary, acute, or specialty care) or participant age. METHOD: A cross-sectional descriptive design with an online survey was used. Completed by 324 NAPNAP members, the survey consisted of a demographic section and 90 statements in two domains: Clinical Priorities and Professional Role Priorities. RESULTS: Survey respondents strongly supported the top priorities with an average overall mean score of 4.0 or above on a 5-point Likert scale. Only three of the top 10 clinical and professional priorities differed by area of practice. No clinical priorities and only three professional priorities differed by age. DISCUSSION: The survey results were used to develop the NAPNAP Research Agenda. Both the survey results and the agenda can provide guidance for the NAPNAP Board, committees and interests groups as they develop initiatives and programs.

Protecting fragile skin: nursing interventions to decrease development of pressure ulcers in pediatric intensive care.

BACKGROUND: The reported incidence of pressure ulcers in critically ill infants and children is 18% to 27%. Patients at risk for pressure ulcers and nursing interventions to prevent the development of the ulcers have not been established. OBJECTIVES: To determine the incidence of pressure ulcers in critically ill children, to compare the characteristics of patients in whom pressure ulcers do and do not develop, and to identify prevention strategies associated with less frequent development of pressure ulcers. METHODS: Characteristics of 5346 patients in pediatric intensive care units in whom pressure ulcers did and did not develop were compared. Multiple logistic regression was used to determine which prevention strategies were associated with less frequent development of pressure ulcers. RESULTS: The overall incidence of pressure ulcers was 10.2%. Patients at greatest risk were those who were more than 2 years old; who were in the intensive care unit 4 days or longer; or who required mechanical ventilation, noninvasive ventilation, or extracorporeal membrane oxygenation. Strategies associated with less frequent development of pressure ulcers included use of specialty beds, egg crates, foam overlays, gel pads, dry-weave diapers, urinary catheters, disposable under-pads, body lotion, nutrition consultations, change in body position every 2 to 4 hours, blanket rolls, foam wedges, pillows, and draw sheets. CONCLUSIONS: The overall incidence of pressure ulcers among critically ill infants and children is greater than 10%. Nursing interventions play an important role in the prevention of pressure ulcers.